Modified Transverse-Vertical Gross Examination: a Better Method for the Detection of Definite Capsular Invasion in Encapsulated Follicular-Patterned Thyroid Neoplasms

Abstract

The diagnosis of encapsulated follicular-patterned thyroid carcinoma (EFPTC) is challenging, and the detection of capsular invasion and/or vascular invasion is essential in distinguishing benign lesions from malignant lesions. In this study, we present a modified transverse-vertical gross examination method with additional vertical cuts at the upper and lower ends of thyroid nodules. In addition, we compared the clinicopathological characteristics of patients with EFPTC between conventional and modified methods. The diagnostic rate of follicular thyroid carcinoma and invasive encapsulated follicular variant of papillary thyroid carcinoma was higher with the modified method (p = 0.003 and p = 0.028, respectively). Furthermore, the paraffin block number and the number of capsular invasion per centimeter were significantly higher with the modified method (p < 0.001 and p = 0.007, respectively). However, vascular invasion was not significantly different between the two methods (p = 0.771). The possibility of identifying capsular invasion was around two times higher with the modified method (odds ratio = 1.91, 95% confidence interval = 1.20–3.07, p = 0.007). A total of 38 samples (23%) in the modified transverse-vertical group had capsular and/or vascular invasion in the additional vertical cuts of the upper/lower ends of the tumor. Our modified transverse-vertical gross examination method was more effective than the conventional transverse examination method for the detection of capsular invasion in EFPTC. This modified gross examination method might allow a better differential diagnosis among various encapsulated micro-follicular proliferative lesions.

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Numbers Have Life: A Commentary on “Predictors of Survival in Patients with Advanced Gastrointestinal Malignancies Admitted to the Intensive Care Unit”

http://bit.ly/2CuistN

Effects of Oral Morphine on Dyspnea in Patients with Cancer: Response Rate, Predictive Factors, and Clinically Meaningful Change (CJLSG1101)

AbstractBackground.Although the efficacy of parenteral morphine for alleviating dyspnea has been previously demonstrated in several studies, little is known regarding the efficacy of oral morphine for dyspnea among patients with cancer, including its response rate and predictive factors of effectiveness. Therefore, the aim of this study was to clarify the effectiveness of oral morphine on dyspnea in patients with cancer and elucidate the predictive factors of its effectiveness.Subjects, Materials, and Methods.In this multicenter prospective observational study, we investigated the change in dyspnea intensity in patients with cancer before and after the administration of oral morphine by using a visual analog scale (VAS). We also administered a self‐assessment questionnaire to determine whether the patients believed oral morphine was effective.Results.Eighty patients were enrolled in the study, and 71 of these patients were eligible. The least square mean of the VAS scores for dyspnea intensity was 53.5 at baseline, which decreased significantly to 44.7, 40.8, and 35.0 at 30, 60, and 120 minutes after morphine administration, respectively. Fifty‐four patients (76.1%) reported that oral morphine was effective on the self‐assessment questionnaire. Among the background factors, a high score for "sense of discomfort" on the Cancer Dyspnea Scale (CDS) and a smoking history of fewer pack‐years were associated with greater effectiveness.Conclusion.Oral morphine was effective and feasible for treating cancer‐related dyspnea. A higher score for "sense of discomfort" on the CDS and a smaller cumulative amount of smoking may be predictive factors of the effectiveness of oral morphine.Implications for Practice.This study demonstrated that oral morphine was effective in alleviating cancer‐related dyspnea due to multiple factors including primary lung lesions, airway narrowing, and pleural effusion. Approximately 76% of patients reported that oral morphine was effective. A higher score for "sense of discomfort" on the Cancer Dyspnea Scale and a lower cumulative amount of smoking may be predictive factors for the effectiveness of oral morphine. Interestingly, respiratory rates in patients who reported the morphine to be effective decreased significantly after oral morphine administration, unlike the respiratory rates in "morphine‐ineffective" patients.

http://bit.ly/2RDZ8F2

Genomic Features for Therapeutic Insights of Chemotherapy‐Resistant, Primary Mediastinal Nonseminomatous Germ Cell Tumors and Comparison with Gonadal Counterpart

AbstractPrimary mediastinal nonseminomatous germ cell tumors (PMNSGCT) frequently become refractory to chemotherapy, and no effective salvage therapy exists. We performed genomic profiling on a series of 44 PMNSGCT and compared the results with those from chemorefractory, metastatic pure seminomatous (Sem, n = 22) and nonseminomatous (NS, n = 86) testicular germ cell tumors. Archival tissues were sequenced by a hybrid capture‐based technology (FoundationONE; Foundation Medicine, Inc., Cambridge, MA). Microsatellite instability (MSI) and tumor mutational burden (TMB, mutations [mut]/Mb) were determined.Statistically significant differences in genomic alterations (GA) of PMNSGCT versus NS included higher TP53 pathway GA (p < .0001), PIK3CA pathway GA (p < .0001), and lower cell‐cycle pathway GA (p = .0004). There were no MSI‐high PMNSGCT cases. Mean TMB was similar between the groups, but there were more ≥10 mut/Mb in the PMNSGCT group versus NS (11.4% vs. 4.6%).The GA identified in PMNSGCT were similar to the findings from NS, with differential opportunities for targeted therapies and immunotherapies. Further study of precision treatments appears warranted.

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Frontal Fibrosing Alopecia: An Update on Pathogenesis, Diagnosis, and Treatment

Abstract

Frontal fibrosing alopecia (FFA), first described by Kossard in the early 1990s, is a form of primary lymphocytic cicatricial alopecia characterized by selective involvement of the frontotemporal hairline and eyebrows. Since the original description, an increasing number of cases have been reported worldwide and the clinical aspects of the disease have been better characterized. However, the pathogenesis is still unknown and several hypotheses have been made about possible triggering factors, including hormones, neurogenic inflammation, smoking, UV filters, and ingredients in leave-on facial products. A genetic basis has also been hypothesized as the disease can occur in siblings and members of the same family. Besides its pathogenesis, research is also focused on treatment; FFA is a chronic condition and at present there is no validated or approved treatment for this disorder. Commonly prescribed topical treatments include corticosteroids, minoxidil, and calcineurin inhibitors. Systemic treatments include 5α-reductase inhibitors, hydroxychloroquine, and retinoids. Intralesional triamcinolone acetonide is also utilized, especially for the eyebrows. Other possible treatments include pioglitazone, naltrexone, tofacitinib, and lasers.

http://bit.ly/2AVEwgW

Spatiotemporal distribution of organotin compounds in the coastal water of the Bahía Blanca estuary (Argentina)

Abstract

Several areas within the Bahía Blanca estuary (BBE), with different maritime traffic intensity, were studied in order to confirm the presence and assess the distribution of tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT) in the water column. The organotin compounds (OTCs) were determined in the water samples—taken in summer, autumn, winter, and spring of 2014—by gas chromatography coupled to mass spectrometry after liquid-liquid extraction with hexane. The incidence of TBT throughout the whole sampling period indicated a continuous presence of this compound to the study area. However, in accordance with the butyltin degradation index (BDI), TBT was not recently introduced in the BBE. Furthermore, the average TBT levels exceeded the international guideline established by the Oslo-Paris commission (0.62 ng Sn L⁻¹). As a result, certain biological effects could be expected to occur in sensitive species such as mussels. While DBT were below the detection limit in the 75% of the samples analyzed, MBT was detected in all the samples and no significant differences were found among the concentrations measured in the different seasons (Kruskal–Wallis test, p > 0.05). In addition, no correlations were found among the OTCs levels and the evaluated physiochemical parameters (Spearman coefficient, p > 0.05).

http://bit.ly/2QVo3Pa

Influence of nutrient formulations on growth, lipid yield, carbon partitioning and biodiesel quality potential of Botryococcus sp. and Chlorella sp.

Abstract

The study was conducted to analyse the influence of three nutrient formulations, namely BG-11 medium, BBM and TAP medium, on growth potential and lipid yield of two microalgal genera (Botryococcus sp. and Chlorella sp.) and to study the roles of N, P and other major nutrients. The study focussed on the general patterns of starch and lipid synthesis and storage and to further assess how photosynthetic carbon partitioning into starch and lipid is altered by conditions in growth media such as N and C presence as seen in BG11 medium which are known to induce neutral lipid production and the lack of it in BBM and TAP medium. BG-11 medium performed better as compared to BBM and TAP medium in terms of biomass productivity and lipid yield. The lipid yield was highest in Botryococcus sp. (63.03% dry wt.) and Chlorella sp. (50.27% dry wt.) at 30th day of incubation. Mean biomass productivity was highest for Botryococcus in BBM medium (6.14 mg/L/day) and for Chlorella in BG-11 medium (4.97 mg/L/day). Mean lipid productivity (50.78% and 39.36%) was highest in BG11 medium for both Botryococcus and Chlorella species, respectively. A sharp decline in sugar content was observed in the late stationary phase of growth from 30th day to 45th day. Fatty acid methyl ester (FAME) profile of the extracted lipids showed predominantly oleic acid, followed by palmitic acid and stearic acid in both the strains when grown in BG-11 medium. The other biodiesel quality parameters were in accordance with the international standards. A complex relationship was found between chemical composition and biodiesel properties. Proximity analysis indicated that the fuel properties of biodiesels are determined by a number of parameters and by the combination of different chemical compositions. The results provide an insight into organic carbon partitioning into lipid compounds and how the organism's lipid metabolism changes due to N-deplete culturing in TAP medium and inorganic carbon source availability as seen in BG-11 and BBM medium.

http://bit.ly/2FxbacI

Comparison of Outcomes in Oncoplastic Pelvic Reconstruction with VRAM versus Omental Flaps: A Large Cohort Analysis

J reconstr Microsurg
DOI: 10.1055/s-0038-1677524

Background The purpose of this study is to describe our experience and outcomes in oncoplastic pelvic reconstruction for patients who underwent either vertical rectus abdominis musculocutaneous (VRAM) or omental flap following abdominoperineal resection (APR) at a single tertiary care institution. Methods All patients who underwent pelvic reconstruction following APR with either VRAM or omental flaps from January 1992 to January 2017 were retrospectively reviewed. Patient demographics and relevant comorbidities including chemotherapy and radiation therapy data were collected and analyzed. In addition, margin status at the time of oncologic resection was analyzed. Flap-specific data were collected for each approach. Oncologic data collected included cancer type, stage at time of APR, and rate of tumor recurrence within the flap. Results A total of 562 patients were identified who underwent pelvic reconstruction with either VRAM or omental pedicle flaps. Of these, 274 (48.8%) underwent VRAM reconstruction and 288 (51.2%) underwent omental flap reconstruction. All margins were negative at time of cancer ablation surgery. Complications data included: seroma (VRAM = 2 [0.36%]; omentum = 32 [5.69%], p < 0.0001), wound dehiscence (VRAM = 31 [5.52%]; omentum = 17 [3.02%], p = 0.022), abscess (VRAM = 4 [0.71%]; omentum = 27 [4.8%], p < 0.0001), cellulitis (VRAM = 2 [0.36%]; omentum = 10 [1.78%], p = 0.025). Statistical comparison of tumor recurrence between these two reconstructive approaches showed a significantly higher recurrence rate in omental flaps compared with VRAM flaps (p = 0.000127). Conclusions The results of this study suggest a significantly higher tumor recurrence rate in omental flap pelvic reconstruction compared with VRAM flaps. This knowledge has the potential to influence surgical planning and flap selection in pelvic reconstruction.
[...]

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Comparison of pre-oxygenation using spontaneous breathing through face mask and high-flow nasal oxygen: A prospective randomised crossover controlled study in healthy volunteers

BACKGROUND High-flow nasal oxygen (HFNO) therapy has been proposed for pre-oxygenation before intubation, but the end-tidal fraction of oxygen (ETO2) obtained remains unknown. OBJECTIVE(S) To compare the ETO2 following a 3 min pre-oxygenation with HFNO and face mask. SETTING Operating room in a primary university hospital. DESIGN A prospective, randomised crossover study. PARTICIPANTS Fifty healthy volunteers. INTERVENTIONS Participants were randomly pre-oxygenated through spontaneous breathing 100% oxygen in a face mask and with HFNO (mouth closed, heated and humidified gas flow at 60 l min–1). In the face mask group, the ETO2 was measured continuously. In the HFNO group, the nasal cannula was quickly exchanged with a face mask while the subject held their breath at end inspiration and the ETO2 was measured after a deep expiration. The protocol ended when ETO2 reached 90% or otherwise at 6 min. MAIN OUTCOME MEASURES The primary endpoint was the ETO2 after 3 min of pre-oxygenation. Secondary endpoints were the proportion of participants with an ETO2 at least 90% and the time until the ETO2 at least 90%. RESULTS The ETO2 after 3 min of pre-oxygenation was 89 (2) % and 77 (12) % in the face mask and HFNO groups [difference 12% (95% confidence interval, 95% CI: 8 to 15]; P 

http://bit.ly/2FEaz9t

Central venous-to-arterial PCO2 difference, arteriovenous oxygen content and outcome after adult cardiac surgery with cardiopulmonary bypass: A prospective observational study

BACKGROUND Rapid identification and treatment of tissue hypoxia reaching anaerobiosis (dysoxia) may reduce organ failure and the occurrence of major postoperative complications (MPC) after cardiac surgery. The predictive ability of PCO2-based dysoxia biomarkers, central venous-to-arterial PCO2 difference (ΔPCO2) and ΔPCO2 to arteriovenous oxygen content difference ratio, is poorly studied in this setting. OBJECTIVES We evaluated the ability of PCO2-based tissue dysoxia biomarkers, blood lactate concentration and central venous oxygen saturation measured 2 h after admission to the ICU as predictors of MPC. DESIGN A prospective, observational cohort study. SETTING Single-centre, academic hospital cardiovascular ICU. PATIENTS We included adult patients undergoing cardiac surgery with cardiopulmonary bypass and measured dysoxia biomarkers at ICU admission, and after 2, 6 and 24 h. MAIN OUTCOME MEASURES The primary endpoint was MPC, a composite of cardiac and noncardiac MPC evaluated in the 48 h following surgery. After univariate analysis of MPC covariates including dysoxia biomarkers measured at 2 h, multivariate logistic regression analyses were performed to identify the association of these biomarkers with MPC for confounders. Areas under the receiver operating characteristic curves were determined for biomarkers which remained independently associated with MPC. RESULTS MPC occurred in 56.5% of the 308 patients analysed. ΔPCO2, blood lactate concentration and central venous oxygen saturation measured at 2 h, but not ΔPCO2 to arteriovenous oxygen content difference ratio, were significantly associated with MPC. However, only ΔPCO2 was independently associated with MPC after multivariate analysis. The areas under the receiver operating characteristic curves of ΔPCO2 measured at 2 h for MPC prediction was 0.64 (95% CI 0.57 to 0.70, P 

http://bit.ly/2FI7Hr6

Programmed intermittent bolus infusion versus continuous infusion of 0.2% levobupivacaine after ultrasound-guided thoracic paravertebral block for video-assisted thoracoscopic surgery: A randomised controlled trial

BACKGROUND The analgesic benefits of programmed intermittent bolus infusion for thoracic paravertebral block remain unknown. OBJECTIVE The aim of this study was to compare the analgesia from intermittent bolus infusion with that of a continuous infusion after thoracic paravertebral block. DESIGN A randomised controlled study. SETTING A single centre between December 2016 and November 2017. Seventy patients scheduled for video-assisted thoracoscopic surgery were included in the study. INTERVENTION(S) Patients were randomly assigned to receive 0.2% levobupivacaine via continuous infusion (5 ml h−1, continuous group) or programmed intermittent bolus infusion (15 ml every 3 h, bolus group) after an initial 15-ml bolus injection of 0.2% levobupivacaine. MAIN OUTCOME MEASURES The main outcome was the amount of rescue fentanyl (per kg of body weight) consumed within 24 h after surgery. Secondary outcomes were postoperative pain scores, plasma levobupivacaine concentrations and the number of dermatomes anaesthetised. RESULTS There was no significant difference between the continuous and bolus groups in the postoperative consumption of fentanyl (median [interquartile range] 5.5 [4 to 9.5] μg kg−1 versus 6 [3.5 to 9] μg kg−1 respectively, P = 0.45) and postoperative pain scores within 24 h. At 20 h after initiating the infusions, there was no statistically significant difference between the two groups in terms of the plasma levobupivacaine concentration. The number of dermatomes anaesthetised to pinprick and cold testing was significantly greater in the bolus group. CONCLUSION Our findings suggest that postoperative pain and opioid usage are similar with either programmed intermittent bolus infusion or continuous infusion after thoracic paravertebral block. Programmed intermittent bolus infusion provides a wider sensory blockade and could benefit patients requiring a wider extent of anaesthesia. TRIAL REGISTRATION UMIN Clinical Trials Registry (UMIN-CTR; URL: http://umin.ac.jp/ctr/, ID: UMIN000023378). Correspondence to Dr. Yasuko Taketa, Department of Anesthesiology and Critical Care, Ehime Prefectural Central Hospital, 83 Kasuga-machi, Matsuyama-City, Ehime 790-0024, Japan. E-mail: suko1231@yahoo.co.jp © 2019 European Society of Anaesthesiology

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Pre-operative ultrasonographic evaluation of inferior vena cava collapsibility index and caval aorta index as new predictors for hypotension after induction of spinal anaesthesia: A prospective observational study

BACKGROUND Hypotension after spinal anaesthesia is a common side effect that may be harmful. Patients' susceptibility to intra-operative hypotension can be affected by many pre-operative factors. OBJECTIVES The current study aimed to evaluate the efficacy of both pre-operative inferior vena cava collapsibility index (IVCCI) and inferior vena cava to aorta diameter (IVC : Ao) index for predicting postspinal anaesthesia hypotension (PSAH). DESIGN Prospective observational blinded study. SETTING Operating room from June 2017 to February 2018. PATIENTS One hundred adult patients of both sexes, American Society of Anesthesiologists' physical status 1 or 2 scheduled for elective surgery under spinal anaesthesia were included in this study. INTERVENTIONS Patients received spinal anaesthesia performed at the level of L3 to 4 or L4 to 5 intervertebral space with the patient in the sitting position then placed in the supine position immediately after neuraxial block and kept supine throughout the study period (30 min). IVCCI and IVC : Ao index were assessed pre-operatively. Baseline noninvasive blood pressure was recorded before administration of spinal anaesthesia then every minute after spinal blockade for 30 min. MAIN OUTCOME MEASURES The primary outcome was to evaluate the predictive values of both IVCCI and IVC : Ao index for detecting PSAH and the secondary outcomes were to compare the predictive values of both IVCCI and IVC : Ao index and to detect other clinical predictors for PSAH using logistic regression analysis. RESULTS Forty-five patients developed PSAH (45%). IVCCI was significantly higher in patients who developed PSAH than in patients who did not, while IVC : Ao index was significantly lower in patients who developed PSAH than in patients who did not. Hypotension after induction of spinal anaesthesia was defined as an absolute value of SBP less than 90 mmHg, a decrease in SBP more than 30% of the baseline value or an absolute value of arterial blood pressure less than 60 mmHg. Logistic regression analysis revealed that IVCCI and IVC : Ao index were good predictors of the occurrence of PSAH. Receiver operating characteristic curve analysis showed that IVC : Ao index had a sensitivity of 96%, a specificity of 88%, and an accuracy of 95% to predict PSAH at a cut-off point less than 1.2. IVCCI had a sensitivity of 84%, a specificity of 77%, and an accuracy of 84% to predict PSAH at a cut-off point more than 44.7%. CONCLUSION Pre-operative IVCCI and IVC : Ao index are good predictors of the occurrence of PSAH. However, IVC : Ao index is a more powerful predictor than IVCCI. TRIAL REGISTRATION This study evaluate accuracy of two diagnostic methods for the occurrence of postspinal anaesthesia hypotension, so not a clinical trial as no intervention is present and no outcome of intervention is measured. Correspondence to Dr Eman Ramadan Salama, MD, Anaesthesia and Surgical ICU, Tanta University Hospital, Tanta, Egypt Tel: +20 1277886405; fax: +20 402231671; e-mail: dr.ers1975@yahoo.com © 2019 European Society of Anaesthesiology

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Comparison among TIRADS (ACR TI-RADS and KWAK- TI-RADS) and 2015 ATA Guidelines in the diagnostic efficiency of thyroid nodules

Abstract

Purpose

To compare the value of Thyroid Imaging Reporting and Data Systems proposed by Kwak (KWAK-TIRADS) and ACR (ACR TI-RADS) and 2015 American Thyroid Association (ATA) guidelines in the diagnosis of surgically resected thyroid nodules.

Methods

From January 2015 to December 2015, 2544 thyroid nodules in 1758 patients who underwent thyroidectomy at our center were included. The KWAK-TIRADS category, ACR TI-RADS and ultrasound (US) pattern based on ATA guidelines were assigned to each thyroid nodule. Nodules were divided into groups according to their maximal diameter further.

Results

Of all the nodules, 863 (33.9%) were benign, whereas 1681 (66.1%) were malignant. The malignancy percentage of ACR TI-RADS category 1, 2, 3, 4, and 5 were 0%, 1.3%, 9.1%, 52.5%, and 88.8%, respectively. KWAK-TIRADS and ATA guidelines showed a better diagnostic efficiency than ACR TI-RADS (P < 0.01). ACR TI-RADS demonstrated a higher specificity (79.7%, P < 0.05), whereas the ATA US pattern had a higher sensitivity (95.5%, P < 0.01). The TIRADS (KWAK-TIRADS and ACR TI-RADS) category and ATA guidelines performed better in differentiating nodules >1 cm. KWAK-TIRADS showed better diagnostic efficiency than the other methods in differentiating nodules >1 cm (AUC: 0.92, P < 0.01).

Conclusions

KWAK-TIRADS and ATA guidelines provide a better diagnostic efficiency than ACR TI-RADS. The TIRADS (KWAK-TIRADS and ACR TI-RADS) category and ATA guidelines perform better in differentiating nodules >1 cm than nodules ≤1 cm. KWAK-TIRADS perform better in differentiating nodules >1 cm than other methods.

http://bit.ly/2T23nHb

Comparison among TIRADS (ACR TI-RADS and KWAK- TI-RADS) and 2015 ATA Guidelines in the diagnostic efficiency of thyroid nodules

Abstract

Purpose

To compare the value of Thyroid Imaging Reporting and Data Systems proposed by Kwak (KWAK-TIRADS) and ACR (ACR TI-RADS) and 2015 American Thyroid Association (ATA) guidelines in the diagnosis of surgically resected thyroid nodules.

Methods

From January 2015 to December 2015, 2544 thyroid nodules in 1758 patients who underwent thyroidectomy at our center were included. The KWAK-TIRADS category, ACR TI-RADS and ultrasound (US) pattern based on ATA guidelines were assigned to each thyroid nodule. Nodules were divided into groups according to their maximal diameter further.

Results

Of all the nodules, 863 (33.9%) were benign, whereas 1681 (66.1%) were malignant. The malignancy percentage of ACR TI-RADS category 1, 2, 3, 4, and 5 were 0%, 1.3%, 9.1%, 52.5%, and 88.8%, respectively. KWAK-TIRADS and ATA guidelines showed a better diagnostic efficiency than ACR TI-RADS (P < 0.01). ACR TI-RADS demonstrated a higher specificity (79.7%, P < 0.05), whereas the ATA US pattern had a higher sensitivity (95.5%, P < 0.01). The TIRADS (KWAK-TIRADS and ACR TI-RADS) category and ATA guidelines performed better in differentiating nodules >1 cm. KWAK-TIRADS showed better diagnostic efficiency than the other methods in differentiating nodules >1 cm (AUC: 0.92, P < 0.01).

Conclusions

KWAK-TIRADS and ATA guidelines provide a better diagnostic efficiency than ACR TI-RADS. The TIRADS (KWAK-TIRADS and ACR TI-RADS) category and ATA guidelines perform better in differentiating nodules >1 cm than nodules ≤1 cm. KWAK-TIRADS perform better in differentiating nodules >1 cm than other methods.

http://bit.ly/2T23nHb

Comparison between Radioiodine therapy and single‐session Radiofrequency ablation of autonomously functioning thyroid nodules: a retrospective study

Abstract

Objective

To compare the efficacy of Radioiodine (RI) and Radiofrequency ablation (RFA) in the treatment of autonomously functioning thyroid nodules (AFTNs). End points: nodule volume reduction (NVR) and thyroid function normalization.

Design, patients and measurements

Twenty‐two patients (2:20 M:F; 51.9±13.9 years) affected by 25 AFTNs, treated by RFA were retrospectively compared with 25 patients (8:17 M:F; 57.2±12.8 years) affected by a single AFTN treated by RI. Both group showed analogous characteristics as to age, gender, toxic/pretoxic phase, and pre‐treatment nodule volume (calculated by the ellipsoid formula). Thyroid hormone levels and autoimmune thyroid profile were assessed before treatment. A fixed RI activity of 555MGb (15mCi) was administered. RFA was performed with an 18G, single‐tipped electrode, by the 'modified moving shot technique'. Thyroid hormones were assessed and the nodule post‐treatment volume calculated 12 months after treatment.

Results

No statistical difference was found between the post‐treatment NVR by comparing RI and RFA (p=0.69). The volume reduction rates were 68.4±28.9% and 76.4±16.9% after RI and RFA, respectively. As to the thyroid function, 5/25 patients developed clinical hypothyroidism after RI. After RFA, all the 22 patients silenced their AFTN and normalized the thyroid hormones. Subclinical hypothyroidism was recorded in 2 patients after both RI and RFA. Thus, the functional therapeutic success, defined as the restoration of euthyroidism, was achieved in 18/25 (72%) patients treated by RI and in 20/22 (90.9%) treated by RFA.

Conclusions

No statistical difference in NVR was found between RI and RFA. All patients responded to RI but 5/25 were 'over‐treated' developing hypothyroidism. RFA was effective in all patients with no case of post‐treatment clinical hypothyroidism. No radiation exposure and lower risk of post‐treatment hypothyroidism might make RFA the favorite option especially for young patients.

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http://bit.ly/2DjXijJ

Hyponatraemia in patients with community acquired pneumonia; prevalence and etiology, and natural history of siad

Abstract

Objective

Hyponatraemia is common in community acquired pneumonia (CAP) and is associated with increased mortality. The mechanism of hyponatraemia in CAP is not completely understood and treatment is therefore ill‐defined. We aimed to define the causation of hyponatraemia in CAP.

Design

Prospective, single‐centre, observational study of all patients with CAP and hyponatremia (≤ 130 mmol/L) during a 9‐month period.

Patients

The prevalence of each subtype of hyponatraemia, and the associated mortality, was determined in 143 admissions with CAP (Study 1). A sub‐cohort of patients with SIAD(n=10) was prospectively followed, to document the natural history of SIAD associated with CAP (Study 2).

Measurements

In Study 2, blood and urine were collected on day 1, 3, 5 and 7 following admission for measurement of plasma vasopressin, sodium, osmolality and urine osmolality.

Results

In study 1, 143/1723(8.3%) of CAP‐patients had hyponatraemia (≤130 mmol/L). 66 had SIAD (46%), 60(42%) had hypovolaemic hyponatraemia (HON), 13(9%) had hypervolaemic hyponatraemia (HEN) and 4(3%) patients had hyponatraemia due to glucocorticoid hormone deficiency. Mortality was higher in the HEN than in the HON, SIAD or normonatraemic groups (p < 0.01). In Study 2, plasma sodium concentration normalised in 8/10 (80%) by day 7. Two patients with persistent hyponatraemia were discovered to have underlying bronchiectasis.

Conclusions

Hyponatraemia in CAP is most commonly secondary to SIAD or hypovolaemia. HEN is less common, but has worse prognosis. Prospective observation demonstrates that in SIAD, plasma AVP and sodium concentrations normalise with antimicrobials; failure of reversal of suggests underlying lung disease, such as bronchiectasis.

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http://bit.ly/2sC10ze

Insulin resistance is associated with hirsutism in unselected reproductive‐aged women

Summary

Objective

Hirsutism affects 5‐10% of reproductive‐aged women worldwide and exhibits clinical importance as a cutaneous manifestation of underlying hyperandrogenism. Racial and genetic factors play roles in manifestation of hirsutism, and the prevalence of hirsutism seems to be low in East Asians. However, the reference value of the modified Ferriman‐Gallway (mFG) score to diagnose hirsutism and the prevalence of hirsutism have not been determined in Korean populations to date. We aimed to investigate the distribution of the mFG score and establish its reference value for defining hirsutism and to examine its relationship with metabolic and reproductive traits in reproductive‐aged Korean women.

Design, Patients and Measurements

We enrolled 2,139 female volunteers of reproductive age (15 ‐ 39 years). We recorded mFG scores from 0 to 4 on 9 different body locations (upper lip, chin, chest, arm, upper abdomen, lower abdomen, upper back, lower back, and thighs). Hirsutism was defined as > 95^th percentile of mFG score. In addition, a 75‐g oral glucose tolerance test was performed, and the homeostasis model assessment of insulin resistance (HOMA‐IR) was calculated.

Results

The mFG values of the 50th, 75th, 90th, and 95th percentiles were 0, 1, 4, and 6, respectively. Therefore, the mFG score was indicative of hirsutism when the score was 6 or greater, which represents the 95^th percentile. In the correlation analysis, total testosterone, free testosterone, fasting plasma insulin, and HOMA‐IR were positively correlated with mFG score (all Ps < 0.05). Multiple linear regression analysis revealed that HOMA‐IR (β = 0.081) was positively associated with mFG score after adjustments for age, body mass index, total testosterone, and the number of menses per year (P < 0.001).

Conclusions

In conclusion, setting the 95^th percentile of the mFG score as normal, the reference value to define hirsutism was 6 in reproductive‐aged Korean women. HOMA‐IR was positively associated with the mFG score even after adjustment for biochemical hyperandrogenism.

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http://bit.ly/2Mjva3l

Altered NOX expression does not seem to account for epidermal NLRP3 inflammasome activation in Hidradenitis Suppurativa

Abstract

Hidradenitis Suppurativa (HS)/ acne inversa is defined as a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep‐seated, inflamed lesions in the apocrine gland‐bearing areas of the body, most commonly the axillae, inguinal and anogenital regions (Dessau definition). It is associated with systemic comorbidities and influenced by genetic predisposition while triggering of the disease occurs by environmental factors. Consecutively, innate immune events appear to play a role. Recently, van der Zee et al. reported increased production of the proinflammatory cytokine IL‐1β in HS.

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http://bit.ly/2ASg9Rj

A retrospective cohort study evaluating the accuracy of clinical diagnosis compared to immunofluorescence and electron microscopy in children with inherited epidermolysis bullosa

Abstract

Traditionally, the diagnosis of epidermolysis bullosa (EB) was made using electron microscopy (EM), and immunofluorescence mapping (IFM). Increasingly, genomics plays a role in the diagnosis of EB, and other genetic conditions, with a result turn‐around‐time as little as 1‐3 weeks. The rapid turn around time and accuracy of genetic testing mandates a rethink on the way that we currently assess infants and children with EB. A biopsy is invasive and can be distressing for caregivers. Given the limitations of skin biopsy in some situations, the future should see genetic testing as a first‐line investigation. However, it is important to note that currently, in severe neonates and infants with EB, a biopsy remains a first line investigation since clinical diagnosis is not accurate using current scoring systems and even when assessed by experts in EB.

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http://bit.ly/2T1A6w5

A qualitative examination of the experience of skin camouflage by people living with visible skin conditions

Abstract

Background

People with a visible skin conditions can experience anxiety and intrusive reactions from others when in social situations. The use of products to conceal marks on the skin is provided in a number of different hospital services and by charities. However, little is known about the experience of people using camouflage as a tool for enhancing quality of life.

Aim

This study aimed to examine the experience of using skin camouflage to cover a visible mark on the skin. It sought to gain a detailed account of the issues associated with camouflage use and the needs of people using it.

Methods

Interpretative Phenomenological Analysis (IPA) was used to gain a detailed understanding of the meaning of camouflage use for participants. Six skin camouflage service‐users completed semi‐structured interviews.

Results

The IPA analysis revealed that the experience of using camouflage was influenced by socio‐cultural factors and the views of others. The use of camouflage was linked to investment in appearance maintenance and functioned to give a sense of control over social interactions, increase social confidence and manage concern about the responses of others.

Conclusions

This study provides an in‐depth insight into the experience of using skin camouflage and suggests that camouflage can play a valuable role in maintaining wellbeing in those living with a visible skin condition.

This article is protected by copyright. All rights reserved.

http://bit.ly/2AS47au

Severe disseminated Nocardia infection associated with ustekinumab treatment for psoriasis

Abstract

Ustekinumab is one of the newer biologic agents on the market, and most clinical experience associated with this agent has been accumulated with the treatment of psoriasis. It exerts its effect through IL‐12/IL‐23p40 antagonism. This immune signaling pathway is associated with Mendelian Susceptibility to Mycobacterial Disease, a genetic condition predisposing to opportunistic infections with mycobacteria and other select organisms. Nonetheless, clinical trial safety data for this agent has suggested its safety, with very few case reports of severe opportunistic infections. It is sometimes considered to be associated with a lesser infectious risk compared to some other biologic agents such as tumor necrosis factor inhibitors. We report a 56‐year‐old patient presenting with an unusually severe disseminated Nocardia farcinica infection associated with ustekinumab treatment: sustained bacteremia, disseminated skin lesions, large renal abscess, septic renal vein thrombosis and pulmonary and cerebral lesions . To our knowledge, this is the first report of disseminated nocardiosis associated with this monoclonal antibody.

This article is protected by copyright. All rights reserved.

http://bit.ly/2SXcw3D

The anti‐inflammatory potency of biologics targeting TNF‐α, IL‐17A, IL‐12/23 and CD20 in hidradenitis suppurativa: an ex vivo study

Abstract

Background

Biologics targeting inflammatory mediators are able to clinically improve hidradenitis suppurativa (HS). However, their clinical efficacy shows great inter‐patient variability in daily practice.

Objective

To investigate the anti‐inflammatory potency of a selection of currently available biologics for the treatment of HS in an ex vivo skin culture system using lesional HS biopsies.

Methods

Lesional skin samples of ten HS patients and skin samples of five healthy controls were cultured ex vivo and exposed to prednisolone or biologics targeting TNF‐α, IL‐17A, IL‐12/23p40, or CD20, respectively adalimumab, infliximab, secukinumab, ustekinumab and rituximab. Real‐Time quantitative PCR and cytokine bead arrays were used to measure the inhibitory effect of the biologics on cytokines and antimicrobial peptides (AMPs).

Results

The relative mRNA expression of all tested cytokines and AMPs was significantly downregulated by all anti‐inflammatory agents (p<0·0001). The protein production of the pro‐inflammatory cytokines TNF‐α, IFN‐ɣ, IL‐1ß, IL‐6, and IL‐17A was significantly inhibited by adalimumab, infliximab, ustekinumab, prednisolone (all p<0·0001) and rituximab (p=0·0071), but not by secukinumab (p=0·0663). On both mRNA and protein level, adalimumab, infliximab and prednisolone reduced the levels of a broader mix of individual cytokines than secukinumab, ustekinumab and rituximab. Moreover, a significant inhibitory effect on the mRNA expression levels of inflammatory markers in healthy control skin was observed only for prednisolone (p=0·0015) and the TNF‐α inhibitors (p<0·0001).

Conclusions

This ex vivo study suggests that TNF‐α inhibitors and prednisolone are the most powerful inhibitors of pro‐inflammatory cytokines and AMPs in HS lesional skin, which is in accordance with our clinical experience in patients with HS.

This article is protected by copyright. All rights reserved.

http://bit.ly/2ARS2SJ

Possible long-term sequelae in hand, foot, and mouth disease caused by Coxsackievirus A6

Publication date: Available online 17 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Francesco Broccolo, Francesco Drago, Giulia Ciccarese, Angelo Genoni, Alice Porro, Aurora Parodi, Konstantin Chumakov, Antonio Toniolo

http://bit.ly/2W0mbsa

Dynamics of blood brain barrier permeability and tissue microstructure following controlled cortical impact injury in rat: A dynamic contrast-enhanced magnetic resonance imaging and diffusion kurtosis imaging study

Publication date: Available online 17 January 2019

Source: Magnetic Resonance Imaging

Author(s): Mengmeng Yu, Mingliang Wang, Dianxu Yang, Xiaoer Wei, Wenbin Li

Abstract

Objective

The blood-brain barrier (BBB) and cerebral tissue microstructure can be impaired following traumatic brain injury (TBI). However, the spatiotemporal changes of BBB leakage and tissue microstructure are not completely understood. In this study, we evaluated the spatiotemporal changes of BBB leakage and tissue microstructure using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion kurtosis imaging (DKI) in controlled cortical impact (CCI) rats.

Materials and methods

The DCE-MRI parameters volume transfer coefficient (K^trans) and DKI parameters were longitudinally measured in bilateral cortex, hippocampus, thalamus and corpus callosum (CC) at baseline (D0), acute stage (D1, D3), and subacute stage (D7, D14 and D28) post-injury. Immunohistochemistry analysis was performed at D28 after MRI scanning. Repeated-measures ANOVA was used to assess the temporal changes of MRI parameters.

Results

K^trans abnormality was only localized to ipsilateral perilesional cortex with a significant temporal change (F = 144.2, p < 0.0001). Compared to baseline, increased mean kurtosis (MK) was observed in ipsilateral regions of cortex and hippocampus and CC for all the time points (p < 0.05 for all). Increased MK was also observed in ipsilateral thalamus (p = 0.005) at subacute stage but not at acute stage while no change was observed with MD and FA (p > 0.05 for both). In ipsilateral cortex, the overall K^trans value of D0, D1, D3, D7, D14, and D28 post-injury were significantly correlated with MK value (r = 0.84, p < 0.0001). The CCI group showed higher staining of glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba-1) and lower staining of neuron-specific nuclear protein (NeuN) and myelin basic protein (MBP) in ipsilateral regions of cortex, hippocampus, thalamus and CC (p < 0.05 for all) as compared to control group. There were no significant differences in the contralateral regions by immunohistochemistry.

Conclusion

The BBB disruption reflected by K^trans correlated well with MK value in ipsilateral cortex. In addition, MK could detect the delayed microstructural changes in thalamus. DCE-MRI and DKI could be used to assess the BBB breakdown and cerebral microstructural changes of TBI.

http://bit.ly/2AQnaSW

Three‐dimensional reconstruction of skin disease using multi‐view mobile images

Abstract

Background/Purpose

In skin beauty area, interest in diagnosis and management methods for acne is increasing. However, it is difficult to diagnose protruding skin disease by two‐dimensional (2D) image. Three‐dimensional (3D) approach is needed. The purpose of this study was to propose a system for reconstructing 3D model (visual hull) of 2D images obtained using mobile devices.

Methods

Acne images were acquired using a 3D printing mobile image acquisition system. Using two attached mirrors, five multi‐view acne silhouette images were obtained. They were then, reconstructed to 3D. To measure the volume of the formed 3D model (visual hull), post‐processing, calculation, and texture mapping were performed. The volume of acne samples designed with 3D printing was compared with the volume calculated in the produced system using statistical analysis program.

Results

The 3D modeling program demonstrated its superiority by showing high correlation (r = 0.783) between the actual volume of acne and the volume calculated by the system. The 3D model (visual hull) was successfully reconstructed by capturing 2D images of actual acne.

Conclusion

In this study, we created a system to reconstruct small sized protruding skin disease images such as acne obtained with mobile devices. The 3D printing system was used to obtain images from mobile camera and reconstructed to 3D. To verify the volume of the reconstructed model, 3D printing samples were produced and compared with the calculated actual volume. It can be used, for initial diagnosis by receiving information about the protruding skin disease without space‐time constraints using a mobile device.

http://bit.ly/2HrTRMe

Edge detector‐based automatic segmentation of the skin layers and application to moisturization in high‐resolution 3 Tesla magnetic resonance imaging

Abstract

Introduction

Previous studies have demonstrated the feasibility to explore moisturization with quantification imaging based on T2 mapping. The aim of this study was to describe and validate the first robust automated method to segment the first layers of the skin.

Materials and Methods

Data were picked from a previous study that included 35 healthy subjects who underwent a 3T MRI (multi spin echo calculation T2‐weighted sequence) with a microscopic coil on the left heel before and one hour after moisturization. The automatic algorithm was composed of the T2 map generation, a Canny filter, a selection of boundaries, and a local regression to delimitate stratum corneum, epidermis, and dermis. An automated affine registration was applied between the exams before and after moisturization.

Results

The failure rate of the algorithm was below 5%. Mean computation time was 139.12s. There was a significant and strong correlation between the automatic measurements and the manual ones for the T2 values (ρ: 0.905, P < 0.001) and for the thickness measurements (ρ: 0.8663; P < 0.001). For registration, mean of the Dice index was 0.64 [0.47; 0.80] and of the Hausdorff distance was 0.29 mm 95% CI: [0.28; 0.30].

Conclusion

The proposed automatic method to study the first skin layers in 3T MRI using micro‐coils was robust and described T2 values and thickness measurements with a strong correlation to manual measurements. The use of an automated affine registration could also permit the generation of a mapping for a visual assessment of moisturization.

http://bit.ly/2RT5KPb

Noninvasive analysis of skin proteins in healthy Chinese subjects using an Orbitrap Fusion Tribrid mass spectrometer

Abstract

Objective

The objective of this study was to perform noninvasive analysis of skin proteins in a healthy Chinese population using label‐free nanoflow liquid chromatography‐mass spectrometry (nLC‐MS).

Materials and Methods

Five consecutive tape strippings were obtained from the volar forearm skin of healthy Chinese subjects. Proteins were extracted, and trypsin‐digested peptides were analyzed by a nanochromatography instrument coupled to an Orbitrap Fusion Tribrid mass spectrometer. Data‐dependent acquisition allowed protein identification, which was performed by using Proteome Discoverer software (v2.2).

Results

In this study, we identified 80 common proteins that were expressed in the skin of healthy Chinese volunteers and divided these proteins into 16 categories, including keratins, cornified envelope proteins, and enzymes associated with substance metabolism. These proteins were closely associated with multiple functions of the skin barrier.

Conclusion

This study provides a noninvasive method to analyze healthy human epidermal proteins, which are closely associated with the skin barrier. In addition, this study provides a reference for further studies on the application of proteomic technologies to investigate the role of human epidermal proteins in health and disease.

http://bit.ly/2Hm6UP1

Di (2-ethylhexyl) phthalate induces cardiac disorders in BALB/c mice

Abstract

Because of the extensive use of phthalates for domestic, medical, and industrial applications, the evaluation of their toxic effects is of major concern to public health. The aim of the present study was to assess the propensity of di (2-ethylhexyl) phthalate (DEHP), one of the most used phthalates, to cause oxidative cardiac damage in mice. DEHP was administered intraperitoneally at doses of 5, 50, and 200 mg/kg body weight for 30 consecutive days in BALB/c mice. We assessed the effect of DEHP on cardiac injury using biochemical profile (such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatinine phosphokinase (CPK), total cholesterol (T-CHOL), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)), parameters related to myocardiac oxidative stress, such as malondialdehyde (MDA) level, protein carbonyl (PC) concentration, and DNA fragmentation. In addition, we evaluated antioxidant status; enzymatic (catalase (CAT) and superoxide dismutase (SOD) activities) and non-enzymatic (protein-bound sulfhydryl concentration (PSH)) antioxidants. Acetylcholinesterase (AChE) activity and histopathological changes were also assessed in heart mice treated with DEHP. Our results showed that DEHP induced an elevation of serum marker enzymes and perturbated the lipid profile. In addition, this phthalate increased lipid peroxidation, protein carbonyl levels, and DNA fragmentation in the heart in a dose-dependent manner. Antioxidant status was also perturbated by the increase of the CAT and SOD activities and the decrease of the protein-bound sulfhydryl concentration. AChE activity was also inhibited in the heart following the treatment with DEHP. These biochemical alterations were also confirmed by histopathological changes. Increased free radical production at various doses of DEHP would result in impairment of the redox status leading to an enhanced dose-dependent cardiotoxicity.

http://bit.ly/2FHpZIY

Anthropogenic impacts in the Changbai Mountain region of NE China over the last 150 years: geochemical records of peat and altitude effects

Abstract

Geochemical records from peatlands are important tools for the interpretation of environmental signals preserved in the peat and the understanding anthropogenic impacts on remote mountain regions. In this paper, six ²¹⁰Pb-dated peat cores located at 500–1900 m above sea level (asl) in the Changbai Mountains were used to reconstruct the pollution history over the past 150 years in northeastern (NE) China. The cores physicochemical parameters and 10 key chemical elements were analyzed by inductively coupled plasma atomic emission spectroscopy (ICP-AES). Results from loss on ignition (LOI), total organic carbon (TOC), and lithogenic element (Ti, Fe, and Mn) analysis show that the peatlands (Ch, Yc1 and Jb) over 900 m asl are ombrotrophic and the lower altitude peatlands (Dng, Jc, and Ha) are minerotrophic. There is a decreasing trend of trace element distribution with the altitude, mainly due to the local source input. The content of the magnetic particles and trace elements (Cu, Ni, Pb and Zn) as well as their accumulation rates document 150 years of pollution history in the Changbai Mountain region. There is a significant elevated pattern of the geochemical records after the New China, which might mark the start date of Anthropocene since the 1950s in this region. The peatlands at the lower altitude (i.e., Dng and Ha) record the earliest fingerprints of metal contamination due to the starting period of massive reclaiming and immigrating in the Changbai Mountain region. The major increase of trace elements since the 1980s probably suggests a significant deterioration of the local environment due to the fast industrial and urbanization development after the Reform and Opening up in China.

http://bit.ly/2FzK8kT

Characteristics and source apportionment of PM 2.5 in Jiaxing, China

Abstract

Herein we investigated the morphology, chemical characteristics, and source apportionment of fine particulate matter (PM_2.5) samples collected from five sites in Jiaxing. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that soot aggregates and coal-fired fly ash were generally the most abundant components in the samples. All the samples were analyzed gravimetrically for mass concentrations and their various compositions were determined. Our results revealed that the PM_2.5 concentrations in the samples were in the following order: winter > spring > autumn > summer. The PM_2.5 concentrations in winter and spring were higher than those in autumn and summer, except for inorganic elements. Carbonaceous species and water-soluble inorganic ions were the most abundant components in the samples, accounting for 26.17–50.44% and 34.27–49.6%, respectively. The high secondary organic carbon/organic carbon ratio indicated that secondary organic pollution in Jiaxing was severe. The average ratios of NO₃⁻/SO₄²⁻, ranging from 1.01 to 1.25 at the five sites, indicated that mobile pollution sources contributed more to the formation of PM_2.5 than stationary sources. The BeP/(BeP + BaP) ratio (0.52–0.71) in samples reflected the influence of transportation from outside of Jiaxing. The positive matrix factorization (PMF) model identified eight main pollution sources: secondary nitrates (26.95%), secondary sulfates (15.49%), secondary organic aerosol (SOA) (19.64%), vehicle exhaust (15.67%), coal combustion (8.6%), fugitive dust (7.7%), ships and heavy oil (5.23%), biomass burning, and other sources (0.91%). Therefore, PM_2.5 pollution in Jiaxing during the winter and spring seasons was more severe than that in the summer and autumn. Secondary aerosols were the most important source of PM_2.5 pollution; therefore, focus should be placed on controlling gaseous precursors.

http://bit.ly/2FHpU88

Unprecedented high percentage of food waste powder filler in poly lactic acid green composites: synthesis, characterization, and volatile profile

Abstract

The attractive qualities of plastics lead us, around the world, to an enormous need for plastic goods, which results in their unsustainable overconsumption. Bio-based products are the core concept of circular economy, yet this sector suffers from the high cost of their production. In practice, biopolymers, such as polylactic acid (PLA), are still limitedly used, due to their expensiveness and not outstanding technological properties. A circular and sustainable solution would be to use waste from the food industry as filler that contributes to reduce the cost of PLA-based materials, thereby encouraging their widespread use. At the same time, this would be a circular approach to wisely upgrade food waste and prevent pollution. Ceramic food waste powder fillers from egg shells and from mussel shells were compounded with PLA at 180 °C to obtain composites, which contain an unprecedented high amount of filler, equal to 140 over 100 parts of PLA. We analyzed volatile organic compounds emitted from PLA and, for the very first time, from its composites via headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS). The molecular fingerprint of the volatiles comprises only three aldehydes, a ketone, and two lactides. Volatiles typical of fossil plastics, that are causative factors of hormone disruption or reproductive dysfunction, are effectively missing. Scanning electron microscopy, used to examine the structure of the composite, indicates that both the egg shells and the mussel shells are suitable fillers, in that they form a sufficiently strong interface with the polymer.

http://bit.ly/2FASTvg

Clinical outcomes and cortical reserve in adrenal histoplasmosis ‐ a retrospective follow‐up study of 40 patients

Summary

Objective

Detailed studies of Addison's disease resulting from disseminated adrenal histoplasmosis (AH) are not available. We describe the presentation and prognosis of AH and cortisol status before and after anti‐fungal therapy.

Design

Single‐center retrospective hospital‐based study of 40 consecutive adults with AH [39 males; age (mean + SD) 53±11 years], conducted between 2006‐2018. The median duration of follow‐up was 2.5 years (range 0.2‐12 years).

Patients and methods

AH was diagnosed by bilateral adrenal enlargement on CT scan and presence of Histoplasma by histology and/or culture of biopsied adrenal tissue. All patients received oral itraconazole and, if required, amphotericin B as per guidelines. ACTH‐stimulated serum cortisol (normal >500 nmol/l) was measured in 38 patients at diagnosis and re‐tested after one‐year of anti‐fungal therapy in 21 patients.

Results

Seventy three percent of patients had primary adrenal insufficiency (PAI) and one‐third had an adrenal crisis at presentation. HIV antibody was negative in all patients. Of the 29 patients who completed anti‐fungal therapy, 25 (86%) were in remission at last follow‐up. Overall, 8 (20%) patients died: 3 had a sudden death, 4 had severe histoplasmosis and 1 died due to adrenal crisis. No patient with PAI became eucortisolemic on re‐testing after one‐year of anti‐fungal therapy. Of the eight patients with normal cortisol at diagnosis, two developed adrenal insufficiency on follow‐up.

Conclusion

All patients with AH tested negative for HIV antibody. While patients achieved a high rate of clinical remission after anti‐fungal therapy, overall mortality was significant. Cortisol insufficiency did not normalize despite treatment.

This article is protected by copyright. All rights reserved.

http://bit.ly/2T8ETvC

Issue Information ‐ Instructions for Authors

http://bit.ly/2ASwqpD

Issue Information ‐ TOC and Editorial Board

http://bit.ly/2T8EOYQ

Study of Human Leukocyte Antigen (HLA) in 13 cases of familial frontal fibrosing alopecia: CYP21A2 gene p.V281L mutation from congenital adrenal hyperplasia linked to HLA class I haplotype HLA‐A*33:01; B*14:02; C*08:02 as a genetic marker

Abstract

Background/Objectives

The aetiology of frontal fibrosing alopecia is unknown, and its genetic aspect remains uncharacterised. The aim of this report is to elucidate if major histocompatibility complex is associated with familial frontal fibrosing alopecia.

Methods

A case–control study was performed of 13 patients with frontal fibrosing alopecia belonging to six families. Their human leukocyte antigen profiles were compared to the data of 636 healthy controls without frontal fibrosing alopecia. Patients underwent high‐resolution genomic typing for human leukocyte antigen class I and II loci by PCR‐SSO for Luminex. In addition, CYP21A2 gene (major histocompatibility complex class III) mutations were detected by PCR‐SSO on strips.

Results

61.5% of patients shared CYP21A2 gene p.V281L linked to the F16A human leukocyte antigen class I haplotype (HLA‐A*33:01; B*14:02; C*08:02; Pc < 0.000001). The patients F16A‐negative shared other human leukocyte antigen class I haplotypes: Y16A (3/13) and S26 (2/13).

Conclusion

CYP21A2 gene p.V281L mutation can be used as a genetic marker for susceptibility to familial frontal fibrosing alopecia. Both the linkage of the mutation to F16A and the fact that F16A‐negative patients share other human leukocyte antigen class I haplotype, point to an antigen‐driven mechanism in susceptible patients with these haplotypes.

http://bit.ly/2sxZy0P

Deep fungal infection caused by Trichophyton rubrum after heart transplantation: A case report with dermoscopy

http://bit.ly/2MhF0md

Granulomatous mycosis fungoides responsive to acitretin and UVA1 treatment

http://bit.ly/2szj3pv

Enhanced lake-eutrophication model combined with a fish sub-model using a microcosm experiment

Abstract

Eutrophication models are effective tools for assessing aquatic environments. The lake ecosystem consists of at least three trophic levels: phytoplankton, zooplankton, and fish. However, only a few studies have included fish sub-models in existing eutrophication models. In addition, no specific value or range is available for certain parameters of the fish sub-model. In the present study, a lake microcosm experimental system was established to determine the range of fish sub-model parameters. A three-trophic-level eutrophication model was established by combining the fish sub-model and eutrophication model. The Bayesian Markov Chain Monte Carlo and genetic algorithm method was used to calibrate the parameters of the eutrophication model. The results show that the maximum relative errors were due to phosphate (5.31%), the minimum relative error was due to nitrate (1.94%), and the relative error of dissolved oxygen, ammonia N, zooplankton, and chlorophyll ranged from 3 to 4%. Compared with the two-trophic-level eutrophication model, the relative errors of ammonia nitrogen (4.17%), phosphate (− 5.31%), and nitrate (1.94%) in the three-trophic-level eutrophication model were lower than those in the two-trophic-level eutrophication model, indicating that the three-trophic-level eutrophication model can obtain highly accurate simulation results and provide a better understanding of eutrophication models for future use.

http://bit.ly/2Hkl1EF

In situ resuspension rate monitoring method in the littoral zone with multi-ecotypes of a shallow wind-disturbed lake

Abstract

Sediment resuspension has been recognized as a crucial internal process in aquatic ecosystems. However, there is still a lack of reliable measuring methods due to the complex hydrodynamic conditions in large shallow eutrophic lakes. In this study, sequential sediment traps (SST) and instantaneous multiple point (IMP) methods were compared at 6 sites located in the littoral zone of Zhushan Bay in Lake Taihu. Results show that the average resuspension rates (RRs) estimated using the IMP method at sites 1 to 6 were 266.39, 272.79, 235.17, 254.95, 392.25, and 483.85 g·m⁻²d⁻¹, respectively. While the RRs estimated using the SST method were 195.16, 236.99, 116.76, 156.23, 389.53, and 509.85 g·m⁻²d⁻¹, respectively. In wind-disturbed areas, both methods were suitable for RR analysis in large and shallow eutrophic lakes and SST provides high-resolution temporal RR estimations. However, in the areas with cyanobacterial blooms and vegetation cover, the IMP method overestimated the RR. Therefore, SST was more suitable across different conditions in large and shallow eutrophic lakes, providing a simple, accurate, and high-resolution temporal estimation of RR, while furthering our understanding of lake evolution processes.

http://bit.ly/2RRj9Y6

PLACK syndrome shows remarkable phenotypic homogeneity

http://bit.ly/2FGelOA

Nicastrin haploinsufficiency alters expression of type I interferon‐stimulated genes: the relationship to familial hidradenitis suppurativa

Summary

Background

Hidradenitis suppurativa (HS), also called acne inversa, is a chronic skin disease. The symptoms can be severe, and include intensely painful nodules and abscesses in apocrine‐gland rich inverse skin, such as the buttocks, under the arms and in the groin. Autosomal dominant forms of HS exist, but are rare. Some of these kindred have heterozygous loss‐of‐function rare variants in the γ‐secretase complex component nicastrin (NCSTN).

Aim

To investigate the effect of NCSTN haploinsufficiency on human keratinocytes and assess potential mechanisms for lesion development.

Methods

NCSTN was knocked down using a small hairpin RNA construct in both a keratinocyte cell line (HEK001) and an embryonic kidney cell line (HEK293), and differential gene expression was assessed using RNA microarray. Using the HEK293 line, a heterozygous deletion of NCSTN was created with CRISPR/Cas9 genome editing, and nuclear factor kappa B activity was assessed using a luciferase reporter.

Results

Compared with controls, the keratinocyte NCSTN knockdown cell line showed a significantly increased expression of genes related to the type I interferon response pathway. Both HEK001 and HEK293 knockdowns demonstrated evidence of altered growth. There was a small but significant increase in nuclear factor kappa B signalling in response to tumour necrosis factor treatment in HEK293 cells genome‐edited for reduced NCSTN.

Conclusions

Our data suggest a role for increased keratinocyte inflammatory responsiveness in familial HS. Confirming this phenotype and characterizing additional effects in different cell types will require study beyond cell lines, such as in primary cells and tissues.

http://bit.ly/2MmaRCk

Lipoedematous scalp

http://bit.ly/2FzMfFx

Psoriasis induced by dupilumab therapy

http://bit.ly/2FFSLd6

Acne conglobata and necrotizing scleritis: a previously unreported association

http://bit.ly/2FzJ1C0

Dermoscopy of naevi in patients with oculocutaneous albinism

Summary

Oculocutaneous albinism (OCA) increases predisposition to skin malignancies. Nevertheless, the differential diagnosis between melanoma and naevi in patients with OCA is still challenging, because pigmentary lesions have rarely been described in this population. We aimed to describe the dermoscopic patterns of naevi in patients with OCA. We prospectively evaluated 83 naevi from 37 patients with OCA in a single centre in Brazil. Lesions were analysed by eye and by dermoscopy and were grouped by dermoscopic pattern. Eight main patterns were identified: homogeneous structureless pattern (n = 28; 33.7%), globular pattern (n = 27; 32.5%), reticular pattern (n = 8; 9.6%), peripheral reticular pattern with central hypopigmentation (n = 8; 9.6%), peripheral globules (n = 8; 9.6%), irregular brown globules with pink background (n = 2; 2.4%), reticular globular disorganized pattern (n = 1; 1.2%) and peripheral reticular globular with central hypopigmentation (n = 1; 1.2%). We found previously undescribed dermoscopic patterns in patients with OCA, in addition to confirming previously described patterns. These descriptions may help the understanding of pigmented naevi in patients with OCA.

http://bit.ly/2FGRnH3

British Association of Dermatologists guidelines for the safe and effective prescribing of oral ciclosporin in dermatology 2018

Abstract

The overall objective of the guideline is to provide up‐to‐date, evidence‐based recommendations for the safe and effective use of oral ciclosporin in the field of dermatology. The document aims to:

offer an appraisal of all relevant literature since 1970 focusing on any key developments

address important, practical clinical questions relating to the primary guideline objective

provide guideline recommendations and, where appropriate, with some health economic implications

discuss potential developments and future directions

The guideline is presented as a detailed review with highlighted recommendations for practical use in the clinic (see section 14), in addition to an updated Patient Information Leaflet (PIL; available on the BAD website, www.bad.org.uk/leaflets).

This article is protected by copyright. All rights reserved.

http://bit.ly/2AQU0mu

Long non‐coding RNA polymorphisms influence susceptibility to endemic pemphigus foliaceus

Abstract

Background

Pemphigus foliaceus (PF) is an epidermal autoimmune disease, characterized by the presence of autoantibodies against the desmosomal protein desmoglein 1. Genetic and environmental factors contribute to PF, a complex disease that is endemic in Brazil and Colombia and neighbouring countries, and in Tunisia. Long non‐coding RNAs (lncRNAs) may participate in gene regulation by interacting with DNA, proteins, and other RNAs. Dysregulation of lncRNAs has recently been recognized as an important co‐player in the onset or progression of complex diseases. In addition, single‐nucleotide polymorphisms (SNP) located in lncRNA genes have been associated with differential risk to cancer, autoimmunity and infection.

Objectives

Here, we aimed to investigate whether SNPs in lncRNA genes are associated with differential susceptibility to endemic PF.

Methods

We integrated data from the lncRNASNP database with genome‐wide genotype data obtained for 229 patients and 6,681 controls. We tested the association between endemic PF and 2,080 SNPs located in lncRNAs applying logistic regression.

Results

The most significantly associated SNP was rs7144332 (OR = 1·63, P = 2·8 x 10^‐6), located in the lncRNA gene AL110292·1. Results for other five SNPs were suggestive of association (P < 0·001). In silico analysis indicated that five of the six SNPs impact transcription, four may influence lncRNA secondary structure, and three of them may alter microRNA‐lncRNA interactions.

Conclusion

We showed, for the first time, that variation in lncRNA genes may influence pemphigus pathogenesis. Our findings highlight the importance of lncRNA variation in autoimmune and possibly other complex diseases and suggest polymorphisms for functional validation.

This article is protected by copyright. All rights reserved.

http://bit.ly/2SZCfs7