Motivation: Predicting gene-disease associations (GDAs) is the problem to determine which gene is associated with a disease. GDA prediction can be framed as a ranking problem where genes are ranked for a query disease, based on features such as phenotypic similarity. By describing phenotypes using phenotype ontologies, ontology-based semantic similarity measures can be used. However, traditional semantic similarity measures use only the ontology taxonomy. Recent methods based on ontology embeddings compare phenotypes in latent space; these methods can use all ontology axioms as well as a supervised signal, but are inherently transductive, i.e., query entities must already be known at the time of learning embeddings, and therefore these methods do not generalize to novel diseases (sets of phenotypes) at inference time. Results: We developed INDIGENA, an inductive disease-gene association method for ranking genes based on a set of phenotypes. Our method first uses a graph projection to map axioms from phenotype ontologies to a graph structure, and then uses graph embeddings to create latent representations of phenotypes. We use an explicit aggregation strategy to combine phenotype embeddings into representations of genes or diseases, allowing us to generalize to novel sets of phenotypes. We also develop a method to make the phenotype embeddings and the similarity measure task-specific by including a supervised signal from known gene-disease associations. We apply our method to mouse models of human disease and demonstrate that we can significantly improve over the inductive semantic similarity baseline measures, and reach a performance similar to transductive methods for predicting gene-disease associations while being more general. Availability and Implementation: https://github.com/bio-ontology-research-group/indigena
Preventative care in inflammatory bowel disease (IBD) is essential to reduce disease- and therapy-related risks. Influenza vaccination (amongst others) is routinely recommended1, yet uptake in people with IBD remains suboptimal despite known benefits and safety2,3. Barriers may include vaccine hesitancy, limited awareness, and fragmented care. We assessed real-world influenza vaccination uptake in IBD and factors linked to suboptimal adherence. People with IBD eligible for government funded influenza vaccination (individuals aged 5–64 years with immunosuppression and all ≥65 years) were included. De-identified data from the Crohn’s Colitis Care clinical quality registry (15 clinical sites across Australia and New Zealand) were analysed in October 2025. Eligibility was assessed in 6539 people, of whom 3629 (mean age 43.2, 53.8% male) were eligible for nationally funded influenza vaccination between February to October 2025. Within this cohort, 2331 (64.2%) had Crohn’s Disease (CD), 1210 (33.3%) had ulcerative colitis (UC), and 88 (2.4%) had IBD-unclassified (IBD-U). The majority had a disease duration >5 years (67.0%). Influenza vaccination uptake was recorded as 9.5% (range 5.6%-38.7% across individual sites, mean 12.8%) in this cohort with no significant differences between CD, UC, and IBD-U. Rates did not significantly differ between individuals aged ≥65 and those <65 years (p = 0.298). Across a continuous range, a gradual increase in predicted vaccination probability rose approximately 7.5% at age 28 to 11.5% at age 64 (p = 0.006). There was a significant association between socioeconomic status (SEIFA decile) and vaccination uptake (p < 0.001), with rates increasing from 6.6% (most disadvantaged) to 17.6% (most advantaged). Similarly, people with post-secondary education were more likely to be vaccinated (13.5%) compared to those without (8.0%) (p = 0.005). Vaccination rates were similar between people residing in metropolitan (9.7%) and non-metropolitan (8.7%) locales. In a logistic regression model, longer disease duration was significantly associated with higher vaccination uptake (OR = 1.023 per year, p = 0.001). The predicted probability of vaccination increased from 8.1% at 3 years to 12.9% at 26 years of disease duration. Influenza vaccination uptake and documentation among people with IBD in a real-world Australasian cohort is low, indicating a persistent gap between guidelines and practice. Strategies to ensure awareness of the need for vaccination and enable easy access and documentation are needed. Integrating consumer controlled digital tools into routine care may help address system fragmentation and enhance preventative health adherence and documentation. References: 1. Farraye FA, Melmed GY, Lichtenstein GR, Barnes EL, Limketkai BN, Caldera F, Kane S. ACG clinical guideline update: Preventive care in inflammatory bowel disease. Official journal of the American College of Gastroenterology| ACG. 2025 Jul 1;120(7):1447-73. doi: 10.1016/j.cgh.2024.12.011 2. Xu F, Dahlhamer JM, Terlizzi EP, Wheaton AG, Croft JB. Receipt of preventive care services among US adults with inflammatory bowel disease, 2015–2016. Digestive diseases and sciences. 2019 Jul 15;64(7):1798-808. doi: 10.1007/s10620-019-05494-w 3. Nakafero G, Grainge MJ, Card T, Mallen CD, Van-Tam JS, Abhishek A. Uptake, safety and effectiveness of inactivated influenza vaccine in inflammatory bowel disease: a UK-wide study. BMJ Open Gastroenterology. 2024 Jun 1;11(1). doi: 10.1136/ bmjgast-2024-001370 Conflict of interest: Dr. Chan, Patrick: No conflicts of interest. Wu, Rodger: No conflicts of interest. Knowles, Simon Robert: No conflicts of interest. Connor, Susan Jane: Research Support: Abbvie, Agency for Clinical Innovation, Amgen, BMS, Chiesi, Celltrion, DrFalk, Ferring, Janssen, Medical Research Future Fund, Pfizer, South Western Sydney Local Health District, Sydney Partnership for Health, Research and Enterprise, Takeda and The Leona M and Harry B Helmsley Charitable Trust Ad Boards: Abbvie, Amgen, BMS, Celltrion, Eli Lilly, Ferring, GSK, Janssen, Organon, Pfizer, Takeda Speaker Fees: Abbvie, Cornerstones Health, Dr Falk, Ferring, Janssen, Pfizer, Sandoz, Sydney IBD School, Takeda Educational Support: DrFalk, Sandoz, Takeda Andrews, Jane Mary: Grant: This project is supported from a grant by The Leona M. and Harry B. Helmsley Charitable Trust. The work I will present was funded via CCCure. CCCure’s funding sources include grants for research and payments for data reports from Pharma including AbbVie, J & J, Takeda, Celltrion, Falk, Ferring, BMS, Janssen, Pfizer, Sandoz
Vision Loss Expert Group of the Global Burden of Disease , the GBD 2019 Blindness and Vision Impairment Collabora
ABSTRACT Purpose To assess burden of blindness and visual impairment (VI) in Sub-Saharan Africa (SSA) as of 2020, the planned end point of the Vision 2020 program. Methods A systematic review and meta-analysis assessed burden, in the better eye, of blindness (presenting distance visual acuity, VA < 3/60), moderate and severe vision impairment (MSVI; VA < 6/18 but ≥ 3/60) and mild vision impairment (VA < 6/12 and ≥ 6/18); and also functional presbyopia (<N6 or N8 in the presence of ≥ 6/12 best-corrected distance visual acuity) in SSA. Results In 2020, an estimated 5,083,000 people (95%Uncertainty Interval, UI, 4,474,000–5,696,000) in SSA were bilaterally blind; 20442,000 more (95%UI 18,568,000–22,430,000) had MSVI. The age-standardized prevalence of blindness in SSA is the highest for any GBD super-region, nearly double the world average (0.99%, 95%UI, 0.85–1.12; vs 0.52%, 95% UI, 0.46–0.59 respectively). The Western (4.15%) and Eastern (3.79%) SSA sub-regions had the highest age-standardized prevalence of blindness for the 50+ age group amongst SSA sub-regions. Improvement in age-specific prevalence since 2000 was less than the Vision 2020 target (−25%) for all subcategories of VI; improvement in blindness was the only category close to the goal (about 80–100% of goal across SSA sub-regions). Conclusions The SSA age-specific prevalence of VI has generally improved since 2000, especially for blindness. However, the number of VI cases has increased with population growth and aging, and Vision 2020 targets were not met. Because most causes of VI require individual-level clinical care, large increases in training and eye care delivery systems development/financing are critical areas of focus.
Abstract Aims/hypothesis The aim of this study was to identify shared and distinct metabolite profiles prospectively associated with nephropathy, retinopathy and neuropathy at 15 years’ follow-up among 1947 participants in the Diabetes Prevention Program Outcomes Study, the long-term follow-up of the Diabetes Prevention Program (DPP). Methods We applied bootstrapped LASSO to 353 annotated metabolites to identify metabolites associated with one or more complication. For these metabolite hits, we tested for an interaction with DPP treatment arm, and ran multivariable models for the pooled sample or within treatment group as appropriate. Results At follow-up, 572 participants had one or more complication ( n =277 nephropathy, n =194 retinopathy, n =212 neuropathy). Of 105 metabolites that predicted any complication, 74 predicted one, 27 predicted two, and four predicted all three. In a pooled analysis of 69 metabolites without treatment arm interactions, histidine predicted lower odds of nephropathy (OR 0.75; 95% CI 0.69, 0.88), and serine predicted lower odds of nephropathy (OR 0.69; 95% CI 0.58, 0.82) and neuropathy (OR 0.68; 95% CI 0.56, 0.84). Of 36 metabolites that interacted with treatment arm, higher N -carbamoyl-β-alanine predicted greater odds of nephropathy (OR 1.99; 95% CI 1.38, 2.99) and C22:0-sphingomyelin predicted lower odds of neuropathy (OR 0.54; 95% CI 0.37, 0.77) in the metformin arm. In the lifestyle intervention arm, quinolinic acid predicted greater odds of neuropathy (OR 1.64; 95% CI 1.24, 2.19). These estimates accounted for sex, race, baseline age, BMI and smoking, and time elapsed during follow-up. Further adjustment for HbA 1c during follow-up, incident diabetes and eGFR did not change the results. Conclusions/interpretation The existence of distinct metabolite profiles associated with single microvascular complications highlights the importance of characterising pathophysiological mechanisms specific to each complication, in addition to studying shared mechanisms across multiple complications. Graphical Abstract
Trilochan Panthee, Khanak K. Nandolia, Pankaj Sharma
et al.
Objective The aim of this study was to assess the value of shear wave elastography (SWE) to predict the presence of esophageal varices (EVs) and to predict high-grade EV in patients with chronic liver disease (CLD).
Internal medicine, Diseases of the digestive system. Gastroenterology
Ananya Joshi, George Khoury, Christodoulas Floudas
Alzheimer's disease is characterized by dangerous amyloid plaques formed by deposits of the protein Beta-Amyloid aggregates in the brain. The specific amino acid sequence that is responsible for the aggregates of Beta-Amyloid is lys-leu-val-phe-phe (KLVFF). KLVFF aggregation inhibitors, which we design in this paper, prevent KLVFF from binding with itself to form oligomers or fibrils (and eventually plaques) that cause neuronal death. Our binder-blocker peptides are designed such that, on one side, they bind strongly to KLVFF, and on the other side, they disrupt critical interactions, thus preventing aggregation. Our methods use optimization techniques and molecular simulations and identify 10 candidate sequences for trial of the 3.2 million possible sequences. This approach for inhibitor identification can be generalized to other diseases characterized by protein aggregation, such as Parkinson's, Huntington's, and prion diseases.
Discovery gene-disease links is important in biology and medicine areas, enabling disease identification and drug repurposing. Machine learning approaches accelerate this process by leveraging biological knowledge represented in ontologies and the structure of knowledge graphs. Still, many existing works overlook ontologies explicitly representing diseases, missing causal and semantic relationships between them. The gene-disease association problem naturally frames itself as a link prediction task, where embedding algorithms directly predict associations by exploring the structure and properties of the knowledge graph. Some works frame it as a node-pair classification task, combining embedding algorithms with traditional machine learning algorithms. This strategy aligns with the logic of a machine learning pipeline. However, the use of negative examples and the lack of validated gene-disease associations to train embedding models may constrain its effectiveness. This work introduces a novel framework for comparing the performance of link prediction versus node-pair classification tasks, analyses the performance of state of the art gene-disease association approaches, and compares the different order-based formalizations of gene-disease association prediction. It also evaluates the impact of the semantic richness through a disease-specific ontology and additional links between ontologies. The framework involves five steps: data splitting, knowledge graph integration, embedding, modeling and prediction, and method evaluation. Results show that enriching the semantic representation of diseases slightly improves performance, while additional links generate a greater impact. Link prediction methods better explore the semantic richness encoded in knowledge graphs. Although node-pair classification methods identify all true positives, link prediction methods outperform overall.
Understanding disease relationships through blood biomarkers offers a pathway toward data driven taxonomy and precision medicine. We constructed a digital blood twin from 103 disease signatures comprising longitudinal hematological and biochemical analytes. Profiles were standardized into a unified disease analyte matrix, and pairwise Pearson correlations were computed to assess similarity. Hierarchical clustering revealed robust grouping of hematopoietic disorders, while metabolic, endocrine, and respiratory diseases were more heterogeneous, reflecting weaker cohesion. To evaluate structure, the tree was cut at a stringent threshold, yielding 16 groups. Enrichment of the largest heterogeneous cluster (Cluster 9) showed convergence on cytokine-signaling pathways, indicating shared immunological and inflammatory mechanisms across clinical boundaries. Dimensionality reduction with PCA and UMAP corroborated these results, consistently separating hematological diseases. Random Forest feature selection identified neutrophils, mean corpuscular volume, red blood cell count, and platelets as the most discriminative analytes, reinforcing hematopoietic markers as key drivers. Collectively, these findings show that blood-derived digital signatures can recover clinically meaningful clusters while revealing mechanistic overlaps across categories. The coherence of hematological diseases contrasts with the dispersion of systemic and metabolic disorders, underscoring both the promise and limits of blood-based classification. This framework highlights the potential of integrating routine laboratory data with computational methods to refine disease ontology, map comorbidities, and advance precision diagnostics.
Mariza Fevereiro-Martins, A. C. Santos, Carlos Marques-Neves
et al.
Retinal neurodevelopment, vascularization, homeostasis, and stress response are influenced by factors such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tyrosine hydroxylase (TH), and erythropoietin (EPO). As retinopathy of prematurity (ROP) is a neurovascular retinal disease, this study analyzed the contributions of NGF (rs6330), BDNF (rs7934165), TH (rs10770141), and EPO (rs507392) genetic functional polymorphisms to the modulation of hematological and biochemical parameters of the first week of life and their association with ROP development. A multicenter cohort of 396 preterm infants (gestational age < 32 weeks or birth weight < 1500 g) was genotyped using MicroChip DNA and iPlex MassARRAY® platform. Multivariate regression followed univariate assessment of ROP risk factors. NGF (GG) genotype was associated with a higher ROP risk (OR = 1.79), which increased further (OR = 2.38) when epistatic interactions with TH (allele C) and BDNF (allele G) were present. Significant circulating biomarker differences, including bilirubin, erythrocytes, monocytes, neutrophils, lymphocytes, and platelet markers, were found between ROP and non-ROP groups, with variations depending on the polymorphism. These findings suggest that NGF (rs6330) and its interactions with related genes contribute to ROP risk, providing valuable insights into the genetic and biological mechanisms underlying the disease and identifying potential predictive biomarkers.
Ibrahim Eker, Hamide Nur Çevik Özdemir, F. Yılmaz
et al.
Objective Preimplantation genetic diagnosis (PGD) with human leukocyte antigen (HLA) typing represents a significant advancement in treating inherited hematological disorders, particularly thalassemia major. This technology enables the birth of healthy children who can serve as compatible stem cell donors for their affected siblings. Türkiye is a world leader in both PGD+HLA typing technology and hematopoietic stem cell transplantation (HSCT) from savior siblings born through PGD+HLA typing. This study investigated the experiences of Turkish parents who underwent successful savior sibling procedures using PGD+HLA typing and then successful HSCT from the savior sibling for the treatment of the child with thalassemia major. We aimed to understand the medical, psychological, and sociocultural dimensions of this complex process within the Turkish healthcare context. Materials and Methods A qualitative study was undertaken using a descriptive phenomenological approach. In-depth interviews were conducted with parents from 16 families who had successfully completed PGD+HLA matching and subsequent stem cell transplantation processes from the savior sibling to the child with thalassemia. Data were analyzed using Colaizzi’s seven-step method and MAXQDA 20.0 software. Results The analysis revealed six main themes: disease stage, treatment, recovery process, social/family, support systems, and recommendations. Parents reported significant emotional challenges but demonstrated unexpected resilience. Religious and cultural factors played nuanced roles, with most parents viewing the process as compatible with their beliefs. Economic burdens, prolonged hospitalizations, and geographical access to treatment centers emerged as key challenges. Extended family support and professional healthcare guidance were identified as crucial support mechanisms. Conclusion This study highlights the complex interplay between advanced medical technologies and traditional values in Turkish society. The findings emphasize the need for comprehensive and culturally sensitive support systems and long-term follow-up for families. The results suggest the value of implementing multidisciplinary care teams and developing specialized support programs for families undergoing savior sibling procedures.
N. Sánchez-Varela, S. Cinza-Sanjurjo, T. Danif-Ferreira
et al.
Objective: The objective of this study was to calculate the epidemiological impact of metabolic dysfunction associated with fatty liver disease (MAFLD) and hepatic fibrosis in primary care (PC). Secondarily, we assessed the correlation between serological markers (FIB-4, ELF test), abdominal ultrasound, and transient elastography in the early detection of MAFLD. Methods: An observational prospective study was designed to determine the prevalence of MAFLD and to assess the correlation between complementary tests. Patients were recruited from five health centres. Eligible participants were adults aged between 18 and 70 years with at least one metabolic risk factor, including being overweight (BMI 25–29.9 kg/m2) or obese (BMI > 30 kg/m2), or diagnosed with type 2 diabetes mellitus (T2DM), dyslipidemia, or metabolic syndrome. The prevalence of MAFLD was calculated. Correlations between diagnostic tests were evaluated using Pearson’s correlation coefficient. Results: A total of 98 patients was included. Using CAP (controlled attenuation parameter) measurements, the prevalence of MAFLD was found to be 67.7%, and the prevalence of hepatic fibrosis was 6.5%. The correlation between conventional ultrasound and CAP from FibroScan® for the diagnosis of MAFLD was low and not statistically significant (0.160 [95% CI: −0.100; 0.400], p = 0.226). In contrast, the diagnosis of hepatic fibrosis using FibroScan® in PC showed a high correlation with diagnoses performed in gastroenterology department (0.942 [95% CI: 0.844; 0.979], p < 0.001). The correlation with biochemical markers was low and not statistically significant for both FIB-4 (0.125 [95% CI: −0.129; 0.363], p = 0.334) and the ELF test (0.159 [95% CI: −0.111; 0.407], p = 0.246). Conclusions: Two out of three patients with metabolic risk factors were diagnosed with MAFLD, while hepatic fibrosis diagnoses were uncommon. These results reinforce the validity of using FibroScan® in PC.
Tóm tắt Đặt vấn đề: Ung thư trực tràng là một bệnh lý ác tính thường gặp của đường tiêu hoá và phẫu thuật là phương pháp điều trị chủ yếu. Báo cáo đầu tiên về việc sử dụng hệ thống Robot Da Vinci để thực hiện phẫu thuật cắt trước cho ung thư trực tràng là của tác giả Pier Cristoforo Giulianotti và các đồng nghiệp vào năm 2001. Cho đến nay, phẫu thuật robot tại Việt Nam ngày càng được ứng dụng nhiều hơn nhưng chưa có nhiều nghiên cứu. Nghiên cứu này nhằm đánh giá kết quả lâu dài ở những người bệnh được phẫu thuật robot cắt trực tràng thấp tại bệnh viện Chợ Rẫy. Đối tượng và phương pháp nghiên cứu: Nghiên cứu mô tả loạt ca. Chọn lựa các người bệnh ung thư trực tràng thấp có sử dụng Robot Da vinci trong phẫu thuật cắt trực tràng thấp. Kết quả: Từ tháng 01/2018 đến tháng 12/2023. Trong 27 người bệnh, tuổi trung vị là 62 ± 11 tuổi, 71,4% nữ giới. 62.96% u ở vị trí 1/3 giữa, 37,04% u ở vị trí 1/3 dưới. Loại phẫu thuật: 71,07% phẫu thuật cắt trước thấp; 25,93% thực hiện cắt trực tràng thấp gian cơ thắt nối ống hậu môn. Tỉ lệ biến chứng chung là 3,7%. Thời gian theo dõi trung vị: 42 tháng (12 - 52). Không có ca nào tái phát, di căn xa là 4 ca (14,81%), tử vong 1 ca (3,7%). Kết luận: Robot mang lại sự đổi mới công nghệ và nhiều lợi ích trong phẫu thuật cắt trực tràng thấp so với Phẫu thuật nội soi nhưng cũng đối mặt với nhiều khó khăn và thách thức. Từ khóa: phẫu thuật robot cắt trực tràng thấp, phẫu thuật robot cắt trực tràng gian cơ thắt nối ống hậu môn, ung thư trực tràng. Robotic surgery in low rectal resection: techniques and long-term outcomes Tran Phung Dung Tien, Duong Minh Nhut Cho Ray Hospital Abtract Introduction: Rectal cancer is a common malignancy of the digestive tract, and surgical intervention is the primary treatment modality. The first report on the use of the da Vinci robotic system to perform an anterior resection for rectal cancer was published by Pier Cristoforo Giulianotti and colleagues in 2001. Although robotic surgery is increasingly utilized in Vietnam, however, there are few reports on this topic. This study aims to \ evaluate the long-term outcomes of patients undergoing robotic low rectal resection at Cho Ray Hospital. Patients and Methods: This was a descriptive case series. We selected patients with low rectal cancer who underwent robotic resection using the Da Vinci system. Results: From January 2018 to December 2023, a total of 27 patients were enrolled. The median age was 62 ± 11 years, and 71.4% were female. Tumors were located in the middle third of the rectum accounted for 62.96% and the lower third in 37.04%. Regarding surgical procedures, 71.07% underwent low anterior resection, and 25.93% underwent intersphincteric resection with anastomosis to the anal canal. The overall complication rate was 3.7%. The median follow-up was 42 months (range: 12–52). No local recurrences were observed, whereas 4 patients (14.81%) developed distant metastases, and there was 1 death (3.7%). Conclusions: Robotic surgery provides technological innovation and numerous advantages in low rectal resection compared to laparoscopic surgery but also faces several difficulties and challenges. Keywords: robotic low rectal resection, robotic surgery, rectal cancer. Tài liệu tham khảo Giulianotti PC, Coratti A, Angelini M, et al. Robotics in general surgery: personal experience in a large community hospital. Archives of surgery. 2003;138(7):777-784. Liu G, Zhang S, Zhang Y, et al. Robotic surgery in rectal cancer: potential, challenges, and opportunities. Current Treatment Options in Oncology. 2022;23(7):961-979. Alipouriani A, Gorgun E. Robotic Rectal Cancer Surgery: Current Controversies. Current Surgery Reports. 2024;12(6):122-128. Ando M, Matsuda T, Sawada R, et al. Feasibility and safety of robotic surgery for low rectal cancer combined with transanal total mesorectal excision. Langenbeck’s Archives of Surgery. 2023;408(1):129. Formisano G, Ferraro L, Salaj A, et al. Robotic Total Mesorectal Excision for Low Rectal Cancer: A Narrative Review and Description of the Technique. Journal of Clinical Medicine. 2023;12(14):4859. Tsukamoto S, Nishizawa Y, Ochiai H, et al. Surgical outcomes of robot-assisted rectal cancer surgery using the da Vinci Surgical System: a multi-center pilot Phase II study. Japanese Journal of Clinical Oncology. 2017;47(12):1135-1140. Wu H, Guo R, Li H. Short-term and long-term efficacy in robot-assisted treatment for mid and low rectal cancer: a systematic review and meta-analysis. International Journal of Colorectal Disease. 2023;39(1):7. Pigazzi A, Ellenhorn J, Ballantyne G, et al. Robotic-assisted laparoscopic low anterior resection with total mesorectal excision for rectal cancer. Surgical Endoscopy and Other Interventional Techniques. 2006;20:1521-1525. Holmer C, Kreis ME. Systematic review of robotic low anterior resection for rectal cancer. Surgical Endoscopy. 2018;32:569-581. Araujo SEA, Seid VE, Klajner S. Robotic surgery for rectal cancer: current immediate clinical and oncological outcomes. World Journal of Gastroenterology: WJG. 2014;20(39):14359. Farah E, Abreu AA, Rail B, et al. Perioperative outcomes of robotic and laparoscopic surgery for colorectal cancer: a propensity score-matched analysis. World Journal of Surgical Oncology. 2023;21(1):272. Kapilraj R, Emmanuel A, Kowthaman B, et al. A Review of Robotic Surgery in Colorectal Surgery. Cureus. 2023;15(4) Download file PDF
Sex differences in AKI continue to be identified. Generally, women are protected from AKI when compared to men. Much of the protection exhibited in women is diminished after menopause. These sex and age effects have also been noted in animal models of AKI. Gonadal hormones, as modifiers of incidence, severity, and progression of AKI, have been offered as likely contributors to this sex and age effect. In animal models of AKI, estrogen and testosterone seem to modulate susceptibility. Questions remain however regarding cellular and molecular changes that are initiated by modulation of these hormones because both estrogen and testosterone have effects across cell types that play a role in AKI. Although findings have largely been informed by studies in males, molecular pathways that are involved in the initiation and progression of AKI may be modulated by gonadal hormones. Compounding the hormone-receptor effects are developmental effects of sex chromosomal complement and epigenetic influences that may confer sex-based baseline differences in gene and protein expression, and gene dosage effects of X inactivation and escape on molecular pathways. Elucidation of sex-based protection may afford a more complete view of AKI and potential therapeutic interventions. Furthermore, the effect on susceptibility to AKI in transgender patients, who receive life-altering and essential gender-affirming hormone therapy, requires greater attention. In this review, several potential contributors to the sex differences observed in humans and animal models are discussed.
Abstract Background While significant research exists on gut microbiota changes after anti-tumor necrosis factor-alpha (anti TNF-α) therapy for ulcerative colitis, little is known about the longitudinal changes related to the effects of anti TNF-α. This study aimed to investigate the dynamics of gut microbiome changes during anti TNF-α (adalimumab) therapy in patients with ulcerative colitis (UC). Results The microbiota composition was affected by the disease severity and extent in patients with UC. Regardless of clinical remission status at each time point, patients with UC exhibited microbial community distinctions from healthy controls. Distinct amplicon sequence variants (ASVs) differences were identified throughout the course of Adalimumab (ADA) treatment at each time point. A notable reduction in gut microbiome dissimilarity was observed only in remitters. Remitters demonstrated a decrease in the relative abundances of Burkholderia-Caballeronia-Paraburkholderia and Staphylococcus as the treatment progressed. Additionally, there was an observed increase in the relative abundances of Bifidobacterium and Dorea. Given the distribution of the 48 ASVs with high or low relative abundances in the pre-treatment samples according to clinical remission at week 8, a clinical remission at week 8 with a sensitivity and specificity of 72.4% and 84.3%, respectively, was predicted on the receiver operating characteristic curve (area under the curve, 0.851). Conclusions The gut microbiota undergoes diverse changes according to the treatment response during ADA treatment. These changes provide insights into predicting treatment responses to ADA and offer new therapeutic targets for UC.
Diseases of the digestive system. Gastroenterology
Acute Severe Ulcerative Colitis (ASUC) is a well-known and potentially fatal disease state, characterized by symptoms of systemic toxicity including fever, severe anemia, elevated inflammatory markers, and autonomic instability. The life-threatening nature of this condition requires clinicians to make prompt diagnoses and take rapid action, either directing patients towards surgical interventions or medical management. Failure to treat ASUC may lead to toxic dilation of the colon, hemorrhage, or sepsis. Current algorithms suggest the use of intravenous (IV) corticosteroids upon diagnosis, with transition to oral corticosteroids, calcineurin inhibitors or tumor necrosis factor (TNF) inhibitors upon reduction of severe symptoms for candidates deemed to be amenable to medical management. Within these classes, TNF inhibitors such as Infliximab (IFX) have proven to be the most safe, efficacious, and tolerable for patients. While IFX has much data supporting its benefits in achieving short term remission, there are still high rates of long-term need for colectomy and failure to maintain remission. This is due to interactions between the inflamed gastrointestinal tract, the increased metabolic activity seen in ASUC, and intrinsic pharmacodynamic properties of IFX. Certain novel studies suggest that Janus Kinase (JAK-STAT) inhibitors such as Tofacitinib and Upadacitinib are potent agents to salvage clinical remission achieved by IFX, upon its failure. Here we discuss methods to optimize the dosing of IFX to maximize its efficacy, while exploring recent work done on the safety and efficacy of JAK-STAT inhibitors as a salvage therapy, therefore suggesting a novel treatment algorithm to improve clinical outcomes in medically managed ASUC patients.
Diseases of the digestive system. Gastroenterology
Abstract Background H. pylori infection has been recognized as a type 1 carcinogen of the gastric malignancy; therefore, early diagnosis and treatment are the corner stone of eradication. Recent findings have also shown that atrophy and intestinal metaplasia remain after successful eradication, which moderately increases the risk of gastric cancer compared with those who have never infected, so the evaluation of gastric mucosa during gastroscopy is important. Aims We aimed to describe and summarize the reliable literature and proposed features of H. pylori infection status and gastritis in research on newly developed endoscopic models that influence clinical practice. In the result, conventional white light endoscopic, image‐enhanced endoscopic models, and studies related to the Kyoto classification of gastritis were searched and reviewed. Results Kyoto classification of gastritis and modified Kyoto classification scoring model for gastritis using conventional white light image (CWLI) endoscopy is an effective tool for evaluating current H. pylori infection status, past infections, eradications, noninfections, and pre‐cancerous conditions. This model is widely used, low cost, and time‐efficient, and is supported by recent findings. Advanced image‐enhanced endoscopic models combined with magnifying endoscopy provide more clear endoscopic features for H. pylori infection status and early gastric cancer. Conclusion According to H pylori infection status, endoscopic prediction of gastric mucosal surface architecture analysis is possible, which influences clinical management. Endoscopic models might lead us to accurate and early diagnose of H. pylori infection status and may not be effective only for the eradication of H. pylori infection but also in the detection of early gastric cancer status.
Diseases of the digestive system. Gastroenterology