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Παρασκευή 30 Νοεμβρίου 2018

Comment on: Keratosis Pilaris and Its Subtypes: Associations, New Molecular and Pharmacologic Etiologies, and Therapeutic Options



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Study on the influence of surface potential on the nitrate adsorption capacity of metal modified biochar

Abstract

Carbon materials, as effective adsorbents to numerous aqueous cationic contaminants, have been hardly applied to remove anions in wastewater. In this work, different modifying agents were used to modify corncob biochars (CC) and the surface potentials of these modified biochars were determined. Based on the findings, modification principle was determined to reveal the relationship between surface potentials of the biochars and their nitrate adsorption capacities. The surface potential was dominated by the metal cations and multivalent cations led to even positive zeta potential. The formation of metal oxide not only led to the augment in surface area but also increase the surface charge. FeCl3-modified biochar (Fe-CC) with the highest positive surface charge was utilized to remove anions (nitrate) from aqueous solutions. Characterization results confirm that Fe2O3 structure were successfully formed on biochar surface. This led to the formation of iron nitrate hydrate (Fe(NO3)3·9H2O), which enabled higher nitrate adsorption performance than that of pristine biochar. Batch experiments showed that nitrate adsorption on the Fe-CC was stable and almost independent of experimental pH and temperature. Based on the Langmuir model results, the maximum nitrate adsorption capacity of Fe-CC was 32.33 mg/g. Coexisting anions had negative influence on the adsorption performance. Findings of this work suggest that the modified biochar can be used in wastewater treatment to remove anions such as nitrate.

Graphic abstract



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Correction to: Analysis of swale factors implicated in pollutant removal efficiency using a swale database

The original publication of this paper contains an error. Correct presentation of Equation 1 is presented in this paper.



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Correction to: Anti-Müllerian hormone serum levels in systemic lupus erythematosus patients: influence of the disease severity and therapy on the ovarian reserve

The original version of this article unfortunately contained a mistake in given and family names of all the authors.



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Correction to: Anti-Müllerian hormone serum levels in systemic lupus erythematosus patients: influence of the disease severity and therapy on the ovarian reserve

The original version of this article unfortunately contained a mistake in given and family names of all the authors.



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Split-mouth evaluation of connective tissue graft with or without enamel matrix derivative for the treatment of isolated gingival recession defects in dogs

Abstract

Objectives

The potential additive effect of an enamel matrix derivative (EMD) to a subepithelial connective tissue graft (CTG) for recession coverage is still controversially discussed. Therefore, the aim of this study was to histologically evaluate the healing of gingival recessions treated with coronally advanced flap (CAF) and CTG with or without EMD in dogs.

Materials and methods

Gingival recession defects (5 mm wide and 7 mm deep) were surgically created on the labial side of bilateral maxillary canines in 7 dogs. After 8 weeks of plaque accumulation and subsequent 2 weeks of chemical plaque control, the 14 chronic defects were randomized to receive either CAF with CTG (CAF/CTG) or CAF with CTG and EMD (CAF/CTG/EMD). The animals were sacrificed 10 weeks after reconstructive surgery for histologic evaluation.

Results

Treatment with CAF/CTG/EMD demonstrated statistically significantly better results in terms of probing pocket depth reduction (P < 0.05) and clinical attachment level gain (P < 0.001). The length of the epithelium was statistically significantly shorter in the CAF/CTG/EMD group than in the CAF/CTG group (1.00 ± 0.75 mm vs. 2.38 ± 1.48 mm, respectively, P < 0.01). Cementum formation was statistically significantly greater in the CAF/CTG/EMD group than following treatment with the CAF/CTG group (3.20 ± 0.89 mm vs. 1.88 ± 1.58 mm, respectively, P < 0.01). The CAF/CTG/EMD group showed statistically significantly greater complete periodontal regeneration (i.e., new cementum, new periodontal ligament, and new bone) than treatment with CAF/CTG (0.54 ± 0.73 mm vs. 0.07 ± 0.27 mm, respectively, P < 0.05).

Conclusion

Within their limits, the present findings indicate that the additional use of EMD in conjunction with CAF + CTG favors periodontal regeneration in gingival recession defects.

Clinical relevance

The present findings support the use of EMD combined with CTG and CAF for promoting periodontal regeneration in isolated gingival recession defects.



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LC3A, LC3B and Beclin-1 Expression in Gastric Cancer

Background: The current study examined the key proteins involved in autophagosome formation and their prognostic role in gastric cancer. Materials and Methods: Paraffin-embedded tissues from 121 consecutive patients treated with surgery for gastric cancer were analyzed immunohistochemically for the expression of autophagic proteins microtubule-associated proteins 1A/1B light chain 3A and 3B (LC3A, LC3B) and beclin-1 (encoded by BECN1 gene). Assessment of proliferative index using E3 ubiquitin-protein ligase (MIB1) and correlations with histopathological parameters and overall survival were performed. Results: Strong cytoplasmic expression was noted for all studied proteins, although to a varying proportion, the median percentage being 30% for LC3A, and 40% for LC3B and beclin-1. The median score of LC3A+ stone-like structures (SLS) was 0.2 (range 0-1) and the median proliferative index was 30% (range=0-95%). A significant association between LC3A, LC3B and beclin-1 expression was confirmed (p<0.01). SLS score was higher in tumors of the gastro-esophageal junction (p=0.009), and beclin-1 was overexpressed in intestinal-type tumors (p=0.001). High SLS score (p=0.008) was significantly related to poor prognosis, and this finding persisted in multivariate analysis (hazard ratio(HR)=2.01, p=0.003). Conclusion: Intense autophagic activity, as assessed by LC3A immunostaining and SLS quantification, is a strong prognostic marker in gastric cancer and can be useful for clinical application.



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Efficacy of Enteral Access in Patients with Esophageal Squamous Cell Carcinoma Under Neoadjuvant Therapy

Background: Enteral feeding tubes used to manage the nutritional status of esophageal cancer were evaluated regarding their effectiveness in patients receiving neoadjuvant therapy. Patients and Methods: A retrospective study evaluating patients with esophageal squamous cell carcinoma undergoing neoadjuvant therapy between 2001 and 2014 was conducted at a medical center. Hospital patients' records for enteral access (EA) insertion and treatment outcomes were statistically analyzed. Results: Patients with EA at initial diagnosis had lower body mass index than the group without EA (p=0.012). Chemotherapy-related adverse events with grade 3-4 mucositis were significantly less frequent in the EA group (p=0.008), and grade 3-4 anemia was significantly more frequent (p=0.012). The 4-year mortality rate was 63.0% in the EA group and 67.7% in the group without EA (pnon-inferiority=0.035), which met the non-inferiority criterion with a non-inferiority margin of 10%. Conclusion: Patients with esophageal squamous cell carcinoma with malnutrition status undergoing neoadjuvant therapy with EA showed an improved outcome at maintaining nutritional status, reduced severity of mucositis and improved survival rate.



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Application of Artificial Intelligence-based Technology in Cancer Management: A Commentary on the Deployment of Artificial Neural Networks

Artificial intelligence was recognised many years ago as a potential and powerful tool to predict disease outcome in many clinical situations. The conventional approaches using statistical methods have provided much information, but are subject to limitations imposed by the complexity of medical data. The structures of the important variants of the machine learning system artificial neural networks (ANN) are discussed and emphasis is given to the powerful analytical support that could be provided by ANN for the prediction of cancer progression and prognosis. The predictive ability of the cellular markers, DNA ploidy and cell-cycle profiles, and molecular markers, such as tumour promoter and suppressor gene, and growth factor and steroid hormone receptors in breast cancer management were also analysed. ANN systems have been successfully deployed to evaluate microRNA profiles of tumours which saliently sway cancer progression and prognosis of the disease, thus counteracting the negative implications of their numerical abundance. Finally, in this setting, the prospective technical improvements in artificial neural networks, as hybrid systems in combination with fuzzy logic and artificial immune networks were also addressed.



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Prognostic Significance of Survivin Expression and Combined Analysis with Cancer Stem Cell and Epithelial-Mesenchymal Transition-related Markers in Patients with Rectal Cancer Undergoing Preoperative Chemoradiotherapy

Aim: To identify the candidate marker predicting treatment response and survival outcome in rectal cancer patients who received preoperative chemoradiotherapy (CRT). Patients and Methods: Between 2000 and 2015, 159 patients with histologically-confirmed rectal adenocarcinoma underwent preoperative CRT followed by surgery. Among them, 70 patients were enrolled and the expression of survivin, cancer stem cell markers (CD44 and CD133) and epithelial–mesenchymal transition markers (E-cadherin and TWIST1) in pretreatment biopsy specimens were evaluated by immunohistochemistry. Associations between the expression of markers and clinical outcomes were evaluated. Results: The median follow-up period of all patients was 71 (range=15-203) months. Five-year overall (OS), disease-free (DFS), locoregional recurrence-free (LRRFS) and distant metastasis-free (DMFS) survival were 80.5%, 60.2% 90.1% and 76.5%, respectively. A significant association between survivin overexpression and worse treatment outcome was shown on univariate analyses for OS, DFS and DMFS (p=0.022, 0.002, and 0.005, respectively). On multivariate analysis, survivin overexpression was an adverse prognosticator for DFS and DMFS (p=0.007 and 0.015, respectively), with a borderline significant trend towards a shorter OS (p=0.069). Four other single biomarkers were not associated with survival outcomes. However, overexpression of both survivin and CD44 was significantly associated with worse OS on multivariate analysis (p=0.003). Conclusion: Survivin combined with CD44 might be a candidate biomarker for the prediction of recurrence and survival in patients who received preoperative CRT for rectal cancer. Further research with a larger population is needed to validate these results.



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Does Transdermal Testosterone Increase the Risk of Developing Breast Cancer? A Systematic Review

Background/Aim: Hypoactive sexual desire disorder (HSDD) is hypothesised to manifest in postmenopausal women at onset of menopause due to decreased oestrogen levels. Transdermal testosterone is a potential treatment option. This systematic review explores the relationship between the incidence of breast cancer and transdermal testosterone use. Materials and Methods: Searches were conducted on the PubMed and Ovid databases. In Ovid, the advanced search function was used: 'transdermal testosterone not male'. In PubMed, the following search terms were used: 'transdermal, testosterone, menopausal, women, breast cancer, women'. Abstracts that fitted our initial criteria were further investigated. Results: A total of 25 publications from PubMed and 192 publications from Ovid were initially assessed. Three randomised control trials were judged to have sufficiently met our inclusion criteria. However, these trials were too heterogeneous for a meta-analysis. A systematic review was deemed the most appropriate analysis of the data available. Conclusion: The publications examined in this systematic review suggest that the use of transdermal testosterone to treat HSDD in postmenopausal women does not increase breast cancer incidence. However, further research in the form of adequately powered randomised controlled trials with breast cancer incidence being the primary end point is required in order to confirm this.



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Chemotherapy in Patients with Hereditary Angioedema

Background: Hereditary angioedema (HAE) is an autosomal dominant hereditary disorder characterized by episodic swelling of many body regions (especially throat and abdomen), potentially triggered by medication. No data are available for HAE in patients with cancer assigned to standard chemotherapy. The aim of our study was to identify circulating mediators potentially predictive of acute HAE attacks during chemotherapy. Patient and Methods: Repeated blood testing (approximately every week) for complement system members (C3, C4, CH50, C1 inhibitor, C1-inhibitor functional C1Q), D-dimers and for routine haematochemistry were performed in a 42-year-old male affected by type 2 HAE during standard adjuvant oxaliplatin/fluorouracil-based chemotherapy administered for stage III radically resected rectal cancer. Pre-medication with 1,000 U Berinert inhibitor C1 was administered every week throughout treatment. Mann–Whitney U-test was used to determine statistical differences in measures between the first 30 days of therapy and beyond day 30 of therapy. Results: Pre-chemotherapy values of tested variables (day 0) were: C3: 101 mg/dl, C4: 5.71 mg/dl, CH50: 74%, C1 inhibitor: 43.4 mg/dl, C1-inhibitor functional: 18%, C1Q: 150 mg/dl, and D-dimers: 113 g/ml. A significant change in circulating values was observed for C3, D-dimers and C1-inhibitor functional. Four HAE attacks were observed, they started from the forth cycle of treatment and all were manageable. Changes in C3, D-dimers and C1-inhibitor functional preceded the attacks. Conclusion: The stress induced by chemotherapy such a standard oxaliplatin/fluorouracil increases the risk of attacks in patients with HAE. However, circulating biomarkers such as D-dimers, C3 and C1-inhibitor functional may serve as early predictors of acute HAE crisis.



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Potent Antitumor T-Cell Memory Is Generated by Curative Viral Oncolytic Immunotherapy But Not Curative Chemotherapy

Background: Late developing breast cancer metastases are common and lethal despite treatment with adjuvant chemotherapy at the time of primary tumor excision. Stimulation of an antitumor immune response is an alternative strategy for preventing this devastating development. Materials and Methods: A mouse model of the human epidermal growth factor receptor 2 (HER2/neu)-positive mammary cancer was used to compare the antitumor memory T-cell response following tumor cure by viral oncolytic immunotherapy, chemotherapy, surgical excision, or surgical excision plus virus infection. Memory T-cell response was assessed by functional in vivo assays. Results: Antitumor T-cell memory was generated most powerfully by curative viral oncolytic immunotherapy and poorly by curative chemotherapy. Cure by surgical excision generated an immune antitumor response which was increased by neo-adjuvant virus infection. CD4 memory T-cells were most potent. Conclusion: Virus infection of tumor generates an antitumor memory immune response and chemotherapy suppresses this response. Clinical trials testing adjuvant immune stimulation instead of chemotherapy may be worth exploring because memory antitumor T-cells have the unique potential to find and eliminate small nests of metastatic cancer cells in sanctuary sites and prevent emergence of tumors from dormant cancer cells.



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Prognostic Significance of 14-3-3{varepsilon}, Aldo-keto Reductase Family 1 B10 and Metallothionein-1 in Hepatocellular Carcinoma

Background/Aim: Expression of 14-3-3 is associated with prognostic outcomes of hepatocellular carcinoma (HCC) patients. Metallothionein-1 (MT-1) proteins and aldo-keto-reductase family 1 B10 (AKR1B10) are considered potential tumor regulators of HCC. The aim of this study, was to examine the prognostic value of 14-3-3, MT-1 and AKR1B10 expression in HCC. Materials and Methods: The expression levels of 14-3-3, MT-1 and AKR1B10 in HCC cell lines and paraffin-embedded tissues were examined by western blotting and immunohistochemical analysis. Results: 14-3-3 positivity was significantly associated with decreased MT-1 expression in HCC. Patients with decreased MT-1 expression had worse survival rates and a higher risk of metastasis than 14-3-3-positive HCC patients with unchanged MT-1 expression. Distinct expression patterns of 14-3-3/MT-1/AKR1B10 were significantly associated with the metastatic incidence and survival rates of HCC patients. Patients with negative 14-3-3 staining in primary tumors had better prognostic outcomes. In contrast, patients with positive 14-3-3 staining, decreased MT-1 expression and no increase in AKR1B10 expression in primary tumors had the worst overall and disease-free survival rates and the highest metastatic risk. Conclusion: 14-3-3, AKR1B10, and MT-1 act as potential prognostic biomarkers of HCC.



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Cytolytic Activity (CYT) Score Is a Prognostic Biomarker Reflecting Host Immune Status in Hepatocellular Carcinoma (HCC)

Background/Aim: The cytolytic activity (CYT) score is a new index of cancer immunity calculated from the mRNA expression levels of GZMA and PRF1. We assessed the clinical significance of the CYT score in HCC. Materials and Methods: The calculated CYT scores of peripheral blood cells (GSE24759), cell lines (CCLE) and HCC tissues (TCGA, GSE14520 and Kyushu cohorts) were assessed. Then, immunohistochemical analysis (IHC) of GZMA and PRF1 was performed. Results: The CYT scores of HCC tissues were lower than those of non-cancerous tissues. The 5-year recurrence-free survival of patients with low CYT scores was significantly shorter than that of patients with high CYT scores. Multivariate analysis indicated that the CYT score was an independent prognostic factor for RFS in TCGA and GSE14520 cohorts. Conclusion: CYT score could be a useful prognostic biomarker in HCC, possibly through reflecting the host immune status.



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A Phase II Study of Tri-weekly Low-dose Nab-paclitaxel Chemotherapy for Patients with Advanced Gastric Cancer

Background/Aim: Nanoparticle albumin-bound (nab)-paclitaxel has demonstrated antitumor activity against advanced gastric cancer. However, gastric cancer patients can be difficult to treat with the recommended dose because of the high incidence of adverse toxicities. The aim of this study was to evaluate the safety and effectiveness of low-dose nab-paclitaxel in a multicenter, single-arm, phase II study. Patients and Methods: Treatment included low doses of 180 mg/m2 nab-paclitaxel administered on day 1 of each 21-day cycle. The primary endpoint was defined as the overall response rate (ORR). The secondary endpoints included progression-free survival (PFS), safety, and overall survival (OS). A total of 34 patients were enrolled in the full-analysis set. Results: The ORR was 5.9%. The median PFS and OS were 2.4 months and 9.2 months, respectively. The most common grade 3/4 toxicities were anemia (8.8%), neutropenia (5.9%), appetite loss (5.9%) and peripheral sensory neuropathy (5.9%). No treatment-related deaths occurred. Conclusion: The tri-weekly low dose of nab-paclitaxel therapy is effective towards advanced gastric cancer patients with good tolerability and an acceptable margin of safety.



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Evaluation of the Usefulness of FDG-PET/CT for Nodal Staging of Breast Cancer

Background/Aim: Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) has recently been used to investigate lymph node (LN) metastases and several predictive features in patients with breast cancer (BC). The aim of this study was to assess the value of this non-invasive imaging procedure for axillary staging. Patients and Methods: Fifty patients with early primary unilateral, locally advanced, or recurrent invasive operable BC were enrolled. All patients underwent preoperative 18F-FDG PET/CT, and the results were compared with the histopathology of dissected axillary LNs and their biological and immunohistochemical characteristics. The diagnostic performance of 18F-FDG PET/CT in detecting LN metastases from primary or recurrent BC was analyzed. The mean values of the initial PET/CT parameters, including the primary tumour (SUV T) and ipsilateral axillary LNs (SUV LN), were compared with the clinicopathological features of patients to determine their usefulness for predicting clinical interactions. Results: The sensitivity, specificity, overall accuracy, positive predictive value, and negative predictive value of 18F-FDG PET/CT for axillary LN staging were 87%, 90%, 88%, 93%, and 82%, respectively. Bivariate analyses showed strong interactions of nuclear grade (p=0.05), progesterone receptor expression (p=0.001), Ki-67 index (0.027), and local relapse with the SUV T. A high SUV LN value was significantly correlated with a higher nuclear grade score (p=0.05), oestrogen receptor negativity (p=0.001), progesterone receptor negativity (p=0.014), a high Ki-67 index (>20%; p=0.048), LN metastasis (p<0.001), a basal tumour (p=0.04), and locoregional recurrence (p<0.001). Conclusion: PET/CT is a reproducible, non-invasive imaging modality that is useful for evaluating a primary BC mass and its relationship with metastatic axillary LNs, thereby predicting tumour behaviour and guiding clinical practice.



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Targeted Therapies for Pancreatic Cancer and Hurdles Ahead

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers with a median survival of 6 months after diagnosis. Intrinsic resistance to chemotherapeutics and lack of effective targeted therapies are the major factors contributing to dismal prognosis. Several important genetic alterations (i.e., mutations, deletions) have been identified to be involved in the initiation and progression of pancreatic cancer, including KRAS and inactivation of tumor suppressors, such as TP53, SMAD4 and CDKN2A. Unique tumor microenvironment with excessive stroma due to desmoplastic reaction is one of the major characteristics of PDAC, promoting tumor growth and leading to treatment failures. In addition, tumor stroma represents an important biological barrier for drug delivery and successful treatment of PDAC. Small interfering RNA (siRNA) has recently emerged as a potential and targeted therapeutic approach which is now evaluated in clinical trials. However, siRNA-based therapeutics face important challenges, including rapid serum degradation, poor tumor cell uptake and cellular uptake, leading to off-target effects. Therefore, there is a great need for the development of safe and effective nanoparticles for better tumor-specific delivery of anti-cancer therapeutics. In this article, the main challenges in the treatment of pancreatic cancer and recent advancements on nano delivery systems of chemotherapeutics and gene-targeted agents, used both in preclinical and clinical trials are reviewed.



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Effect of Combined Epigenetic Treatments and Ectopic NIS Expression on Undifferentiated Thyroid Cancer Cells

Background: Poorly differentiated (PDTC) and anaplastic thyroid (ATC) cancer cells are characterized by the acquisition of epigenetic abnormalities, leading to the silencing of both the sodium iodide co-transporter and the Coxsackie adenovirus receptor. As aberrant histone acetylation and DNA methylation represent epigenetic mechanisms involved in neoplastic transformation, our study investigated the anticancer properties of epigenetic modifiers in thyroid carcinoma. Materials and Methods: The cytotoxicity and gene expression modulation of histone deacetylase and DNA methyltransferase inhibitors were evaluated in both PDTC and ATC. Results: Epigenetic treatments were cytotoxic to tumor thyrocytes and restored sodium iodide co-transporter and Coxsackie adenovirus receptor, expression as well as radioiodine uptake, in PDTC but not in ATC. However, ectopic expression sodium iodide co-transporter re-activated radioiodine incorporation in ATC. Conclusion: The ability of epigenetic treatments to interfere with tumor proliferation and induce Coxsackie adenovirus receptor expression, coupled with the ability of ectopic sodium iodide co-transporter to restore radioiodine uptake, raise the possibility that these therapeutic approaches may provide clinical benefit to patients with thyroid carcinoma refractory to radioiodine treatment.



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Outcomes of Stereotactic Body Radiotherapy for Hepatocellular Carcinoma with Severe Cirrhosis and Ineligibility for Transplant

Background/Aim: Our study reviewed the results of patients with hepatocellular carcinoma and Child–Pugh score 8-11 cirrhosis treated with stereotactic body radiotherapy when liver transplant was not an option. Patients and Methods: A retrospective review was performed on 15 patients with Child–Pugh class B and C cirrhosis treated with stereotactic body radiotherapy. The median total dose was 35 Gy in 4-5 fractions. None were listed for a liver transplant due to either being outside of the Milan criteria or to medical contraindications. Results: The overall survival was 26.7% at 6 months, with a mean survival of 152 days. The mean survival with and without ascites was 3.3 months and 8.3 months, respectively. Conclusion: For hepatocellular carcinoma with cirrhosis of Child–Pugh score 8 or more, prognosis after liver stereotactic body radiotherapy was suboptimal. While irradiation achieved local tumor control, progressive cirrhosis was a common cause of death. Patients without ascites at the time of radiotherapy had the best prognosis.



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Embryonal Origin of Metanephric Adenoma and its Differential Diagnosis

Background/Aim: The association of Wilms' tumor (WT), papillary renal cell tumor (PRCT) and mucinous tubular and spindle cell carcinoma (MTSCC) with embryonal rests has already been documented, but the cellular origin of metanephric adenoma (MA) is not yet known. The aim of this study was to understand their developmental evolution and find diagnostic markers. Materials and Methods: CD57, KRT7, AMACR, SCEL, WT1 and CDH17 expression was analysed by immunohistochemistry in the four types of tumors and the associated pre-neoplastic lesions. Results: Immunohistochemistry was able to differentiate WT, MA, MTSCC and PRCT. A phenotypic correlation between MA and perilobar nephrogenic rest associated with WT was identified. Conclusion: Perilobar nephrogenic rest and MA arise from differentiation arrested cells of the proximal domain of the S-shape body. We propose that WT1, MA, MTSCC and PRCT derive from different forms of maturation arrested embryonal rests.



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Prognostic Factors and a Survival Score in Patients Irradiated for Metastatic Epidural Spinal Cord Compression from Urothelial Carcinoma Cancer of the Bladder

Background/Aim: Prognoses of patients with metastatic epidural spinal cord compression (MESCC) from urothelial carcinoma of the bladder are generally poor. This study aimed to identify prognostic factors that can facilitate personalized care of these patients. Patients and Methods: In 46 patients, 10 factors were evaluated for overall response (OR), post-radiotherapy (RT) ambulatory status, local control of MESCC and overall survival (OS). Independent predictors of OS were incorporated in a scoring system. Results: Being ambulatory post-RT was associated with pre-RT ambulatory status (p<0.001) and better performance score (p<0.001). No factor was significantly associated with OR and local control. On multivariate analyses, lack of visceral metastases (p=0.002), being ambulatory pre-RT (p=0.001) and performance score 1-2 (p=0.004) were associated with improved OS. Based on these factors, there were three distinct prognostic groups with 0, 1-2 and 3 points and median OS times of 2, 4 and 11.5 months, respectively. Conclusion: Prognostic factors were identified and a new survival score was created that will help physicians aiming to personalize treatment for patients with MESCC from urothelial carcinoma of the bladder.



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Cell Harvesting Methods Affect Cellular Integrity of Adherent Cells During Apoptosis Detection

Background/Aim: Annexin V and propidium iodide (PI) dual staining is commonly applied in bioscience as a method to detect apoptosis. However, excessive handling of adherent cells may interfere with the integrity of plasma membrane and hence impede the accuracy of this method. Here, we exploited PI uptake as an indicator of cell integrity and investigated how cell harvesting methods and solutions involved in common apoptosis detection techniques affected measurement results. Materials and Methods: Different cell harvesting techniques, staining with PI and flow cytometry were performed. Results: Non-fixed scrapped cells revealed significantly higher fractions of PI-positive staining compared to non-fixed trypsinized cells. In the case of harvesting cells by scrapping, samples stained in binding buffer (68.30±3.55%) showed consistently higher PI-positive staining than samples stained in PBS (36.37±5.90%) in a significant manner (p=0.015). Conclusion: Enzymatic harvesting using 0.25% trypsin instead of mechanical harvesting by rubber scraper caused less damage of cell integrity. Furthermore, the binding buffer used in the apoptosis detection protocol aggravated the existing plasma membrane damage caused by the rubber scraper.



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No Renal Toxicity After Repeated Treatment with Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in Patients with Unresectable Peritoneal Metastasis

Background/Aim: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a recent approach for intraperitoneal chemotherapy with promising results for patients with peritoneal metastasis (PM). The aim of this study was to report renal toxicity for patients who received at least 3 repeated PIPAC procedures. Patients and Methods: All patients who underwent at least 3 PIPAC cycles of cisplatin (7.5 mg/m2) and doxorubicin (1.5 mg/m2) for unresectable PM from December 2015 to September 2017, were analysed regarding postoperative renal toxicity. Results: Among 103 patients registered in a prospective single center database, 43 patients underwent at least 3 PIPAC cycles representing a total of 175 PIPAC. Median age was 59.8 years, 24 (55.8%) patients were female and median BMI was 22.2 kg/m2. Most common origins of PM were gastric 22 (51.1%) and ovarian 11 (25.6%) cancer. Median peritoneal cancer index (PCI) was 17 (range=5-39). For 39 (90.1%) patients, systemic chemotherapy was performed in addition to PIPAC. Forty-three (100%), 17 (39.5%), 14 (32.5%), 8 (18.6%), 3 (7%), 2 (4.7%) and 2 (4.7%) patients underwent three, four, five, six, seven, eight and nine PIPAC procedures, respectively. Repeated PIPAC did not induce significant acute nor cumulative renal toxicity in any patients. Conclusion: Repeated PIPAC did not induce clinically relevant renal toxicity. This study confirms the previous published results in a larger group of patients.



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Expression of CK7 and CDKN2 in Cervical Intraepithelial Neoplasia and Correlation with Clinical Outcome

Aim: To evaluate cyclin-dependent kinase inhibitor 2A (CDKN2A) and cytokeratin 7 (CK7) expression in cervical intraepithelial neoplasia (CIN) formalin-fixed samples. Materials and Methods: Staining with antibody clones G175-405 for CDKN2A and OV-TL 12/30 for CK7 were evaluated and the detection of protein expressions were compared in 147 patients with CIN. Results: Clinical follow-up of patients with CIN1 and CIN2 showed that most patients had a favorable outcome. Single CDKN2A or CK7 expression and their combined expression had a greater sensitivity and negative predictive value in CIN1, corresponding to the non-development of the disease. The positive predictive value of CDKN2A was greater than that of CK7. Combined expression of CDKN2A and CK7 showed that the sensitivity, specificity, positive predictive values, and negative predictive values had their maximum index in the CIN1 group. Analysis of combined expression of CDKN2A and CK7 showed that 85.7% of patients presented unfavorable clinical outcomes, with positive expression for both markers identified in CIN2. Conclusion: Combined expression of CK7 and CDKN2A was associated with a better diagnosis of CIN, and negative expression in CIN1/2 groups had a greater negative predictive value for patient clinical outcome.



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Outcomes After Radiotherapy Alone for Metastatic Spinal Cord Compression in Patients with Oligo-metastatic Breast Cancer

Background/Aim: Patients with oligo-metastatic breast cancer are a unique patient subgroup with more favourable outlook than most patients with metastatic disease. Prognostic factors in these patients with metastatic spinal cord compression (MSCC) were evaluated. Patients and Methods: In 159 patients irradiated for MSCC from oligo-metastatic breast cancer, seven characteristics were retrospectively analyzed including age, interval between breast cancer diagnosis and irradiation of MSCC, time developing motor deficits, ambulatory status, involved vertebrae, performance score (ECOG-PS) and radiotherapy regimen. Results: Improvement of motor function was significantly associated with time developing motor deficits (p=0.017), post-radiotherapy ambulatory status with pre-radiotherapy ambulation (p=0.012) and ECOG-PS 1-2 (p=0.029). Radiation doses of 39-40 Gy (equivalent doses) resulted in 1- and 2-year local control of 100% and 95%. On multivariate analyses, higher doses were associated with local control (p=0.011). Pre-radiotherapy ambulatory status (p=0.001) and ECOG-PS 1-2 (p=0.002) were associated with survival. Conclusion: Significant prognostic factors were identified for patients with MSCC from oligo-metastatic breast cancer. Higher radiation doses improved local control.



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Challenges in diffusion MRI tractography – Lessons learned from international benchmark competitions

Publication date: Available online 29 November 2018

Source: Magnetic Resonance Imaging

Author(s): Kurt G. Schilling, Alessandro Daducci, Klaus Maier-Hein, Cyril Poupon, Jean-Christophe Houde, Vishwesh Nath, Adam W. Anderson, Bennett A. Landman, Maxime Descoteaux

Abstract

Diffusion MRI (dMRI) fiber tractography has become a pillar of the neuroimaging community due to its ability to noninvasively map the structural connectivity of the brain. Despite widespread use in clinical and research domains, these methods suffer from several potential drawbacks or limitations. Thus, validating the accuracy and reproducibility of techniques is critical for sound scientific conclusions and effective clinical outcomes. Towards this end, a number of international benchmark competitions, or "challenges", has been organized by the diffusion MRI community in order to investigate the reliability of the tractography process by providing a platform to compare algorithms and results in a fair manner, and evaluate common and emerging algorithms in an effort to advance the state of the field. In this paper, we summarize the lessons from a decade of challenges in tractography, and give perspective on the past, present, and future "challenges" that the field of diffusion tractography faces.



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Sex, Microbes, and Polycystic Ovary Syndrome

Publication date: Available online 29 November 2018

Source: Trends in Endocrinology & Metabolism

Author(s): Varykina G. Thackray

Recent studies have shown that sex and sex steroids influence the composition of the gut microbiome. These studies also indicate that steroid regulation of the gut microbiome may play a role in pathological situations of hormonal excess, such as PCOS. Indeed, studies demonstrated that PCOS is associated with decreased alpha diversity and changes in specific Bacteroidetes and Firmicutes, previously associated with metabolic dysregulation. These studies suggest that androgens may regulate the gut microbiome in females and that hyperandrogenism may be linked with a gut 'dysbiosis' in PCOS. Future mechanistic studies will be required to elucidate how sex steroids regulate the composition and function of the gut microbial community and what the consequences of this regulation are for the host.



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Πέμπτη 29 Νοεμβρίου 2018

A case of multinucleate cell angiohistiocytoma in a 14‐year old boy showing two different clinical and histopathological findings

Multinucleate cell angiohistiocytoma (MCAH) is a rare cutaneous disease entity characterized by multiple red‐to‐brown or violaceous papules usually located on the acral regions such as the face and the distal arms and legs. It affects elderly women more than men and hardly occurs at a young age. The exact pathogenic mechanism of MCAH is not yet clearly understood.

We report an exceptionally rare case of a 14‐year old boy who presented with multiple asymptomatic erythematous papules and a single flat brownish plaque on the left chest. The brownish plaque lesion histologically showed proliferation of dilated small vessels in the upper‐mid dermis and numerous oddly shaped multinucleate cells intermingled with lymphocytes and macrophages. The erythematous papules also showed dilated small vessels in the upper‐mid dermis and multiple interstitial histiocytic infiltrations, but no multinucleate cells were detected. In immunohistochemistry studies, CD68 and vimentin staining were positive for both specimens. Based on the clinicopathological findings and immunohistochemistry studies, MCAH was diagnosed.

To the best of our knowledge, this is the first case report of MCAH occurring in young age and showing two different clinical and histological phases at the same time.

This article is protected by copyright. All rights reserved.



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Patient Navigation to Enhance Access to Care for Underserved Patients with a Suspicion or Diagnosis of Cancer

AbstractBackground.Interventions aimed at improving access to timely cancer care for patients in low‐ and middle‐income countries (LMIC) are urgently needed. We aimed to evaluate a patient navigation (PN) program to reduce referral time to cancer centers for underserved patients with a suspicion or diagnosis of cancer at a public general hospital in Mexico City.Materials and Methods.From January 2016 to March 2017, consecutive patients aged >18 years with a suspicion or diagnosis of cancer seen at Ajusco Medio General Hospital in Mexico City who required referral to a specialized center for diagnosis or treatment were enrolled. A patient navigator assisted patients with scheduling, completing paperwork, obtaining results in a timely manner, transportation, and addressing other barriers to care. The primary outcome was the proportion of patients who obtained a specialized consultation at a cancer center within the first 3 months after enrollment.Results.Seventy patients (median age 54, range 19–85) participated in this study. Ninety‐six percent (n = 67) identified >1 barrier to cancer care access. The most commonly reported barriers to health care access were financial burden (n = 50) and fear (n = 37). Median time to referral was 7 days (range 0–49), and time to specialist appointment was 27 days (range 1–97). Ninety‐one percent of patients successfully obtained appointments at cancer centers in <3 months.Conclusion.Implementing PN in LMIC is feasible, and may lead to shortened referral times for specialized cancer care by helping overcome barriers to health care access among underserved patients.Implications for Practice.A patient navigation program for patients with suspicion or diagnosis of cancer in a second‐level hospital was feasible and acceptable. It reduced patient‐reported barriers, and referral time to specialized appointments and treatment initiation were within international recommended limits. Patient navigation may improve access to care for underserved patients in developing countries.

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Use of Metformin and Platelet Reactivity in Diabetic Patients Treated with Dual Antiplatelet Therapy

05-2018-0177-dia_10-1055-a-0787-1382-1.j

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0787-1382

Background Enhanced platelet reactivity represents one of the major determinants of cardiovascular risk among diabetic patients. The aim of the present study was to evaluate the impact of metformin use on platelet reactivity in diabetic patients receiving dual antiplatelet therapy (DAPT). Methods We included diabetic patients treated with DAPT after an acute coronary syndrome or percutaneous coronary intervention. Platelet reactivity was assessed at 30–90 days by Multiple-electrode aggregometry. In an additional cohort of diabetic patients naïve to antiplatelet therapy, we assessed platelet reactivity by light transmission aggregometry, surface expression of P-selectin and plasma concentration of Thromboxane B2 (TxB2). Results We included 219 diabetic patients, 117 (53.4%) treated with metformin. Metformin was associated with younger age (p=0.03), male gender (p=0.02), lower rate of hypertension (p=0.04), active smoker (p=0.002), previous MI (p<0.001) renal failure (p<0.001), fibrinogen (p<0.001) and C-reactive protein (p=0.04), larger use of diuretics (p=0.04) calcium antagonists (p=0.05), better glycemic control (p<0.001) and higher haemoglobin (p=0.003). The prevalence of HAPR did not significantly differ according to hypoglycemic treatment (p=0.73; adjusted OR[95%CI]=5.63[0.42-76], p=0.19). Moreover, no impact of metformin was observed for HRPR (p=0.77; adjusted OR[95%CI]=1.15[0.55-2.4], p=0.71). Among an additional cohort of 42 diabetic patients naïve to antiplatelet therapy, we confirmed no impact of metformin or insulin on aggregation. Conclusions Our study found no apparent association in diabetic patients treated with DAPT, between the use of metformin and platelet reactivity or the rate of HPR.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



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The Quality of Systematic Reviews Addressing Peripheral Nerve Repair and Reconstruction

While systematic reviews are regarded as the strongest level of medical evidence, inconsistency in the quality and rigor of systematic reviews raises concerns about their use as a tool in guiding quality delivery in evidence-based clinical practice. The objective of this present study was to assess methodological soundness of systematic reviews with a particular focus on peripheral nerve repair and reconstruction.We performed a comprehensive search using PubMed and Scopus to identify all systematic reviews published on peripheral nerve reconstruction in 9 high-impact surgical journals.

https://ift.tt/2Q86rUQ

Xerostomia Risk After Radiation Therapy and Association With Parotid Dose

This cohort study investigates the association between radiation doses in the parotid glands and self-reported xerostomia among adults treated with whole-brain radiation therapy.

https://ift.tt/2KJvDee

Regional Hyperthermia With Neoadjuvant Chemotherapy for Treatment of Soft Tissue Sarcoma

To the Editor Issels et al analyzed long-term local progression-free survival (LPFS), disease-free survival (DFS), and overall survival (OS) data from an important clinical trial evaluating the efficacy of regional hyperthermia (RHT) added to neoadjuvant chemotherapy (NACT) for localized high–risk soft tissue sarcoma. In the article, added value from RHT was summarized mainly with hazard ratios (HRs). For instance, for DFS, an HR of 0.71 was reported (95% CI, 0.55-0.93; P = .01) in favor of RHT. Median DFS times were 2.8 (95% CI, 2.0-4.9) and 1.5 years (95% CI, 1.1-2.1) for NACT with RHT and NACT alone, respectively. These median CIs overlap, indicating that the difference in median DFS time might not be statistically significant. For OS, the HR was 0.73 (95% CI, 0.54-0.98; P = .04), but median OS time for NACT with RHT was not available. In panels A to C of Figure 2 from the study by Issels et al, the Kaplan-Meier curves of the 2 arms appeared to be parallel after 3 years. Moreover, as noted in the article, NACT with RHT showed delayed OS benefit. These factors suggest that HRs are not constant over time and are difficult to interpret clinically as summary measures for treatment effect.

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Regional Hyperthermia With Neoadjuvant Chemotherapy for Treatment of Soft Tissue Sarcoma—Reply

In Reply We thank Dr Sun et al and Dr Roussakow for their thoughtful comments on our recent article in JAMA Oncology.

https://ift.tt/2KGg4Eb

Regional Hyperthermia With Neoadjuvant Chemotherapy for Treatment of Soft Tissue Sarcoma

To the Editor The report by Issels et al on long-term survival in the randomized clinical trial of regional hyperthermia (RHT) plus neoadjuvant chemotherapy vs neoadjuvant chemotherapy alone for treatment of soft tissue sarcoma is misleading. This report is a post hoc analysis of the initial study results, which showed no benefit in overall survival (OS) associated with RHT (hazard ratio [HR], 0.88; 95% CI, 0.64-1.21; P = .43). Issels et al reported the result of a competing-risks analysis that indicated that the specific risk of death from sarcoma was significantly lower after RHT (HR, 0.73; 95% CI, 0.54-0.98; P = .04), though the reported number of non–sarcoma-related deaths suggests that this risk was significantly higher after RHT (15 vs 6 deaths; odds ratio, 2.76; 95% CI, 1.04-7.29; P = .04 by 2-tailed χ2 test). In general, there is no gain in OS associated with neoadjuvant therapy with RHT. Instead of reporting the result as a secondary analysis, the authors presented it as the primary result of the study. They did not mention that there was no actual benefit in OS, presented the competing risks-based sarcoma-specific survival (SSS) as the initial study end point, and omitted the significant increase in the non–sarcoma-related mortality. Moreover, in the recent study there is a risk for selection bias because the authors excluded 12 patients apparently owing to withdrawal of consent or metastatic disease, though this exclusion was not included in the previous report after 3 years of follow-up. Interestingly, the authors stated the additional reason for the exclusion in the supplement: these patients did not start their allocated treatment after randomization. This additional reason for exclusion is confusing because it appears that 7 patients were excluded from the RHT arm in the most recent article, whereas the earlier study stated that only 4 did not start treatment. The recent study result is presented as a robust intention-to-treat analysis, though after the exclusions, this is a less reliable per-protocol analysis. Furthermore, the SSS is confounded by fewer cycles of chemotherapy in the control arm (median, 5 cycles) than in the RHT arm (median, 8 cycles), and apparently no adjustment for the confounding was applied. Other possible confounders, including the end point substitution, the competing risks-based nature of the end point, and selection bias resulting from the excluded patients, were not properly addressed. Thus, the conclusion that the advantage in SSS is owing to the longer follow-up may not be justified. In my opinion, this report does not show an advantage of RHT plus neoadjuvant chemotherapy vs neoadjuvant chemotherapy alone. I highlight these issues to prevent possible misinterpretation of this trial's results as positive and to avoid unproven treatments being used in clinical practice.

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Abiraterone Acetate for Nonmetastatic Castration-Resistant Prostate Cancer

This Viewpoint uses results of randomized clinical trials to explore whether the use of abiraterone acetate plus prednisone is a cost-effective and appropriate treatment option for patients with nonmetastatic castration-resistant prostate cancer.

https://ift.tt/2KIk1rQ

Burden of Multiple Myeloma in Taiwan

To the Editor Cowan et al explored the global burden of multiple myeloma (MM) from 1990 to 2016 and reported on the incidence, treatment choices, and frequency of stem cell transplant (SCT) worldwide. As a part of East Asia, Taiwan was reported to have an increase in MM incidence, and lenalidomide and bortezomib were approved for treatment of the disease. However, the frequency of SCT in Taiwan was not shown in Figure 2 of the study by Cowan et al. In Taiwan, at least 15 hospitals are performing SCT. Based on a survey from 2005, 7% of patients undergoing SCT were diagnosed with MM. By analyzing data from the longitudinal Taiwan Health Insurance Database from 2007 to 2015, Chang et al found that about 15.5% of patients with MM underwent SCT. Moreover, according to the Taiwan Bone Marrow Transplant Registry, the overall survival rate of patients with MM who underwent SCT was 76.9% at 3-year follow-up. We hope that this information is helpful to better understand the SCT status in Taiwan.

https://ift.tt/2BGyzWg

Burden of Multiple Myeloma in Taiwan—Reply

In Reply To determine the use of stem cell transplant worldwide, we cited prior data published by the World Bone Marrow Transplant network, which did not include transplant rates for Taiwan. We thank the authors for providing this information, which will be helpful to include in future iterations of the Global Burden of Disease study to improve estimates of diseases requiring stem cell transplant.

https://ift.tt/2KLggCc

Anlotinib for Refractory Advanced Non–small Cell Lung Cancer in China

To the Editor Aguiar and colleagues reported the negative cost-effectiveness of first-line osimertinib for EGFR-mutated advanced non–small cell lung cancer (NSCLC). Anlotinib hydrochloride (AL3818), a novel oral multitarget tyrosine kinase inhibitor, was approved as a third-line treatment for refractory advanced NSCLC by the China Food and Drug Administration (CFDA) on May 9, 2018. Anlotinib targets vascular endothelial growth factor receptors, fibroblast growth factor receptors, platelet-derived growth factor receptors, and c-kit, which are involved in broad-spectrum inhibition of tumor angiogenesis and growth. In the phase 1 trial, anlotinib appeared to have broad antitumor capacity for refractory advanced solid tumors, with acceptable and manageable toxic effects, including hypertension, dermal toxic effects, and hypertriglyceridemia. In the phase 2 trial (NCT01924195) on refractory metastatic or recurrent NSCLC, third-line anlotinib treatment had a significant progression-free survival benefit compared with placebo (4.8 vs 1.2 months; P < .001). Subsequently, in the phase 3 trial (NCT02388919) in a similar setting, anlotinib improved the overall survival compared with placebo (9.6 vs 6.3 months; P = .002), with manageable toxic effects. Based on these serial phase 1 to 3 trials, the CFDA gave anlotinib rapid approval to market according to the updated governmental strategy for accelerated new drug approval. The drug met the requirements of controlling the heavy burden associated with lung cancer and decreasing the cost of new drug development in China.

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Association Between Polycystic Ovary Syndrome and Cancer Risk

This cohort study of Swedish register data examines the association between polycystic ovary syndrome and cancer risk in females aged 15 to 50 years between 1985 and 2009.

https://ift.tt/2KLg7yE

Cost-effectiveness of Maintenance Capecitabine and Bevacizumab for Metastatic Colorectal Cancer

This Markov model study assesses the cost-effectiveness of capecitabine and bevacizumab maintenance therapy after induction chemotherapy for treatment of metastatic colorectal cancer.

https://ift.tt/2BFPNTn

Incidence of Y chromosome microdeletions in patients with Klinefelter syndrome

Abstract

Purpose

The aim of this study was to study the incidence of Y chromosome microdeletions in a Caucasian population of Klinefelter syndrome (KS) patients and to investigate the possible association between Y chromosome microdeletions and KS.

Materials and methods

We conducted a retrospective study on 118 KS patients, 429 patients with non-obstructive azoospermia (NOA), and 155 normozoospermic men. Eight of the 118 KS patients had undergone testicular sperm extraction (TESE). All patients underwent semen examination and Y chromosome microdeletions evaluated by PCR, using specific sequence tagged site (STS) primer sets, which spanned the azoospermia factor AZFa, AZFb, and AZFc regions of the Y chromosome.

Results

Semen analysis of the KS group revealed: 1 patient with oligozoospermia, 1 with severe oligoasthenoteratozoospermia, 2 with cryptozoospermia, and 114 with azoospermia. Eight of the 114 azoospermic KS patients underwent TESE, and spermatozoa were recovered from three of these, all of whom had non-mosaic karyotype 47, XXY. 10.7% of the NOA patients presented AZF microdeletions. In 429 cases with NOA, 8 cases had AZFa + b + c deletion, 6 cases had AZF b + c deletion, 4 cases had AZFa microdeletion, 8 cases had AZFb microdeletion, and 20 cases had AZFc microdeletion. Just one KS patient (0.8%) presented microdeletion in the AZFc region.

Conclusion

The percentage of microdeletions in KS patients was lower than in NOA patients, suggesting that AZF microdeletions and KS do not have a causal relationship and that Y chromosome microdeletions are not a genetic factor linked to KS.



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Case of malignant melanoma responding to dacarbazine following nivolumab



https://ift.tt/2Q3VXpo

Factors associated with successful switching between biologic therapies for the treatment of psoriasis in daily dermatological real‐life practice: The Resoswitch study

The main aim of this study was to describe switching practices in daily practice. Patients included were those seen in daily routine practice. Efficacy was defined as the achievement of at least 75% improvement in the PASI score (PASI75). A total of 1,157 patients were included. The frequency of switching was 29.9% and switching was efficient in 71.9% of the cases. The study's results allows a better understanding of the profile of patients who require switch and he appears a change of therapeutic class appears to be more effective in psoriasis patients who require a switch in their therapy.

This article is protected by copyright. All rights reserved.



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Remembering actions without proprioception

Publication date: Available online 29 November 2018

Source: Cortex

Author(s): Elena Daprati, Angela Sirigu, Daniele Nico

Abstract

It has been suggested that agency signals generated by enactment provide memories with an enduring, episodic, marker that can successively be exploited to facilitate recall. Current theories of motor awareness highlight the role of prospective and retrospective sensorimotor cues in the construction of sense of agency (SA). To explore how these signals impact on memory for actions, we studied the effect of enactment in a patient with complete loss of somatic sensation below nose level, and compared her performance to that of a group of neurologically intact individuals. A memory advantage for enacted material was clearly detectable in the control group and, interestingly, also in sensory deafferented patient GL. This novel finding shows that robust memory for actions can be obtained even in the absence of somatosensory reafferences. We hypothesize that the neural processes evoked by intention to move, together with visual experience about one's actions, provide the long-lasting agency signals that are responsible for the special quality of self-performed actions and may support autobiographical experience. Proprioceptive cues, being more time-constrained, are critical to online SA but do not necessarily partake in offline action representations.



https://ift.tt/2raosTn

The time course of spatial attention during naturalistic visual search

Publication date: Available online 28 November 2018

Source: Cortex

Author(s): Elisa Battistoni, Daniel Kaiser, Clayton Hickey, Marius V. Peelen

Abstract

In daily life, attention is often directed to high-level object attributes, such as when we look out for cars before crossing a road. Previous work used MEG decoding to investigate the influence of such category-based attention on the time course of object category representations. Attended object categories were more strongly represented than unattended categories from 180 ms after scene onset. In the present study, we used a similar approach to determine when attention is spatially focused on the target. Participants completed two tasks. In the first, they detected cars and people at varying locations in photographs of real-world scenes. In the second, they detected a cross that appeared at salient locations in an array of lines. Multivariate classifiers were trained on data of the artificial salience experiment and tested on data of the naturalistic visual search experiment. Results showed that the location of both target and distracter objects could be accurately decoded shortly after scene onset (50 ms). However, the emergence of spatial attentional selection – reflected in better decoding of target location than distracter location – emerged only later in time (240 ms). Target presence itself (irrespective of location and category) could be decoded from 180 ms after stimulus onset. Combined with earlier work, these results suggest that naturalistic category search operates through an initial spatially-global modulation of category processing that then guides attention to the location of the target.



https://ift.tt/2FMIddR

A systematic review of randomised controlled trials investigating the efficacy and safety of testosterone therapy for female sexual dysfunction in postmenopausal women

Summary

The clinical sequelae of oestrogen deficiency during menopause are undoubted. However, the pathophysiological role of testosterone during the menopause is less clear. Several randomised, placebo–controlled clinical trials suggest that testosterone therapy improves sexual function in post‐menopausal women. Some studies suggest that testosterone therapy has additional effects which include increased bone mineral density and decreased serum high density lipoprotein (HDL) cholesterol. Furthermore, the long‐term safety profile of testosterone therapy in post‐menopausal women is not clear. This article will provide a concise and critical summary of the literature, to guide clinicians treating post‐menopausal women.

This article is protected by copyright. All rights reserved.



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Thyrotrophin Receptor Antibody Concentration And Activity, Several Years After Treatment For Graves’ Disease

Summary

Objective

TSH receptor antibodies (TRAb) are responsible for autoimmune hyperthyroid disease (Graves' disease; GD) with TRAb levels tending to decrease following treatment. Measurement of TRAb activity during follow up could prove valuable to better understand treatment effectiveness.

Study Design

TRAb concentration and stimulating (TSAb) and blocking (TSBAb) activity of patient serum were assessed following different treatment modalities and follow up length.

Methods

Sixty‐six subjects were recruited following treatment with carbimazole (n=26), radioiodine (n=27) or surgery (n=13). TRAb, TPO‐Ab, Tg‐Ab and GAD‐Ab were measured at a follow up visit as well as bioassays of TSAb and TSBAb activity.

Results

Forty five percent of all patients remained TRAb positive for more than one year and 23% for more than 5 years after diagnosis, irrespective of treatment method. Overall, TRAb concentration fell from a median (IQR) of 6.25 (3.9‐12.7) to 0.65 (0.38‐3.2) U/L. Surgery conferred the largest fall in TRAb concentration from 11.4 (6.7‐29) to 0.58 (0.4‐1.4) U/L. Seventy percent of TRAb positive patients were positive for TSAb and 1 patient (3%) was positive for TSBAb. TRAb and TSAb correlated well (r = 0.83). In addition, 38/66 patients were Tg‐Ab positive, 47/66 TPO‐Ab positive and 6/66 were GADAb positive at follow up.

Conclusions

TRAb levels generally decreased after treatment but persisted for over 5 years in some patients. TRAb activity was predominantly stimulatory, with only one patient demonstrating TSBAb. A large proportion of patients were Tg‐Ab/TPO‐Ab positive at follow up. All treatment modalities reduced TRAb concentrations, however surgery was most effective.

This article is protected by copyright. All rights reserved.



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Cosyntropin testing does not predict response to glucocorticoids in community‐acquired pneumonia in a randomized controlled trial

Summary

Objective

Glucocorticoids have been shown to improve outcome in community‐acquired pneumonia (CAP). However, glucocorticoids have potential side‐effects, and treatment response may vary. It is thus crucial to select patients with high likelihood to respond favorably. In critical illness, cosyntropin testing is recommended to identify patients in need for glucocorticoids. We investigated whether consyntropin testing predicts treatment response to glucocorticoids in CAP.

Design

Predefined secondary analysis of a randomized controlled trial

Patients

Hospitalized patients with CAP

Measurements

We performed 1μg cosyntropin tests in a randomized trial comparing prednisone 50mg for seven days to placebo. We investigated whether subgroups based on baseline and stimulated cortisol levels responded differently to glucocorticoids with regards to time to clinical stability (TTCS) and other outcomes by inclusion of interaction terms into statistical models.

Results

326 patients in the prednisone and 309 patients in the placebo group were evaluated. Neither basal cortisol nor a Δcortisol<250nmol/L after stimulation nor the combination of basal cortisol and Δcortisol predicted treatment response as measured by TTCS (all p for interaction>0.05). Similarly, we found no effect modification with respect to mortality, rehospitalization, antibiotic treatment duration or CAP‐related complications (all p for interaction>0.05). However, glucocorticoids had a stronger effect on shortening length of hospital stay in patients with a baseline cortisol of ≥938 nmol/L (p for interaction=0.015).

Conclusions

Neither baseline nor stimulated cortisol after low‐dose cosyntropin testing at a dose of 1 μg predicted glucocorticoid responsiveness in mild to moderate CAP. A treatment decision for or against adjunct glucocorticoids in CAP should not be made depending on cortisol values or cosyntropin testing results.

This article is protected by copyright. All rights reserved.



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Palliative care in everyday practice of radiation oncologists

Abstract

Purpose

Little is known about the attitudes of radiation oncologists towards palliative care, about their competences in this field, and about the collaboration with palliative care specialists. Our aim was to close this gap and understand more about the importance of an additional qualification in palliative care.

Methods

Medical members of the German Society for Radiation Oncology (DEGRO) were electronically surveyed during November–December 2016.

Results

The survey was emailed successfully to 1110 addressees, whereas a total of 205 questionnaires were eligible for analysis (response rate 18.4%). 55 (26.8%) of the respondents had an additional qualification in palliative care. Physicians who had an additional qualification in palliative care (PC qualification) reported palliative care needs for their patients more frequently than the other respondents (89.0 vs. 82.7%, p = 0.008). Furthermore, they were most likely to report a high confidence in palliative care competences, such as "communication skills & support for relatives" (83.6 vs. 59.3%, p = 0.013), "symptom control," and "pain management" (94.5 vs. 67.7%, p < 0.001 and 90.9 vs. 73.3%, p = 0.008, respectively). Respondents with a PC qualification more often involved palliative care specialists than the other respondents (63.3 vs. 39.3%, p = 0.007). Perceived main barriers regarding palliative care in radiation oncology included time aspects (9.2%), stigmata (8.5%), and the lack of interdisciplinary collaboration (8.5%).

Conclusions

This analysis demonstrated that aspects of palliative care strongly impact on daily practice in radiation oncology. Additional qualifications and comprehensive training in palliative medicine may contribute to improved patient care in radiation oncology.



https://ift.tt/2BEo3OX

Perspectives of Sunless‐Only Tanning Business Owners

Abstract

To date, 16 states in the US restrict minors from using tanning beds.1 The principal argument against policy restricting indoor tanning is the concern it would harm small businesses.2‐4 One counterargument is that tanning businesses could stay financially viable by offering UV‐free sunless tanning services (e.g., spray or airbrush tanning) which would serve customers' desire for a tan while not exposing them to the risks associated with ultraviolet (UV) radiation exposure. Sunless only tanning businesses are already in existence and owners may provide insights on this alternative business model.

This article is protected by copyright. All rights reserved.



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A prospective, observational safety study of patients with BRAFV600‐mutated unresectable or metastatic melanoma treated with vemurafenib [Zelboraf Safety Study (ZeSS)]

Abstract

Vemurafenib is approved in more than 90 countries for the treatment of patients with BRAF V600‐mutated metastatic melanoma.1,2 In the pivotal BRIM‐3 trial, treatment‐emergent cutaneous side effects were associated with vemurafenib, including the development of epithelial tumours and, in rare cases, new primary melanomas.3,4 QTc interval prolongation and hepatic laboratory abnormalities were also noted.3,4

This article is protected by copyright. All rights reserved.



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Comparison of microneedling and full surface erbium laser dermabrasion for autologous cell suspension grafting in non‐segmental vitiligo: a randomized controlled trial

Abstract

Autologous cell suspension is a well‐demonstrated effective approach for treating segmental or stable and localized forms of vitiligo1. Full surface dermabrasion is considered as the gold standard technique for preparing the skin before grafting. Fractional ablative laser or microneedling have been shown to enhance the penetration into the skin of topical agents2.

This article is protected by copyright. All rights reserved.



https://ift.tt/2FO0oQe

Association of Pyrin mutations and Autoinflammation with Complex Phenotype Hidradenitis Suppurativa: A Case Control Study

Abstract

Background

Hidradenitis suppurativa (HS) is a rare, debilitating neutrophilic dermatosis characterised by chronic inflammation of hair follicles. Many inflammatory conditions may accompany HS.

Aim

To investigate the association of variants of the MEFV gene with a complex HS phenotype.

Methods

First, we identified the clinical characteristics of 119 HS patients with a complex phenotype (Hurley stage III disease and/or additional inflammatory symptoms). Then, we searched for MEFV variants among these patients. The odds ratios (OR) for pathogenic MEFV mutations were calculated using data from these HS patients and 191 healthy controls.

Results

The male/female ratio was higher, and the mean age of onset was earlier, in our complex HS group compared with HS patients in general. Five of the HS patients (4.2%) had a diagnosis of familial Mediterranean fever (FMF) with a standardized morbidity ratio of 45 (CI: 16.50‐99.84, p<0.001) when compared with the frequency of FMF in the general Turkish population. Of the patients with complex HS, 38% were positive for pathogenic variants of MEFV. The odds ratio for carrying a pathogenic MEFV allele was 2.80 (CI: 1.31‐5.97, p<0.001).

Conclusion

The frequency of MEFV mutations in a group of patients with complex HS was higher than that in healthy controls, suggesting that MEFV mutations may contribute to the pathogenesis of HS. Understanding the role of autoinflammation in HS is of fundamental importance for the development of novel therapies.

This article is protected by copyright. All rights reserved.



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Safety of guselkumab in patients with moderate‐to‐severe psoriasis treated through 100 weeks: a pooled analysis from the randomised VOYAGE 1 and VOYAGE 2 studies

Summary

Background

Long‐term evaluation is required to confirm the safety profile of newer biologic agents. Objectives

To report on pooled safety data from the on‐going VOYAGE 1 (NCT02207231) and VOYAGE 2 (NCT02207244) trials through 100 weeks of follow‐up.

Methods

Patients were randomized to guselkumab 100 mg at weeks 0 and 4 and every‐8‐weeks thereafter; placebo at weeks 0, 4, 12 followed by guselkumab 100 mg at weeks 16 and 20 and every‐8 weeks thereafter; or adalimumab 80 mg at week 0, 40 mg at week 1, and 40 mg every 2 weeks thereafter. Adalimumab patients crossed over to guselkumab at week 52 (VOYAGE1) and at/after week 28 based on clinical response (VOYAGE2). Open‐label extensions, when all patients received guselkumab, started at week 52 (VOYAGE1) and week 76 (VOYAGE2). Rates of adverse events (AEs) per 100 patient‐years [PY] are presented through 100 weeks of follow up.

Results

Through week 52, observed rates for guselkumab‐ and adalimumab‐treated patients, respectively, were 262.45/100PY and 328.28/100PY for AEs, 6.20/100PY and 7.77/100PY for serious AEs (SAEs), 1.22/100PY and 1.79/100PY for serious infections (SIs), 0.28/100PY and 0.40/100PY for malignancies other than nonmelanoma skin cancers (NMSCs), 0.56/100PY and 0.40/100PY for NMSCs, and 0.47/100PY and 0.40/100PY for MACE. Rates among guselkumab‐treated patients through week 52 and week 100, respectively, were (262.45/100PY and 210.41/100PY) for AEs, 6.20 and 6.29/100PY), for SAEs, 1.22/100PY and 1.06/100PY for SIs, 0.28/100PY and 0.38/100PY for malignancies, 0.56/100PY and 0.39/100PY for NMSCs, and 0.47/100PY and 0.38/100PY for MACE. Among adalimumab‐treated patients, rates of AEs (328.28/100PY vs 160.15/100PY), SAEs (7.77/100PY vs 4.44/100PY), SIs (1.79/100PY vs 0/100PY), malignancies (0.40/100PY vs 0.40/100PY), NMSCs (0.40/100PY vs 0.81/100PY), and MACE (0.40/100PY vs 0.20/100PY) showed some variability before and after crossover to guselkumab, though no new safety signals were noted after crossover.

Conclusions

The safety profile for guselkumab remains favorable through 100 weeks of treatment in patients with moderate‐to‐severe psoriasis.

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Reticulate acropigmentation of Kitamura with a novel mutation in ADAM10



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Facial comedonal acne in orofaciodigital syndrome type 1 caused by a novel frameshift variant in OFD1



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Oral tranexamic acid for the treatment of melasma



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Mild clinical presentation of a patient with a mutation in the NSDHL gene



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Assessing changes in some facial signs of fatigue in Chinese women, induced by a single working day

Abstract

Background

The impacts of physical fatigue upon some facial signs, induced by a whole day work, have been previously described on Caucasian women. The present study aimed at assessing those possibly experienced by Chinese working women under comparable conditions.

Material and Methods

Standard photographs of 60 Chinese women working in the same company (aged 20–40 y) were taken at three occasions during their working day (just before, at 4 and 8 hours). Focusing on facial signs allowed a panel of experts to grade their respective severities, helped by a referential atlas dedicated to Asian skin. A naïve panel, comprising 64 Chinese women (aged 20–60 y) graded, through an analogic 0–10 scale, the global facial aspect of each subject, particularly its tired‐look and dullness and estimated the age of each subject (perceived age). Paired‐comparisons in blind and random modes (T0/T4, T4/T8, T0/T8) allowed this naive panel to assess the subjects with a younger/older look, a dullest aspect.

Results

A daily work induces, in Chinese women, changes in some facial signs (Nasolabial, Periorbital and Inter‐ocular wrinkles, Cheek skin pores). The latter appear more marked between T0 and T4 than between T4 and T8. As compared to those observed among Caucasian women, these changes, although subtle, are of a higher amplitude and concern different facial signs. The naïve panel allowed to describe an increase in the tired look and dullness along the day, more so among the older group (31–40 y), together with an increased perceived age. Tired look, dullness and perceived age appear strongly linked.

Conclusion

Despite some possible differences in working conditions, some facial signs of Chinese women seem more affected by a fatigue induced by a working day in urban environment, than those of Caucasian women in similar conditions.

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Scholar : Undersea "Hyperbaric Medicine" - νέα αποτελέσματα

[HTML] ВЛИЯНИЕ ГИПЕРОКСИИ И ГИПОКСИИ НА АДАПТАЦИЮ ПРИ МЫШЕЧНОЙ РАБОТЕ

АС Радченко, ПД Шабанов - Обзоры по клинической фармакологии и …, 2018
В настоящем кратком обзоре излагается мнение об использовании
гипероксии (ГО) в спортивной тренировке, которая в последние годы
рекомендуется некоторыми авторами для повышения специальной …
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Scholar : CPAP - νέα αποτελέσματα

Effect of Adaptive Servo-Ventilation on Periodic Limb Movements in Sleep in Patients With Heart Failure

J Xie, N Covassin, AA Chahal, PJ Schulte, P Singh… - The American Journal of …, 2018
… effectively reduces CSA. Prior data have shown PLMS decreased in patients with mild
obstructive sleep apnea (OSA) after treatment of continuous positive airway pressure
(CPAP), but increased in subjects with severe OSA. 13 To …
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Management of severe bronchiolitis: impact of NICE guidelines

B Griffiths, S Riphagen, J Lillie - Archives of Disease in Childhood, 2018
… 2015–2016 (p<0.001). There was a trend towards reduction in CPAP use (44%
vs 36%) and increase in the use of bilevel positive airway pressure but neither
reached statistical significance. Antibiotics. The use of antibiotics …
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[PDF] EFFECTS OF MECHANICAL INSPIRATION AND EXPIRATION EXERCISE ON VELOPHARYNGEAL INCOMPETENCE IN SUBACUTE STROKE PATIENTS

J Kyung Won - J Rehabil Med, 2019
… One study showed that treatment with continuous positive airway pressure (CPAP) was
effective in patients with VPI (14) … Like the CPAP therapy, MIE exercise also might
strengthen the oropharyngeal muscles, which are involved in velopharyngeal closure …
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Impact of prone positioning in infants with Pierre Robin sequence: a polysomnography study

L Coutier, A Guyon, P Reix, P Franco - Sleep Medicine, 2018
… There were 15 (83%) infants who did not have respiratory support; before PSG, the PP
was used for 14 infants, and the SP was used for 4 infants (1 in ambient air and 3 with
respiratory support). 2 already had NIV (CPAP settings: 6 cmH2O), and 1 had an NPT …
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Sedation and neurodevelopmental outcomes in PICU: identification of study groups

DE Withington, R Mujallid, Z Al Sabaa - Pediatric Anesthesia
… are presented in Table 1. Ten of thirty-three patients had CPAP/BIPAP before intubation,
failure to tolerate either the mask or CPAP/BIPAP or lack of improvement with this strategy …
In the CPAP group 18/39 cases had RSV positive bronchiolitis with others having …
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[PDF] Häusliche Betreuung nichtinvasiv heimbeatmeter Patienten durch ein spezialisiertes Team (TAB)

KK Herberger - 2018
… ASB assisted spontaneous breathing (Beatmungsmodus) assPCV assisted
pressure controlled ventilation (Beatmungsmodus) aVK ambulante
Verlaufskontrolle BMI Body Mass Index CO2 Kohlendioxid COPD Chronic …
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[PDF] Análise comparativa de fórmulas preditivas de avaliação da capacidade funcional com o teste cardiopulmonar de jogadoras de futebol profissional

A Fenley, RS Floriano, TO Chaves, I Nasser, MS Reis - Fisioterapia e Pesquisa, 2018
… Eur J Heart Fail. 2004;6(7):917-26. doi: 10.1016/j. ejheart.2004.02.010 15.
Reis HV, Borghi-Silva A, Catai AM, Reis MS. Impact of CPAP on physical
exercise tolerance and sympathetic- vagal balance in patients with chronic …
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[HTML] Comparative analysis of predictive formulas for the evaluation of functional capacity with cardiopulmonary test in professional female soccer players

A Fenley, RS Floriano, TO Chaves, I Nasser, MS Reis - Fisioterapia e Pesquisa, 2018
… 2004;6(7):917-26. doi: 10.1016/j.ejheart.2004.02.010 [ Links ]. 15. Reis
HV, Borghi-Silva A, Catai AM, Reis MS. Impact of CPAP on physical
exercise tolerance and sympathetic-vagal balance in patients with chronic …
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[PDF] Partilha de experiências e conhecimento com o pulmão no centro

CR Cordeiro, S Valente
Page 1. SALETE VALENTE, MD E CARLOS ROBALO CORDEIRO, PhD
DESCENTRALIZAR O DEBATE O pulmão no centro da questão CONGRESSO JORNAL
CPC Esta publicação está também disponível em formato digital Faça o download gratuito …
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[PDF] Red Cell and blood component Transfusion in Neonates

VR Kairamkonda, S Armitage
… Table 1. Summary of BCSH recommendations for neonatal top- up transfusions Postnatal
age Suggested transfusion threshold Hb (g/L) Ventilated On oxygen/CPAP Off oxygen
First 24 hours <120 <120 <100 ≤Week 1 (days 1–7) <120 <100 <100 …
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