Ιατρικά Άρθρα

Τετάρτη 12 Ιουλίου 2017

Determination of cyclic volatile methylsiloxanes in personal care products by gas chromatography

Abstract

Objective

Organosiloxanes are prevalent in personal care products (PCPs) due to the desired properties they impart in the usage and application of such products. However, the European Chemical Agency (ECHA) has recently published restriction proposals on the amount of two cyclic siloxanes, octamethylcyclotetrasiloxane (D4) and decamethylcyclotetrasiloxane (D5) allowed in wash off products such as shampoos and conditioners which are discharged down the drain during consumer use. This legislation will require that reliable analytical methods are available for manufacturers and government agencies to use in documenting compliance with the restrictions. This paper proposes a simple analytical method to enable accurate measurement of these compounds down to the circa 0.1 weight percent level in PCPs.

Methods

While gas chromatography methods are reported in the literature for quantitation of D4 and D5 in several matrices including PCPs, the potential for generation of false positives due to contamination, co-elution, and in-situ generation of cyclic volatile methylsiloxanes (cVMS) is always present and needs to be controlled. This report demonstrates the applicability of using a combination of emulsion break, liquid-liquid extraction and silylation sample preparation followed by GC-FID analysis as a suitable means of analyzing PCPs for specific cVMS.

Results

The reliability and limitations of such methodology was demonstrated through several round robin studies conducted in the laboratories of a consortium of silicone manufacturers. In addition, this report presents examples of false positives encountered during development of the method and presents a comparative analysis between this method and a published QuEChERS sample preparation procedure to illustrate the potential for generation of false positives when an inappropriate approach is applied to determination of cVMS in personal care products.

Conclusion

This report demonstrates that an approach to determine cVMS levels in personal care products is to perform an emulsion break on the sample, isolate the nonpolar phase from the emulsion break and treat with a silylation reagent to abate potential in situ formation of cyclics during the course of GC-FID analysis. Round robin studies conducted in laboratories representing multiple siloxane manufacturers demonstrated the reliability of the GC-FID method when measuring cVMS in PCPs down to circa 0.1%.

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Conventional sunscreen application does not lead to sufficient body coverage

Abstract

Objective

This study aimed to assess sunscreen application habits and relative body coverage after single whole body application.

Methods

Fifty-two healthy volunteers were asked to use the test product once, following their usual sunscreen application routine. Standardized UV photographs (UVP), which were evaluated by Image Analysis (IA), were conducted before and immediately after product application to evaluate relative body coverage. In addition to these procedures, the volunteers completed an online self-assessment questionnaire (SAS) to assess sunscreen usage habits.

Results

After product application, the front side showed significantly less non-covered skin (4.35%) than the backside (17.27%) (p=0.0000). Females showed overall significantly less non-covered skin (8.98%) than males (13.16%) (p=0.0381). On the backside, females showed significantly less non-covered skin (13.57%) (p=0.0045) than males (21.94%) while on the front side this difference between females (4.14%) and males (4.53%) was not significant.

Conclusion

In most cases, the usual sunscreen application routine does not provide complete body coverage even though an extra light sunscreen with good absorption properties was used. On average, 11 % of the body surface was not covered by sunscreen at all. Therefore, appropriate consumer education is required to improve sunscreen application and to warrant effective sun protection.

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Novel amino acid-based surfactant for silicone emulsification and its application in hair care products: A promising alternative to quaternary ammonium cationic surfactants

Abstract

Objective

Quaternary ammonium cationic surfactants (ACSs) and N-[3-alkyl(12,14)oxy-2-hydroxypropyl]-L-arginine hydrochloride (N-AOHPA) were used to emulsify silicone. The potential of the resulting emulsions in hair conditioning products was investigated.

Methods

The emulsions were prepared using a homogenizer and/or high-pressure homogenizer. ACSs and N-AOHPA were used as silicone emulsifiers. The stability of the emulsions were evaluated by measuring particle sizes, creaming fractions, polydispersity indexes and zeta potentials. Moreover, the N-AOHPA-stabilized emulsion was compared with the ACS-stabilized emulsion to evaluate the adsorption amount of silicone on healthy and bleached hair surfaces and the inhibitory effects on amino acid dissolution from bleached hair. The adsorption site of the N-AOHPA-stabilized emulsion was observed using a scanning electron microscope.

Results

For all surfactants, the silicone emulsions prepared using the high-pressure homogenizer were more stable than those prepared using the homogenizer. When N-AOHPA was used as the surfactant, the silicone emulsion was especially stable. Furthermore, the d50 value of the N-AOHPA-stabilized emulsion was smaller than that of the ACS-stabilized emulsion. The adsorption behavior of the silicone droplets in the different emulsions varied depending on the nature of the surfactant and the preparation method. The amount of ACS-stabilized silicone adsorbed on healthy hair was higher than that adsorbed on bleached hair, especially when the emulsion was prepared using the homogenizer. In contrast, the amount of N-AOHPA-stabilized silicone adsorbed on bleached hair was high, and no differences were observed between the N-AOHPA-stabilized emulsions prepared using the homogenizer and high-pressure homogenizer. The emulsified droplets, especially the N-AOHPA-stabilized droplets prepared using the high-pressure homogenizer, prevented amino acid dissolution from bleached hair. It was concluded that the silicone droplet adsorption site affected the dissolution process because the small N-AOHPA-stabilized droplets adsorbed at cuticle edges.

Conclusion

This study shows that N-AOHPA has good potential for use as an emulsifier in products used for improving the condition of damaged hair.

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Understanding the effects of topography on skin moisturization measurement via 2 dimensional capacitance imaging

Abstract

Objective

Methods which assess skin moisturization based on changes in its electrical properties are widely used in both cosmetic and medical research industries. However the devices themselves often give results which are significantly different to each other. Recently 2 dimensional imaging moisturization systems have become commercially available, which have the capability to provide a more detailed assessment of what is contributing to measured skin moisturization. Presented here is a new in vitro method for preparing textured model test substrates for use with these devices, and results of their use to provide a clearer insight into the devices operation.

Methods

A variety of different textured model test substrates were measured using a commercially available skin moisturization measurement device, the Epsilon. The response of the Epsilon was also tested against conventional skin moisturization devices.

Results

Surface morphology of model test substrates was found to have a significant influence on the measurement of its electrical properties with both the conventional and 2 dimensional skin moisturization measurement devices. Through modification of the areas of the image being assessed for the 2 dimensional moisturization mapping device, the parts of the model test substrate in contact with the device were indentified and analysed separately to areas not in contact with the sensor. This provided a more robust assessment of the electrical properties of substrate itself, rather than being influenced by texture like the conventional skin moisturization measurement devices.

Conclusions

While the 2 dimensional moisturization mapping systems can be used like a conventional electrical skin measurement device giving a simple overall reading of skin moisturization for the test area, their true value over existing electrical measures comes from its ability to isolate the skin itself from areas which are not in contact with the sensor.

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Recovery from Bell Palsy after Transplantation of Peripheral Blood Mononuclear Cells and Platelet-Rich Plasma

Summary: Peripheral blood mononuclear cells (PBMCs) are multipotent, and plasma contains growth factors involving tissue regeneration. We hypothesized that transplantation of PBMC-plasma will promote the recovery of paralyzed facial muscles in Bell palsy. This case report describes the effects of PBMC-plasma transplantations in a 27-year-old female patient with right side Bell palsy. On the affected side of the face, the treatment resulted in both morphological and functional recovery including voluntary facial movements. These findings suggest that PBMC-plasma has the capacity of facial muscle regeneration and provides a promising treatment strategy for patients suffering from Bell palsy or other neuromuscular disorders.

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Lymphaticovenous Bypass: Adaptations and Lessons Learned

Summary: Advances in microsurgical instruments and techniques have allowed for introduction of lymphaticovenous anastomosis as a potential surgical treatment for patients with upper and lower extremity lymphedema. This article reviews the approach to lymphaticovenous anastomosis patient selection and technical modifications that improve the ease and efficiency of the procedure.

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The Effect of the Timing of Radiotherapy on Clinical and Patient-Reported Outcomes After Latissimus Dorsi Breast Reconstruction: A 10-Year Study

Background: Breast reconstruction (BR) is considered to be adversely affected by radiotherapy (RT), particularly when an implant is used. The aim of this study was to compare clinical and patient-reported outcomes after expander-assisted latissimus dorsi breast reconstruction depending on the timing of RT. Methods: Patients undergoing BR over a 10-year period (follow-up mean, 56 [14–134] months) were divided into 3 groups. Group 1, RT after mastectomy and BR, Group 2, RT before mastectomy and BR, and Group 3, RT after mastectomy but before BR. The primary endpoints were early and late surgical interventions. Validated questionnaires were circulated to all study patients and matched controls. Results: Three hundred thirteen patients underwent 389 BRs. One hundred eighteen patients received RT, of which 65 had undergone expander-assisted latissimus dorsi breast reconstruction. Both use and timing of RT influenced clinical outcomes. Overall, use of RT resulted in a 3-fold increase in complications (P = 0.003). Postreconstruction RT resulted in more than double the number of complications compared with prereconstruction RT (P = 0.008) and delaying BR until after mastectomy and RT reduced complications to levels observed in control patients (P = nonsignificant). Complications were halved in patients undergoing autologous LD reconstruction (P = 0.0001). Patient-reported outcomes were similar for emotional well-being, satisfaction, and shoulder symptoms, although a nonsignificant increase in chronic breast symptoms was reported by the RT group. Conclusion: The timing and type of LD reconstruction chosen by patients receiving RT has a significant impact on the risk of subsequent complications and unplanned interventions but has little impact on longer term patient well-being or satisfaction.

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Lipoabdominoplasty with Progressive Traction Sutures

Background: Proactively preserving Scarpa's fascia and thus its intrinsic lymphatic drainage and tensile strength for suture placement can eliminate the need for drains after lipoabdominoplasty and therefore reduce the rate of seroma development. In this article, we describe the effectiveness of a modified progressive traction suture (PTS) technique, which enables us to lessen the most common complications and avoid hospital readmission; these sutures take 3–5 minutes of additional surgery time. Methods: Two hundred seventy-six patients (mean age, 38 years; range, 19–67 years), with a mean body mass index of 25 were included in this study. All patients underwent complete lipoabdominoplasty with ultrasound-assisted liposuction (VASER) throughout the abdomen and flanks. Abdominal rectus plication was performed in 100% of cases. All patients were operated on under spinal anesthesia and stayed overnight in hospital. Results: Of the 276 patients, 1.8% developed postoperative seromas. No patients developed hematomas. New wound closure was needed in 1.4% of patients, performed within 7–10 days of surgery, scar revision in 4.7%, residual liposuction under local anesthesia in 9.7%, and liposuction under sedation in 1%; deep vein thrombosis without thromboembolic phenomenon developed in 1%, none resulting in death. In addition, the use of a PTS technique is a time-saving procedure because it takes the surgeons between 3–5 minutes of operative time, unlike that of adhesion and/or separate traction, which takes between 30 and 45 minutes. Conclusions: The use of PTSs helped diminish complications such as seroma and hematoma and prevent additional cost involving hospital readmission and/or further surgery. Furthermore, use of these sutures required only 3–5 minutes of additional operative time.

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Tc-99m-Human Serum Albumin Transit Time as a Measure of Arm Breast Cancer-Related Lymphedema

Background: Lymphoscintigraphy has often been used for evaluating arm lymphatic dysfunction, but no optimal approach for quantification has so far emerged. We propose a quantifiable measure of lymphatic function that we applied in patients treated for breast cancer. Methods: Eleven patients, aged 34–68 years, with unilateral arm lymphedema following breast cancer treatment underwent bilateral lymphoscintigraphy using intradermal injection in both hands of technetium-99m–labeled human serum albumin and sequential 5 min imaging for 5 hours. The mean transit time (MTT) in the arms was calculated based on time activity curves generated from injection site and arm regions. Visual lymphedema scoring was performed based on dermal backflow and lymph node presence. Excess arm volume was calculated from circumference measurements. Results: The MTT (mean ± SD) was significantly longer in the lymphedema arm than in the normal arm: 60.1 ± 27.7 versus 5.4 ± 2.5 minutes (mean difference, 54.7 minutes; 95% confidence interval, 36.5–72.9 minutes; P

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Using the Venous Pectoral Branch from the Thoracoacromial System as a Lifeboat in Autologous Breast Reconstruction

Summary: The most common recipient vessels for autologous free flap breast reconstruction are the internal mammary vessels. At times, there are problems with the exposed internal mammary vein (IMV) that require other options such as using the contralateral IMV, superior rib resection to access proximal IMV, retrograde IMV use, and thoracodorsal vein access with or without a vein graft. This case demonstrates using the pectoral branch of the thoracoacromial venous system without a vein graft as a lifeboat option when the IMV is not suitable for anastomosis. C.W. was a 65-year-old female who underwent right-sided mastectomy with placement of a tissue expander. After adjuvant radiation therapy, C.W. underwent deep inferior epigastric perforator free flap breast reconstruction. During exposure of the internal mammary artery and IMV, an iatrogenic venotomy occurred that precluded the use of this vessel as a reliable recipient. The deep inferior epigastric perforator flap pedicle was then dissected proximal to isolate the artery and vein, and the vein was successfully anastomosed to the venous pectoral branch of the thoracoacromial system. The postoperative course was uneventful and patient was discharged home on postoperative day 4. Using the venous pectoral branch of the thoracoacromial is a safe and valuable option that can be considered in difficult situations when the IMV is not a suitable option.

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Direct to Implant Reconstruction in Nipple Sparing Mastectomy: Patient Selection by Preoperative Digital Mammogram

Background: Digital mammography clearly distinguishes gland tissue density from the overlying nonglandular breast tissue coverage, which corresponds to the existing tissue between the skin and the superficial layer of the fascia superficialis surrounding the gland (i.e., dermis and subcutaneous fat). Preoperative digital imaging can determine the thickness of this breast tissue coverage, thus facilitating planning and reducing the rate of necrotic complications after direct to implant (DTI) reconstruction in nipple sparing mastectomy (NSM). Methods: Thirty NSMs in 22 patients with type 3 tissue coverage (subcutaneous tissue thickness of 2 cm or more) were selected for DTI reconstruction after NSM to evaluate immediate skin flap/nipple areola complex ischemic complications and patient satisfaction. Results: We experienced no wound healing problems or ischemic complications immediately after surgery in our population. Only 1 seroma was observed as a short-term complication. Quality of life and patients' satisfaction level were optimal at 3 and 6 months follow-up, respectively. The aesthetic results have been evaluated as good/excellent in all cases. Conclusions: DTI immediate reconstruction with silicone implants following NSM appears to be a safe option in selected cases with enough tissue coverage, also providing a high level of patient satisfaction. The possibility of selecting cases for this procedure according to the preoperative digital mammogram showing more than 2 cm of superficial tissues thickness may help reducing the risk of immediate ischemic complications.

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Team Work: Mastectomy, Reconstruction, and Radiation

No abstract available

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Acellular Dermal Matrix Versus Inferior Deepithelialized Flap Breast Reconstruction: Equivalent Outcomes, with Increased Cost

Background: Approximately 250,000 new cases of breast cancer are diagnosed yearly in the U.S. resulting in more postmastectomy breast reconstructions (PMBRs). The acellular dermal matrix (ADM) expander-implant method became popular in the mid-2000s, but newer techniques such as the inferior deepithelialized flap (IDF) has more recently been described. We hypothesize that ADMs and IDFs provide comparable aesthetic outcomes, with no difference in complication rates and operative characteristics. Methods: A retrospective, single-institution study was performed between July 1, 2012, and June 30, 2014, examining all PMBR's (ADM and IDF). Outcomes were categorized as clinical (e.g., complications requiring surgical intervention) or aesthetic. Results: A total of 65 patients (41 ADM; 24 IDF; mean age, 53.4 ± 10.7 years) were included, with 101 PMBR's evaluated (63 ADM and 38 IDF). Patients who underwent IDFs had higher body mass index (32 versus 25; P

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Unilateral Internal Mammary Recipient Vessels for Bilateral DIEP Flap Breast Reconstruction

Summary: The deep inferior epigastric perforator flap has become increasingly popular for breast reconstruction with the most common recipient vessels being the internal mammary artery and vein. In certain cases, however, these recipient vessels are inadequate due to an absent or diminutive vein. Moreover, patients at high risk for future coronary artery disease may sacrifice the best conduit for coronary revascularization if the internal mammary recipients are used. Alternative recipient vessels, including the thoracodorsal, thoracoacromial, external jugular, and cephalic vessels have significant limitations. In this report, we describe a novel technique using unilateral internal mammary recipient vessels for bilateral free flap breast reconstruction. Two cases are presented that represent distinct indications for this technique: (1) absence or inadequacy of unilateral recipient vessels and (2) preservation of the left internal mammary system for future bypass in patients at high risk for coronary artery disease.

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Goldilocks Mastectomy: A Safe Bridge to Implant-Based Breast Reconstruction in the Morbidly Obese

Background: Reconstructive surgeons are encountering an increasing number of obese women requiring postmastectomy reconstruction. These patients are poor candidates for autologous and prosthetic-based reconstructions as they have a high rate of reconstructive failure, surgical complications, and poor aesthetic outcomes. We demonstrate here the utility of the previously described Goldilocks mastectomy with free nipple grafts as a safe bridge to second stage implant-based breast reconstruction. Methods: Ten consecutive morbidly (BMI > 40) or super obese (BMI>50) women underwent bilateral Goldilocks mastectomy with free nipple grafts followed by second stage subpectoral implant placement at least three months postoperatively. Patients were assessed for implant-related complications including malposition, capsular contracture, dehiscence, and extrusion. Results: Ten postmastectomy reconstructions in patients with BMIs ranging from 37 to 50 with a mean BMI of 45 underwent bilateral Goldilocks mastectomy with free nipple grafts. Two patients had wound healing complications after Goldilocks mastectomy but were completely healed within 8 weeks. There were no instances of delayed wound healing or reconstructive failure after prosthetic placement. With at least 9 months of follow-up on all patients, no patient has had a capsular contracture, significant malposition, or other complication requiring reoperation. Conclusion: The obese patient poses a significant reconstructive challenge for which no reproducible approach has been described. Here, we present a 2-stage strategy: the previously described Goldilocks mastectomy with free nipple grafts followed by second stage subpectoral definitive implant placement. This is the first proposed description of a reliable strategy for postmastectomy reconstruction in the morbidly and super obese.

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Relationship between Keloid Formation and YAP/TAZ Signaling

Summary: YAP (yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are part of a classical pathway that controls contact inhibition in the Hippo pathway. YAP and TAZ were recently reported to act as nuclear relays of mechanical signals that communicate extracellular matrix rigidity and cell shape. However, the role of YAP/TAZ signaling in keloid formation is unclear. Here, we used immunohistochemistry to investigate YAP/TAZ expression in keloid and nonaffected lesions. YAP/TAZ expression in keloid fibroblasts had a greater tendency to localize to the nucleus relative to that seen in fibroblasts from unaffected tissues. Meanwhile, keratinocytes or endothelial cells from either keloid or unaffected tissues showed no significant differences in YAP/TAZ expression patterns. These results suggest that YAP/TAZ nuclear localization in keloid fibroblasts might activate Hippo signaling and may play an important role in gene expression that affects keloid formation and stiffness.

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Long-Term Health-Related Quality of Life after Breast Reconstruction: Comparing 4 Different Methods of Reconstruction

Background: Studies have confirmed that breast reconstruction is beneficial to improve health-related quality of life (HR-QoL) in breast cancer patients. Our aim was to compare 4 different methods of breast reconstruction on patient satisfaction and HR-QoL using both general and specific patient-reported outcome instruments. Methods: Retrospectively, 459 patients who underwent breast reconstruction with a deep inferior epigastric artery perforator (DIEP) flap, latissimus dorsi flap, lateral thoracodorsal flap, or expander with secondary implant and who had responded to the questionnaires were enrolled. Questionnaire answers, together with demographic and follow-up data, were statistically analyzed and compared between groups. Short-Form 36 Health Survey (SF-36) results were also compared with those from a sample of 930 age-matched women from the Swedish population. Results: There were slight differences in the SF-36 results but no significant differences in Psychological General Well-Being Index and EuroQoL-5 Dimension Questionnaire results between groups. Analysis of Breast-Q showed that the DIEP group had significantly higher score on the scale satisfaction with breast, significantly higher score in satisfaction with outcome than the lateral thoracodorsal flap (P = 0.014) and EXP groups (P = 0.024). There were no significant differences in most of the domains of the HR-QoL instruments. The higher satisfaction with breasts and outcome in the DIEP group is interesting, considering the higher complication rates associated with this reconstruction method. Conclusions: Patients who underwent breast reconstruction with a DIEP flap were more satisfied with their reconstructed breast and outcome than the other 3 groups. Breast reconstruction centers should make DIEP reconstruction widely available to patients after mastectomy.

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fMRI after Phalloplasty with Nerve Anastomosis in a Trans-Man Patient

Summary: We report on a case of a trans-man patient, who underwent penile reconstruction with the use of a radial forearm flap, urethroplasty, vaginectomy and scrotoplasty, insertion of testicle implants, and penile erection implants, similar to previously described methods. One of the requirements for an ideal phalloplasty is the preservation of erogenous sensitivity, which is often demanded by the patients for fulfilling their sexual well-being. For the first time known to us, we use a functional magnetic resonance imaging following radial forearm flap phalloplasty with nerve anastomosis to assess the cortical activation after clitoral stimulation. The patient was poked with a plastic pen on the neophallus and the groin. Regular block design with T1 and BOLD-T2* images were used. The results contradict the classic Penfield and Rasmussen homunculus, that is, the activations in the primary somatosensory cortex (S1) were bilateral with a left-sided dominance in the lateral parts of the medial postcentral gyrus (same region as the groin), and no activations were observed in the mesial parts of the postcentral gyrus. We also reported bilateral activations with a left-sided dominance in the secondary somatosensory cortex (S2) and near Broca's area at the sylvian fissure just posterior to ramus ascendens. Our findings are similar to previous studies reporting on imaging related to genital sensitivity.

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Acute A4 Pulley Reconstruction with a First Extensor Compartment Onlay Graft

Background: The integrity of the flexor tendon pulley apparatus is crucial for unimpaired function of the digits. Although secondary reconstruction is an established procedure in multi-pulley injuries, acute reconstruction of isolated, closed pulley ruptures is a rare occurrence. There are 3 factors influencing the functional outcome of a reconstruction: gapping distance between tendon and bone (E-space), bulkiness of the reconstruction, and stability. As direct repair is rarely done, grafts are used to reinforce the pulley. An advantage of the first extensor retinaculum graft is the synovial coating providing the possibility to be used both as a direct graft with synovial coating or as an onlay graft after removal of the synovia when the native synovial layer is present. Methods: A graft from the first dorsal extensor compartment is used as an onlay graft to reinforce the sutured A4 pulley. This technique allows reconstruction of the original dimensions of the pulley system while stability is ensured by anchoring the onlay graft to the bony insertions of the pulley. Results: Anatomical reconstruction can be achieved with this method. The measured E-space remained 0 mm throughout the recovery, while the graft incorporated as a slim reinforcement of the pulley, displaying no bulkiness. Conclusions: The ideal reconstruction should provide synovial coating and sufficient strength with minimal bulk. Early reconstruction using an onlay graft offers these options. The native synovial lining is preserved and the graft is used to reinforce the pulley.

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Venous Thromboembolism Risk Stratification and Chemoprophylaxis: A Meta-Analysis Finds No Benefit, More Risk

No abstract available

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Early Cleft Lip Repair Revisited: A Safe and Effective Approach Utilizing a Multidisciplinary Protocol

Background: The optimal timing for cleft lip repair has yet to be established. Advances in neonatal anesthesia, along with a growing body of literature, suggesting benefits of earlier cleft lip and nasal repair, have set the stage for a reexamination of current practices. Methods: In this prospective study, cleft lip and nasal repair occurred on average at 34.8 days (13–69 days). Nasal correction was achieved primarily through molding the nasal cartilage without the placement of nasal sutures at the time of repair. A standardized anesthetic protocol aimed at limiting neurotoxicity was utilized in all cases. Anesthetic and postoperative complications were assessed. A 3-dimensional nasal analysis compared pre- and postoperative nasal symmetry for unilateral clefts. Surveys assessed familial response to repair. Results: Thirty-two patients were included (27 unilateral and 5 bilateral clefts). In this study, the overall complication rate was 3.1%. Anthropometric measurements taken from 3-dimensional-image models showed statistically significant improvement in ratios of nostril height (preoperative mean, 0.59; postoperative mean, 0.80), nasal base width (preoperative mean, 1.96; postoperative mean, 1.12), columella length (preoperative mean, 0.62; postoperative mean, 0.89; and columella angle (preoperative mean, 30.73; postoperative mean, 9.1). Survey data indicated that families uniformly preferred earlier repair. Conclusions: We present evidence that early cleft lip and nasal repair can be performed safely and is effective at improving nasal symmetry without the placement of any nasal sutures. Utilization of this protocol has the potential to be a paradigm shift in the treatment of cleft lip and nasal deformity.

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Gender Confirmation Surgery: Cosmetic or Reconstructive Procedure?

No abstract available

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A Population-Based Exploration of the Social Implications Associated with Cleft Lip and/or Palate

Background: Clefts of the lip and/or palate (CL/P) carry a social stigma that often causes psychosocial stress. The purpose of this study was to consider the association of cleft phenotype and age with self-reported aspects of psychosocial stress. Methods: Children with nonsyndromic CL/P and unaffected children born between 1997 and 2003 were identified through the North Carolina Birth Defects Monitoring Program and North Carolina birth records, respectively. The psychosocial concerns of children with CL/P were assessed via a 29-question subset of a larger survey. Responses were analyzed according to school age and cleft phenotype (cleft lip with/without cleft alveolus, CL ± A; cleft palate only, CP; or cleft lip with cleft palate, CL + P). Results: Surveys were returned for 176 children with CL/P and 333 unaffected children. When compared with unaffected children, responses differed for CL ± A in 4/29 questions, for CP in 7/29 questions, and for CL + P in 8/29 questions (P

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Using the Gluteal Artery Perforator Flap to Reconstruct Sacral Sore

No abstract available

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Clinical utility of contrast-enhanced spectral mammography as an adjunct for tomosynthesis-detected architectural distortion

Publication date: Available online 12 July 2017
Source:Clinical Imaging
Author(s): Bhavika K. Patel, Michelle E. Naylor, Heidi E. Kosiorek, Yania M. Lopez-Alvarez, Adrian M. Miller, Victor J. Pizzitola, Barbara A. Pockaj
ObjectiveSupplement tomosynthesis-detected architectural distortions (AD) with CESM to better characterize malignant vs benign lesions.MethodsRetrospective review CESM prior to biopsied AD. Pathology: benign, radial scar, or malignant.Results49 lesions (45 patients). 29 invasive, 1 DCIS (range, 0.4–4.7cm); 9 radial scars; 10 benign. 37 (75.5%) ADs had associated enhancement. PPV 78.4% (29/37), sensitivity 96.7% (29/30); specificity, 57.9% (11/19); NPV, 91.7% (11/12). False-positive rate 21.6% (8/37); false-negative rate, 8.3% (1/12). Accuracy 81.6% (40/49).ConclusionsHigh sensitivity and NPV of CESM in patients with AD is promising as an adjunct tool in diagnosing malignancy and avoiding unnecessary biopsy, respectively.

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Thyroglossal duct cysts in children: Sonographic features every radiologist should know and their histopathological correlation

Publication date: Available online 12 July 2017
Source:Clinical Imaging
Author(s): Emilio Inarejos Clemente, Modupe Oyewumi, Evan Probst, Bo-Yee Ngan, Mary-Louise Greer
Distinguishing between thyroglossal duct cysts (TGDC) and dermoid cysts (DC) sonographically can be challenging. We illustrate the three sonographic features in neck masses in children recently identified as being most suggestive of TGDC (septa, irregular wall and solid elements) and their corresponding histopathology. These three variables form a proposed predictive model for TGDC as a guide to surgical intervention. Pediatric radiologists should be familiar with these key imaging features, as compared with other imaging features described in TGDC also illustrated here, which are less discriminating.

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Assessing tumor extent on contrast-enhanced digital mammography versus full-field digital mammography and ultrasound

Publication date: Available online 12 July 2017
Source:Clinical Imaging
Author(s): Bhavika Patel, Sandra Alheli Garza, Sarah Eversman, Yania Lopez-Alvarez, Heidi Kosiorek, Barbara Pockaj
ObjectivesThe objective of our study was to compare breast tumor size measurements on full-field digital mammography (FFDM), contrast-enhanced Digital mammography (CEDM), and ultrasound (US), with histologic tumor size used as the reference standard.Material and methodsThe study comprised 88 women with newly diagnosed breast cancer who underwent FFDM and CEDM. Breast density and maximum tumor measurements were recorded: 88 women had FFDM and CEDM; 74 also had US.ResultsPearson correlation coefficients for FFDM, US, and CEDM vs histopathology were 0.598, 0.639, and 0.859, respectively (P<0.001). Of the 88 patients, 48 had dense and 40 had nondense breasts. The following correlation coefficients were calculated for dense breasts: histopathology vs FFDM (0.555), US (0.633), and CEDM (0.843) (P<0.001); for nondense breasts, they were FFDM (0.618), US (0.512), and CEDM (0.885) (P<0.001). For size difference, the mean (SD) for histopathology vs FFDM, US, and CEDM was −1.3 (11.9) mm, −2.8 (11.1) mm, and 2.9 (9.5) mm, respectively. Limits of agreement were −24.8 to 22.0mm, −24.5 to 18.8mm, and −15.6 to 21.4mm, respectively.ConclusionsIn biopsy proven patients with biopsy-proven malignancy, size measurements coreelated well histopathologic size, and were higher on CEDM than those for FFDM and US in patients with dense or nondense breasts. The added value of CEDM as a supplement to FFDM in determining tumor size, however, was greater in patients with dense breasts. CEDM may be a promising alternative preoperative measurement tool for breast cancer patients with dense breasts or limited access or contraindications to MRI.

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Measuring liver cyst volumes on MRI or cyst volumes above in autosomal dominant polycystic kidney disease (ADPKD)

Publication date: Available online 12 July 2017
Source:Clinical Imaging
Author(s): Zerwa Farooq, Ashkan Heshmatzadeh Behzadi, Jon D. Blumenfeld, Yize Zhao, Martin R. Prince
PurposeTo compare segmentation methods for measuring liver cyst volumes in ADPKD.MethodsLiver cyst volumes in 42 ADPKD patients were measured using region growing, thresholding and cyst diameter techniques. Manual segmentation was the reference standard.ResultsRoot mean square deviation was 113, 155, and 500 for cyst diameter, thresholding and region growing respectively. Thresholding error for cyst volumes below 500ml was 550% vs 17% for cyst volumes above 500ml (p<0.001).ConclusionCyst diameter and manual segmentation are recommended to measure volume of small number of cysts. For severe disease with numerous, large hepatic cysts, thresholding is an acceptable alternative.

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Mitteilungen der DGKFO

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Surgical Training Improves Performance in Minimally Invasive Left Ventricular Assist Device Implantation Without Cardiopulmonary Bypass

Publication date: Available online 12 July 2017
Source:Journal of Surgical Education
Author(s): Lu-Feng Zhang, Hai-Bo Feng, Zhi-Guo Yu, Shi Jing, Feng Wan
ObjectiveWe introduced a live animal model for training of minimally invasive implantation of a continuous-flow left ventricular assist device (CF-LVAD) without cardiopulmonary bypass for operator's performance improvement.DesignAfter watching a videotape of LVAD implantation on the beating heart through the cardiac apex, the surgical team performed implantation of LVADs into 5 pigs during 3 training sessions in a time series. The procedure success rate, operating time, and technical and global performances by self-evaluation and senior evaluation were compared among the sessions.SettingAnimal Experiment Center in Peking University Third Hospital.ParticipantsSurgical team comprising a surgical operator, surgical assistant, anesthetist, and scrub nurse performed 3 training sessions in a time series.ResultsThe urgent situations requiring proper management were myocardial laceration, massive blood loss, and ventricular arrhythmia induced by hemodynamic instability. After practice, the success rate increased to 100% in session 3. The operating times of session 2 (189.80 ± 14.34min) and session 3 (149.00 ± 22.85min) were significantly lower than that of session 1 (262.20 ± 28.26min). The technical and global performances by self-evaluation and senior evaluation were significantly better in session 3 than session 1.ConclusionSimulation training with high-fidelity in vivo model for minimally invasive CF-LVAD implantation improves the surgical team's global performance, success rate, and the ability to manage emergency situations in surgery.

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Epigenetics of pituitary tumors: Pathogenetic and therapeutic implications

Publication date: Available online 12 July 2017
Source:Molecular and Cellular Endocrinology
Author(s): Shereen Ezzat, Sonia Cheng, Sylvia L. Asa
Genetic mutations involving oncogenes or tumor suppressor genes are relatively uncommon in human sporadic pituitary tumors. Instead, increasing evidence has highlighted frequent epigenetic alterations including DNA methylation, histone modifications, and enhanced miRNA expression. This review covers some of this evidence as it illuminates mechanisms of tumorigenesis and highlights therapeutic opportunities.

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The epigenetic landscape of differentiated thyroid cancer

Publication date: Available online 12 July 2017
Source:Molecular and Cellular Endocrinology
Author(s): Sylvia L. Asa, Shereen Ezzat
Differentiated thyroid carcinoma of follicular cell-derivation is the most common endocrine neoplasm with a rapidly increasing incidence. The majority represent papillary carcinomas; more rarely, they are follicular carcinomas. The vast majority have indolent behavior, however a significant proportion progress to develop lymph node metastases and a smaller proportion disseminate systemically. While common and frequent genetic events have been described to underlie the development of these neoplasms, the factors contributing to differing behaviors among tumors with similar genetic alterations remain unclear. This review focuses on epigenetic mechanisms targeting major signaling pathways that underlie the spectrum of biological behaviors and that may have potential diagnostic, prognostic and therapeutic value.

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Do anabolic-androgenic steroids have performance-enhancing effects in female athletes?

Publication date: Available online 12 July 2017
Source:Molecular and Cellular Endocrinology
Author(s): Grace Huang, Shehzad Basaria
Doping with anabolic androgenic steroids (AAS) is common among both male and female athletes and is a growing public health problem. Review of historical data of systematic state-sponsored doping programs implemented by the German Democratic Republic in elite female athletes and from the clinical trials of testosterone administration in non-athlete women suggests that AAS have ergogenic effects in women. The use of AAS in female athletes has been associated with adverse effects that include acne, hirsutism, deepening of the voice and menstrual disturbances; life-threatening adverse effects such as cardiac arrhythmias and sudden death have also been reported. Therefore, detection of AAS abuse in female athletes is important to ensure fairness in the competition; at the same time, the athletes should be educated regarding the adverse consequences of AAS use. Although administration of exogenous androgens have been associated with ergogenic effects, it remains unclear whether endogenous hyperandrogenism seen in some medical conditions such as disorders of sexual development (DSD), congenital adrenal hyperplasia and polycystic ovarian syndrome, confers any competitive advantage. Well-designed studies are needed to determine the effects of endogenous hyperandrogenism on athletic performance in female athletes.

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Pathologic Findings in Breast, Fallopian Tube and Ovary Specimens in non-BRCA Hereditary Breast and/or Ovarian Cancer Syndromes: A Study of 18 Patients with Deleterious Germline Mutations in RAD51C, BARD1, BRIP1, PALB2, MUTYH or CHEK2

Publication date: Available online 12 July 2017
Source:Human Pathology
Author(s): J. Kenneth Schoolmeester, Ann M. Moyer, McKinsey L. Goodenberger, Gary L. Keeney, Jodi M. Carter, Jamie N. Bakkum-Gamez
Germline BRCA mutations account for a significant proportion of genetic/familial risk of breast and ovarian cancer (GBOC) susceptibility, but a broader spectrum of GBOC susceptibility genes has emerged in recent years. Genotype to phenotype correlations are known for some established forms of GBOC, however whether such correlations exist for less common GBOC variants is unclear. We reviewed our institution's experience with non-BRCA GBOC, looking specifically for trends in pathologic and clinical features. Eighteen women with deleterious germline mutations in RAD51C (5 patients), BARD1 (1 patient), BRIP1 (2 patients), PALB2 (3 patients), MUTYH (2 patients) or CHEK2 (5 patients) were identified between January 2011 and December 2016. Thirteen (72%) of 18 patients developed carcinoma of either the breast, fallopian tube or ovary, with 1 patient developing 2 separate primary neoplasms. Twelve (86%) of 14 tumors occurred in the breast. One (7%) arose in the fallopian tube and another (7%) arose in the ovary. Evidence of genotype–phenotype correlation was not identified. However, some data suggest that the type of alteration in select genes may influence tumor behavior and patient outcome. In our PALB2 mutation cohort, 2 patients with frameshift mutations led to early onset and rapid progression to stage IV breast cancer in contrast to stage IA breast cancer in 1 patient with a nonsense mutation. Despite no apparent genotype–phenotype trends, our data indicate that some loss-of-function variants in PALB2 may lead to differences in tumor behavior and patient outcome.

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Working at the intersection of context, culture, and technology: Provider perspectives on antimicrobial stewardship in the emergency department using electronic health record clinical decision support

Publication date: Available online 12 July 2017
Source:American Journal of Infection Control
Author(s): Phillip Chung, Jean Scandlyn, Peter S. Dayan, Rakesh D. Mistry
BackgroundAntibiotic stewardship programs (ASPs) have not been fully developed for the emergency department (ED), in part the result of the barriers characteristic of this setting. Electronic health record–based clinical decision support (EHR CDS) represents a promising strategy to implement ASPs in the ED. We aimed to determine the cultural beliefs and structural barriers and facilitators to implementation of antimicrobial stewardship in the pediatric ED using EHR CDS.MethodsInterviews and focus groups were conducted with hospital and ED leadership, attending ED physicians, nurse practitioners, physician assistants, and residents at a single health system in Colorado. We reviewed and coded the data using constant comparative analysis and framework analysis until a final set of themes emerged.ResultsTwo dominant perceptions shaped providers' perspectives on ASPs in the ED and EHR CDS: (1) maintaining workflow efficiency and (2) constrained decision-making autonomy. Clinicians identified structural barriers to ASPs, such as pace of the ED, and various beliefs that shaped patterns of practice, including accommodating the prescribing decisions of other providers and managing parental expectations. Recommendations to enhance uptake focused on designing a simple yet flexible user interface, providing clinicians with performance data, and on-boarding clinicians to enhance buy-in.ConclusionsDeveloping a successful ED-based ASP using EHR CDS should attend to technologic needs, the institutional context, and the cultural beliefs of practice associated with providers' antibiotic prescribing.

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A phase II trial of erlotinib monotherapy in advanced pancreatic cancer as a first- or second-line agent

Abstract

Introduction

Pancreatic adenocarcinoma carries a grim prognosis. In 2007, gemcitabine with erlotinib emerged as an appropriate treatment option for patients with advanced inoperable or metastatic disease (APC). In this phase II trial we sought to evaluate the efficacy of erlotinib monotherapy in patients with APC who had disease refractory to or ineligibility for gemcitabine-based therapy.

Methods

Eligible patients who had received 0 or 1 non-EGFR inhibitor containing gemcitabine-based chemotherapy for APC were recruited prospectively and treated with erlotinib 150 mg orally daily until unacceptable toxicity or disease progression. Primary endpoint was progression-free survival (PFS). Correlations of clinical response with smoking, rash, steady-state concentration of erlotinib and its metabolite (OSI-420) as well as the nicotine metabolite cotinine were performed.

Results

The trial was terminated early for futility. Eighteen of the 34 planned subjects were recruited. Median PFS and OS were 42 and 95 days, respectively. Best response was stable disease (21%). There was a trend for improved PFS and OS in never smokers compared to current and past smokers (128.5, 39, 42 days and 173, 100, 88 days, respectively). Past/current smokers had lower steady-state concentrations of erlotinib and OSI-420 compared to never smokers. There was evidence of recent smoking exposure in 30% of patients self-identified as past smokers. Rash was infrequent, with no cases of grade III/IV rash and it was not related to treatment outcomes.

Conclusions

Overall, erlotinib monotherapy failed to improve outcomes compared to historical controls in patients with APC after 0–1 prior systemic therapies. There was a trend for improved PFS and OS in never smokers.

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Mitteilungen der DGKFO

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Cushing’s syndrome: a model for sarcopenic obesity

Abstract

Purpose

Obesity and its metabolic impairments are discussed as major risk factors for sarcopenia leading to sarcopenic obesity. Cushing's syndrome is known to be associated with obesity and muscle atrophy. We compared Cushing's syndrome with matched obese controls regarding body composition, physical performance, and biochemical markers to test the hypothesis that Cushing's syndrome could be a model for sarcopenic obesity.

Methods

By propensity score matching, 47 controls were selected by body mass index and gender as obese controls. Fat mass and muscle mass were measured by bioelectrical impedance analysis. Muscle function was assessed by chair rising test and hand grip strength. Biochemical markers of glucose and lipid metabolism and inflammation (hsCRP) were measured in peripheral blood.

Results

Muscle mass did not differ between Cushing's syndrome and obese controls. However, Cushing's syndrome patients showed significantly greater chair rising time (9.5 s vs. 7.3 s, p = 0.008) and significantly lower hand grip strength (32.1 kg vs. 36.8 kg, p = 0.003). Cushing's syndrome patients with impaired fasting glucose have shown the highest limitations in hand grip strength and chair rising time.

Conclusions

Similar to published data in ageing medicine, Cushing's syndrome patients show loss of muscle function that cannot be explained by loss of muscle mass. Impaired muscle quality due to fat infiltration may be the reason. This is supported by the observation that Cushing's syndrome patients with impaired glucose metabolism show strongest deterioration of muscle function. Research in sarcopenic obesity in elderly is hampered by confounding comorbidities and polypharmacy. As Cushing's syndrome patients are frequently free of comorbidities and as Cushing's syndrome is potentially curable we suggest Cushing's syndrome as a clinical model for further research in sarcopenic obesity.

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TMS-evoked long-lasting artefacts: A new adaptive algorithm for EEG signal correction

Publication date: September 2017
Source:Clinical Neurophysiology, Volume 128, Issue 9
Author(s): Elias P. Casula, Alessandra Bertoldo, Vincenza Tarantino, Michele Maiella, Giacomo Koch, John C. Rothwell, Gianna M. Toffolo, Patrizia S. Bisiacchi
ObjectiveDuring EEG the discharge of TMS generates a long-lasting decay artefact (DA) that makes the analysis of TMS-evoked potentials (TEPs) difficult. Our aim was twofold: (1) to describe how the DA affects the recorded EEG and (2) to develop a new adaptive detrend algorithm (ADA) able to correct the DA.MethodsWe performed two experiments testing 50 healthy volunteers. In experiment 1, we tested the efficacy of ADA by comparing it with two commonly-used independent component analysis (ICA) algorithms. In experiment 2, we further investigated the efficiency of ADA and the impact of the DA evoked from TMS over frontal, motor and parietal areas.ResultsOur results demonstrated that (1) the DA affected the EEG signal in the spatiotemporal domain; (2) ADA was able to completely remove the DA without affecting the TEP waveforms; (3). ICA corrections produced significant changes in peak-to-peak TEP amplitude.ConclusionsADA is a reliable solution for the DA correction, especially considering that (1) it does not affect physiological responses; (2) it is completely data-driven and (3) its effectiveness does not depend on the characteristics of the artefact and on the number of recording electrodes.SignificanceWe proposed a new reliable algorithm of correction for long-lasting TMS-EEG artifacts.

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Diagnostic utility of distal nerve conduction studies and sural near-nerve needle recording in polyneuropathy

Publication date: September 2017
Source:Clinical Neurophysiology, Volume 128, Issue 9
Author(s): Mustafa Aykut Kural, Páll Karlsson, Kirsten Pugdahl, Baris Isak, Anders Fuglsang-Frederiksen, Hatice Tankisi
ObjectiveThe electrodiagnosis of polyneuropathy (PNP) may benefit from examination using near-nerve needle technique (NNT) and from inclusion of distal nerves. This study compared the diagnostic utility of distal nerve conduction studies (NCS) and NNT recording.MethodsBilateral NNT and surface recording of the sural nerve and surface recording of the dorsal sural and medial plantar nerves were prospectively done in 91 patients with clinically suspected PNP. Distal NCS were additionally done in 37 healthy controls. Diagnostic reference standard was the final clinical diagnosis retrieved from the patients medical records after 1–4years.ResultsThe clinical follow-up diagnosis confirmed PNP in 68 patients. Equally high sensitivities of the dorsal sural (72%), medial plantar (75%), and sural nerve with NNT recording (77%) were seen, while the sensitivity of conventional surface recording of the sural nerve was lower (60%). Sural NCS with both NNT and surface recording and dorsal sural NCS showed high specificities (85–95%) and positive predictive values (94–98%), while a lower specificity was seen for the medial plantar nerve (68%).ConclusionNCS of distal nerves, especially the dorsal sural nerve, have high diagnostic power equalling sural NNT recording.SignificanceThe electrodiagnostic evaluation of patients with suspected PNP benefits from NCS of distal nerves.

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Interrater agreement in visual scoring of neonatal seizures based on majority voting on a web-based system: the Neoguard EEG database

Publication date: Available online 12 July 2017
Source:Clinical Neurophysiology
Author(s): Anneleen Dereymaeker, Amir H. Ansari, Katrien Jansen, Perumpillichira J Cherian, Jan Vervisch, Paul Govaert, Leen De Wispelaere, Charlotte Dielman, Vladimir Matic, Alexander Caicedo Dorado, Maarten De Vos, Sabine Van Huffel, Gunnar Naulaers
ObjectiveTo assess interrater agreement based on majority voting in visual scoring of neonatal seizures.MethodsAn online platform was designed based on a multicentre seizure EEG-database. Consensus decision based on 'majority voting' and interrater agreement was estimated using Fleiss' Kappa. The influences of different factors on agreement were determined.Results1919 Events extracted from 280h EEG of 71 neonates were reviewed by 4 raters. Majority voting was applied to assign a seizure/non-seizure classification. 44% of events were classified with high, 36% with moderate, and 20% with poor agreement, resulting in a Kappa value of 0.39. 68% of events were labelled as seizures, and in 46%, all raters were convinced about electrographic seizures. The most common seizure duration was <30s. Raters agreed best for seizures lasting 60-120s. There was a significant difference in electrographic characteristics of seizures versus dubious events, with seizures having longer duration, higher power and amplitude.ConclusionsThere is a wide variability in identifying rhythmic ictal and non-ictal EEG events, and only the most robust ictal patterns are consistently agreed upon. Database composition and electrographic characteristics are important factors that influence interrater agreement.SignificanceThe use of well-described databases and input of different experts will improve neonatal EEG interpretation and help to develop uniform seizure definitions, useful for evidence-based studies of seizure recognition and management.

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Cushing’s syndrome: a model for sarcopenic obesity

Abstract

Purpose

Methods

Results

Conclusions

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Traitements péri-opératoires des carcinomes bronchiques non à petites cellules

Publication date: Available online 12 July 2017
Source:Revue des Maladies Respiratoires
Author(s): S. Brosseau, C. Naltet, M. Nguenang, V. Gounant, P. Mordant, B. Milleron, Y. Castier, G. Zalcman
La chirurgie reste le traitement central des cancers bronchiques non à petites cellules de stades localisés, mais si la survie à 5 ans des stades IA opérés dépasse 80 %, celle des stades II chute rapidement avec la taille de la tumeur, l'extension ganglionnaire ou à la plèvre viscérale. Ce risque métastatique majeur justifie les traitements péri-opératoires systémiques ou locorégionaux. Les essais de phase 3 modernes ont validé le rôle de la chimiothérapie adjuvante ou néo-adjuvante des stades II à III conforté par plusieurs méta-analyses, montrant un gain de plus de 5 % de survie à 5 ans, et une diminution du risque relatif de décès de 12 à 25 %. Les traitements péri-opératoires des stades IA et IB ne sont cependant pas validés. La radio-chimiothérapie néo-adjuvante des formes plus étendues (IIIA à IIIB) n'a pas prouvé son intérêt. L'essor de la chirurgie vidéo-assistée a facilité la réalisation des traitements systémiques postopératoires, les rendant accessibles aux sujets âgés. Les traitements ciblés péri-opératoires des patients avec CBNPC et altération moléculaire EGFR ou ALK sont évalués par l'essai Alchemist. La place de la radiothérapie adjuvante dans les tumeurs N2 est testée par l'essai Lung-ART/IFCT-0503. Enfin, la place des inhibiteurs de check-points immunitaires est évaluée, tant en adjuvant dans l'essai BR31/IFCT-1401, que dans l'essai néo-adjuvant IONESCO/IFCT-1601, mais les résultats de ces essais ne seront pas disponibles avant 5 à 7 ans.Surgery is still the main treatment in early-stage of non-small cell lung cancer with 5-year survival of stage IA patients exceeding 80%, but 5-year survival of stage II patients rapidly decreasing with tumor size, N status, and visceral pleura invasion. The major metastatic risk in such patients has supported clinical research assessing systemic or loco-regional perioperative treatments. Modern phase 3 trials clearly validated adjuvant or neo-adjuvant platinum-based chemotherapy in resected stage I–III patients as a standard treatment of which value has been reassessed several independent meta-analyses, showing a 5% benefit in 5y-survival, and a decrease of the relative risk for death around from 12 to 25%. Conversely perioperative treatments were not validated for stage IA and IB patients. In more advanced stage patients, neo-adjuvant radio-chemotherapy has not been validated either. Adjuvant radiotherapy for N2 patients is currently tested in the large international phase 3 trial Lung-ART/IFCT-0503. The development of video-assisted thoracic surgery (VATS) has helped adjuvant chemotherapies for elderly patients. Perioperative targeted treatments in NSCLC with EGFR or ALK molecular alterations is currently assessed in the U.S. ALCHEMIST prospective trial. Finally, the role of immune check-points inhibitors is currently evaluated in a large international phase 3 trial testing adjuvant anti-PD-L1 monoclonal antibody, the BR31/IFCT-1401 trial, while a proof-of principle neo-adjuvant trial IONESCO/IFCT-1601, has just begun by the end of the 2016 year, with survival results of both trials expected in 5 to 7 years.

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Early clinical manifestations of Sézary syndrome: A multicenter retrospective cohort study

Publication date: Available online 11 July 2017
Source:Journal of the American Academy of Dermatology
Author(s): Aaron R. Mangold, Agnieszka K. Thompson, Mark D. Davis, Ieva Saulite, Antonio Cozzio, Emmanuella Guenova, Emmilia Hodak, Iris Amitay-Laish, Ramon M. Pujol, Mark R. Pittelkow, Robert Gniadecki
BackgroundClassic Sézary syndrome (SS) is defined by erythroderma, generalized lymphadenopathy, and leukemic blood involvement. Clinical observations suggest that SS begins as a nonerythrodermic disease.ObjectiveTo describe the early clinical characteristics of patients with SS.MethodsA retrospective, multicenter chart review was performed for 263 confirmed cases of SS diagnosed during 1976-2015.ResultsErythroderma was the earliest recorded skin sign of SS in only 25.5% of cases, although most patients (86.3%) eventually developed erythroderma. In patients without erythroderma during their initial visit, the first cutaneous signs of SS were nonspecific dermatitis (49%), atopic dermatitis-like eruption (4.9%), or patches and plaques of mycosis fungoides (10.6%). The mean diagnostic delay was 4.2 years overall, 2.2 years for cases involving erythroderma at the initial presentation, and 5.0 years for cases not involving erythroderma at the initial presentation.LimitationsThis study is retrospective.ConclusionErythroderma is uncommon as an initial sign of SS. Early SS should be considered in cases of nonerythrodermic dermatitis that is refractory to conventional treatments. In these cases, examination of the blood by PCR for monoclonal T-cell receptor rearrangement and by flow cytometry to identify an expanded or aberrant T-cell population should be considered.

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Squamous proliferations on the legs of women: Qualitative examination of histopathology, TP53 sequencing, and implications for diagnosis in a series of 30 cases

Publication date: Available online 11 July 2017
Source:Journal of the American Academy of Dermatology
Author(s): Christine J. Ko, Earl J. Glusac, Jennifer M. McNiff, Nemanja Rodic, David J. Leffell
BackgroundWomen with multiple squamous cell carcinomas (SCCs) of the legs have a striking clinical phenotype. Numerous tumors can develop in a short period of time.ObjectiveBecause histopathologic findings can vary in women with multiple SCC lesions, from keratoacanthoma-like to well-differentiated SCC, we hypothesized that TP53 variants might shed light on the appropriate classification.MethodsWe sequenced TP53 in 30 SCCs from 6 women who had multiple SCCs on their legs during a 21-month time frame.ResultsHistopathologic analysis showed 16 of the 30 lesions did not have prominent cytologic atypia and were distinguished by having expanded follicle-like structures composed of large, glassy, eosinophilic keratinocytes; these lesions resembled keratoacanthoma and were categorized as keratoacanthoma-like squamous proliferations (KASPs). The 14 remaining tumors had more prominent cytologic atypia and remained classified as SCC. Twenty of 30 tumors (including the KASPs) from the 6 different patients lacked detectable TP53 mutations. Ten of the 14 tumors that remained classified as SCC had detectable TP53 mutations.LimitationsThis is a small series.ConclusionThese findings suggest that some cutaneous squamous proliferations on the legs of women with multiple lesions lack prominent cytologic atypia as well as TP53 mutations and might be more akin to keratoacanthoma than SCC or might represent a reactive phenomenon.

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Role of Demodex mite infestation in rosacea: A systematic review and meta-analysis

Publication date: Available online 12 July 2017
Source:Journal of the American Academy of Dermatology
Author(s): Yin-Shuo Chang, Yu-Chen Huang
BackgroundThe reported prevalence and degrees of Demodex mite infestation in rosacea vary widely.ObjectiveWe sought to conduct an evidence-based meta-analysis of the prevalence and degrees of Demodex mite infestation in patients with rosacea.MethodsSystematic literature review and meta-analysis were conducted. Odds ratios for prevalence of infestation and standardized mean difference (SMD) for Demodex density in patients with rosacea were pooled. Subgroup analysis for type of rosacea, control group, and sampling and examination methods were also performed.ResultsTwenty-three case-control studies included 1513 patients with rosacea. Compared with the control patients, patients with rosacea were more likely to be infested by Demodex mites [odds ratio, 9.039; 95% confidence interval (CI), 4.827-16.925] and had significantly higher Demodex density (SMD, 1.617; 95% CI, 1.090-2.145). Both erythematotelangiectatic rosacea (SMD, 2.686; 95% CI, 1.256-4.116) and papulopustular rosacea (SMD, 2.804; 95% CI, 1.464-4.145) had significantly higher Demodex density than did healthy control patients.LimitationsInterstudy variability was high, and a causal relationship could not be established by case-control studies.ConclusionsPatients with rosacea had significantly higher prevalence and degrees of Demodex mite infestation than did control patients. Demodex mites may play a role in both erythematotelangiectatic rosacea and papulopustular rosacea.

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Ambulatory blood pressure monitoring-derived short-term blood pressure variability in primary hyperparathyroidism

Abstract

Introduction

Primary hyperparathyroidism is associated with a cluster of cardiovascular manifestations, including hypertension, leading to increased cardiovascular risk.

Purpose

The aim of our study was to investigate the ambulatory blood pressure monitoring-derived short-term blood pressure variability in patients with primary hyperparathyroidism, in comparison with patients with essential hypertension and normotensive controls.

Methods

Twenty-five patients with primary hyperparathyroidism (7 normotensive,18 hypertensive) underwent ambulatory blood pressure monitoring at diagnosis, and fifteen out of them were re-evaluated after parathyroidectomy. Short-term-blood pressure variability was derived from ambulatory blood pressure monitoring and calculated as the following: 1) Standard Deviation of 24-h, day-time and night-time-BP; 2) the average of day-time and night-time-Standard Deviation, weighted for the duration of the day and night periods (24-h "weighted" Standard Deviation of BP); 3) average real variability, i.e., the average of the absolute differences between all consecutive BP measurements.

Results

Baseline data of normotensive and essential hypertension patients were matched for age, sex, BMI and 24-h ambulatory blood pressure monitoring values with normotensive and hypertensive-primary hyperparathyroidism patients, respectively. Normotensive-primary hyperparathyroidism patients showed a 24-h weighted Standard Deviation (P < 0.01) and average real variability (P < 0.05) of systolic blood pressure higher than that of 12 normotensive controls. 24-h average real variability of systolic BP, as well as serum calcium and parathyroid hormone levels, were reduced in operated patients (P < 0.001). A positive correlation of serum calcium and parathyroid hormone with 24-h-average real variability of systolic BP was observed in the entire primary hyperparathyroidism patients group (P = 0.04, P = 0.02; respectively).

Conclusion

Systolic blood pressure variability is increased in normotensive patients with primary hyperparathyroidism and is reduced by parathyroidectomy, and may potentially represent an additional cardiovascular risk factor in this disease.

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Community Violence as a Population Health Issue: Proceedings of a Workshop.

On June 16, 2016, the Roundtable on Population Health Improvement held a workshop at the Lutheran Church of the Good Shepherd in Brooklyn, New York, to explore the influence of trauma and violence on communities. The workshop highlighted examples of community-based organizations using trauma-informed approaches to treat violence and build safe and healthy communities. Presentations showcased examples that can serve as models in different sectors and communities and shared lessons learned. This publication summarizes the presentation and discussion of the event.

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Integrating Clinical Research into Epidemic Response: The Ebola Experience.

The 2014–2015 Ebola epidemic in western Africa was the longest and most deadly Ebola epidemic in history, resulting in 28,616 cases and 11,310 deaths in Guinea, Liberia, and Sierra Leone. The Ebola virus has been known since 1976, when two separate outbreaks were identified in the Democratic Republic of Congo (then Zaire) and South Sudan (then Sudan). However, because all Ebola outbreaks prior to that in West Africa in 2014–2015 were relatively isolated and of short duration, little was known about how to best manage patients to improve survival, and there were no approved therapeutics or vaccines. When the World Heath Organization declared the 2014–2015 epidemic a public health emergency of international concern in August 2014, several teams began conducting formal clinical trials in the Ebola affected countries during the outbreak.

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Driving Action and Progress on Obesity Prevention and Treatment: Proceedings of a Workshop.

After decades of increases in the obesity rate among U.S. adults and children, the rate recently has dropped among some populations, particularly young children. What are the factors responsible for these changes? How can promising trends be accelerated? What else needs to be known to end the epidemic of obesity in the United States?

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Low-Level Radioactive Waste Management and Disposition: Proceedings of a Workshop.

The Department of Energy's Office of Environmental Management (DOE) is responsible for the safe cleanup of sites used for nuclear weapons development and government-sponsored nuclear energy research. Low-level radioactive waste (LLW) is the most volumetrically significant waste stream generated by the DOE cleanup program. LLW is also generated through commercial activities such as nuclear power plant operations and medical treatments.

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Lignocellulosic biowastes as carrier material and slow release electron donor for sulphidogenesis of wastewater in an inverse fluidized bed bioreactor

Abstract

Industrial wastewaters containing high concentrations of sulphate, such as those generated by mining, metallurgical and mineral processing industries, require electron donor for biological sulfidogenesis. In this study, five types of lignocellulosic biowastes were characterized as potential low-cost slow release electron donors for application in a continuously operated sulphidogenic inverse fluidized bed bioreactor (IFBB). Among them, natural scourer and cork were selected due to their high composition of volatile solids (VS), viz. 89.1 and 96.3%, respectively. Experiments were performed in batch (47 days) and in an IFBB (49 days) using synthetic sulphate-rich wastewater. In batch, the scourer gave higher sulphate reduction rates (67.7 mg SO₄²⁻ L⁻¹ day⁻¹) in comparison to cork (12.1 mg SO₄²⁻ L⁻¹ day⁻¹), achieving >82% sulphate reduction efficiencies. In the IFBB packed with the natural scourer, the average sulphate reduction efficiency was 24 (±17)%, while the volumetric sulphate reduction rate was 167 (±117) mg SO₄²⁻ L⁻¹ day⁻¹. The long incubation time in the batch experiments (47 days) allowed higher sulphate reduction efficiencies in comparison to the short hydraulic retention time (24 h) in the IFBB. This suggests the hydrolysis-fermentation was the rate-limiting step and the electron donor supply (through hydrolysis of the lignocellulosic biowaste) was limiting the sulphate reduction.

Lignocellulose as carrier material and slow release electron donor for sulphidogenesis

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A novel biocoagulant agent from mushroom chitosan as water and wastewater therapy

Abstract

A new commercial cationic polyelectrolyte chitosan (CM), obtained from the waste of mushroom production, was examined using models of water and wastewater namely kaolin and palm oil mill effluent (pome). As it is biocompatible, widely available, and economically feasible, chitosan mushroom has high potential to be a suitable replacement for alum. Also, it can be a promising alternative to chitosan obtained traditionally from Crustaceans due to its higher zeta potential and homogeneity based on the raw material required for its production. A wide range of coagulant dose (5–60 mg l⁻¹) and wastewater pH (2–12) were taken into account to find the optimal conditions of coagulation. The optimal doses are 10 and 20 mg l⁻¹ at best pH (11 and 3) when treated with kaolin and palm oil mill effluent, respectively, while 1200 mg l⁻¹ of alum was not enough to reach the efficiency of chitosan mushroom. On the other hand, the optimum dose of chitosan mushroom (20 mg l⁻¹) at pH 3 of pome produced (75, 73, and 98%) removal of chemical oxygen demand (COD), biological oxygen demand (BOD), and total suspended solids (TSS), respectively. The significant potential of chitosan mushroom was proved by zeta potential measurement. Indeed, it possesses the highest zeta potential (+70 mV) as compared to the traditional chitosan produced from crustaceans. In short, chitosan mushroom as a biocoagulant is eco-friendly and it enhances water quality that meets the requirements of environmental conservatives.

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Kinetics of 210 Po accumulation in moss body profiles

Abstract

Radionuclide concentration analysis of total moss bodies often gave relatively different results than a separate analysis of each different morphological part of the same sample. The dynamics of the transfer of metals by dust uplifted from the soil and another approach, based on the diffusion of the two radionuclides to the moss, have been analyzed. In the proposed model, short- and long-term approaches have been applied. Each part of a moss's profile can show different radionuclides accumulation ability, including both ²¹⁰Pb and ²¹⁰Po isotopes. A first-order kinetic model has been used for ²¹⁰Po and ²¹⁰Pb transport between three body components of mosses. This mathematical approach has been applied for ²¹⁰Po activity concentration in the air estimation. For relatively clean deep forest region, calculated concentrations were from 17.2 to 43.8 μBqm⁻³, while for urban air concentrations were higher from 49.1 to 104.9 μBqm⁻³.

http://ift.tt/2vcsWc9

Ambulatory blood pressure monitoring-derived short-term blood pressure variability in primary hyperparathyroidism

Abstract

Introduction

Primary hyperparathyroidism is associated with a cluster of cardiovascular manifestations, including hypertension, leading to increased cardiovascular risk.

Purpose

Methods

Results

Conclusion

http://ift.tt/2tMEEL2

Erratum to “Externally validated HPV-based prognostic nomogram for oropharyngeal carcinoma patients yields more accurate predictions than TNM staging” [Radiother Oncol 113 (2014) 324–30]

Publication date: Available online 11 July 2017
Source:Radiotherapy and Oncology
Author(s): Emmanuel Rios Velazquez, Frank Hoebers, Hugo J.W.L. Aerts, Michelle M. Rietbergen, Ruud H. Brakenhoff, René C. Leemans, Ernst-Jan Speel, Jos Straetmans, Bernd Kremer, Philippe Lambin

http://ift.tt/2sPZ6t0

Effects of progressive resistance training on cardiovascular autonomic regulation in patients with Parkinson`s Disease: a randomized controlled trial

Publication date: Available online 10 July 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Hélcio Kanegusuku, Carla Silva-Batista, Tiago Peçanha, Alice Nieuwboer, Natan D. Silva, Luiz A.R. Costa, Marco T. de Mello, Maria E.P. Piemonte, Carlos Ugrinowitsch, Cláudia L.M. Forjaz
ObjectiveTo evaluate the effects of a progressive resistance training (RT) on cardiac autonomic modulation and on cardiovascular responses to autonomic stress tests in patients with Parkinson disease (PD).DesignRandomized clinical trial.SettingThe Brazilian Parkinson Association.Participants30 patients with PD (modified Hoehn and Yahr stages 2-3) were randomly divided into 2 groups: a progressive RT group (PDT) and a control group (PDC). In addition, a group of paired healthy control subjects without PD (HC) was evaluated.InterventionsPDT group performed 5 resistance exercises, 2 to 4 sets, 12 to 6 repetitions maximum per set. PDC group maintained their usual lifestyle.Main Outcome MeasuresPDT and PDC groups were evaluated before and after 12-weeks. HC group was evaluated once. Autonomic function was assessed by spectral analysis of heart rate (HR) variability and cardiovascular responses to autonomic stress tests (deep breathing, Valsalva maneuver and orthostatic stress).ResultsCompared with baseline, normalized low-frequency component of HR variability decreased significantly after 12 weeks in the PDT group only (PDT = 61±17 vs. 47±20 nu and PDC = 60±14 vs. 63±10 nu, interaction P<0.05). Similar result was observed for systolic blood pressure fall during orthostatic stress that also reduced only in the PDT group (PDT = -14±11 vs. -6±10 mmHg and PDC = -12±10 vs. -11±10 mmHg, interaction P<0.05). In addition, after 12 weeks, these parameters in the PDT achieved values similar to the HC group.ConclusionIn patients with PD, progressive RT improved cardiovascular autonomic dysfunction.

http://ift.tt/2vcnSVj

Can primary care for back and/or neck pain in the Netherlands benefit from stratification for risk groups according to the STarT Back Tool-classification?

Publication date: Available online 12 July 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Jasper D. Bier, Janneke J.W. Sandee-Geurts, Raymond W.J.G. Ostelo, Bart W. Koes, Arianne P. Verhagen
ObjectiveTo evaluate whether current Dutch primary-care clinicians offer tailored treatment to patients with lower-back pain (LBP) or neck pain (NP) according to their risk stratification, based on the Keele STarT (Subgroup Targeted Treatment) Back-Screening Tool (SBT).DesignProspective cohort study with 3 month follow-upSettingPrimary careParticipantsGeneral practitioners (GPs) and physiotherapists (PTs) included patients with non-specific LBP and/or NP.InterventionsPatients completed a baseline questionnaire, including the Dutch SBT, for either LBP or NP. A follow-up measurement was conducted after 3 months to determine recovery (using the Global Perceived Effect (GPE) scale), pain (using the Numeric Pain-Rating Scale (NPRS)) and function (using the Roland Disability Questionnaire (RDQ) or the Neck Disability Index (NDI)). A questionnaire was sent to the GPs and PTs to evaluate the provided treatment.Main outcome measuresPrevalence of patients' risk profile and clinicians' applied care, and the percentage of patients with persisting disability at follow-up. A distinction was made between patients receiving the advised treatment and those receiving the non-advised treatment.ResultsIn total, 12 GPs and 33 PTs included patients. After 3 months, we analyzed 184 patients with LBP and 100 patients with NP. In the LBP group, 52.2% of the patients were at low risk for persisting disability, 38.0% were at medium risk and 9.8% were at high risk. Overall, 24.5% of the LBP patients received a low-risk treatment approach, 73.5% a medium-risk and 2.0% a high-risk treatment approach. The specific agreement between the risk profile and the received treatment for patients with LBP was poor for the low-risk and high-risk patients (respectively 21.1% and 10.0%), and fair for medium-risk patients (51.4%). In the NP group, 58.0% of the patients were at low risk for persisting disability, 37.0% were at medium risk and 5.0% were at high-risk. Only 6.1% of the patients with NP received the low-risk treatment approach. The medium-risk treatment approach was offered the most (90.8%) and the high-risk approach was applied in only 3.1% of the patients. The specific agreement between the risk profile and received treatment for NP patients was poor for low-risk and medium-risk patients (resp. 6.3% and 48.0%); agreement for high-risk patients could not be calculated.ConclusionCurrent Dutch primary care for patients with non-specific LBP and/or NP does not correspond to the advised stratified-care approach based on the SBT as the majority of patients receive medium risk treatment. The majority of "low-risk" patients are over-treated and the majority of "high-risk" patients are undertreated. Although the stratified-care approach has not yet been validated in Dutch primary care, these results indicate that there may be substantial room for improvement.

http://ift.tt/2vcow4R

Efficacy and Safety of Nintedanib Plus Docetaxel in Patients with Advanced Lung Adenocarcinoma: Complementary and Exploratory Analyses of the Phase III LUME-Lung 1 Study

Abstract

Background

Nintedanib is a triple angiokinase inhibitor approved with docetaxel for adenocarcinoma non-small cell lung cancer after first-line chemotherapy (FLT). In the phase III LUME-Lung 1 study, overall survival (OS) was significantly longer with nintedanib/docetaxel than with placebo/docetaxel in all adenocarcinoma patients and those with time from start of FLT (TSFLT) <9 months.

Objective

This study sought to extend analyses from the LUME-Lung 1 study, specifically for adenocarcinoma patients, to explore the impact of clinically relevant characteristics on outcomes such as time to progression after FLT.

Patients and Methods

Exploratory analyses were conducted of the overall and European LUME-Lung 1 adenocarcinoma population according to age, prior therapy, and tumor dynamics. Analyses also used TSFLT and time from end of FLT (TEFLT).

Results

Treatment with nintedanib/docetaxel significantly improved OS in European patients independently of age or prior therapy. Analyses of several patient subgroups showed improvements in median OS: TSFLT <6 months, 9.5 versus 7.5 months (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.55–0.98); chemorefractory to FLT, 9.1 versus 6.9 months (HR 0.72, 95% CI 0.52–0.99); progressive disease (PD) as best response to FLT, 9.8 versus 6.3 months (HR 0.62, 95% CI 0.41–0.94); TEFLT ≤6 months, 11.3 versus 8.2 months (HR 0.75, 95% CI 0.61–0.92); and TEFLT <3 months, 11.0 versus 8.0 months (HR 0.74, 95% CI 0.58–0.94).

Conclusions

Nintedanib/docetaxel demonstrated significant OS benefits in adenocarcinoma patients, which were more pronounced in patients with shorter TSFLT or TEFLT, or with PD as best response to FLT.

This study was registered at ClinicalTrials.gov: NCT00805194.

http://ift.tt/2teoUOR

Comparison of ketamine and ketofol for deep sedation and analgesia in children undergoing laser procedure

Abstract

The aim of our study was to research and evaluate cardiovascular and respiratory stability, clinical efficacy, and safety of two different anesthetic agents in pediatric patients who underwent Pulse dye (wavelength 595 nm, pulse duration 0–40 ms, power 0–40 J) and CO₂ (wavelength 10,600 nm, intensity-fraxel mod with SX index 4 to 8, power 0–30 W) laser procedure. This prospective non-blinded study included 203 pediatric patients ASA I-II, aged between 1 month and 12 years who underwent short-term procedural sedation and analgesia for the laser procedure. After oral premedication with midazolam, 103 children were analgo-sedated with ketamine and fentanyl (K group) and 100 with ketofol and fentanyl (KT group). Vital signs, applied drug doses, pulse oximetry, and parental satisfaction questionnaire were used to compare these two groups. Statistical differences were tested using Student's t test, Mann-Whitney U test, chi-square test, and Fisher's exact test. Receiver operating characteristic (ROC) curve analysis was used to assess the cut-off value of the duration of anesthesia predicting apnea. Tachycardia was recorded in a significantly higher number of patients who received ketamine as the anesthetic agent (35.9 vs. 3% respectively). Hypertension was also significantly more frequent in patients who received ketamine in comparison with patients who received ketofol (25.2 vs. 3%). Laryngospasm was not observed in both examined groups. There was no statistically significant difference between groups in satisfaction of parents and doctors. Apnea and respiratory depression occurred significantly more frequent in ketofol than in ketamine group (12 vs. 0.97% and 13 vs. 0%). Based on ROC analysis for apnea, we found a significantly higher number of patients with apnea in the ketofol group when duration of anesthesia was longer than 17 min. Our study has shown that ketofol is more comfortable than ketamine in short-term laser procedures in children, causing less hemodynamic alteration with mild respiratory depression and less post-procedural adverse events.

http://ift.tt/2t3DiOQ

Ruthenium complexes/polypeptide self-assembled nanoparticles for identification of bacterial infection and targeted antibacterial research

Publication date: October 2017
Source:Biomaterials, Volume 141
Author(s): Na Huang, Xu Chen, Xufeng Zhu, Mengmeng Xu, Jie Liu
Bacterial infection has been a threat to human health, and so early diagnosis and treatment of bacterial infection is an urgent problem that needs to be solved. In this work, a multifunctional theranostic selenium nanoplatform (Se@PEP-Ru NPs) with early imaging diagnosis and efficient treatment of bacterial infections was designed and constructed. First, the antibacterial peptide UBI29-41 (PEP) was linked to functionalized Selenium nanoparticles (NPs), which enhanced the stability of the antimicrobial peptide and also caused the nanocomposites to specifically target bacterial infection. Ruthenium complexes with good antibacterial activity and fluorescence properties were then coated on to their outer layers. It was worth mentioning that, when the resulting nanoprobe was injected into mice by intravenous injection it was found to be sensitive to sites of bacterial infection for selective fluorescence imaging and targeted therapy. Thus, it can be used to distinguish between bacterial infection, inflammation, and tumor-induced tissue infection with high specificity. In the further antibacterial activity experiments, Ruthenium complexes showed synergistic antimicrobial activity with Se NPs, which indicated that the antibacterial activity of Se@PEP-Ru NPs was the strongest that could promote wound healing. Thus, Se@PEP-Ru NPs appears to be a promising antimicrobial with good biocompatibility, excellent selectivity, and potent antimicrobial activity.

http://ift.tt/2tIaQ3U

Adaptive Treatment De-escalation in Favorable Risk HPV-Positive Oropharyngeal Carcinoma

Conditions: Oropharyngeal Carcinoma; HPV Positive Oropharyngeal Squamous Cell Carcinoma
Interventions: Radiation: Standard Radiation Treatment; Radiation: Dose-Deescalated Treatment; Drug: Cisplatinum
Sponsor: New York University School of Medicine
Recruiting - verified July 2017

http://ift.tt/2uia4Mo

RAI Plus Immunotherapy for Recurrent/Metastatic Thyroid Cancers

Condition: Thyroid Cancer
Interventions: Drug: Durvalumab (Medi4736); Radiation: Radioiodine (RAI)
Sponsors: Memorial Sloan Kettering Cancer Center; AstraZeneca; MedImmune LLC
Recruiting - verified July 2017

http://ift.tt/2uR0e18

CDx Biopsies for Detection of Laryngopharyngeal Reflux and Laryngeal Lesions

Conditions: Laryngeal Disease; Laryngeal Tumor; Laryngopharyngeal Reflux
Intervention: Device: Endo CDx Brush biopsy
Sponsors: CDx Diagnostics; Rambam Health Care Campus
Not yet recruiting - verified July 2017

http://ift.tt/2uhXaho

Seeing-Moving-Playing: Early Rehabilitation Utilizing Visual and Vestibular Technology Following Traumatic Brain Injury

Condition: Mild Traumatic Brain Injury; Concussion
Interventions: Other: Vestibular-Visual Intervention; Behavioral: standard care
Sponsor: McGill University Health Center
Not yet recruiting - verified July 2017

http://ift.tt/2uRaExQ

Phase 1/2 Study of LOXO-195 in Patients With Previously Treated NTRK Fusions or Non-fusion NTRK Cancers

Conditions: Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms; Sarcoma; Colorectal Neoplasms; Salivary Gland Neoplasms; Biliary Tract Neoplasms; Brain Neoplasm, Primary; Breast Ductal Carcinoma NOS; Melanoma; Solid Tumors Cancer of Unknown Primary; Glioblastoma; Bile Duct Neoplasms; Astrocytoma; Head and Neck Squamous Cell Carcinoma; Pontine Glioma; Pancreatic Neoplasms; Ovarian Neoplasms; Carcinoma, Renal Cell; Cholangiocarcinoma; Skin Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Intestinal Neoplasms; Thyroid Cancer; GIST; Malignant Peripheral Nerve Sheath Tumors; Breast Secretory Carcinoma; Uterine Neoplasms
Intervention: Drug: LOXO-195
Sponsor: Loxo Oncology, Inc.
Recruiting - verified July 2017

http://ift.tt/2tHSfol

Northern Alberta Psychosocial Telecare (NAPT) Screening for HNC Patients

Condition: Cancer Distress
Intervention: Other: NAPT
Sponsor: University of Alberta
Not yet recruiting - verified July 2017

http://ift.tt/2uihTS6

Water quality and health in northern Canada: stored drinking water and acute gastrointestinal illness in Labrador Inuit

Abstract

One of the highest self-reported incidence rates of acute gastrointestinal illness (AGI) in the global peer-reviewed literature occurs in Inuit communities in the Canadian Arctic. This high incidence of illness could be due, in part, to the consumption of contaminated water, as many northern communities face challenges related to the quality of municipal drinking water. Furthermore, many Inuit store drinking water in containers in the home, which could increase the risk of contamination between source and point-of-use (i.e., water recontamination during storage). To examine this risk, this research characterized drinking water collection and storage practices, identified potential risk factors for water contamination between source and point-of-use, and examined possible associations between drinking water contamination and self-reported AGI in the Inuit community of Rigolet, Canada. The study included a cross-sectional census survey that captured data on types of drinking water used, household practices related to drinking water (e.g., how it was collected and stored), physical characteristics of water storage containers, and self-reported AGI. Additionally, water samples were collected from all identified drinking water containers in homes and analyzed for presence of Escherichia coli and total coliforms. Despite municipally treated tap water being available in all homes, 77.6% of households had alternative sources of drinking water stored in containers, and of these containers, 25.2% tested positive for total coliforms. The use of transfer devices and water dippers (i.e., smaller bowls or measuring cups) for the collection and retrieval of water from containers were both significantly associated with increased odds of total coliform presence in stored water (OR_{transfer device} = 3.4, 95% CI 1.2–11.7; OR_dipper = 13.4, 95% CI 3.8–47.1). Twenty-eight-day period prevalence of self-reported AGI during the month before the survey was 17.2% (95% CI 13.0–22.5), which yielded an annual incidence rate of 2.4 cases per person per year (95% CI 1.8–3.1); no water-related risk factors were significantly associated with AGI. Considering the high prevalence of, and risk factors associated with, indicator bacteria in drinking water stored in containers, potential exposure to waterborne pathogens may be minimized through interventions at the household level.

http://ift.tt/2tecS89

Vascular plants as ecological indicators of metals in alpine vegetation (Karkonosze, SW Poland)

Abstract

Calluna vulgaris, Carex rigida, Deschampsia flexuosa, Nardus stricta and Vaccinium myrtillus are abundant in the vegetation of mountainous areas in Northern and Central Europe. Knowledge of their ability to accumulate increased amounts of metals could be useful in the evaluation of environmental pollution in the alpine tundra of high mountains. Additionally, this investigation may contribute to understanding the rate and direction of recent vegetation change in Karkonosze and similar types of environments. Our investigation revealed that Carex rigida, C. vulgaris and V. myrtillus contain excessive Mn concentrations in shoots with the highest BF for this element compared to the BFs of other elements. C. rigida, with Cu, Mn and Zn concentrations exceeding the toxicity thresholds for plants, seems to be the best metal phytoaccumulator for Nardus stricta grasslands Carici (rigidae)-Nardetum (CrN) and alpine heathlands Carici (rigidae)-Festucetum airoidis (CrFa) associations in the Karkonosze. Based on relevant BFs >1, it can be stated that the following plant available metals were transferred to shoots: Cu, Mn and Ni by C. vulgaris; Cd, Cu, Mn, Ni and Zn by C. rigida; Cd, Cu, Mn, Ni and Zn by D. flexuosa; Cu, Mn, Ni and Zn by N. stricta and Cu, Mn and Zn by V. myrtillus.

http://ift.tt/2tI5DZU

Micrometer Scale Guidance of Mesenchymal Stem Cells to Form Structurally Oriented Large-Scale Tissue Engineered Cartilage

Publication date: Available online 11 July 2017
Source:Acta Biomaterialia
Author(s): Chih-Ling Chou, Alexander L. Rivera, Valencia Williams, Jean F. Welter, Joseph M. Mansour, Judith A. Drazba, Takao Sakai, Harihara Baskaran
Current clinical methods to treat articular cartilage lesions provide temporary relief of the symptoms but fail to permanently restore the damaged tissue. Tissue engineering, using mesenchymal stem cells (MSCs) combined with scaffolds and bioactive factors, is viewed as a promising method for repairing cartilage injuries. However, current tissue engineered constructs display inferior mechanical properties compared to native articular cartilage, which could be attributed to the lack of structural organization of the extracellular matrix (ECM) of these engineered constructs in comparison to the highly oriented structure of articular cartilage ECM. We previously showed that we can guide MSCs undergoing chondrogenesis to align using microscale guidance channels on the surface of a two-dimensional (2-D) collagen scaffold, which resulted in the deposition of aligned ECM within the channels and enhanced mechanical properties of the constructs. In this study, we developed a technique to roll 2-D collagen scaffolds containing MSCs within guidance channels in order to produce a large-scale, three-dimensional (3-D) tissue engineered cartilage constructs with enhanced mechanical properties compared to current constructs. After rolling the MSC-scaffold constructs into a 3-D cylindrical structure, the constructs were cultured for 21 days under chondrogenic culture conditions. The microstructure architecture and mechanical properties of the constructs were evaluated using imaging and compressive testing. Histology and immunohistochemistry of the constructs showed extensive glycosaminoglycan (GAG) and collagen type II deposition. Second harmonic generation imaging and Picrosirius red staining indicated alignment of neo-collagen fibers within the guidance channels of the constructs. Mechanical testing indicated that constructs containing the guidance channels displayed enhanced compressive properties compared to control constructs without these channels. In conclusion, using a novel roll-up method, we have developed large scale MSC based tissue-engineered cartilage that show microscale structural organization and enhanced compressive properties compared to current tissue engineered constructs.Statement of SignificanceTissue engineered cartilage constructs made with human mesenchymal stem cells (hMSCs), scaffolds and bioactive factors are a promising solution to treat cartilage defects. A major disadvantage of these constructs is their inferior mechanical properties compared to the native tissue, which is likely due to the lack of structural organization of the extracellular matrix of the engineered constructs. In this study, we developed three-dimensional (3-D) cartilage constructs from rectangular scaffold sheets containing hMSCs in micro-guidance channels and characterized their mechanical properties and metabolic requirements. The work led to a novel roll-up method to embed 2-D microscale structures in 3-D constructs. Further, micro-guidance channels incorporated within the 3-D cartilage constructs led to the production of aligned cell-produced matrix and enhanced mechanical function.

Graphical abstract

http://ift.tt/2tHT0hu

Hydrogel elasticity and microarchitecture regulate dental-derived mesenchymal stem cells -host immune system cross-talk

Publication date: Available online 12 July 2017
Source:Acta Biomaterialia
Author(s): Sahar Ansari, Chider Chen, Mohammad Mahdi Hasani-Sarabadi, Bo Yu, Homayoun H. Zadeh, Benjamin M Wu, Alireza Moshaverinia
The host immune system (T-lymphocytes and their pro-inflammatory cytokines) has been shown to compromise bone regeneration ability of mesenchymal stem cells (MSCs). We have recently shown that hydrogel, used as an encapsulating biomaterial affects the cross-talk among host immune cells and MSCs. However, the role of hydrogel elasticity and porosity in regulation of cross-talk between dental-derived MSCs and immune cells is unclear. In this study, we demonstrate that the modulus of elasticity and porosity of the scaffold influence T-lymphocyte-dental MSC interplay by regulating the penetration of inflammatory T cells and their cytokines. Moreover, we demonstrated that alginate hydrogels with different elasticity and microporous structure can regulate the viability and determine the fate of the encapsulated MSCs through modulation of NF-kB pathway. Our in vivo data show that alginate hydrogels with smaller pores and higher elasticity could prevent pro-inflammatory cytokine-induced MSC apoptosis by down-regulating the Caspase-3- and 8- associated proapoptotic cascades, leading to higher amounts of ectopic bone regeneration. Additionally, dental-derived MSCs encapsulated in hydrogel with higher elasticity exhibited lower expression levels of NF-kB p65 and Cox-2 in vivo. Taken together, our findings demonstrate that the mechanical characteristics and microarchitecture of the microenvironment encapsulating MSCs, in addition to presence of T-lymphocytes and their pro-inflammatory cytokines, affect the fate of encapsulated dental-derived MSCs.Statement of SignificanceIn this study, we demonstrate that alginate hydrogel regulates the viability and the fate of the encapsulated dental-derived MSCs through modulation of NF-kB pathway. Alginate hydrogels with smaller pores and higher elasticity prevent pro-inflammatory cytokine-induced MSC apoptosis by down-regulating the Caspase-3- and 8- associated proapoptotic cascade, leading to higher amounts of ectopic bone regeneration. MSCs encapsulated in hydrogel with higher elasticity exhibited lower expression levels of NF-kB p65 and Cox-2 in vivo. These findings confirm that the fate of encapsulated MSCs are affected by the stiffness and microarchitecture of the encapsulating hydrogel biomaterial, as well as presence of T-lymphocytes/pro-inflammatory cytokines providing evidence concerning material science, stem cell biology, the molecular mechanism of dental-derived MSC-associated therapies, and the potential clinical therapeutic impact of MSCs.

Graphical abstract

http://ift.tt/2tHXTqB

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Τετάρτη 12 Ιουλίου 2017

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