Stijn J M Niessen, Robert Shiel, Astrid Wehner
et al.
Simple Summary After having achieved international consensus over disease, diagnosis, classification, and monitoring concepts in the area of companion animal diabetes mellitus, Cushing’s syndrome, and hypoadrenocorticism, a group of 14 experts and one chair embarked on the third cycle of project “Agreeing Language in Veterinary Endocrinology” (ALIVE), this time focusing on thyroid disease terminology. This cycle’s methods followed, like previous ones, a modified Delphi-approach with small changes to improve efficiency and flexibility, including an off-site chair. For the first time, additionally, feedback on definitions of a previous cycle was incorporated, leading to an update of diabetes mellitus related definitions of ALIVE Cycle 1. This third cycle was completed successfully, accomplishing a majority-based consensus among panellists and international veterinary endocrinology society memberships over 78 thyroid related terminology and five updated diabetes mellitus definitions. As has been the case with the definitions created for other hormonal diseases, it is hoped this work will improve education, research, diagnosis, and treatment in cats and dogs with endocrine disease.
Immunoglobulin G4-related disease (IgG4-RD) is a chronic, systemic fibroinflammatory autoimmune disorder characterized by multi-organ involvement, elevated serum IgG4 levels, and dense infiltration of IgG4+ plasma cells. The disease can affect nearly any organ, and its clinical spectrum has continued to expand in recent years; involvement of the genitourinary system has been increasingly recognized, although direct involvement of the male external genitalia is extremely rare. We report a case of a 29-year-old man with IgG4-RD who initially presented with an unexplained penile mass. Clinical evaluation and laboratory testing revealed right inguinal lymphadenopathy along with elevated serum IgG4 and C-reactive protein (CRP) levels. Histopathological examination demonstrated fibrosis and an increased number of IgG4+ plasma cells, confirming the diagnosis of IgG4-RD. The patient received prednisone at 30 mg/day for four consecutive weeks, which resulted in a marked reduction of the lesion and improvement in symptoms, followed by a taper to a maintenance dose of 6 mg/day. During follow-up, no recurrence of symptoms has been observed. This case indicates that IgG4-RD should be considered in patients presenting with unexplained penile masses, and early recognition with multidisciplinary collaboration among urology, pathology, and rheumatology is essential to prevent unnecessary surgical procedures.
BACKGROUND Fournier's Gangrene (FG) is a rare, life-threatening necrotizing fasciitis of the perineum and genitourinary regions with high morbidity and mortality rates. Despite advancements in healthcare, FG remains a challenge due to its rapid progression and the need for aggressive intervention. This study aims to investigate the factors influencing mortality in FG patients, assess the effectiveness of laboratory parameters and scoring systems, and emphasize the role of blood glucose regulation in improving survival. METHODS This retrospective study included 36 patients diagnosed with FG at Bolu Abant İzzet Baysal University Medical Faculty Hospital between January 2014 and September 2024. Patients with incomplete data, a history of isolated perineal, gynecological, or perianal surgeries unrelated to FG, and those under 18 years of age were excluded. For all patients, Neutrophil-Lymphocyte Ratio (NLR), Platelet-Lymphocyte Ratio (PLR), Lymphocyte-Monocyte Ratio (LMR), CRP-Albumin Ratio (CAR), and Prognostic Nutritional Index (PNI), Inflammatory Prognostic Index (IPI), Systemic Inflammation Index (SII), Urology and Plastics Index (CUPI), Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC), Fournier's Gangrene Severity Index (FGSI), and Uludağ Fournier's Gangrene Severity Index (UFGSI) scores were calculated. A comparison was made between the results obtained from laboratory parameters and scoring systems and the effect of blood sugar regulation on survival. Statistical analyses were performed using SPSS 27. RESULTS The mean age of the patients was 64.67±13.25 years, with a male-to-female ratio of 3: 1. Diabetes Mellitus (DM) was present in 61.1% of cases and 66.7% of deceased patients. The mortality rate was 16.7%. Elevated blood glucose levels at admission were significantly associated with mortality (p=0.024). The cut-off value of 186.5 mg/dL for glucose predicted mortality with 83.3% sensitivity and specificity. Scoring systems such as LRINEC and CUPI also demonstrated predictive utility, but glucose was found to be a simpler, faster marker. Among inflammatory markers, Neutrophil-Lymphocyte Ratio (NLR) was significant (p=0.016) with a cut-off of 14.04, showing 83.3% sensitivity and 76.7% specificity. CONCLUSION FG is a rapidly progressing disease requiring early diagnosis and multidisciplinary management. While scoring systems and inflammatory markers are valuable for predicting mortality, blood glucose level stands out as a simple, rapid, and effective predictor. Ensuring blood sugar regulation can significantly improve prognosis and survival in FG patients, underscoring the need for immediate attention to glucose levels in clinical practice.
Alessandro Marquis, Jonathan Olivier, Tavya G. R. Benjamin
et al.
<b>Background/Objectives:</b> Focal therapy (FT) for prostate cancer (PCa) is an alternative to radical treatments that aims to balance cancer control and quality of life preservation in well-selected patients. Understanding its general principles and outcomes is key for its widespread adoption and proper implementation. <b>Methods</b>: The International Consultation on Urological Diseases nominated a committee to review the literature on FT for PCa. A comprehensive PubMed search was conducted to identify articles focused on the different aspects of FT, including patient selection, imaging techniques, treatment modalities, cancer control and safety outcomes, integration with other approaches and future perspectives. <b>Results</b>: FT for PCa was introduced in the 1990s with cryotherapy and high-intensity focused ultrasound (HIFU) as pioneering modalities. Though initially guided by transrectal ultrasound (TRUS) and large biopsy templates, FT implementation expanded significantly with the advent of multiparametric magnetic resonance imaging (MRI) and the validation of the index lesion concept. Appropriate patient selection is key for FT and relies on prostate-specific antigen (PSA) metrics, MRI findings and targeted biopsy information. Multiple energy sources are now available, each with specific technical characteristics. Cancer control rates vary by energy modality, tumor characteristics, and institutional experience, demonstrating comparable outcomes to radical treatments in well-selected patients. The safety profile is excellent, with high rates of urinary continence and sexual function preservation. Post-treatment surveillance integrates PSA measurements, imaging, and histological assessment. Future directions for further FT adoption include the availability of long-term data, protocol standardization and technological improvements to enhance patient selection and treatment planning and delivery. <b>Conclusions</b>: FT is a valuable therapeutic option for selected patients with localized PCa, demonstrating promising oncological outcomes and better functional preservation compared to radical treatments. Understanding its principles and technical aspects is essential for offering comprehensive PCa care.
Crop diseases pose significant threats to global food security, agricultural productivity, and sustainable farming practices, directly affecting farmers' livelihoods and economic stability. To address the growing need for effective crop disease management, AI-based disease alerting systems have emerged as promising tools by providing early detection and actionable insights for timely intervention. However, existing systems often overlook critical aspects such as data privacy, market pricing power, and farmer-friendly usability, leaving farmers vulnerable to privacy breaches and economic exploitation. To bridge these gaps, we propose AgriSentinel, the first Privacy-Enhanced Embedded-LLM Crop Disease Alerting System. AgriSentinel incorporates a differential privacy mechanism to protect sensitive crop image data while maintaining classification accuracy. Its lightweight deep learning-based crop disease classification model is optimized for mobile devices, ensuring accessibility and usability for farmers. Additionally, the system includes a fine-tuned, on-device large language model (LLM) that leverages a curated knowledge pool to provide farmers with specific, actionable suggestions for managing crop diseases, going beyond simple alerting. Comprehensive experiments validate the effectiveness of AgriSentinel, demonstrating its ability to safeguard data privacy, maintain high classification performance, and deliver practical, actionable disease management strategies. AgriSentinel offers a robust, farmer-friendly solution for automating crop disease alerting and management, ultimately contributing to improved agricultural decision-making and enhanced crop productivity.
Serverless computing has redefined cloud application deployment by abstracting infrastructure and enabling on-demand, event-driven execution, thereby enhancing developer agility and scalability. However, maintaining consistent application performance in serverless environments remains a significant challenge. The dynamic and transient nature of serverless functions makes it difficult to distinguish between benign and anomalous behavior, which in turn undermines the effectiveness of traditional anomaly detection methods. These conventional approaches, designed for stateful and long-running services, struggle in serverless settings where executions are short-lived, functions are isolated, and observability is limited. In this first comprehensive vision paper on anomaly detection for serverless systems, we systematically explore the unique challenges posed by this paradigm, including the absence of persistent state, inconsistent monitoring granularity, and the difficulty of correlating behaviors across distributed functions. We further examine a range of threats that manifest as anomalies, from classical Denial-of-Service (DoS) attacks to serverless-specific threats such as Denial-of-Wallet (DoW) and cold start amplification. Building on these observations, we articulate a research agenda for next-generation detection frameworks that address the need for context-aware, multi-source data fusion, real-time, lightweight, privacy-preserving, and edge-cloud adaptive capabilities. Through the identification of key research directions and design principles, we aim to lay the foundation for the next generation of anomaly detection in cloud-native, serverless ecosystems.
Accurate diagnosis of Mendelian diseases is crucial for precision therapy and assistance in preimplantation genetic diagnosis. However, existing methods often fall short of clinical standards or depend on extensive datasets to build pretrained machine learning models. To address this, we introduce an innovative LLM-Driven multi-agent debate system (MD2GPS) with natural language explanations of the diagnostic results. It utilizes a language model to transform results from data-driven and knowledge-driven agents into natural language, then fostering a debate between these two specialized agents. This system has been tested on 1,185 samples across four independent datasets, enhancing the TOP1 accuracy from 42.9% to 66% on average. Additionally, in a challenging cohort of 72 cases, MD2GPS identified potential pathogenic genes in 12 patients, reducing the diagnostic time by 90%. The methods within each module of this multi-agent debate system are also replaceable, facilitating its adaptation for diagnosing and researching other complex diseases.
Rare diseases affect over 300 million individuals worldwide, yet timely and accurate diagnosis remains an urgent challenge. Patients often endure a prolonged diagnostic odyssey exceeding five years, marked by repeated referrals, misdiagnoses, and unnecessary interventions, leading to delayed treatment and substantial emotional and economic burdens. Here we present DeepRare, a multi-agent system for rare disease differential diagnosis decision support powered by large language models, integrating over 40 specialized tools and up-to-date knowledge sources. DeepRare processes heterogeneous clinical inputs, including free-text descriptions, structured Human Phenotype Ontology terms, and genetic testing results, to generate ranked diagnostic hypotheses with transparent reasoning linked to verifiable medical evidence. Evaluated across nine datasets from literature, case reports and clinical centres across Asia, North America and Europe spanning 14 medical specialties, DeepRare demonstrates exceptional performance on 3,134 diseases. In human-phenotype-ontology-based tasks, it achieves an average Recall@1 of 57.18%, outperforming the next-best method by 23.79%; in multi-modal tests, it reaches 69.1% compared with Exomiser's 55.9% on 168 cases. Expert review achieved 95.4% agreement on its reasoning chains, confirming their validity and traceability. Our work not only advances rare disease diagnosis but also demonstrates how the latest powerful large-language-model-driven agentic systems can reshape current clinical workflows.
Immunotherapy is defined as a therapeutic approach that targets or manipulates the immune system. A deeper understanding of the cellular and molecular composition of the tumour environment, as well as the mechanisms controlling the immune system, has made possible the development and clinical investigation of many innovative cancer therapies. Historically, immunotherapy has played an essential role in treating urologic malignancies, while in the modern era, the development of immune checkpoint inhibitors (ICIs) has been critical to urology. Urothelial carcinoma is a common type of cancer in the genitourinary system, and treatment strategies in this area are constantly evolving. Intravesical and systemic immunotherapeutic agents have begun to be used increasingly frequently in treating urothelial carcinoma. These agents increase the anti-tumour response by affecting the body's defence mechanisms. Immunotherapeutic agents used in urothelial carcinoma include various options such as BCG, interferon, anti-PD-1 (pembrolizumab, nivolumab) and anti-PD-L1 (atezolizumab, avelumab, durvalumab). Renal cell carcinoma (RCC) has been known for many years as a tumour with unique sensitivity to immunotherapies. The recent emergence of ICIs that block PD-1/PD-L1 (pembrolizumab, nivolumab, atezolizumab) or CTLA4 (ipilimumab) signalling pathways has reestablished systemic immunotherapy as central to the treatment of advanced RCC. In light of randomized clinical trials conducted with increasing interest in the application of immunotherapies in the adjuvant setting, combination therapies (nivolumab/ipilimumab, nivolumab/cabozantinib, pembrolizumab/ axitinib, pembrolizumab/lenvantinib) have become the standard first-line treatment of metastatic RCC. Prostate cancer is in the immunologically "cold" tumour category; on the contrary, in recent years, immunotherapeutic agents have come to the fore as an essential area in the treatment of this disease. Especially in the treatment of castration-resistant prostate cancer, immunotherapeutic agents constitute an alternative treatment method besides androgen deprivation therapy and chemotherapy. Ipilimumab, nivolumab, pembrolizumab, atezolizumab, and Sipuleucel T (Vaccine-based) are promising alternative treatment options. Considering ongoing randomized clinical trials, immunotherapeutic agents promise to transform the uro-oncology field significantly. In this review, we aimed to summarize the role of immunotherapy in urothelial, renal and prostate cancer in the light of randomized clinical trials.
Diseases of the genitourinary system due to their high prevalence in the population and the frequent development of complications are an urgent medical and social problem and require timely, effective and high-quality medical care. In the Russian Federation, urolithiasis, prostate adenoma, obstructive (reflux) uropathies occupy the leading positions in the structure of hospitalized morbidity in urological departments of hospitals, which account for more than 3/4 of all hospitalizations. Improving the efficiency and quality of medical activities in providing specialized medical care to patients with diseases of the genitourinary system in hospital settings requires the use of high-tech diagnostic and treatment methods. The purpose of the study is to study the dynamics of morbidity of the adult population of the Orenburg region with diseases of the genitourinary system, and to assess the effectiveness and quality of specialized medical care for patients in the urological department of the Orenburg Regional Clinical Hospital. Materials and methods. The study analyzes information copied from information statistical collections of the Ministry of Health of the Orenburg Region and the Federal State Statistics Service. The indicators of general and primary morbidity of diseases of the genitourinary system among the adult population of the Orenburg region are analyzed. The dynamics of changes in morbidity rates was studied for the period from 2017 to 2021 by constructing dynamic series and calculating special indicators: absolute increase/decrease, growth/decrease rate, growth/decrease indicator, visibility indicator. To assess the effectiveness and quality of specialized medical care for patients with diseases of the genitourinary system, the urological department of the Orenburg Regional Clinical Hospital named after V. I. Voynov was selected as the base of the study. During the study, the bed performance indicators and special indicators of the effectiveness and quality of medical activities were analyzed. Study period: 2019–6 months of 2023. In addition, a comparative analysis of the department’s performance in 2007 and 2022 was carried out. The following research methods were used: statistical and analytical. Statistical processing of the materials included the calculation of absolute, relative and average values. Results. In the Orenburg region, from 2017 to 2021, the level of general morbidity of the adult population with diseases of the genitourinary system decreased by 14,4%. At the same time, in the studied region over the past period, the indicator of primary morbidity of the adult population with diseases of the genitourinary system had a more pronounced decrease, which amounted to 37,4% over five years. It has been established that over the past 5 years, when high-tech operations using endoscopic and laser technologies were widely performed in the urological department of the hospital, the overall performance of the department has improved. The exception was in 2020, when a tense epidemiological situation was recorded for the new coronavirus infection Covid‑19. In the last 3 years, there has been a decrease in the average length of patient stay in bed, which allowed an increase by 19,3% in the number of treated patients, as well as to perform more operations – in 2022, 1 019 surgical interventions were performed compared to 905 in 2019. The urology department of the hospital has a low mortality rate, which was minimal (0,3%) in 2019 and 2023. As a result of a comparative analysis of the performance of the urological department in 2022 and in 2007, it was found that in recent years, the average length of stay in a bed has decreased in 2,5 times. If in 2007 the number of operations amounted to 385, then in 2022 their number increased to 1019. At the same time, the turnover of the bed increased 2,6 times. There was also a 27,5% increase in surgical activity. Conclusions. Thus, in the Orenburg region over the past five years, there has been a decrease in the level of general morbidity of the adult population with diseases of the genitourinary system by 14,4%, and the level of primary morbidity of the adult population with diseases of the genitourinary system by 37,4%. The introduction of high-tech methods of surgical treatment, including endoscopic and laser technologies, in the urological department of the V. I. Voynov State Medical University has significantly improved the efficiency and quality of specialized medical care for patients with diseases of the genitourinary system.
Nguyen Xuong Duong, Minh Sam Thai, Ngoc Sinh Tran
et al.
Kidney transplantation (KT) is a preferred treatment for end-stage renal disease (ESRD) because it offers better long-term survival and cost-effectiveness compared to dialysis. Significant global disparities persist in access to KT, particularly in low- and middle-income countries (LMICs). This study aims to assess the epidemiology and outcomes of KT in LMICs while examining the relationship between a country’s income level and its KT prevalence. A systematic review of the literature was conducted, with searches of PubMed, Scopus, and Web of Science from inception to 31 May 2024. Relevant articles reporting on the epidemiology and outcomes of KT or ESRD patients undergoing kidney replacement therapy (KRT) in LMICs were included. A total of 8054 articles were identified, with 972 articles selected for full-text screening after initial title and abstract review. Following full-text screening, 35 articles met the inclusion criteria. The data showed significant variation in KRT and KT prevalence across different geographical locations. Higher-income countries within LMICs tended to have higher KT prevalence rates. Barriers such as inadequate healthcare infrastructure, limited financial resources, and insufficient organ donation frameworks were identified as contributing factors to the low KT rates in these regions. The study highlights the disparities in KT access and prevalence in LMICs, underscoring the need for targeted interventions and international collaboration to address these gaps. Efforts to increase both living and deceased donor transplants, expand health system capacity, and incorporate KT in healthcare planning are needed to close this gap. Global partnerships spearheaded by organizations such as The Transplantation Society (TTS) and the International Society of Nephrology (ISN) are crucial for improving KT rates and outcomes in LMICs.
The use of Electronic Health Records (EHRs) has increased dramatically in the past 15 years, as, it is considered an important source of managing data od patients. The EHRs are primary sources of disease diagnosis and demographic data of patients worldwide. Therefore, the data can be utilized for secondary tasks such as research. This paper aims to make such data usable for research activities such as monitoring disease statistics for a specific population. As a result, the researchers can detect the disease causes for the behavior and lifestyle of the target group. One of the limitations of EHRs systems is that the data is not available in the standard format but in various forms. Therefore, it is required to first convert the names of the diseases and demographics data into one standardized form to make it usable for research activities. There is a large amount of EHRs available, and solving the standardizing issues requires some optimized techniques. We used a first-hand EHR dataset extracted from EHR systems. Our application uploads the dataset from the EHRs and converts it to the ICD-10 coding system to solve the standardization problem. So, we first apply the steps of pre-processing, annotation, and transforming the data to convert it into the standard form. The data pre-processing is applied to normalize demographic formats. In the annotation step, a machine learning model is used to recognize the diseases from the text. Furthermore, the transforming step converts the disease name to the ICD-10 coding format. The model was evaluated manually by comparing its performance in terms of disease recognition with an available dictionary-based system (MetaMap). The accuracy of the proposed machine learning model is 81%, that outperformed MetaMap accuracy of 67%. This paper contributed to system modelling for EHR data extraction to support research activities.
Sara Mansoorshahi, Cindy Scurlock, Scientific Advisory Board of the Turner Syndrome Society of t Research Registry
et al.
Background Many different clinical specialists provide care to patients with Turner syndrome (TS), who have highly variable clinical manifestations. Therefore, a national TS registry is essential to inform a cohesive approach to healthcare and research. In 2015, the Turner Syndrome Society of the United States (TSSUS) created the Turner Syndrome Research Registry (TSRR) to engage directly with community participants who voluntarily provide longitudinal data about their experiences with TS. TSRR projects are collaborative partnerships between people with TS, TSSUS, and researchers. Results To ensure that registry workflows conform to the data privacy choices of participants, TSSUS collaborated with UTHealth Houston in 2021 to create a new version of the TSRR that completely separates participant health data (stored at UTHealth) and personal identifiers (maintained at TSSUS). We developed an innovative Visual Basic (VB) script that, when embedded into Microsoft Outlook, redirects REDCap surveys through TSSUS to participants by matching registry IDs to participant email addresses. Additionally, the utilization of REDCap allows for portability of data as it is an open source platform. Conclusion In this report, we will highlight three recent changes that more closely align the TSRR with this mission: a unique and equal collaborative partnership between UTHealth and TSSUS, an open-source platform, REDCap, that ensures data portability and compatibility across institutions, and an innovative survey routing system that retains participant confidentiality without sacrificing REDCap survey distribution capabilities to connect researchers with thousands of participants.
People with type 1 and type 2 diabetes are at risk of developing progressive chronic kidney disease (CKD) and end-stage kidney failure. Hypertension is a major, reversible risk factor in people with diabetes for development of albuminuria, impaired kidney function, end-stage kidney disease and cardiovascular disease. Blood pressure control has been shown to be beneficial in people with diabetes in slowing progression of kidney disease and reducing cardiovascular events. However, randomised controlled trial evidence differs in type 1 and type 2 diabetes and different stages of CKD in terms of target blood pressure. Activation of the renin-angiotensin-aldosterone system (RAAS) is an important mechanism for the development and progression of CKD and cardiovascular disease. Randomised trials demonstrate that RAAS blockade is effective in preventing/ slowing progression of CKD and reducing cardiovascular events in people with type 1 and type 2 diabetes, albeit differently according to the stage of CKD. Emerging therapy with sodium glucose cotransporter-2 (SGLT-2) inhibitors, non-steroidal selective mineralocorticoid antagonists and endothelin-A receptor antagonists have been shown in randomised trials to lower blood pressure and further reduce the risk of progression of CKD and cardiovascular disease in people with type 2 diabetes. This guideline reviews the current evidence and makes recommendations about blood pressure control and the use of RAAS-blocking agents in different stages of CKD in people with both type 1 and type 2 diabetes.