bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive Capabilities of Three Widely Used Pathology Classification Systems and a Simplified Classification (Beijing Classification) in Primary IgA Nephropathy
Authors: Duan Shu-Wei , Mei Yan , Liu Jian , Chen Pu , Li Ping , Chen Yi-Zhi , Lin Shu-Peng , Zhang Xue-Guang , Liu Jiao-Na , Sun Xue-Feng , Xie Yuan-Sheng , Cai Guang-Yan , Liu Shu-Wen , Wu Jie , Chen Xiang-Mei
Published: September 2019

Background/Aims: Several pathological classification systems were commonly used in clinical practice to predict the prognosis of IgA nephropathy (IgAN). However, how prognostic value differs between these systems is unclear. The aim of this study was to compare the Lee grade, the Oxford classification, and the Haas classification and to find a simplified classification. Methods: We retrospectively analyzed IgAN cases diagnosed between January 2002 and December 2007. The endpoints were progression to end-stage renal disease (ESRD) or a ≥50% decline in estimated glomerular filtration rate (eGFR). The predictive capabilities were evaluated by comparing the ability of discrimination (continuous net reclassification) and calibration (Akaike information criterion [AIC]). Results: A total of 412 IgAN patients were included in the study. The average follow-up period was 80.62 ± 23.63 months. A total of 44 (10.68%) patients progressed to ESRD, and 70 (16.99%) patients showed a ≥50% decline in eGFR. All multivariate Cox regression models had limited power for high AIC values. The prognostic values of the Lee grade and the Oxford classification were higher than those of models containing only established baseline clinical indicators for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.50, 95% CI 0.21–0.74; Oxford classification 0.48, 95% CI 0.28–0.71). The prognostic value of the Haas classification was lower than that of the other pathological classification systems for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.53, 95% CI 0.23–0.92; Oxford classification 0.59, 95% CI 0.10–0.74). The prognostic value of hierarchical classification (Beijing classification) using M and T lesion was similar to the Oxford classification. Conclusions: Both the Lee grade and the Oxford classification showed incremental prognostic values beyond established baseline clinical indicators. The Haas classification was slightly inferior to the Lee grade and the Oxford classification. The hierarchical classification (Beijing classification) using less pathological parameters does not lose predictive efficiency.
Fetal Cystoscopy and Vesicoamniotic Shunting in Lower Urinary Tract Obstruction: Long-Term Outcome and Current Technical Limitations
Authors: Vinit Nicolas , Gueneuc Alexandra , Bessières Bettina , Dreux Sophie , Heidet Laurence , Salomon Rémi , Lapillonne Alexandre , De Bernardis Gaston , Salomon Laurent J. , Stirnemann Julien J. , Blanc Thomas , Ville Yves
Published: September 2019

Background: In utero therapeutic approaches for lower urinary tract obstruction (LUTO) have been developed to salvage the fetal kidney function. Objective: The aim of this work was to report the long-term survival, nephrological, and urological outcome of children treated prenatally for LUTO using operative fetal cystoscopy (FC) and vesicoamniotic shunting (VAS) or both. Methods: A retrospective study of 48 procedures (23 FC, 25 VAS) was performed on 33 patients (between 2008 and 2018). Reviewed data included prenatal management and clinical follow-up by a pediatric nephrologist and a pediatric urologist. Both intention-to-treat and per-protocol analyses were conducted. Results: The median follow-up was 3.6 years (0.5–7) for FC and 2.5 years (1.1–5.1) for VAS. There was no difference between FC and VAS in terms of survival (92 vs. 83%, p = 1), complication rate (74 vs. 92%, p = 0.88), or chronic kidney disease (58 vs. 50%, p = 1). The number of procedures was higher in the VAS group: 1.7 (1–3) versus 1.1 (1–2), p = 0.01. With a 30% rate of technical failure, FC added diagnostic value in 3 out of 21 cases. Conclusions: No difference was found between FC and VAS regarding survival, long-term kidney function, or urological outcome. Despite overly optimistic reports on FC, it lacks reproducibility due to posterior-urethra inadequate visualization and inappropriate instrumentation.
Influence of Helicobacter pylori Infection and Atrophic Gastritis on the Gut Microbiota in a Japanese Population
Authors: Iino Chikara , Shimoyama Tadashi , Chinda Daisuke , Sakuraba Hirotake , Fukuda Shinsaku , Nakaji Shigeyuki
Published: September 2019

Background: Although infection with Helicobacter pylori and subsequent atrophic gastritis modulate the gastric conditions, their relationship with the gut microbiota in ­Japanese population has not been clearly characterized. Methods: A cohort of 1,123 subjects who participated in a health survey was studied. Infection of H. pylori was defined by both serum antibody and stool antigen test. The presence and severity of atrophic gastritis were defined by serum levels of pepsinogens. The relative abundance of each bacterial species in fecal samples was calculated by using 16S ribosomal RNA amplification, and the composition ratios of bacterial taxa were evaluated using propensity score matching. Results: The abundance of 3 orders, 4 families, and 4 genera was significantly higher in H. pylori-infected subjects than in noninfected subjects (false discovery rate [FDR] <0.05). In H. pylori-infected subjects with severe atrophic gastritis, the abundance of the class Bacilli, order Lactobacillales, family Streptococcaceae, and genus Streptococcus was significantly higher than that in H. pylori-infected subjects without atrophic gastritis (FDR < 0.05). Conclusions: A significant increase in the relative abundance of several taxa was observed in gut microbiota of Japanese subjects with H. pylori infection. Among the subjects with severe atrophic gastritis, the increase in the genus Streptococcus is a remarkable characteristic.
Expression and Relationship of SAMHD1 with Other Apoptotic and Autophagic Genes in Acute Myeloid Leukemia Patients
Authors: Jiang Huinan , Li Chuan , Liu Zhuogang , Shengjing Hospital  ,   Hu
Published: September 2019

Background: SAM domain- and HD domain-containing protein 1 (SAMHD1) is a cellular enzyme which is responsible for blocking replication in viruses and participates in the progression of many cancers. Objective: The aim of this study was to correlate the expression level of SAMHD1 with other apoptotic and autophagic genes in acute myeloid leukemia (AML) patients. Methods: In the present study, mRNA levels of SAMHD1 with other apoptotic and autophagic-related genes were evaluated in patients who were newly diagnosed with AML. Results: SAMHD1, Bcl-xl, Bax, Bak, XIAP, and cIAP1 were downregulated in the AML group compared to the non-AML group (p < 0.05). SAMHD1 expression did not correlate with the other genes, while most apoptotic genes were positively correlated with each other. SAMHD1 expression was not associated with the blood routine or blast percentage of the AML patients, while Bax, Bak, cIAP2, and LC3 were significantly correlated with white blood cells. No statistically significant differences were found between the studied genes and prognosis stratifications, but Bcl-xl, Bak, cIAP1, and Mcl-1, LC3 were expressed at lower levels in the unfavorable AML group compared to the controls. Conclusion: SAMHD1 and Bcl-xl, Bax, Bak, XIAP, and cIAP1 were downregulated in AML patients, while there were no significant differences in the clinical characteristics and prognosis with reference to SAMHD1 expression.
Improving Diagnostic Yield of Capsule Endoscopy in Coeliac Disease: Can Flexible Spectral Imaging Colour Enhancement Play a Role?
Authors: Chetcuti Zammit Stefania , McAlindon Mark E. , Ellul Pierre , Rondonotti Emanuele , Carretero Cristina , Sanders David S. , Sidhu Reena
Published: September 2019

Introduction: Flexible spectral imaging colour enhancement (FICE) is a form of virtual chromoendoscopy that is incorporated in the capsule reading software and that can be used by reviewers to enhance the delineation of lesions in the small bowel. This has been shown to be useful in the detection of pigmented (ulcers, angioectasias) lesions. However, its application to coeliac disease (CD) images from small bowel capsule endoscopies (SBCEs) has rarely been studied. Methods: This was a European, multicentre study that included 5 expert capsule reviewers who were asked to evaluate a number of normal and abnormal de-identified images from SBCEs of patients with CD to determine whether the use of FICE and blue light can improve the detection of CD-related changes. Results: Sensitivity and specificity of conventional white light in the delineation of CD-related changes were 100%. The next best image modification was FICE 1 with a sensitivity of 80% and a specificity of 100%. There was no difference between conventional white light, FICE and blue light for the identification of CD-related changes. There was a low agreement (Fleiss kappa 0.107; p = 0.147) between expert reviewers in selecting the best image modification that detected CD-related changes. Conclusions: FICE and blue light were not found to be superior to conventional white light in the delineation of macroscopic changes related to CD on SBCEs.
Invasive Hemodynamic Predictors of Renal Outcomes after Percutaneous Coronary Interventions
Authors: Lo Kevin Bryan , Penalver Jorge , Mostafavi Toroghi Hesam , Jeon Hee Do , Habib Nawal , Hung Pinto Wikien , Ram Pradhum , Gupta Shuchita , Rangaswami Janani
Published: September 2019

Objectives: To determine the association of right heart invasive hemodynamic parameters with post-percutaneous coronary intervention (PCI) acute kidney injury (AKI). Background: AKI after PCI is associated with a high morbidity and mortality. Various mechanisms are implicated in AKI after PCI. However, the association between filling pressures and invasive hemodynamic measures of right heart function with post-PCI AKI has not been described. Methods: This is a retrospective single-center analysis of patients of who underwent simultaneous right heart catheterization (RHC) and left heart catheterization with PCI at the Einstein Medical Center, Philadelphia, between January 2010 and December 2016. We included patients who had hemodynamic parameters from the concomitant RHC as well as measurements of kidney function up to 1 month after the procedure. We excluded patients with ST elevation myocardial infarction, end-stage renal disease, cardiogenic shock, and PCI with a need for mechanical circulatory device support. Multivariate linear regression analysis was used to analyze the association between the various right ventricular hemodynamic parameters and eGFR within 1 week and 1 month after catheterization after adjusting for age, race, gender, diabetes and hypertension, contrast volume, cardiac index, and baseline eGFR. Results: Right atrial (RA) pressure was inversely associated with eGFR within 1 week (β = –1.66; 95% CI –3.06 to –0.25; p = 0.021) and 1 month after PCI (β = –2.14; 95% CI –4.08 to –0.20; p = 0.031). Conclusion: Elevated RA pressure is associated with a worsening kidney function after cardiac catheterization and PCI.
Emergent and Urgent Craniotomies in Pediatric Patients: Resource Utilization and Cost Analysis
Authors: Ajmera Sonia , Motiwala Mustafa , Lingo Ryan , Khan Nickalus R. , Smith Lydia J. , Giles Kim , Vaughn Brandy , Klimo Jr. Paul
Published: September 2019

Background: Pediatric neurosurgeons are occasionally tasked with performing surgery expeditiously to preserve a child’s neurologic faculties and life. Objective: This study examines the etiologies, outcomes, and costs for urgent or emergent craniotomies at a Level I Pediatric Trauma center over a 7-year time period. Methods: A retrospective review was conducted for each patient who underwent an emergent or urgent craniotomy within 24 hours of presentation between January 2010 and April 2017. Demographic, clinical, and surgical details were recorded for a total of 48 variables. Any readmission within 90 days was analyzed. Hospital charges for each admission and readmission were collected and adjusted for inflation to October 2018 values. Results: Among the 223 children who underwent urgent or emergent craniotomies, the majority were admitted for traumatic injuries (n = 163, 73.1%). The most common traumatic mechanism was fall (n = 51, 22.9%), and the most common non-traumatic cause was tumor (n = 21, 9.4%). Overall, craniotomies were typically performed for hematoma evacuation of one type or combination (n = 115, 51.6%) during off-peak times (n = 178, 79.8%). Seventy-seven (34.5%) subjects experienced 1 or more postoperative events, 22 of whom returned to the operating room. There were 13 (5.8%) and 33 (14.8%) readmissions within 30 days and 90 days of discharge, respectively. Non-trauma patients (compared with trauma patients) and polytrauma (compared with isolated head injury) had greater healthcare needs, resulting in higher charges. Conclusion: Most urgent or emergent pediatric craniotomies were performed for the treatment of traumatic injuries involving hematoma evacuation, but non-traumatic patients were more complex requiring greater resources.
Serum Periostin Level Has Limited Usefulness as a Biomarker for Allergic Disease in 7-Year-Old Children
Authors: Sung Myongsoon , Baek Hey Sung , Yon Dong Keon  , Lee Seung Won  , Ha Eun Kyo , Lee Kyung Suk , Jee Hye Mi , Sheen Youn Ho , Ono Junya , Izuhara Kenji , Han Man Yong
Published: September 2019

Background: Previous studies have used serum periostin levels as a biomarker of Th2-driven inflammatory responses. However, no population-based study has yet examined the association of serum periostin levels with the allergic status of children. Objectives: The aim of this study was to determine the usefulness of periostin as a biomarker for allergy in a group of 7-year-old Korean children. Method: This prospective cross-sectional study examined 451 children (aged 7 years to 7 years and 11 months) from the general pediatric population who attended 6 different schools between June and July 2016. A total of 249 children, all of whom completed the questionnaire and skin prick test and provided blood samples, were included in the final analysis. Results: The geometric mean serum periostin level was 107.6 ng/mL (95% CI 104.5–110.7). After adjustment for confounding, serum periostin levels were significantly associated with sensitization to poly-allergens (adjusted odds ratio, aOR 1.032, 95% CI 1.006–1.059, p = 0.016) and pollen (aOR 1.020, 95% CI 1.002–1.039, p = 0.026). Serum periostin levels were also associated with eosinophil levels (adjusted β = 0.023, SE = 0.009, p = 0.010), but were unrelated to body mass index, sex, obesity, or presence of an allergic disease. Conclusions: Our results suggest thatserum periostin level may have limited usefulness as a biomarker of allergic disease in children.
Mechanical Prosthetic Heart Valve Thrombosis in a Patient Receiving Rivaroxaban
Authors: Carvalho Silva Daniela Marisa , Braga Ana , de Jesus Ilídio , Neves José
Published: September 2019

Direct oral anticoagulants are not approved for use in patients with mechanical valves. When used to replace vitamin K antagonists, they may cause catastrophic consequences. The authors describe the case of a patient who, after discontinuation of warfarin and introduction of rivaroxaban, developed thrombosis of his mechanical mitral prosthesis.
Undergarment and Fabric Selection in the Management of Hidradenitis Suppurativa
Authors: Loh Tiffany Y. , Hendricks Aleksi J. , Hsiao Jennifer L. , Shi Vivian Yan
Published: September 2019

Hidradenitis suppurativa (HS) is a chronic inflammatory condition manifesting as recurrent and exquisitely painful nodules in intertriginous regions. The role of mechanical stress in HS pathogenesis is gaining attention, as factors including intertriginous distribution of lesions, obesity, sweating, and suboptimal clothing contribute to increased friction and exacerbation of disease. Undergarment and clothing selection are often-overlooked components of HS management and should be addressed with patients as practical lifestyle changes that can decrease the frequency of disease flares and reduce symptoms of pain and irritation at involved sites. Selection of breathable and absorbent fabrics can also aid in reducing microbial colonization, sweat retention, and odor. This discussion is based on expert recommendations and aims to provide practitioners with the rationale for appropriate undergarment and clothing selection for HS patients. We propose practical principles for choosing undergarment design and fabrics for breathability, absorbency, and skin pressure reduction.
Skin Care and Synbiotics for Prevention of Atopic Dermatitis or Food Allergy in Newborn Infants: A 2 × 2 Factorial, Randomized, Non-Treatment Controlled Trial
Authors: Dissanayake Eishika , Tani Yumi , Nagai Kazue , Sahara Masumi , Mitsuishi Chisako , Togawa Yaei , Suzuki Yoichi , Nakano Taiji , Yamaide Fumiya , Ohno Hiroshi , Shimojo Naoki
Published: September 2019

Background: Atopic dermatitis (AD) and food allergy (FA) are common childhood diseases, which may either be interrelated or be the result of skin barrier disruption and gut mucosal dysbiosis. Although some evidence suggests the efficacy of emollients and synbiotics, there is no conclusive evidence on the use of these interventions alone or in combination. Objectives: This study is aimed at identifying the efficacy of emollients and synbiotics in preventing AD and FA in children during the first year of life. Methods: The babies of mothers recruited prenatally received either an emollient, synbiotic, both or neither. The intervention was carried out from birth up to 6 months of age. The age of occurrence of AD and FA were reported in multiple questionnaires at 1, 6, and 9 months and at 1 year of age. AD was diagnosed by a pediatrician at 9 months of age. Results: A ­total of 459 babies qualified for the outcome assessment at 1 year of age. Neither the emollient nor the synbiotic showed any effect on reducing the development of AD and FA at 1 year of age. Conclusions: This study did not provide any evidence to show that emollients and synbiotics, alone or in combination are sufficient to prevent the occurrence of AD or FA in children up to 1 year of age.
Upregulation of Mitochondrial Transcription Factor A Promotes the Repairment of Renal Tubular Epithelial Cells in Sepsis by Inhibiting Reactive Oxygen Species-Mediated Toll-Like Receptor 4/p38MAPK Signaling
Authors: Dai Xin-Gui , Li Tao , Huang Wei-Bo , Zeng Zhen-Hua , Li Qiong , Yang Yang , Duan Ze-Peng , Wang Yu-Jing , Ai Yu-Hang
Published: September 2019

Background: Mitochondrial transcription factor A (TFAM) plays multiple pathophysiologic roles in mitochondrial DNA (mtDNA) maintenance. However, the role of TFAM in sepsis-induced acute kidney injury (AKI) remains largely unknown. Methods: Lipopolysaccharide (LPS) treatment of HK-2 cells mimics the in vitro model of AKI inflammation. pcDNA3.1 plasmid was used to construct pcDNA3.1-TFAM. sh-TFAM-543, sh-TFAM-717, sh-TFAM-765, sh-TFAM-904 and pcDNA3.1-TFAM were transfected into HK-2 cells using Lipofectamine 2000. MtDNA transcriptional levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay was performed to assess the cell viability. Changes in reactive oxygen species (ROS) and mitochondrial membrane potential in HK-2 cells were detected using the corresponding kits. Immunofluorescence experiment was used to investigate the displacement of TFAM. mRNA and protein expression levels of TFAM and its related genes were measured by qRT-PCR and western blot respectively. Mice in sepsis were administered cecal ligation and puncture surgery. Results: LPS treatment was a non-lethal influencing factor, leading to the upregulation of ROS levels and downregulation of mtDNA copy number and NADH dehydrogenase subunit-1 (ND1) expression, and caused damage to the mitochondria. As the LPS treatment time increased, TFAM was displaced from the periphery of the nucleus to cytoplasm. TFAM reduced ROS and P38MAPK levels by inhibiting toll-like receptor 4 (TLR4) expression, ultimately inhibiting inflammation and repairing mtDNA. Conclusions: Our results indicate that TFAM repairs mtDNA by blocking the TLR4/ROS/P38MAPK signaling pathway in inflammatory cells, thereby repairing septic tubular epithelial cells, and TFAM may serve as a new target for sepsis therapy.
Research Domain Criteria: Strengths, Weaknesses, and Potential Alternatives for Future Psychiatric Research
Authors: Ross Christopher A. , Margolis Russell L.
Published: September 2019

The Research Domain Criteria (RDoC) paradigm was launched 10 years ago as a superior approach for investigation of mental illness. RDoC conceptualizes normal human behavior, emotion, and cognition as dimensional, with mental illnesses as dimensional extremes. We suggest that RDoC may have value for understanding normal human psychology and some conditions plausibly construed as extremes of normal variation. By contrast, for the most serious of mental illnesses, including dementia, autism, schizophrenia, and bipolar disorder, we argue that RDoC is conceptually flawed. RDoC conflates variation along dimensional axes of normal function with quantitative measurements of disease phenotypes and with the occurrence of diseases in overlapping clusters or spectra. This moves away from the disease model of major mental illness. Further, RDoC imposes a top-down approach to research. We argue that progress in major mental illness research will be more rapid with a bottom-up approach, starting with the discovery of etiological factors, proceeding to investigation of pathogenic pathways, including use of cell and animal models, and leading to a refined nosology and novel, targeted treatments.
Health-Related Quality of Life in Patients with Moderate to Severe Ulcerative Colitis: Surgical Intervention versus Immunomodulatory Therapy
Authors: Portela Francisco , Ministro Paula , de Deus João , Cravo Marilia , Cotter José , Duque Gabriela , Ferreira Frederico , Rosa Bruno , Ferreira Pedro Lopez , Dias Claudia Camila , Magro Fernando ,   Portuguese IBD Study Group (GEDII)
Published: September 2019

Purpose: Ulcerative colitis (UC) can be managed with immunomodulation or surgery. We aimed to understand whether these strategies had a different impact on patients’ health-related quality of life (HRQoL). Methods: This was a retrospective, cross-sectional study: patients who had a moderate to severe UC episode that prompted the utilization of immunomodulatory drugs or surgery were invited to complete a generic (short form [36] health survey [SF-36]) and a disease-specific (inflammatory bowel disease questionnaire [IBDQ]) survey. Results: We included 157 patients, 65 (41.4%) surgically treated. The therapeutic procedure had a minimal impact on HRQoL: only the social dimension of the IBDQ and the physical function component of the SF-36 were significantly different between the study arms – lower for the surgically treated patients. The type of surgery had no impact, but the occurrence of pouchitis, namely, in a chronic form, was associated with a lower HRQoL. Regression analysis confirmed surgery as an independent predictor of lower scores in the social dimension of the IBDQ (–4.646, 95% CI –6.953 to –2.339) and in the physical functioning (–9.622, 95% CI –17.061 to –2.183) and physical role functioning (–3.669, 95% CI –7.339 to 0.001) dimensions of the SF36. Conclusions: Although usually feared by patients, surgery has a limited impact on UC patients HRQoL when compared to medical management with immunomodulatory drugs.
The Current Situation of the Tyrolean Iceman
Authors: Zink Albert R. , Maixner Frank
Published: September 2019

The Tyrolean Iceman, commonly known as Ötzi, is the world’s oldest glacier mummy and one of the best investigated ancient human remains in the world. Since the discovery of the 5,300-year-old Copper Age individual in 1991, in a glacier in the Eastern Italian Alps, a variety of morphological, biochemical, and molecular analyses have been performed that revealed important insights into his origin, his life habits, and the circumstances surrounding his demise. In more recent research, the mummy was subjected to cutting-edge modern research methodologies currently focusing on high-throughput sequence analysis of ancient biomolecules (DNA, proteins, lipids) that are still preserved in the mummified tissues. This application of innovative “-omics” technologies revealed novel insights on the ancestry, disease predisposition, diet, and the presence of pathogens in the glacier mummy. In this review, the most important and actual results of the molecular studies will be highlighted.
Deletion in the A4GALT Gene Associated with Rare “P null” Phenotype: The First Report from India
Authors: Shastry Shamee , Satyamoorthy Kapaettu , Acharya Kiran V. , Reddy Vijay Ram , Mohan Ganesh , Deepika Chenna , Reghunathan Dinesh , Joshi Manjunath B.
Published: September 2019

Background: The present report illustrates a case with rare “P null” phenotype due to a large deletion in chromosome 22q13.2 and with clinically significant anti-PP1Pk antibody. Patient blood management in such cases is challenging. Case Report: The transfusion center supporting the tertiary care referral center in the southern part of India received a blood sample from a trauma case for pre-transfusion testing. An antibody to a high-frequency blood group antigen was initially suspected. Following extensive immune-hematological workup, the patient was diagnosed to have naturally occurring anti-PP1Pk antibody and a rare “P null” phenotype. The genomic DNA of the patient was analyzed by exome sequencing followed by Sanger’s sequencing. Molecular diagnostics revealed a large 21-bp deletion in chromosome 22q13.2 which encodes the A4GALT gene, resulting in truncation of seven amino acids I245–251P and resulted in rare “P null” phenotype. Patient blood management strategies were adopted to manage the patient conservatively without blood transfusion. Conclusion: A large deletion in chromosome 22q13.2 had resulted in a rare “P null” phenotype in the present case. The patient was a victim of a road traffic accident, required emergency hospitalization, as well as surgical intervention, and his plasma had antibodies to high-frequency antigens. A rare donor registry plays a major role in providing transfusion support to such cases.
Monotherapy for Alopecia Areata: A Systematic Review and Network Meta-Analysis
Authors: Gupta Aditya K. , Carviel Jessie L. , Foley Kelly A. , Shear Neil H. , Piraccini Bianca Maria , Piguet Vincent , Tosti Antonella
Published: September 2019

Background: There are many treatments available for alopecia areata; however, none are approved by the US Food and Drug Administration. Thus, there is clinician benefit in efficacy comparison. Methods: A network meta-analysis was used to create direct and indirect comparisons of alopecia areata studies in addition to an inconsistency analysis, risk of bias, and quality of evidence assessment. Results: For mild disease, intralesional corticosteroids were ranked the most likely to produce a response at 78.9% according to SUCRA (surface under the cumulative ranking curve) followed by topical corticosteroids (67.9%), prostaglandin analogs (67.1%), diphenylcyclopropenone (DPCP, 63.4%), topical minoxidil (61.2%), and squaric acid dibutylester (SADBE, 35.0%). In contrast, for moderate to severe disease (>50% scalp hair loss), DPCP was the top-ranked treatment (87.9%), followed by laser (77.9%), topical minoxidil (55.5%), topical corticosteroids (50.1%), SADBE (49.7%), and topical tofacitinib (47.6%). There were insufficient eligible trials to include oral tofacitinib in the network. Conclusion: Statistically significant evidence is presented for the use of intralesional and topical corticosteroids for treatment of mild disease and DPCP, laser, SADBE, topical minoxidil and topical corticosteroids for moderate to severe disease. Further controlled trials are required to analyze the relative efficacy of oral tofacitinib.
Gut Environment and Dietary Habits in Healthy Japanese Adults and their Association with Bowel Movement
Authors: Tanabe Atsushi , Adachi Kazunori , Yamaguchi Yoshiharu , Izawa Shinya , Yamamoto Sayuri , Hijikata Yasutaka , Ebi Masahide , Funaki Yasushi , Ogasawara Naotaka , Goto Chiho , Sasaki Makoto , Kasugai Kunio
Published: September 2019

Introduction: Constipation is a common symptom that impairs the quality of life (QOL). This study aimed to investigate the relationship between bowel movement and gut microbiota and dietary intake. Methods: To investigate correlations among bowel movement, food intake, and gut environment, 60 healthy Japanese participants were recruited. Bowel movement was assessed using the Bristol stool form scale (BSFS) and constipation scoring system (CSS). Dietary habit was assessed with a self-administered questionnaire wherein the food intake frequency was classified into 8 categories for 72 food/food groups. Gut microbiota was analyzed using terminal restriction fragment length polymorphism analysis. Results: The constipation rate was significantly higher in females than in males. The QOL was significantly impaired in the constipated group. The fecal count of Bacteroides was decreased and that of Clostridium cluster IV was increased in participants with constipation. The BSFS score was negatively associated with the fecal count of Clostridium cluster XI and positively associated with the fecal count of Clostridium cluster XVIII and consumption of green tea. The total CSS score was positively associated with the fecal Prevotella count and negatively associated with fecal acetate levels and consumption of vegetables. Discriminant analysis estimated that constipation could be predicted correctly in 83% (p < 0.001) of the participants based on fecal microbiota and fecal short-chain fatty acids. Discussion/Conclusion: Bowel movement was strongly affected by gut environment and food intake in Japanese participants. Improvement in dietary habits could promote bowel movement through the improvement of the environment in the gut, resulting in ameliorated QOL issues in healthy adults.
Xiaoyaosan Produces Antidepressant Effects in Rats via the JNK Signaling Pathway
Authors: Zhao Hong-Bo , Jiang You-Ming , Hou Ya-Jing , Yan Zhi-Yi , Liu Yue-Yun , Li Xiao-Juan , Gong Wei-Jun
Published: September 2019

Background: Xiaoyaosan (XYS) has achieved definite curative effects in clinic. However, the mechanism is not clear. Previous studies of our team indicated XYS improved anxiety-like behaviors through inhibiting c-Jun N-terminal kinase (JNK) signaling pathway of hippocampus. Objectives: In the study, we explored whether the JNK signaling pathway is involved in the mechanism of XYS treating depression. Method: Forty-eight rats were divided randomly into 4 groups (n = 12): the control group (deionized water, p.o.), the model group (deionized water, p.o.), the fluoxetine group (2.08 mg/kg/day, p.o.), and the XYS group (3.9 g/kg/day, p.o.). All rats except for the control group were given continuous 21 days of chronic immobilization stress (CIS; 3 h/day). On day 29, the body weights and the behavioral tests, including the novelty suppressed feeding test, the open field test, and the elevated plus maze test, were measured. On day 30, all the rats were sacrificed, and three indices of the JNK signaling pathway were tested by Western blot. Results: The body weight and behavioral tests of all groups indicated that 21 days of CIS induced depression-like behaviors. After 21 days of treatment with fluoxetine and XYS, changes were seen in body weight, behaviors, and JNK, phosphorylated JNK (P-JNK), and phosphorylated c-Jun (P-c-Jun) levels in the hippocampus. Conclusions: XYS ameliorated the depression-like behaviors, potentially through affecting the JNK signaling pathway in the hippocampus.
Basal Cell Carcinoma among Cutaneous Tumours in “Caricature,” Painted by Bartolomeo Passerotti (1529–1592)
Authors: Wincewicz Andrzej , Woltanowski  Piotr 
Published: September 2019

A fine and fair depiction of basal cell carcinoma is documented with great fidelity in “Caricature” by Bartolomeo Passerotti (1529–1592). The cancer is pearly white and contains an elevated centre with a sharp and somewhat depressed outline due to ulceration of the lesion. The painting is of essential didactic worth for practicing medical doctors. In addition, the masterpiece contains images of the brown elevated lesions that could turn out to be verrucous melanocytic nevi or pigmented seborrheic keratoses, but it cannot be excluded that these nodules are also basal cell carcinomas covered by a brownish crust. It is standard that microscopic verification is required for all these tumours. However, a pearly white irregular tumour is the most characteristic macroscopic presentation of basal cell carcinoma.
Health-Related Quality of Life, Satisfaction with Care, and Cosmetic Results in Relation to Treatment among Patients with Keratinocyte Cancer in the Head and Neck Area: Results from the PROFILES Registry
Authors: Arts Lindy Paulina Johanna , Waalboer-Spuij Rick , de Roos Kees-Peter , Thissen Monique R.T.M. , Scheijmans Luc J. , Aarts Mieke J. , Oerlemans Simone , Lybeert Marnix L.M. , Louwman Marieke W.J.
Published: September 2019

Background: Little is known about the impact of keratinocyte cancer (KC) and its treatment on health-related quality of life (HRQoL). Objectives: The objectives of the present study were (1) to evaluate HRQoL among patients with KC in a population-based setting and compare this with an age- end sex-matched normative population and (2) to compare HRQoL, satisfaction with care, and cosmetic results among patients who underwent conventional excision, Mohs’ micrographic surgery, or radiotherapy. Method: A random sample of 347 patients diagnosed with cutaneous basal cell or squamous cell carcinoma in the head and neck area between January 1, 2010, and December 31, 2014, were selected from the Netherlands Cancer Registry (NCR) and were invited to complete a questionnaire on HRQoL, satisfaction with care, and cosmetic results. Data were collected within Patient-Reported Outcomes Following Initial Treatment and Long-term Evaluation of Survivorship (PROFILES). Outcomes were compared to an age- and sex-matched normative population. Results: Two hundred fifteen patients with KC returned a completed questionnaire (62% response). Patients with KC reported better global quality of life (79.6 vs. 73.3, p < 0.01) and less pain (p < 0.01) compared to the normative population. No statistically significant differences in HRQoL, satisfaction with care, and cosmetic results were found between patients with KC who underwent conventional excision, Mohs’ micrographic surgery, or radiotherapy. Conclusions: The impact of KC and its treatment seems relatively low and more positive than negative as patients reported better HRQoL compared to an age- and sex-matched normative population, probably due to adaptation. No statistically significant differences between treatment types were found concerning HRQoL, patient satisfaction, and cosmetic results. This information could be used by healthcare professionals involved in KC care to improve patients’ knowledge about different aspects of the disease as patient’s preference is an important factor for treatment choice.
Synergetic Effect of EP1 Receptor Antagonist and (-)-Epigallocatechin-3-gallate in Hepatocellular Carcinoma
Authors: Yang Hui , Wang Menglin , Sun Haolu , Zhu Siya , Jin Juan
Published: September 2019

Epigallocatechin-3-gallate (EGCG), the principal catechin of green tea, modulates different molecular mechanisms underlying hepatocellular carcinoma (HCC). Accumulating studies showed that the activation of prostaglandin (PG) receptor EP1 promotes cell migration and invasion in different cancers, which could be inverted by blocking the EP1 receptor. This study investigated the synergetic effects of EP1-selective antagonist ONO-8711 and EGCG treatment on HCC to better understand the potential strategy to treat HCC. We found that EGCG significantly inhibited PGE2 and EP1-selective agonist induced migration of HCC cells and increased the ratio of Bax/Bcl-2 even in the presence of ONO-DI-004 or PGE2. ONO-8711 significantly inhibited PGE2-induced HCC proliferation while increased the inhibitory effect of EGCG on HCC cell viability and migration ability compared with EGCG alone. These findings suggest that a combination of ONO-8711 and EGCG is a potential treatment for HCC therapy.
Collateral Scores and Outcomes after Endovascular Treatment for Basilar Artery Occlusion
Authors: Antunes Dias Francisco , Castro-Afonso Luis Henrique , Zanon Zotin Maria Clara , Alessio-Alves Frederico Fernandes , Martins Filho Rui Kleber do Vale , Camilo Millene Rodrigues , Nakiri Guilherme Seizem , Abud Daniel Giansante , Pontes-Neto Octavio Marques
Published: September 2019

Background: Basilar artery occlusion (BAO) is a rare stroke subtype with high mortality rates. Best BAO reperfusion strategy is still controversial. Objective: We aim to describe outcomes of BAO patients submitted to mechanical thrombectomy (MT) in a comprehensive stroke center in Brazil and analyze which previous published computed tomography angiography (CTA) collateral score better predict functional outcomes. Methods: Retrospective analysis of consecutive BAO patients. CTA was used to evaluate the posterior circulation collateral score (PC-CS), the basilar artery on CTA score, and for the presence of posterior communicating arteries. A favorable outcome was defined as modified Rankin Score ≤3 at 90-days. After univariate analyses, multivariate logistic regression was used to identify if any collateral score independently predicts favorable outcomes. Results: Between January 2011 and April 2017, 27 (85% male) BAO patients with median NIHSS 26 (IQR 15–32) were identified. Twenty-five (93%) patients were treated with MT devices, and only 2 (7%) patients were treated with angioplasty and stenting. Successful recanalization rate was 85%, and only 1 (3.7%) patient had symptomatic hemorrhagic transformation. Favorable outcomes were reached in 10 (37%) patients. In univariate analysis, female sex, NIHSS, Glasgow coma scale, mild-to-moderate symptoms on admission, onset-to-groin time, and PC-CS predicted favorable outcomes. In multivariate analysis, PC-CS (OR 1.69; 95% CI 1.10–2.60; p = 0.016) and NIHSS (OR 0.84; 95% CI 0.77–0.93; p = 0.001) remained the only independent predictors of favorable outcomes. The PC-CS AUC was 0.80 (95% CI 0.62–0.98; p = 0.012). Conclusions: MT is a promising strategy for BAO treatment. Among collateral scores, PC-CS was the only independent predictor of favorable outcomes in the present study.
Morphine Promotes the Angiogenesis of Postoperative Recurrent Tumors and Metastasis of Dormant Breast Cancer Cells
Authors: Cheng Shi , Guo Mingyan , Liu Zhongqi , Fu Yanni , Wu Haixuan , Wang Chengli , Cao Minghui
Published: September 2019

Background: Surgery plays a significant role in the comprehensive treatment of breast cancer, and opioids are often the first-choice analgesics in the perioperative period. However, recent studies showed that opioids may enhance the angiogenesis of breast cancer and the recurrence and metastasis of tumor cells. Objectives: We aim to investigate the influence of opioids on recurrence and metastasis of breast cancer in nude mice. Methods: Forty female nude mice with breast tumor were randomly divided into 4 groups (n = 10). They were treated with (i) normal saline (10 mL/kg), (ii) morphine (10 mg/kg), (iii) morphine plus naloxone (10 + 4 mg/kg), and (iv) naloxone (4 mg/kg) for 2 weeks. Four groups of MDA-MB-231 cells were administered (i) Dulbecco’s Modified Eagle’s Medium, (ii) morphine (10 μmol/mL), (iii) morphine plus naloxone (10 + 10 μmol/mL), and (iv) naloxone (10 μmol/mL). The influence of morphine in each treated group was evaluated by immunocytochemistry and Western blotting. Results: Mice in the morphine group had higher rates of Ki67-positive cells, lower rates of apoptotic index, and a significant increase in the microvessels density of the tumor as evidenced by CD31 staining (p < 0.05). Furthermore, the MDA-MB-231 cells in the morphine group showed an increase in p-Akt, c-Myc, and thrombosponin-1 expression. Conclusion: In the current study, we found that morphine promotes the angiogenesis of the recurrent postoperative tumors of nude mice with breast cancer and the proliferation of tumor cells and such promotion may be related to the PI3K-c-Myc signaling pathway.
Low DHEAS Concentration in a Girl Presenting with Short Stature and Premature Pubarche: A Novel PAPSS2 Gene Mutation
Authors: Eltan Mehmet , Yavas Abali Zehra , Arslan Ates Esra , Kirkgoz Tarik , Kaygusuz Sare Betul , Türkyılmaz Ayberk , Bereket Abdullah , Turan Serap , Guran Tulay
Published: September 2019

Objective: Dehydroepiandrosterone (DHEA) sulfotransferase (SULT2A1) converts DHEA to DHEA sulfate (DHEAS) which prevents bioactive androgen excess. This enzymatic reaction requires PAPS (3′-phospho-adenosine-5′-phosphosulfate) biosynthesis mediated by PAPS synthase 2 (PAPSS2). Here, we report a patient presenting with short stature and premature pubarche due to a novel homozygous mutation in the PAPPS2 gene. Case Report: A 7.5-year-old girl was referred for short stature. She was born at term with a birth weight of 2,850 g and her parents were first cousins. At presentation, her height was 113.0 cm (–2.1 SDS) and weight was 28.3 kg (+0.9 SDS), her arm span was 115.0 cm, and upper to lower segment ratio was 1.2. Her pubic hair and breast development were at Tanner stage III and I, respectively. Radiographs revealed mild lumbar scoliosis and platyspondyly and irregular vertebral endplates in the thoracolumbar region. Her serum DHEAS was low (39 ng/mL). The plasma DHEAS/DHEA ratio was significantly decreased on 2 separate measurements (4.4 and 19.8; normal range 31–345). PAPSS2 gene analysis identified a homozygous p.L440Wfs*12 (c.1318_1330 delCTACTACACCCTC) variant. This is the first report of a large deletion leading to a frameshift effect in the PAPSS2 gene and a truncated PAPSS2 protein. Conclusion: We describe the third case with PAPSS2 deficiency presenting with premature pubarche, and the first large deletion in the PAPSS2 gene. Although PAPSS2 deficiency is a rare cause of premature pubarche and adrenal androgen excess, it should be considered, especially in cases with disproportionate short stature and clinical hyperandrogenism associated with low plasma DHEAS concentration.
Vinflunine in Metastatic Urothelial Carcinoma of the Bladder in Progression after a Platinum-Containing Regimen
Authors: De Luca Rossella , Profita Giuseppe , Vella Marco , Cicero Giuseppe
Published: September 2019

Background: Vinflunine is a microtubule inhibitor of the vinca alkaloid class approved for the treatment of urothelial bladder carcinoma after a platinum-containing regimen. Methods: To evaluate the effectiveness of vinflunine, we enrolled 80 subjects with a histologically confirmed diagnosis of metastatic urothelial bladder carcinoma that had previously undergone chemotherapy with a platinum-containing regimen and had measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST). The patients (n = 80) received vinflunine (Javlor®) every 3 weeks at 320 mg/m2 via 20-min intravenous infusion. The endpoints were progression-free survival (PFS), objective response rate, overall survival (OS), and tolerability. The cumulative survival of the patients was analyzed using the Kaplan-Meier method. Results: In this retrospective study, vinflunine treatment was well tolerated and resulted in a good level of disease control (complete response + partial response + stable disease >50%), with a manageable toxicity profile. The median PFS and OS were 3.2 and 6.8 months, respectively. A significant correlation between pain and PFS was also noted. The major hematologic adverse event was neutropenia, observed in 47% of the patients. The most common nonhematologic adverse events were constipation in 48% of the patients and fatigue in 26%. Discussion: In this real-word non-randomized clinical trial setting, the data showed that vinflunine is an efficacious and safe therapeutic option for second-line treatment of patients with metastatic urothelial carcinoma of the bladder after a platinum-containing regimen.
Impact, Screening, and Therapy of HLA Antibodies in Patients before and after Lung Transplantation
Authors: Dick Andrea , Humpe Andreas , Kauke Teresa ,   on behalf of the Munich Lung Transplant Group (MLTG)
Published: September 2019

Since almost 30 years, lung transplantation is a considerable therapeutic option in patients suffering from end-stage lung disease. Up to now, the impact of donor-specific antibodies directed against donor HLA (human leukocyte antigen) before and after transplantation is still a matter of debate. As histocompatibility testing is not required for each patient according to the current national guidelines and Eurotransplant recommendations for lung transplantation, each transplantation unit has to establish a local protocol together with the tissue typing laboratory how to implement an immunological risk assessment strategy for their patients while enabling access to transplantation. Desensitization regimens might help in case of highly alloimmunized patients waiting for urgent transplantation.
Etomidate Modulates the Tactile Stimulation-Evoked Field Potential Responses in Cerebellar Granule Cell Layer in vivo in Mice
Authors: Pan Wen , Cui Li-Na , Chu Chun-Ping , Jin Wen-Zhe , Qiu De-Lai
Published: September 2019

Etomidate (ET) produces sedation by binding on the γ-aminobutyric acid type A (GABAA) receptors. We previously found that ET inhibited cerebellar Purkinje cells activity via both GABAA and glycine receptors in vivo in mice, suggesting that ET modulated sensory information synaptic transmission in cerebellar cortex. In this study, we investigated the effect of ET on the sensory stimulation-evoked responses in the cerebellar granule layer (GL) in urethane-anesthetized mice, using electrophysiological and pharmacological methods. Our results showed that cerebellar surface perfusion of ET (100 μmol/L) significantly decreased amplitude and area under the curve (AUC) of the sensory stimulation-evoked excitatory component (N1) in the cerebellar GL. Application of GABAA receptor antagonist, SR95531 (20 μmol/L) significantly attenuated, but not abolished the ET-induced decrease in amplitude and AUC of facial stimulation-evoked responses. However, application of a mixture of SR95531 (20 μmol/L) and cannabinoid 1 receptor (CB1) antagonist, AM-251 (5 μmol/L), completely blocked the ET-induced decrease in amplitude and AUC of facial stimulation-evoked responses. Furthermore, application of the CB1 receptor agonist, WIN55212-2, induced a decrease in amplitude and AUC of N1 in the absence of GABAA receptors activity, as well occluded the ET-induced depression of N1. Moreover, the ET-induced changes in amplitude and AUC of N1 in absence of GABAA receptors activity were abolished by a specific protein kinase A (PKA) inhibitor, KT5720. These results indicate that ET facilitates CB1 receptors in the absence of GABAA receptors activity, resulting in a depression of the sensory stimulation-evoked synaptic transmission via PKA signaling pathway in mouse cerebellar GL.