bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testicular biopsies in men with testicular microlithiasis and additional risk factors for cancer: A case series
Authors: Frandsen Rasmus Hassing , Durukan Emil , von Rohden Elena , Jensen Christian Fuglesang S. , Thamsborg Andreas Key Milan , Azawi Nessn , Fode Mikkel 
Published: February 2024

AbstractBackgroundTesticular microlithiasis is the presence of small calcifications in the testicular parenchyma. The association between testicular microlithiasis and germ cell neoplasia in situ, a precursor to testicular cancer, is still unclear.ObjectivesTo determine the incidence of germ cell neoplasia in situ in men with testicular microlithiasis and evaluate the indication for testicular biopsy according to risk factors in the form of male infertility/reduced semen quality, testicular atrophy, and history of cryptorchidism.Materials and methodsThis retrospective case series included all patients diagnosed with testicular microlithiasis who underwent testicular biopsies at three hospitals in Denmark between 2007 and 2021. The medical records of 167 patients were reviewed, and data on patient demographics, testicular microlithiasis characteristics, risk factors, histological findings, and treatments were collected. The main outcome measure was the incidence of germ cell neoplasia in situ in relation to each risk factor. The data were analyzed using descriptive statistics. Logistic regression was used to examine the odds ratio of germ cell neoplasia in situ in patients with testicular microlithiasis and testicular atrophy.ResultsGerm cell neoplasia in situ was found in 13 out of 167 patients (7.8% [95% confidence interval: 4.3, 13.2]). Eleven of these had testicular atrophy resulting in a significantly higher incidence in this group than other risk factors (odds ratio 9.36 [95% confidence interval: 2.41, 61.88]; p = 0.004).DiscussionThe study comprises the largest cohort to date of men who have undergone testicular biopsies because of testicular microlithiasis and additional risk factors. Limitations include its retrospective design, and relatively low absolute numbers of patients with germ cell neoplasia in situ on biopsies.ConclusionThis study found that men with testicular microlithiasis and testicular atrophy are at an increased risk of germ cell neoplasia in situ. Additionally, our results indicate that biopsies should be considered in men with a combination of subfertility and bilateral testicular microlithiasis. Our findings do not support testicular biopsies for men with testicular microlithiasis and other risk factors.
Eculizumab dose tapering should take into account the nonlinearity of its pharmacokinetics
Authors: Le Tilly Olivier , Gatault Philippe , Semlali Saida , Sberro‐Soussan Rebecca , Passot Christophe , Bertrand Dominique , Desvignes Céline , Caillard Sophie , Paintaud Gilles , Halimi Jean‐Michel , Ternant David 
Published: February 2024

AimsEculizumab is a monoclonal antibody targeting complement protein C5 used in renal diseases. As recommended dosing regimen leads to unnecessarily high concentrations in some patients, tailored dosing therapeutic drug monitoring was proposed to reduce treatment cost. The objectives of the present work were (i) to investigate the target‐mediated elimination of eculizumab and (ii) whether a pharmacokinetic model integrating a nonlinear elimination allows a better prediction of eculizumab concentrations than a linear model.MethodsWe analysed 377 eculizumab serum concentrations from 44 patients treated for atypical haemolytic uraemic syndrome and C3 glomerulopathy with a population pharmacokinetic approach. Critical concentrations (below which a non‐log‐linear decline of concentration over time is evidenced) were computed to estimate the relevance of the target‐mediated elimination. Simulations of dosing regimens were then performed to predict probabilities of target attainment (i.e. trough >100 mg/L).ResultsPharmacokinetics of eculizumab was nonlinear and followed a mixture of first‐order (CL = 1.318 mL/day/kg) and Michaelis–Menten elimination (Vmax = 26.07 mg/day, Km = 24.06 mg/L). Volume of distribution (72.39 mL/kg) and clearance were weight‐dependent. Critical concentrations (Vmax/CL) ranged from 144.7 to 759.7 mg/L and were inversely related to body weight (P = .013). Nonlinearity was thus noticeable at therapeutic concentrations. Simulations predicted that 1200 mg of eculizumab every 21 days would allow 85% and 76% of patients to maintain a therapeutic exposure, for 50 or 90 kg body weight, respectively.ConclusionsOur study investigates the nonlinear elimination of eculizumab and discusses the importance of accounting for eculizumab target‐mediated elimination in therapeutic drug monitoring.
The prevalence of impostor phenomenon and its association with burnout amongst urologists
Authors: Jefferson Francis A. , Fadel Anthony , Findlay Bridget L. , Robinson Maraika O. , Seyer Amanda K. , Koo Kevin , Granberg Candace F. , Boorjian Stephen A. , Anderson Katherine T. 
Published: February 2024

ObjectivesTo characterise the prevalence of impostor phenomenon (IP; tendency for high‐achieving individuals to perceive themselves as fraudulent in their successes) amongst attending staff in urology, to identify variables that predict more severe impostorism, and to study the association of IP with burnout.Subjects and MethodsA survey composed of the Clance Impostor Phenomenon Scale (CIPS), demographic information, practice details, and burnout levels was e‐mailed to urologists via urological subspecialty societies. Survey results were analysed to identify associations between IP severity, survey respondent characteristics, and symptoms of professional burnout. This study was conducted in the United States of America.ResultsA total of 614 survey responses were received (response rate 11.0%). In all, 40% (n = 213) of responders reported CIPS scores qualifying as either ‘frequent’ or ‘intense’ impostorism (i.e., scores of 61–100). On multivariable analysis, female gender, fewer years in practice (i.e., 0–2 years), and lower academic rank were all independently associated with higher CIPS scores (adjusted P < 0.05). Regarding burnout, 46% of responders reported burnout symptoms. On multivariable analysis, increase in CIPS score was independently associated with higher odds of burnout (odds ratio 1.06, 95% confidence interval 1.04–1.07; P < 0.001).ConclusionImpostor phenomenon is prevalent in the urological community and is experienced more severely in younger and female urologists. IP is also independently associated with burnout. Increased female representation may improve IP amongst our female colleagues. More work is needed to determine strategies that are effective in mitigating feelings of IP and professional burnout amongst urologists, particularly those earlier in their careers.
Genetic and phenotypic landscape of pediatric‐onset epilepsy in 142 Indian families: Counseling and therapeutic implications
Authors: Majethia Purvi , Kaur Namanpreet , Mascarenhas Selinda , Rao Lakshmi Priya , Pande Shruti , Narayanan Dhanya Lakshmi , Bhat Vivekananda , Nayak Shalini S. , Nair Karthik Vijay , Prasannakumar Adarsh Pooradan , Chaurasia Ankur , Hunakunti Bhagesh , Jadhav Nalesh , Farooqui Sheeba , Yeole Mayuri , Kothiwale Vishaka , Naik Rohit , Bhat Veena , Aroor Shrikiran , Lewis Leslie , Purkayastha Jayashree , Bhat Y. Ramesh , Praveen B. K. , Yatheesha B. L. , Patil Siddaramappa J. , Nampoothiri Sheela , Kamath Nutan , Siddiqui Shahyan , Bielas Stephanie , Girisha Katta Mohan , Sharma Suvasini , Shukla Anju 
Published: February 2024

AbstractThe application of genomic technologies has led to unraveling of the complex genetic landscape of disorders of epilepsy, gaining insights into their underlying disease mechanisms, aiding precision medicine, and providing informed genetic counseling. We herein present the phenotypic and genotypic insights from 142 Indian families with epilepsy with or without comorbidities. Based on the electroclinical findings, epilepsy syndrome diagnosis could be made in 44% (63/142) of the families adopting the latest proposal for the classification by the ILAE task force (2022). Of these, 95% (60/63) of the families exhibited syndromes with developmental epileptic encephalopathy or progressive neurological deterioration. A definitive molecular diagnosis was achieved in 74 of 142 (52%) families. Infantile‐onset epilepsy was noted in 81% of these families (61/74). Fifty‐five monogenic, four chromosomal, and one imprinting disorder were identified in 74 families. The genetic variants included 65 (96%) single‐nucleotide variants/small insertion‐deletions, 1 (2%) copy‐number variant, and 1 (2%) triplet‐repeat expansion in 53 epilepsy‐associated genes causing monogenic disorders. Of these, 35 (52%) variants were novel. Therapeutic implications were noted in 51% of families (38/74) with definitive diagnosis. Forty‐one out of 66 families with monogenic disorders exhibited autosomal recessive and inherited autosomal dominant disorders with high risk of recurrence.
Multi‐gene panel sequencing in highly consanguineous families and patients with congenital forms of skeletal dysplasias
Authors: Kakar Naseebullah , Rehman Fazal ur , Kaur Ramandeep , Bhavani Gandham SriLakshmi , Goyal Manisha , Shah Hitesh , Kaur Karandeep , Sodhi Kushaljit Singh , Kubisch Christian , Borck Guntram , Panigrahi Inusha , Girisha Katta Mohan , Kornak Uwe , Spielmann Malte 
Published: February 2024

AbstractSkeletal dysplasias (SKDs) are a heterogeneous group of more than 750 genetic disorders characterized by abnormal development, growth, and maintenance of bones or cartilage in the human skeleton. SKDs are often caused by variants in early patterning genes and in many cases part of multiple malformation syndromes and occur in combination with non‐skeletal phenotypes. The aim of this study was to investigate the underlying genetic cause of congenital SKDs in highly consanguineous Pakistani families, as well as in sporadic and familial SKD cases from India using multigene panel sequencing analysis. Therefore, we performed panel sequencing of 386 bone‐related genes in 7 highly consanguineous families from Pakistan and 27 cases from India affected with SKDs. In the highly consanguineous families, we were able to identify the underlying genetic cause in five out of seven families, resulting in a diagnostic yield of 71%. Whereas, in the sporadic and familial SKD cases, we identified 12 causative variants, corresponding to a diagnostic yield of 44%. The genetic heterogeneity in our cohorts was very high and we were able to detect various types of variants, including missense, nonsense, and frameshift variants, across multiple genes known to cause different types of SKDs. In conclusion, panel sequencing proved to be a highly effective way to decipher the genetic basis of SKDs in highly consanguineous families as well as sporadic and or familial cases from South Asia. Furthermore, our findings expand the allelic spectrum of skeletal dysplasias.
Patterns of recovery in extant and extirpated seabirds after the world's largest multipredator eradication
Authors: Bird Jeremy P. , Fuller Richard A. , Shaw Justine D. 
Published: February 2024

AbstractEradicating invasive predators from islands can result in substantial recovery of seabirds, but the mechanisms that drive population changes remain poorly understood. Meta‐analyses have recently revealed that immigration is surprisingly important to the recovery of philopatric seabirds, but it is not known whether dispersal and philopatry interact predictably to determine rates of population growth and changes of distribution. We used whole‐island surveys and long‐term monitoring plots to study the abundance, distribution, and trends of 4 burrowing seabird species on Macquarie Island, Australia, to examine the legacy impacts of invasive species and ongoing responses to the world's largest eradication of multiple species of vertebrates. Wekas (Gallirallus australis) were eradicated in 1988; cats (Felis catus) in 2001; and rabbits (Oryctolagus cuniculus), black rats (Rattus rattus), and mice (Mus mus) in 2011–2014. We compared surveys from 1976–1979 and 2017–2018 and monitoring from the 1990s and 2000s onward. Antarctic prions (Pachyptila desolata) and white‐headed petrels (Pterodroma lessonii) increased ∼1% per year. Blue petrels (Halobaena caerulea) and gray petrels (Procellaria cinerea) recolonized following extirpation from the main island in the 1900s but remained spatially and numerically rare in 2018. However, they increased rapidly at 14% and 10% per year, respectively, since cat eradication in 2001. Blue and gray petrel recolonization occurred on steep, dry, west‐facing slopes close to ridgelines at low elevation (i.e., high‐quality petrel habitat). They overlapped <5% with the distribution of Antarctic prion and white‐headed petrels which occurred in suboptimal shallow, wet, east‐facing slopes at high elevation. We inferred that the speed of population growth of recolonizing species was related to their numerically smaller starting size compared with the established species and was driven by immigration and selection of ideal habitat.
Tixagevimab/cilgavimab for the prevention of COVID‐19 in solid organ transplant recipients
Authors: Eribes Emily , Votruba Cassandra , Tinkham Tyler , Huang Angela , Ilges Dan , Kunze Katie , Hudson Madeline 
Published: February 2024

AbstractTixagevimab/cilgavimab (tix/cil) received emergency use authorization in December 2021 for pre‐exposure prophylaxis against COVID‐19 in moderately to severely immunocompromised patients. Our study aimed to describe the incidence of COVID‐19 infection and assess the immunologic risks associated with tix/cil in kidney, pancreas, liver, and heart transplant recipients. Retrospective chart review was completed to provide descriptive analysis. Outcomes data included COVID‐19 infection, severity of COVID‐19 infection, graft function, and rejection. Safety outcomes included cardiovascular (CV) and hypersensitivity events post tix/cil administration. A total of 410 transplant patients were included in the analysis: 20 heart, 92 liver, 243 kidney, 25 simultaneous pancreas/kidney, 23 simultaneous liver/kidney, and seven simultaneous heart/kidney. Twenty‐seven (6.5%) patients tested positive for COVID‐19 via PCR or antigen test post tix/cil. No apparent difference was observed in patients testing positive for COVID‐19 by type of organ transplant (p = .122). Twenty‐five of the 27 patients testing positive for COVID‐19 reported symptomatic infection, only nine of whom were hospitalized. No patients were mechanically ventilated and no deaths due to COVID‐19 occurred. No significant changes in graft function were observed. Clinically significant rejection was diagnosed and treated in four patients. COVID‐19 breakthrough infection rates remained low in immunocompromised solid organ transplant recipients who received tix/cil. No significant immunologic risks were observed.
De novo hepatitis B infection following liver transplantation with core antibody positive grafts: The role of surface antibody status in guiding long‐term prophylaxis
Authors: Busebee Brad , Myhre Laura , Mara Kristin , Aqel Bashar , Taner Timucin , Watt Kymberly D. 
Published: February 2024

AbstractLiver transplantation (LT) with hepatitis B core antibody (anti‐HBc) positive grafts to hepatitis B surface‐antigen (HBsAg) negative recipients is safe and has likely contributed to improvements in organ access over the years. The incidence of de novo hepatitis B infection (HBV) in these instances is low with appropriate prophylaxis and is affected by recipient immunologic status. There is debate as to whether hepatitis B surface antibody (anti‐HBs) positivity may safely inform prophylaxis discontinuation post‐LT. In this retrospective study of all hepatitis B surface antigen (HBsAg) negative recipients of anti‐HBc positive organs at three large academic centers between January 2014 and December 2019, nine LT recipients discontinued prophylaxis after developing anti‐HBs antibodies 1 year or later post‐LT. Three of the nine patients (33%) developed de novo HBV, defined by positive HBsAg or hepatitis B virus (HBV) DNA, during the study period. The remaining six patients had no evidence of HBV infection after a mean follow‐up of 37 months. The patients without de novo HBV had higher anti‐HBs titers at the time of prophylaxis discontinuation and were less likely to have negative anti‐HBs at the time of transplant or negative anti‐HBc at any time point. These results suggest that quantitative anti‐HBs titer thresholds rather than qualitative anti‐HBs positivity at 1 year or later after LT should be used to identify patients at decreased risk of de novo infection and help guide prophylaxis duration.
Cannabis use is associated with reduced access to kidney transplantation and an increased risk of acute rejection post‐transplant
Authors: Rodríguez‐Ramírez Sonia , Tang Evan , Li Yanhong , Famure Olusegun , Mucsi Istvan , Kim Sang Joseph 
Published: February 2024

AbstractBackgroundThe association between cannabis use and access to waitlisting, transplantation, and post‐transplant outcomes remains uncertain.MethodsPatients referred for kidney transplant (KT) to the University Health Network from January 1, 2003, to June 30, 2020, and followed until December 31, 2020, were included. Predictors of reported cannabis use were examined using a logistic regression model. The association between cannabis use and time to clearance for KT, undergoing KT, and post‐transplant outcomes was evaluated using Cox proportional hazards models.ResultsAmong 3734 patients, the prevalence of reported cannabis use was 11.8%. Cannabis use was associated with a lower likelihood of KT clearance (adjusted hazard ratio [aHR] .82 [95% confidence interval (CI): .72, .94]). Once cleared for KT, cannabis use did not predict the subsequent receipt of KT (aHR .92, [95% CI: .79, 1.08]). Among 2091 KT recipients, cannabis use was associated with a higher likelihood of biopsy‐proven acute rejection (aHR 1.55, [95% CI: 1.06, 2.27]). The relative hazard of death‐censored graft failure was similarly elevated (aHR 1.60 [95% CI: .95, 2.72]). Cannabis use did not predict total graft failure (aHR 1.33 [95% CI: .90, 1.96]), death with graft function (aHR 1.06 [95% CI: .59, 1.89]), or hospital readmission in the first‐year post‐transplant (aHR 1.26 [95% CI: .95, 1.68]).ConclusionsCannabis users have less access to transplantation and an increased risk of acute rejection, possibly leading to more graft loss. Further studies are warranted to understand possible mechanisms for the increased risk of allograft immune injury among cannabis users.
Upper gastrointestinal haemorrhage patients' survival: A causal inference and prediction study
Authors: Deng Fuxing , Cao Yaoyuan , Zhao Shuangping 
Published: February 2024

AbstractBackgroundUpper gastrointestinal (GI) bleeding is a common medical emergency. This study aimed to develop models to predict critically ill patients with upper GI bleeding in‐hospital and 30‐day survival, identify the correlation factor and infer the causality.MethodsA total of 2898 patients with upper GI bleeding were included from the Medical Information Mart for Intensive Care‐IV and eICU‐Collaborative Research Database, respectively. To identify the most critical factors contributing to the prognostic model, we used SHAP (SHapley Additive exPlanations) for machine learning interpretability. We performed causal inference using inverse probability weighting for survival‐associated prognostic factors.ResultsThe optimal model using the light GBM (gradient boosting algorithm) algorithm achieved an AUC of .93 for in‐hospital survival, .81 for 30‐day survival in internal testing and .87 for in‐hospital survival in external testing. Important factors for in‐hospital survival, according to SHAP, were SOFA (Sequential organ failure assessment score), GCS (Glasgow coma scale) motor score and length of stay in ICU (Intensive critical care). In contrast, essential factors for 30‐day survival were SOFA, length of stay in ICU, total bilirubin and GCS verbal score. Our model showed improved performance compared to SOFA alone.ConclusionsOur interpretable machine learning model for predicting in‐hospital and 30‐day mortality in critically ill patients with upper gastrointestinal bleeding showed excellent accuracy and high generalizability. This model can assist clinicians in managing these patients to improve the discrimination of high‐risk patients.
miR‐619‐5p and cardiogenic shock in patients with ST‐segment elevation myocardial infarction
Authors: Escate Rafael , Padró Teresa , Suades Rosa , Sans‐Roselló Jordi , Devaux Yvan , Lakkisto Päivi , Harjola Veli‐Pekka , Sionis Alessandro , Badimon Lina 
Published: February 2024

AbstractBackgroundCardiogenic shock (CS) is a severe myocardial dysfunction secondary to various cardiac conditions including ST‐segment elevation acute myocardial infarction (STEMI) and associated with a high risk of death. Little is known on epigenetic determinants in CS. Here, we investigated plasma miRNAs in relation to CS stratification in STEMI‐patients.MethodsSTEMI‐patients (n = 49), with (CS, n = 25) and without CS (non‐CS, n = 24) fulfilling inclusion criteria were included from HSCSP‐cohort (Derivation‐cohort). CS‐miRNAs were analysed by Affymetrix‐microarray and RT‐PCR. Results were validated in a second cohort of CS‐patients (CardShock: n = 35) with similar inclusion/exclusion criteria as the derivation cohort. In silico analysis were performed to identify potential miRNA target genes.ResultsOf the 5‐miRNA signature obtained from microarray analysis, miR‐619‐5p showed higher levels in CS than in Non‐CS patients (p = .003) and discriminating power for CS by ROC (AUC: .752, p = .003). miR‐619‐5p directly associated with risk scores [GRACE, p = .001; CardShock, p < .001]. Furthermore, miR‐619‐5p showed discrimination power for death in CS. Thus, miRNA levels were significantly higher in patients with mortality outcome both in the Derivation HSCSP‐cohort (p = .02; AUC: .78 ± .095) and the Validation CardShock‐cohort (p = .017; AUC: .737 ± .086) By in silico analysis, miR‐619‐5p target genes and TNF‐alpha were involved in the regulation of inflammation. miR‐619‐5p and TNF‐alpha levels discriminated mortality outcome in CS‐patients during 30‐day follow‐up (Validation‐Cohort: ROC: .812, p = .002; HR: 9.99, p = .003).ConclusionsUp‐regulation of miR‐619‐5p is found in the plasma of STEMI‐patients with CS and mortality outcome. These findings highlight the specificity of epigenetic regulation of inflammation on the disease severity of MI.