bluuebunny/crossref_metadata_2025 huggingface dataset:
Staghorn Calculus with Adenomatoid Tumor: A Case Report
Authors: Tashkandi Emad
Published: October 2023

Testicular adenomatoid tumor is very rare. More understanding of the tumor and treatment is required for better outcomes. A 63-year-old man visited a urologist for staghorn calculus. During follow-up, he had recurrent left flank pain and intermittent hematuria. Computed tomography demonstrated left staghorn calculus, and then further assessment revealed left testicular swelling. Ultrasound showed epididymal mass. Percutaneous nephrolithotomy was deferred and we performed left radical orchiectomy. A pathologic examination revealed testicular adenomatoid tumor. This case highlights the importance of awareness of a very rare benign tumor in a patient with staghorn calculus.
Diagnostic Yield of Shape-Sensing Robotic-Assisted Bronchoscopy for Ground-Glass Nodules and Subsolid Nodules with a Solid Component Less than 6 mm
Authors: Abia-Trujillo David , Chandra Nikitha C. , Koratala Anoop , Yu Lee-Mateus Alejandra , Garza-Salas Ana , Barrios-Ruiz Alanna , Patel Neal M. , Chadha Ryan M. , Hazelett Britney N. , Fernandez-Bussy Sebastian
Published: October 2023

Background: Ground-glass pulmonary nodules (GGNs) are most commonly sampled by percutaneous transthoracic biopsy. Diagnostic yield for ground-glass nodules using robotic-assisted bronchoscopy has been scarcely described, with a reported yield of 70.6%. Objectives: The aim of this study is to assess diagnostic yield for GGNs using shape-sensing robotic-assisted bronchoscopy (ssRAB). Method: A retrospective study of patients who underwent ssRAB for evaluation of GGNs, from September 2021 to April 2023. Primary outcome was diagnostic yield of ssRAB for GGNs, secondary outcomes were sensitivity for malignancy, and complications that required admission or intervention. Results: A total of 23 nodules were biopsied from 22 patients. Median age was 71 years (IQR 66–81), 63.6% were female, and 40.9% had a previous history of cancer. Forty-three percent of nodules were in the right upper lobes, and the median lesion size was 1.8 × 1.21. Twelve were subsolid nodules (SSNs), and 11 were pure GGNs. Overall diagnostic yield was 87%, with a sensitivity for malignancy of 88.9%. Adenocarcinoma was the most common malignancy diagnosed (70%). No procedure-related complications were reported. Conclusion: The use of ssRAB shows a high diagnostic yield for diagnosing GGN and SSN with less than 6 mm solid component with a low risk for complications.
Utility of RNA Expression to Determine the Tissue of Origin of Malignancies with an Inconclusive Histopathology
Authors: Mahadevia Himil , Kujtan Lara , Roth Marc , Sharma Parth , Buckley Jennifer R. , Ewing Eric , Bansal Dhruv
Published: October 2023

We present 2 cases of cancer of unknown origin in which RNA-based cancer classification testing provided vital insight and directed treatment management. The tissue of origin could not be determined in both of these patients utilizing morphology and immunohistochemical analysis of the tissue samples. Next-generation sequencing and tumor-of-origin testing using an RNA-based molecular cancer classifier were performed to elucidate the possible tissue of origin. A 61-year-old male with a history of localized basal cell carcinoma presented with a 4.4-cm axillary lymph node in addition to upper extremity edema and supraclavicular lymphadenopathy. RNA-based tumor origin testing revealed skin basal or squamous cell carcinoma as the likely tissue of origin, with a probability of 97%. He received vismodegib, a hedgehog inhibitor, after progression on cemiplimab and experienced a partial response by RECIST criteria, which is currently ongoing for over a year. A 74-year-old female patient with a remote history of ovarian cancer for which she underwent resection and adjuvant chemotherapy presented 15 years later with abdominal pain. The diagnostic workup revealed a 2-cm pancreatic mass and enlarged peritoneal lymph nodes. RNA sequencing revealed a 99% likelihood of the tissue of origin being serous ovarian carcinoma. Subsequently, she underwent surgery and adjuvant chemotherapy and is currently in remission with letrozole maintenance. Genomic data already plays a crucial role in therapeutic decision-making for individuals with cancer. These cases highlight the complementary role of genomic data in the diagnostic workup of cancer, leading to favorable patient outcomes.
A Knowledge Map of the Relationship between Diabetes and Stroke: A Bibliometric Analysis Study
Authors: Liang Yitong , Fan Tingting , Bai Min , Tang Meng , Cui Na , Chen Yue , Chen Jinyi , Wang Jingwen , Guan Yue
Published: October 2023

Introduction: The correlation between diabetes and stroke has been studied extensively in epidemiological research. Here, we used bibliometric software to visualize and analyze the literature related to diabetic stroke to provide an overview of the current state of research, hotspots, and future trends in the field. Methods: Based on the Web of Science Core Collection (WoSCC) database, we collected studies related to diabetic stroke from 2007 to December 2022. We used CiteSpace (version 6.1.R5), VOSviewer, and Scimago Graphica to create knowledge maps and conduct visual analyses on authors, countries, institutions, cited references, and keywords, and Origin for statistical analysis. Results: We included a total of 5,171 papers on diabetic stroke from the WoSCC database. Overall, there was a steady increase in the number of publications, with a high number of emerging scientists. The USA was the most productive and influential country, which dominated national collaborations. The most common subject category was “neurology.” In total, 12 major clusters were generated from the cited references. Keyword analysis showed that keywords related to poststroke injury and treatment are those with the highest burst intensity and latest burst time. Conclusions: Individual disease treatment remains a hot topic, and how to balance acute stroke treatment and glycemic control is currently a difficult clinical problem. At the same time, the mechanism of their interaction and the prevention and treatment of related causative factors remain a hot topic of current and future research.
Future Directions in Optimizing Anesthesia to Reduce Perioperative Acute Kidney Injury
Authors: Zeng Bin , Liu Yinuo , Xu Jiawei , Niu Liyan , Wu Yuting , Zhang Deju , Tang Xiaoyi , Zhu Zicheng , Chen Yixuan , Hu Leilei , Yu Shuchun , Yu Peng , Zhang Jing , Wang Wenting
Published: October 2023

Background: Perioperative acute kidney injury (AKI) is common in surgical patients and is associated with high morbidity and mortality. There are currently few options for AKI prevention and treatment. Due to its complex pathophysiology, there is no efficient medication therapy to stop the onset of the injury or repair the damage already done. Certain anesthetics, however, have been demonstrated to affect the risk of perioperative AKI in some studies. The impact of anesthetics on renal function is particularly important as it is closely related to the prognosis of patients. Some anesthetics can induce anti-inflammatory, anti-necrotic, and anti-apoptotic effects. Propofol, sevoflurane, and dexmedetomidine are a few examples of anesthetics that have protective association with AKI in the perioperative period. Summary: In this study, we reviewed the clinical characteristics, risk factors, and pathogenesis of AKI. Subsequently, the protective effects of various anesthetic agents against perioperative AKI and the latest research are introduced. Key Message: This work demonstrates that a thorough understanding of the reciprocal effects of anesthetic drugs and AKI is crucial for safe perioperative care and prognosis of patients. However, more complete mechanisms and pathophysiological processes still need to be further studied.
Unmet Needs of Pediatricians in Transgender-Specific Care: Results of a Short-Term Training
Authors: Santamaria Fabiana , Scandurra Cristiano , Mezzalira Selene , Bochicchio Vincenzo , Salerno Mariacarolina , Di Mase Raffaella , Capalbo Donatella
Published: October 2023

Introduction: The aim of this study was to evaluate (i) the knowledge about different dimensions of sexual identity in a group of family pediatricians and (ii) the efficacy of a training program to improve knowledge and reduce genderism and heteronormativity. Methods: A pre-post-follow-up study was conducted with 96 Italian pediatricians (48 men and 48 women) who participated in a 6-h training program and divided into 2 sections. The first section was theoretical and focused on the conceptual foundations of sexual identity, the depathologizing approach to gender diversity, and the role of pediatricians as the first contacts of children’s or adolescents’ family. The second part was experiential and included the presentation of a clinical case and the activation of a group reflection on the management of gender-diverse youth. Knowledge about sexual identity, genderism, and heteronormativity was measured. Results: Pre-training questionnaires revealed that the mean score of knowledge about sexual identity was 7.13 ± 3.21. One-way within-subject ANOVA revealed significant effects from pre- to post-training and from pre- to follow-up assessment but not from post-training to follow-up assessment, suggesting that significant changes in the knowledge about sexual identity (F = 39.75, p < 0.001), in personal biases related to genderism (F = 7.46, p < 0.01), and in heteronormative attitudes (F = 44.99, p < 0.001) and behaviors (F = 79.29, p < 0.001) were achieved through the training and maintained at follow-up. Conclusion: These findings indicate the importance of training pediatricians to work with gender-diverse youth and provide them with the best clinical interventions.
The Additive Effect of Left Ventricular Filling Pressure and Renal Function on Long-Term Prognosis of High-Risk Patients Undergoing Coronary Angiography
Authors: Teodorovich Nicholay , Fabrikant Yakov , Gandelman Gera , Swissa Moshe , Jonas Michael , George Jacob , Shimoni Sara
Published: October 2023

Introduction: Impaired relaxation is the earliest manifestation of ischemic cascade. Risk factors and renal function abnormalities are associated with coronary disease and diastolic dysfunction as well. We aimed to study the association of noninvasive assessment of left ventricular filling pressures and renal function with mortality in high-risk patients undergoing coronary angiography. Patients and Methods: An observational prospective study of 564 consecutive patients undergoing coronary angiography was conducted. The median follow-up was 2,293 days. Patients were categorized into 2 groups according to presence of significant diastolic dysfunction: group 1, 382 patients, with normal and group 2, 182 patients, with elevated filling pressure. Renal insufficiency was determined as calculated glomerular filtration rate <60 mL/min. Patients demographic, clinical, echocardiography, laboratory, and angiographic data were prospectively collected. Results: Fifty-three percent of patients underwent angiography due to acute coronary syndrome (ACS), 85.5% had coronary artery disease, 53.4% had reduced (<50%) left ventricular ejection fraction (LVEF), and 47.4% had abnormal renal function. The mortality during the follow-up period was 30.0%. Patients with elevated filling pressure had significantly higher mortality (50.5% vs. 20.2%, p < 0.0001). Impaired renal failure as well, was associated with higher mortality (48% vs. 15%, p < 0.001). The association remained significant in subgroups of patients with and without ACS and reduced and preserved LVEF. In Cox regression model which combined elevated filling pressure, renal insufficiency, age, diabetes mellitus, hypertension, presence of atrial fibrillation, LVEF, and anemia, elevated filling pressure and renal function impairment were independently associated with higher mortality (HR: 3.717, CI: 1.623–8.475, p < 0.0001 and HR: 0.972, CI: 0.958–0.985, p = 0.0001, respectively). There was an incremental prognostic value of elevated filling pressures and renal function impairment on mortality. Conclusions: Advanced diastolic dysfunction and impaired renal function are signals toward worse outcomes and are associated with mortality in high-risk patients undergoing coronary angiography.
Systematic Review and Meta-Analysis: Association between Preoperative Ustekinumab and Surgical Complications in Crohn’s Disease Patients
Authors: Li Lingna , Jiang Ke , Lou Dandi , Zhang Mengting , Shi Yetan , Shen Jingyi , Fu Xiaojun
Published: October 2023

Introduction: The impact of ustekinumab (UST) therapy on surgical complications in patients with Crohn’s disease (CD) remains controversial. The aim of this meta-analysis is to explore the link between these two. Methods: Databases (PubMed, Web of Science, Cochrane, and Springer Link) were searched until April 2022. Studies of CD patients who received UST and no UST prior to surgery (including no biological therapy, anti-tumor necrosis factor-α [anti-TNF-α] agent, and vedolizumab [VDZ]) were included. Primary outcomes included overall complications, infectious complications, and noninfectious complications. Results: Nine studies totaling 3,225 CD patients were enrolled; 332 patients received UST treatment. There was no evidence of difference in the overall complications (odds ratio [OR] = 0.84, p = 0.37, 95% confidence interval [CI] = [0.57–1.23], I2 = 40%) between CD patients who had UST treatment preoperatively and those who had no UST treatment. There was no evidence of a difference in infectious complications (OR = 1.15, p = 0.35, 95% CI = [0.86–1.53], I2 = 2%). Additionally, there was no significant evidence of difference between these groups in terms of noninfectious complications and death. Specifically, there was no evidence of difference in overall complications, infection complications (including wound complications, sepsis, abscess, and anastomotic leakage), and noninfection complications (ileus, readmission, and return to operation), compared with no biological therapy and anti-TNF-α agents. At the same time, no significant evidence of difference was discovered in the comparison of preoperative UST and VDZ therapy in terms of overall complications, infectious complications (sepsis and abscess), and noninfectious complications (intestinal obstruction, readmission, and recovery surgery). Conclusion: In general, compared with other biological agents, preoperative use of UST in the treatment of CD patients is usually safe and does not increase surgical complications.
Prevalence and Risk Factors of Metabolic Dysfunction-Associated Fatty Liver Disease with Renal Insufficiency in Overweight/Obese Adults
Authors: Shi Ameng , Deng Jiang , Ma Juan , Yang Longbao , Tantai Xinxing , Wang Qian , Chang Danyan , Wang Jinhai , Guo Xiaoyan , Lu Xiaolan , Shi Haitao
Published: October 2023

Introduction: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) with renal insufficiency in recent years and the association between MAFLD and renal insufficiency are not entirely clear, especially in overweight/obesity. The aim of this study was to analyze the prevalence and risk factors of MAFLD with renal insufficiency in overweight/obese adults. Methods: Individuals who attended checkup at the Second Affiliated Hospital of Xi’an Jiaotong University from 2016 to 2021 were included. The prevalence of MAFLD with renal insufficiency (estimated glomerular filtration rate ≤90 mL/min/1.73 m2) in overweight/obesity was estimated. Propensity score-matched analysis, univariate and multivariate analyses were used to determine the risk factors for MAFLD with renal insufficiency. Results: From 2016 to 2021, the prevalence of MAFLD in overweight/obesity reached its highest of 44.7% in 2017 and its lowest of 36.9% in 2018; and 33.9% in 2021 and 21.8% in 2019 is the highest and lowest prevalence of MAFLD with renal insufficiency, respectively. MAFLD was more common in men, old individuals, and persons with a higher body mass index (BMI) and was characterized by significant renal insufficiency. MAFLD with renal insufficiency was more common in women, old individuals, and persons with a higher BMI and was characterized by significant metabolic dysfunction and liver fibrosis. Multivariable analysis showed that BMI, uric acid, and fibrosis (evaluated with noninvasive liver fibrosis score [fibrosis-4]) were independent risk factors for MAFLD with renal insufficiency. Conclusion: The prevalence of MAFLD with renal insufficiency in overweight/obese adults is quite high in the last 5 years. BMI, uric acid, and fibrosis are independent risk factors for MAFLD with renal insufficiency.
Analysis of Dopamine Receptor D2 Gene Polymorphism and Correlation with Dyslipidemia in the Chinese Population
Authors: Tan Haibo , Wang Zhixue , Zhang Jiaxuan , Huang Maohua , Chen Jide , Li Fengqi , Tang Liangjun
Published: October 2023

Objective: The study aimed to explore the genotype and allele distributions of dopamine D2-like receptor (DRD2) gene -141C and C957T polymorphisms in the Chinese Han population with dyslipidemia, as well as their association with serum lipid levels. Methods: One hundred fifty patients with dyslipidemia and 150 healthy people were recruited as the case and the control groups, respectively. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol levels were detected. The target sequence of DRD2 polymorphisms was amplified by polymerase chain reaction and genotyped via Sanger sequencing. Results: In DRD2 gene C957T (rs6277), three genotypes of CC, CT, and TT were detected with the frequencies of 92.67%, 6.67%, 0.67% in dyslipidemia cases, and 83.33%, 14.67%, 2.00% in the controls, respectively. The CT genotype and T allele frequencies were significantly low in the case group relative to the control group. After adjusting to other clinical indicators, the CT genotype of C957T polymorphism (hazard ratio = 0.401, 95% confidence interval = 0.181–0.890, p < 0.05) was still related to a significantly reduced risk of dyslipidemia. The C957T CT genotype carriers had the lowest values of serum TC, TG, LDL, and the highest values of serum HDL-C. Conclusion: DRD2 gene C957T polymorphism was an independent influencing factor associated with the susceptibility to dyslipidemia, and the CT genotype was associated with decreased odds of susceptibility to dyslipidemia.
Development and Validation of a Nomogram for Predicting All-Cause Mortality in Patients with Hemodialysis Having Pulmonary Hypertension
Authors: Wu Huimin , Huan Chunyan , Hu Yue , Xiao Shengjue , Xu Tao , Guo Minjia , Wang Xiaotong , Liu Ailin , Sun Jiayi , Wang Chunqing , Wang Jia , Zhu Hong , Pan Defeng
Published: October 2023

Introduction: Patients with end-stage renal disease receiving hemodialysis (HD) have a high morbidity and mortality rate associated with pulmonary hypertension (PH). A nomogram was developed to predict all-cause mortality in HD patients with PH. In this study, we aimed to validate the usefulness of this nomogram. Methods: A total of 274 HD patients with PH were hospitalized at the Affiliated Hospital of Xuzhou Medical University between January 2014 and June 2019 and followed up for 3 years. Echocardiography detected PH when the peak tricuspid regurgitation velocity (TRV) was more than 2.8 m/s. To evaluate the all-cause mortality for long-term HD patients with PH, Cox regression analysis was performed to determine the factors of mortality that were included in the prediction model. Next, the area under the receiver-operating characteristic curve (AUC-ROC) was used to assess the predictive power of the model. Calibration plots and decision curve analysis (DCA) were used to assess the accuracy of the prediction results and the clinical utility of the model. Results: The all-cause mortality rate was 29.20% throughout the follow-up period. The nomogram comprised six commonly available predictors: age, diabetes mellitus, cardiovascular disease, hemoglobin, left ventricular ejection fraction, and TRV. The 1-year, 2-year, and 3-year AUC-ROC values were 0.842, 0.800, and 0.781, respectively. The calibration curves revealed excellent agreement with the nomogram, while the DCA demonstrated favorable clinical practicability. Conclusion: The first developed nomogram for predicting all-cause mortality in HD patients with PH could guide clinical decision-making and intervention planning.
Lung Adenocarcinoma Size Decrease after SARS-CoV-2 Vaccination during Long-Term Pembrolizumab Treatment: A Case Report
Authors: Fujii Koki , Fukuda Kensuke , Kawakami Masanori , Mitani Akihisa , Tanaka Goh , Kage Hidenori
Published: October 2023

A man in his late 40s was diagnosed with clinical stage 4B lung adenocarcinoma with a PD-L1 tumor proportion score of 100% and high tumor mutational burden. A partial response was achieved after administration of pembrolizumab. The patient received two doses of a SARS-CoV-2 vaccine (BNT162b2) after 59 courses, and a chest computed tomography revealed consolidation in the peri-tumoral area, which subsequently disappeared, and the tumor continued to shrink in the next 4 months. This case provides indirect evidence for the persistence of cancer immunity during long-term treatment with immune checkpoint inhibitors and the potential for further activation.
Neuropsychiatric Outcomes and Sleep Dysfunction in COVID-19 Patients: Risk Factors and Mechanisms
Authors: Karkala Aliki , Tzinas Asterios , Kotoulas Seraphim , Zacharias Athanasios , Sourla Evdokia , Pataka Athanasia
Published: October 2023

The ongoing global health crisis due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly impacted all aspects of life. While the majority of early research following the coronavirus disease caused by SARS-CoV-2 (COVID-19) has focused on the physiological effects of the virus, a substantial body of subsequent studies has shown that the psychological burden of the infection is also considerable. Patients, even without mental illness history, were at increased susceptibility to developing mental health and sleep disturbances during or after the COVID-19 infection. Viral neurotropism and inflammatory storm damaging the blood-brain barrier have been proposed as possible mechanisms for mental health manifestations, along with stressful psychological factors and indirect consequences such as thrombosis and hypoxia. The virus has been found to infect peripheral olfactory neurons and exploit axonal migration pathways, exhibiting metabolic changes in astrocytes that are detrimental to fueling neurons and building neurotransmitters. Patients with COVID-19 present dysregulated and overactive immune responses, resulting in impaired neuronal function and viability, adversely affecting sleep and emotion regulation. Additionally, several risk factors have been associated with the neuropsychiatric sequelae of the infection, such as female sex, age, preexisting neuropathologies, severity of initial disease and sociological status. This review aimed to provide an overview of mental health symptoms and sleep disturbances developed during COVID-19 and to analyze the underlying mechanisms and risk factors of psychological distress and sleep dysfunction.
Strict versus Liberal Use of Sentinel Node Biopsy in Breast Cancer Surgery: Any Clinical Outcome Differences? A 20-Year Clinical Experience
Authors: Barco Israel , García-Font Marc , García-Fdez Antonio , Fraile Manel , Vallejo Elena , Vidal MCarmen , González Sonia , González Clarisa , Beatriz Mitru Claudia , Porta Oriol , Chabrera Sanz Carolina
Published: October 2023

Introduction: As applied to early breast cancer (BC) patients, sentinel node biopsy (SNB) has undergone major changes over the years, especially concerning the widening of indication criteria or skipping systematic axillary lymph node dissection (ALND) after a positive SN. We aimed to ascertain whether a strict versus a more liberal use of SNB resulted in different clinical outcomes in our clinical experience. Methods: We studied consecutive BC patients undergoing SNB between January 1, 2000, and March 31, 2020. There were 1,587 patients and 1,634 SNB procedures. Cases were divided into two study groups: the “strict” SNB group (unifocal tumors up to 35 mm in which ALND was always performed for a positive SN, amounting to 1,183 SNBs), and the “liberal” SNB group (extended tumor size up to selected T3 cases, as well as multifocal or bilateral disease, and patients with previous contralateral BC, not always followed by ALND after a positive SN, amounting to 451 SNBs). Patients were closely followed up to the end of the study. Results: Clinico-pathological variables were strikingly different between study groups, with the liberal group showing a higher risk profile. Cox regression analysis for disease recurrence did not show significant differences in axillary, lymph node, or locoregional recurrence rates or distant relapse. There were no differences in survival between groups. Conclusion: It seems reasonable to adopt the liberal SNB approach, as the goal of surgical management in early BC patients must be attaining optimal locoregional disease control, no matter the differences in distant metastatic spread rates across different BC risk profiles.
Venetoclax-Azacitidine Bridging PTCy-haplo-PBSCT for Refractory Acute Myeloid Leukemia with IDH2 Mutations
Authors: Daido Yusuke , Sugiura Hiroyuki , Ishikawa Tatsunori , Kuroi Taiga , Okamoto Sachiyo , Nomura Naho , Masunari Taro , Sezaki Nobuo , Nannya Yasuhito , Ogawa Seishi , Tanimoto Mitsune
Published: October 2023

Venetoclax and azacitidine combination therapy (VEN+AZA) is a promising novel therapy for elderly or unfit patients with acute myeloid leukemia (AML). Recently, VEN+AZA with subsequent allo-hematopoietic stem cell transplantation has been reported, and human leukocyte antigen-haploidentical peripheral blood stem cell transplantation using posttransplant cyclophosphamide (PTCy-haplo-PBSCT) from related donors appears to be a suitable option. Here, we report two elderly patients with refractory AML harboring an IDH2 mutation, who were successfully treated with VEN+AZA bridged to PTCy-haplo-PBSCT. This report suggests the efficacy and safety of VEN+AZA as a bridging treatment for PTCy-haplo-PBSCT in refractory AML.
Hair-to-Hair Trichoscopy: An Objective Method to Assess Effectiveness of Botulinum Toxin in a Clinical Trial for Androgenetic Alopecia
Authors: Melo Daniel Fernandes , Donda André Luiz Vairo , Cortez de Almeida Rita Fernanda , Antelo Daniela Alves Pereira , Muller-Ramos Paulo , Machado Carla Jorge , Frattini Sidney , Tosti Antonella , Barcaui Carlos Baptista
Published: October 2023

Introduction: Androgenetic alopecia (AGA) is the most common alopecia affecting both genders leading to a potential decrease in quality of life and self-esteem. A current concern in trichology is how to accurately measure clinical response in both daily medical practice and academic research. Hair-to-hair (H2H)-matching technology™ has recently emerged as a technique to evaluate variations in follicular units, hair shaft number, and thickness. This study aimed to describe the methodology employed in a clinical trial using this technology to test the efficacy of botulinum toxin (BT) for male AGA. Methods: This pilot study is a triple-blind, randomized, split scalp, placebo-controlled clinical trial. Patients enrolled were submitted to injections half of the scalp with 50 IU of BT and the other half with 1 mL of normal saline as a control. The trial involved three visits (weeks 0, 12, and 24) and 8 global clinical photographs followed by H2H-matching trichoscopy were captured before the injections at each visit. Paired t test analysis was employed for matched pairs of the following parameters: total hair count, the total number of terminal hair strands, average shaft thickness, and the number of hairs lost or gained during each visit. Then, the software compared the differences between the two sides (BT vs. placebo) per scalp zone and a long time. Conclusion: The combination of manually corrected image processing, follicular map, and H2H-matching technology™ appears to be the most precise way to evaluate changes in hair count and thickness over time. The design is reproducible and can help other researchers and dermatologists in their clinical practice to obtain reliable results in similar scientific research.
Prevalence of Subclinical Cardiovascular Disease in Patients with Nonalcoholic Fatty Liver Disease: Analysis of the Paracelsus 10,000 Cohort Study
Authors: Koutny Florian , Aigner Elmar , Datz Christian , Gensluckner Sophie , Maieron Andreas , Mega Andrea , Iglseder Bernhard , Langthaler Patrick , Frey Vanessa , Paulweber Bernhard , Trinka Eugen , Wernly Bernhard
Published: October 2023

Background: In patients with nonalcoholic fatty liver disease (NAFLD), cardiovascular diseases are more often the cause of death than the liver disease itself. However, the prevalence of atherosclerotic manifestations in individuals with NAFLD is still uncertain. This study aimed to explore the association between NAFLD and coronary artery calcification (CAC) in a Central European population. Methods: A total of 1,743 participants from the Paracelsus 10,000 study were included. The participants underwent CAC scoring and were assessed for fatty liver index (FLI), fibrosing nonalcoholic steatohepatitis (NASH) index (FNI), and fibrosis-4 index (FIB-4 score), which are indicators for steatosis and fibrosis. Multivariable logistic regression models were calculated. Results: Results revealed an association between liver steatosis/fibrosis and CAC. An FLI >60 was associated with higher odds of NAFLD (odds ratio [OR] 3.38, 95% CI: 2.61–4.39, p < 0.01) and increased prevalence of CAC score >300 compared to FLI <30 (9% vs. 3%, p < 0.01), even after adjusting for traditional cardiometabolic risk factors. While the crude ORs of the FIB-4 scores ≥ 1.3 and FNI score were significantly associated with increased odds of CAC, they became nonsignificant after adjusting for age, sex, and MetS. Conclusion: This study reveals a significant association between NAFLD and CAC. The findings suggest that assessing liver fat and fibrosis could enhance the assessment of cardiovascular risk, but further research is needed to determine whether hepatic fat plays an independent role in the development of atherosclerosis and whether targeting liver steatosis can mitigate vascular risk.
Osteopontin Is Associated with Dementia in the Presence of Cerebral Small Vessel Disease
Authors: Ghare Smita , Gardener Hannah , Ariko Taylor , Gutierrez Jose , Wright Clinton B. , Goldberg Ronald B. , Elkind Mitchell S.V. , Cooper Gregory E. , Shields Christopher B. , Barve Shirish , Rundek Tatjana
Published: October 2023

Background: Osteopontin (OPN) is a proinflammatory cytokine that has been recently implicated in neuroinflammation and neurodegeneration. We hypothesized that an increase in plasma OPN is a deleterious neuroinflammatory marker in people with dementia and cerebral small vessel disease (CSVD). Methods: A pilot study was conducted on participants in the Northern Manhattan Study (NOMAS). Three groups were selected based on their dementia status and evidence of subclinical CSVD and chosen to be similar in age, sex, and education attainment: No dementia/No CSVD (n = 19), Dementia/No CSVD (n = 22), and Dementia + CSVD (n = 21). Dementia (any type) was diagnosed by consensus adjudication following a series of comprehensive neuropsychological assessments and a review of the medical history. CSVD was indicated by silent brain infarcts, enlarged perivascular spaces, cerebral microbleeds, and white matter hyperintensity volumes (WMHV) on MRI. Multinomial logistic regression was used to examine the difference in OPN levels across groups, adjusting for key determinants of CSVD and neurodegeneration. Results: Plasma OPN levels were elevated in the Dementia+CSVD group (mean = 70.69 ± 39.00 ng/mL) but not in the Dementia/No CSVD group (mean = 45.46 ± 19.11 ng/mL) compared to the No Dementia/No CSVD group (mean = 36.43 ± 15.72 ng/mL). OPN was associated with Dementia+CSVD (Odds Ratio [OR] per ng/mL = 1.06, 95% CI 1.02–1.11) after adjusting for covariates, including brain volume. OPN was strongly correlated with WMHV (Spearman’s rank correlation ρ = 0.46, p = 0.0001) but not with other components of CSVD. Conclusion: In this pilot, greater levels of plasma OPN were associated with dementia with evidence of CSVD. This link was predominately driven by the contribution of OPN to dementia through the burden of white matter lesions.
The Fatty Liver Index, the Strongest Risk Factor for Low Testosterone Level
Authors: Liu Luna , Li Man , Chen Pengcheng , Li Yuchen , Song Qianmei , Han Junming , Fang Li , Guan Qingbo , Yu Chunxiao
Published: October 2023

Introduction: The study aimed to determine if hepatic steatosis assessed by fatty liver index (FLI) was an independent risk factor for male low testosterone level and whether the FLI was the strongest risk factor for low testosterone level in two different age groups. Methods: Two cross-sectional studies were performed. A total of 3,443 male participants (aged 46–75) were recruited into study A (part of lONgitudinal study (REACTION)). Then a total of 267 male participants (aged 25–45) were recruited into study B. Serum total testosterone (TT) and sex hormone-binding globulin (SHBG) levels, indicators for assessing hepatic steatosis were measured. The Pearson correlation and regression analysis were performed to investigate the risk factors for low testosterone level. Results: The FLI had the strongest negative correlation with serum testosterone in the study A (r = −0.436) and B (r = −0.542). Compared with patients with a FLI lower than 30, the risk for low testosterone level increased by 3.48-fold in subjects with a FLI higher than 60 adjusted for potential risk factors in study A. In study B, the odds ratio of low testosterone level in patients with potential hepatic steatosis was 4.26 (1.57–11.60) after adjusted for age and homeostasis model assessment of insulin resistance (HOMA-IR) and 0.59 (0.14–2.60) after adjusted for age, HOMA-IR, waist circumference, body mass index, and SHBG. Conclusions: FLI was the strongest risk factor for male low testosterone level independent of insulin resistance in male populations of different ages; however, the association can be modulated by SHBG levels in the young. Significance Statement: In the study, FLI was the strongest negative risk factor for low testosterone level in the Chinese adult male population. The results suggested that hepatic steatosis assessed by the FLI was the main risk factor for male low testosterone level, independent of age, insulin resistance, smoking, and drinking status; however, the association of FLI and TT levels can be modulated by SHBG levels. Taken together these findings indicate that clinical physicians should pay more attention to the FLI index and hepatic steatosis, so that they can take advantage of them for assessing the risk of developing of low testosterone level in the male population.
Erosive Pustular Dermatosis of the Scalp Arising on Long-Standing Burn Scars: A Report of Three Cases and Brief Review of Literature
Authors: Kim Jin Seop , Chae Seoung Wan , Lee Ga-Young , Choi Young-Jun
Published: October 2023

Introduction: Erosive pustular dermatosis of the scalp (EPDS) is a rare and recalcitrant condition in which chronic scalp pustules and erosive patches are diagnosed by nondiagnostic laboratory tests and histopathological tests. Although various precipitating factors including trauma have been reported, erosive pustular dermatosis arising on the long-standing burn scars is rare. Case Presentation: We report three cases of EPDS arising on long-standing burn scars. Based on clinical and histological findings, erosive pustular dermatosis was diagnosed and successfully treated with topical steroid ointment. Conclusion: We propose that chronic burn scar is another precipitating factors for EPDS and clinicians should consider EPDS in differential diagnoses of erosive pustular dermatosis in long-standing burn scars on the scalp.
Associations between Differential Aging and Lifestyle, Environment, Current, and Future Health Conditions: Findings from Canadian Longitudinal Study on Aging
Authors: Song Yipeng , Liu Yang S. , Talarico Fernanda , Zhang Yanbo , Hayward Jake , Wang Mengzhe , Stroulia Eleni , Dixon Roger A. , Greiner Russell , Li Xinmin , Greenshaw Andrew , Jie Sui , Cao Bo
Published: October 2023

Introduction: An aging population will bring a pressing challenge for the healthcare system. Insights into promoting healthy longevity can be gained by quantifying the biological aging process and understanding the roles of modifiable lifestyle and environmental factors, and chronic disease conditions. Methods: We developed a biological age (BioAge) index by applying multiple state-of-art machine learning models based on easily accessible blood test data from the Canadian Longitudinal Study of Aging (CLSA). The BioAge gap, which is the difference between BioAge index and chronological age, was used to quantify the differential aging, i.e., the difference between biological and chronological age, of the CLSA participants. We further investigated the associations between the BioAge gap and lifestyle, environmental factors, and current and future health conditions. Results: BioAge gap had strong associations with existing adverse health conditions (e.g., cancers, cardiovascular diseases, diabetes, and kidney diseases) and future disease onset (e.g., Parkinson’s disease, diabetes, and kidney diseases). We identified that frequent consumption of processed meat, pork, beef, and chicken, poor outcomes in nutritional risk screening, cigarette smoking, exposure to passive smoking are associated with positive BioAge gap (“older” BioAge than expected). We also identified several modifiable factors, including eating fruits, legumes, vegetables, related to negative BioAge gap (“younger” BioAge than expected). Conclusions: Our study shows that a BioAge index based on easily accessible blood tests has the potential to quantify the differential biological aging process that can be associated with current and future adverse health events. The identified risk and protective factors for differential aging indicated by BioAge gap are informative for future research and guidelines to promote healthy longevity.
Coexistence of Low Muscle Mass and Osteoporosis as a Predictor of Fragility Fractures in Long-Term Kidney Transplant Recipients
Authors: Hori Mayuko , Takahashi Hiroshi , Kondo Chika , Matsuoka Yutaka , Tsujita Makoto , Nishihira Morikuni , Uchida Kazuharu , Takeda Asami , Morozumi Kunio , Maruyama Shoichi
Published: October 2023

Introduction: Sarcopenia and osteoporosis are highly prevalent among kidney transplant recipients (KTRs). Although osteoporosis is known to increase fracture risk in KTRs, it is unclear whether sarcopenia or osteosarcopenia is associated with this increased risk. Thus, we aimed to investigate the association of the coexistence of low muscle mass (LMM) and osteoporosis with the risk of fracture in long-term KTRs. Methods: Exactly 342 stable KTRs underwent dual-energy X-ray absorptiometry and skeletal muscle mass index (SMI) measurement using bioelectrical impedance analysis. Results: LMM and osteoporosis were observed in 109 (31.9%) and 93 patients (27.2%), respectively. During a follow-up period of 5.1 years, 48 (14.0%) fractures occurred. KTRs with LMM had a higher fracture risk, but this was not significant (adjusted hazard ratio [aHR] 1.82, 95% confidence interval [CI] 0.94–3.50, p = 0.073). Similar results were obtained in KTRs with osteoporosis (aHR 1.84, 95% CI 0.96–3.47, p = 0.063). We divided the KTRs into four groups according to the presence of LMM and/or osteoporosis. The cumulative incidence rates of fractures were 13.0%, 11.1%, 10.5%, and 31.3% in the KTRs without both LMM and osteoporosis, those with LMM alone, those with osteoporosis alone, and those with both, respectively. The KTRs with both LMM and osteoporosis had a 2.92fold higher risk of fractures (95% CI 1.29–6.49; p = 0.010) than those without both LMM and osteoporosis. Conclusion: Long-term KTRs with the coexistence of LMM and osteoporosis had an independently higher risk of fragility fractures than those without both LMM and osteoporosis. The combination of SMI and osteoporosis definitions can be used to identify KTRs with a high fracture risk.
Comparison of a Multiplex Real-Time PCR Technique with Oxford Nanopore Technologies Next-Generation Sequencing for Identification of SARS-CoV-2 Variants of Concern
Authors: Ahmadi Zahra , Maleki Ali , Eybpoosh Sana , Fereydouni Zahra , Tavakoli Mahsa , Kashanian Setareh , Farhan Asadi Laya , Nemati Amir Hesam , Salehi-Vaziri Mostafa
Published: October 2023

Introduction: The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and their potential to endangering the global health has increased the demand for a fast-tracking method in comparison to the next-generation sequencing (NGS) as a gold standard assay, particularly in developing countries. This study was designed to evaluate the performance of a commercial multiplex real-time PCR technique (GA SARS-CoV-2 OneStep RT-PCR Kit, Iran) for identification of SARS-CoV-2 variants of concern (VOCs) compared to the Oxford Nanopore NGS assay. Methods: A total of 238 SARS-CoV-2-positive respiratory samples from different waves of COVID-19 in Iran were randomly selected in this study. To determine the SARS-CoV-2 VOC, the samples were analyzed via the commercial triple target assay, GA SARS-CoV-2 OneStep RT-PCR Kit, and NGS as well. Results: The results revealed good concordance between GA SARS-CoV-2 OneStep RT-PCR Kit and NGS for identification of SARS-CoV-2 VOCs. GA SARS-CoV-2 OneStep RT-PCR Kit identified Wuhan, Alpha, and Delta variants with 100% relative sensitivity and specificity. Regarding Omicron subvariants of BA.1, BA.2, and BA.4/5, the relative sensitivity of 100%, 100%, and 81.5% and the relative specificity of 95.3%, 93.5%, and 100% were observed. Conclusion: Overall, GA SARS-CoV-2 OneStep RT-PCR Kit can be used as a rapid and cost-effective alternative to NGS for identification of SARS-CoV-2 VOCs.
Lessons Learned from 17 Years of Multidisciplinary Care for Differences of Sex Development Patients at a Single Indonesian Center
Authors: Faradz Sultana M.H. , Listyasari Nurin , Utari Agustini , Ariani Mahayu Dewi , Juniarto Achmad Zulfa , Santosa Ardy , Ediati Annastasia , Rinne Tuula K , Westra Dineke , Claahsen-van der Grinten Hedi , de Jong Frank H , Drop Stenvert L.S. , Ayers Katie , Sinclair Andrew
Published: October 2023

Background: Our multidisciplinary team (MDT) is a large specialized team based in Semarang, Indonesia, that cares for a wide variety of pediatric and adult individuals with differences of sex development (DSD) from across Indonesia. Here, we describe our work over the last 17 years. Methods: We analyzed phenotypic, hormonal, and genetic findings from clinical records for all patients referred to our MDT during the period 2004–2020. Results: Among 1,184 DSD patients, 10% had sex chromosome DSD, 67% had 46,XY DSD, and 23% had 46,XX DSD. The most common sex chromosome anomaly was Turner syndrome (45,X) (55 cases). For patients with 46,XY DSD under-masculinization was the most common diagnosis (311 cases), and for 46,XX DSD, a defect of Müllerian development was most common (131 cases) followed by congenital adrenal hyperplasia (CAH) (116 cases). Sanger sequencing, MLPA, and targeted gene sequencing of 257 patients with 46,XY DSD found likely causative variants in 21% (55 cases), with 13 diagnostic genes implicated. The most affected gene codes for the androgen receptor. Molecular analysis identified a diagnosis for 69 of 116 patients with CAH, with 62 carrying variants in CYP21A2 including four novel variants, and 7 patients carrying variants in CYP11B1. In many cases, these genetic diagnoses influenced the clinical management of patients and their families. Conclusions: Our work has highlighted the occurrence of different DSDs in Indonesia. By applying sequencing technologies as part of our clinical care, we have delivered a number of genetic diagnoses and identified novel pathogenic variants in some genes, which may be clinically specific to Indonesia. Genetics can inform many aspects of DSD clinical management, and while many of our patients remain undiagnosed, we hope that future testing may provide answers for even more.
Targeting Monocyte Derived CCL17 Attenuates Murine Crescentic Glomerulonephritis by Affecting Renal CCR4+ Regulatory T-Cell Recruitment
Authors: Song Ning , Paust Hans-Joachim , Asada Nariaki , Peters Anett , Kaffke Anna , Krebs Christian F. , Panzer Ulf , Riedel Jan-Hendrik
Published: October 2023

Introduction: The chemokine receptor CCR4 is expressed by diverse CD4+ T cell subsets including regulatory T cells (Tregs) but its functional importance for leukocyte recruitment and the relevance of its two corresponding chemokines CCL17 and CCL22 have not been studied in immune-mediated crescentic glomerulonephritis (cGN). Methods: Utilizing the single-cell RNA sequencing (scRNAseq) data in analyzing leukocytes isolated from both human and murine nephritic kidneys, we identified CCL17 as a potential therapeutic target in immune-mediated renal disease. Using a mouse model of murine cGN, we then delineated the effects of targeting CCL17 by neutralizing antibodies and in Ccl17 gene-deficient mice. Results: Unsupervised scRNAseq analyses identified the CCL17-CCR4 axis as a mechanism potentially involved in renal T-cell migration. Analyses of functional kidney impairment and histopathological kidney damage revealed an attenuation of crescentic GN in anti-CCL17 antibody-treated mice which was corroborated using in Ccl17 gene-deficient mice. Immunohistochemical analyses revealed that these changes were accompanied by an affected renal Treg recruitment in both experimental approaches. Conclusion: The chemokine receptor CCR4 and its corresponding chemokine CCL17 are expressed in human and murine cGN and targeting the CCR4-CCL17 axis by neutralizing antibodies as well as Ccl17 gene deficiency led to increased renal Treg recruitment and reduced histological and functional kidney damage in murine cGN.