Trends in mortality from gastrointestinal, hepatic, and pancreatic cancers in the United States: A comprehensive analysis (1999-2020).

Background and Aim: This study investigates temporal trends in gastrointestinal cancer-related mortality in the United States between 1999 and 2020, focusing on differences by sex, age, and race. Methods: We investigated the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research multiple causes of death database (Years 1999-2020) for gastrointestinal cancer-related mortality with a focus on the underlying cause of death. Results: A total of 3 115 243 gastrointestinal cancer-related deaths occurred from 1999 to 2020. The overall age-adjusted mortality rate decreased from 46.7 per 100 000 in 1999 to 38.4 per 100 000 in 2020. The average annual percent change (AAPC) for the study period was -0.9% (95% CI: -1.0%, -0.9%, P < 0.001), with no significant difference in AAPC between the sexes but some difference between races and related to individual cancers. African Americans and Asian Americans, and Pacific Islanders experienced a greater decrease in mortality compared with Whites. Mortality rates for American Indian and Alaskan Native populations also decreased significantly from 1999 to 2020 (P < 0.001). There were significant declines in esophageal, stomach, colon, rectal, and gallbladder cancer-related mortality but increases in the small bowel, anal, pancreatic, and hepatic cancer-related mortality (P < 0.001), with variation across different sexes and racial groups. Conclusion: While overall gastrointestinal cancer-related mortality declined significantly in the United States from 1999 to 2020, mortality from some cancers increased. Furthermore, differences between sexes and racial groups underscore crucial differences in gastrointestinal cancer mortality, highlighting areas for future research.

Artificial intelligence in gastrointestinal endoscopy: a comprehensive review.

Integrating artificial intelligence (AI) into gastrointestinal (GI) endoscopy heralds a significant leap forward in managing GI disorders. AI-enabled applications, such as computer-aided detection and computer-aided diagnosis, have significantly advanced GI endoscopy, improving early detection, diagnosis and personalized treatment planning. AI algorithms have shown promise in the analysis of endoscopic data, critical in conditions with traditionally low diagnostic sensitivity, such as indeterminate biliary strictures and pancreatic cancer. Convolutional neural networks can markedly improve the diagnostic process when integrated with cholangioscopy or endoscopic ultrasound, especially in the detection of malignant biliary strictures and cholangiocarcinoma. AI's capacity to analyze complex image data and offer real-time feedback can streamline endoscopic procedures, reduce the need for invasive biopsies, and decrease associated adverse events. However, the clinical implementation of AI faces challenges, including data quality issues and the risk of overfitting, underscoring the need for further research and validation. As the technology matures, AI is poised to become an indispensable tool in the gastroenterologist's arsenal, necessitating the integration of robust, validated AI applications into routine clinical practice. Despite remarkable advances, challenges such as operator-dependent accuracy and the need for intricate examinations persist. This review delves into the transformative role of AI in enhancing endoscopic diagnostic accuracy, particularly highlighting its utility in the early detection and personalized treatment of GI diseases.

Prediction of early-onset colorectal cancer mortality rates in the United States using machine learning.

INTRODUCTION: The current study, focusing on a significant US (United States) colorectal cancer (CRC) burden, employs machine learning for predicting future rates among young population. METHODS: CDC WONDER data from 1999 to 2022 was analyzed for CRC-related mortality in patients younger than 56 years. Temporal trends in age-adjusted mortality rates (AAMRs) were assessed via Joinpoint software. Future mortality rates were forecasted using an optimal Autoregressive Integrated Moving Average (ARIMA) model. RESULTS: From 1999 to 2022, we observed 150,908 deaths with CRC listed as the underlying cause, predominantly in males, with an upward trend in AAMR. The ARIMA model projects an increase in CRC mortality by 2035, estimating an average annual percent change (AAPC) of 1.3% overall, 1% for females, and 1.5% for males. CONCLUSION: Our study findings emphasize the need for more robust preventive measures to reduce future CRC mortality among younger population. These results have significant implications for public health policies, particularly for males under 56, and underscore the importance of early screening and lifestyle modifications.

Beyond Human Limits: Harnessing Artificial Intelligence to Optimize Immunosuppression in Kidney Transplantation.

The field of kidney transplantation is being revolutionized by the integration of artificial intelligence (AI) and machine learning (ML) techniques. AI equips machines with human-like cognitive abilities, while ML enables computers to learn from data. Challenges in transplantation, such as organ allocation and prediction of allograft function or rejection, can be addressed through AI-powered algorithms. These algorithms can optimize immunosuppression protocols and improve patient care. This comprehensive literature review provides an overview of all the recent studies on the utilization of AI and ML techniques in the optimization of immunosuppression in kidney transplantation. By developing personalized and data-driven immunosuppression protocols, clinicians can make informed decisions and enhance patient care. However, there are limitations, such as data quality, small sample sizes, validation, computational complexity, and interpretability of ML models. Future research should validate and refine AI models for different populations and treatment durations. AI and ML have the potential to revolutionize kidney transplantation by optimizing immunosuppression and improving outcomes. AI-powered algorithms enable personalized and data-driven immunosuppression protocols, enhancing patient care and decision-making. Limitations include data quality, small sample sizes, validation, computational complexity, and interpretability of ML models. Further research is needed to validate and enhance AI models for different populations and longer-term dosing decisions.

Increasing nonalcoholic fatty liver disease-related mortality rates in the United States from 1999 to 2022.

BACKGROUND: We examined trends in NAFLD-related mortality in the United States from 1999 to 2022, focusing on sex, racial differences, and specific age groups. METHODS: We analyzed age-adjusted mortality rates (AAMRs) for NAFLD-related deaths using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database and assessed differences between sex and racial groups. RESULTS: Between 1999 and 2022, NAFLD-related mortality rose from an age-adjusted mortality rate (AAMR) of 0.2 to 1.7 per 100,000, with an average annual percent change (AAPC) of 10.0% (p < 0.001). In all, 85.4% of the cases were reported after 2008. Females (0.2-2 per 100,000, AAPC: 11.7%, p < 0.001) saw a steeper increase than males (0.2-1.3 per 100,000, AAPC: 9.3%, p < 0.001). White individuals' AAMR rose from 0.2 to 1.9 per 100,000 (AAPC: 10.8%, p < 0.001). Asian or Pacific Islanders (AAPI) increased from 0.2 in 2013 to 0.5 in 2022 (AAPC: 12.13%, p = 0.002), and American Indians or Alaska Natives (AI/AN) from 1 in 2013 to 2.2 in 2022 (AAPC: 7.9%, p = 0.001). African Americans (AA) showed an insignificant change (0.3-0.5 per 100,000, AAPC: 0.7%, p = 0.498). Regarding age, individuals 45-64 saw AAMR rise from 0.3 to 1.2 per 100,000 (AAPC: 6.5%, p < 0.001), and those 65+ from 0.2 to 6 per 100,000 (AAPC: 16.5%, p < 0.001). No change was observed in the 25-44 age group (AAMR: 0.2 per 100,000, AAPC: 0.0%, p = 0.008). CONCLUSION: We report increased NAFLD-related mortality among both sexes and certain racial groups. The mortality rate increased for older populations, emphasizing the need for targeted public health measures and evidence-based interventions.

Seronegative Atypical Anti-Glomerular Basement Membrane Glomerulonephritis Associated With Thrombotic Microangiopathy: Case Report and Literature Analysis.

Anti-glomerular basement membrane (GBM) antibody nephritis is defined by linear immunofluorescence staining of GBM by immunoglobulin G (IgG), typically associated with GBM rupture, fibrinoid necrosis, and crescent formation. Clinically, the patients present with rapidly worsening renal function, often with hematuria. Typical renal pathologic findings include necrotizing and crescentic glomerulonephritis. In contrast, thrombotic microangiopathy (TMA) is characterized by microvascular thrombosis, which can also lead to acute kidney injury. Thrombotic microangiopathy is associated with some systemic diseases and has characteristic clinical features of microangiopathic hemolytic anemia, platelet consumption, and multiple organ failure. Anti-GBM nephritis associated with TMA has rarely been reported. We describe an unusual case of atypical anti-GBM disease without crescent formation or necrosis but with light microscopic and ultrastructural features consistent with endothelial cell injury and glomerular-limited TMA.

Rising alcohol-associated liver disease-related mortality rates in the United States from 1999 to 2022.

We examined trends in alcohol-associated liver disease (ALD)-related mortality in the United States from 1999 to 2022, focusing on sex, racial differences, and specific age groups. We analyzed age-adjusted mortality rates for ALD-related deaths using the CDC WONDER database and assessed differences between sex and racial groups. ALD-related mortality rates increased significantly between 1999 and 2022, with a more pronounced increase in females. White, Asian, Pacific Islander (AAPI), and American Indian or Alaska Native (AI/AN) groups showed significant uptrends in ALD-related mortality, while African Americans (AA) experienced a nonsignificant decline. Age-specific trends revealed substantial increases in crude mortality rates across various age groups, with the largest increase observed in the younger age groups of 25-34 years, with an average percent change of 11.12% from 2006 to 2022 (average annual percent change of 7.1% for the study period), and 35-44 years, which showed an average percent change of 17.2% from 2018 to 2022 (average annual percent change of 3.8% for the study period). This study reveals increased ALD-related mortality rates in the United States from 1999 to 2022, with disparities among sex, racial groups, and younger age groups. Continued monitoring and evidence-based interventions are needed to address the growing burden of ALD-related mortality, particularly in the younger population.

Incidental detection of operational tolerance in a deceased donor kidney transplant recipient lost to follow-up for more than 10 years: A case report and literature review.

Graft tolerance is a clinical state of absence of an immune response in the recipient toward a donor allograft without any exogenous immunosuppression. Although more prevalent in liver transplantation recipients, it has rarely been reported in renal transplant recipients. We present a 62-year-old deceased donor kidney transplant recipient who exhibited operational tolerance as they stopped immunosuppressant medications for more than 10 years and yet demonstrated stable graft function. Although various hypotheses, such as deletion, anergy, immunoregulation, and clonal exhaustion, have been experimentally validated, clinical "operational tolerance" of a renal allograft on a prolonged basis has been infrequently reported in the medical literature. This review intends to highlight possible etiologies and make clinicians aware of this possible rare condition to which more research is needed.

Reduction in Maintenance Immunosuppression in Kidney Transplant Recipients With Stable Donor-Derived Cell-Free DNA Measurements: A Case Series.

Personalization of maintenance immunosuppression in kidney transplant recipients has long remained a goal in the transplant community. The recent addition of donor-derived cell-free DNA assays to detect allograft rejection and monitor allograft health may permit for reductions in maintenance immunosuppression in recipients with stable levels. Herein, we described 5 patients with stable donor-derived cell-free DNA levels who underwent reduction in maintenance immunosuppression without precipitation of clinical rejection, proteinuria, or de novo donor specific antibody formation.

A rare case of AIDS co-infected with COVID-19 presenting with disseminated Herpes zoster complicated with CMV and Varicella zoster virus meningoencephalitis.

During the COVID-19 pandemic, numerous co-infections have been reported, with some studies indicating that patients with HIV/AIDS have worse outcomes when co-infected with COVID-19. Here, we present the case of a young adult male who presented with disseminated Varicella and was simultaneously diagnosed with AIDS and COVID-19 virus with several infection-related complications.  A 25-year-old African-American male presented to the Emergency Department with vesicular, blistering rashes in multiple dermatomes including his eyelids. The screening test in the ED was positive for COVID-19. Given his high-risk sexual history, he was tested for HIV which returned positive with a CD4 count of zero. He was started on IV antivirals for disseminated varicella with zoster ophthalmicus. The patient was intubated for worsening respiratory failure and required intensive care. During the hospital course, he developed worsening encephalopathy and CSF analysis was positive for CMV and VZV. The patient has a prolonged hospital stay and exhibited evidence of infectious CNS vasculitis and HIV myelopathy. Anti-retroviral therapy was started after the acute period and the patient showed slow but definite clinical improvement. To the best of our knowledge, this is the first case report of a patient with AIDS with COVID-19 and disseminated VZV and with multiple complex infection-related complications.

Rhizobium radiobacter-Induced Peritonitis: A Case Report and Literature Analysis.

Rhizobium radiobacter (R. radiobacter) is a gram-negative bacterium, primarily a soil contaminant and rarely pathogenic to humans. Only a few cases of peritonitis secondary to R. radiobacter have been reported worldwide. A 66-year-old male with end-stage renal disease who was on peritoneal dialysis (PD) developed R. radiobacter-induced peritonitis. We have treated the infection successfully with intraperitoneal antibiotics and managed to keep his PD catheter intact without interruption in PD treatment. More prolonged antibiotic therapy and frequent clinical follow-up is required to treat this infection. Better clinician awareness is needed to prevent this rare infection.

Elevated Anion Gap Metabolic Acidosis With High Osmolar Gap and Increased Serum Acetone Level: A Case Report.

Acetone poisoning, although not very common, can present with varied signs and symptoms. High acetone levels in serum can be due to exogenous exposure or endogenous production of acetone. Unlike certain alcohol toxicities, acetone does not cause high anion gap metabolic acidosis. A 69-year-old male presented to our service with shock and acute encephalopathy and required intensive care support. Initial laboratory investigation showed high anion gap metabolic acidosis with high osmolar gap. Serum acetone level was elevated. Clinicians need to be aware of how to elucidate such metabolic disturbances and associated toxicities.

Kinin B1 Receptor Mediates Renal Injury and Remodeling in Hypertension.

Despite many readily available therapies, hypertensive kidney disease remains the second most prevalent cause of end-stage renal disease after diabetes, and continues to burden patient populations and escalate morbidity and mortality rates. Kinin B1 receptor (B1R) activation has been shown to have a role in the development of hypertension, one of the major etiologies for chronic kidney disease. However, the role of B1R in hypertension induced renal injury and remodeling remains unexplored. Using a DOCA-salt-induced hypertensive mouse model, we investigated whether B1R deficiency reduces hypertensive renal injury and fibrosis. To further recognize the translational role of B1R, we examined the expression of B1R and its correlation with collagen deposition in renal biopsies from control and hypertensive kidney disease patients. Our data indicates that renal B1R expression was upregulated in the kidneys of DOCA-salt hypertensive mice. Genetic ablation of B1R protected the mice from DOCA-salt-induced renal injury and fibrosis by preventing inflammation and oxidative stress in the kidney. Cultured human proximal tubular epithelial cells expressed B1R and stimulation of B1R with an agonist resulted in increased oxidative stress. In human kidney biopsy samples, we found that the B1R immunoreactivity was not only significantly increased in hypertensive patients compared to normotensive patients, but also there is a positive correlation between B1R expression and renal fibrosis levels. Taken together, our results identify a critical role of B1R in the development of inflammation and fibrosis of the kidney in hypertension.

In vitro and in vivo correlates of physiological and neoplastic human Fallopian tube stem cells.

High-grade serous cancer (HGSC) progresses to advanced stages without symptoms and the 5-year survival rate is a dismal 30%. Recent studies of ovaries and Fallopian tubes in patients with BRCA1 or BRCA2 mutations have documented a pre-metastatic intramucosal neoplasm that is found almost exclusively in the Fallopian tube, termed 'serous tubal intraepithelial carcinoma' or STIC. Moreover, other proliferations, termed p53 signatures, secretory cell outgrowths (SCOUTs), and lower-grade serous tubal intraepithelial neoplasms (STINs) fall short of STIC but share similar alterations in expression, in keeping with an underpinning of genomic disturbances involved in, or occurring in parallel with, serous carcinogenesis. To gain insight into the cellular origins of this unique tubal pathway to high-grade serous cancer, we cloned and both immortalized and transformed Fallopian tube stem cells (FTSCs). We demonstrated that pedigrees of FTSCs were capable of multipotent differentiation and that the tumours derived from transformed FTSCs shared the histological and molecular features of HGSC. We also demonstrated that altered expression of some biomarkers seen in transformed FTSCs and HGSCs (stathmin, EZH2, CXCR4, CXCL12, and FOXM1) could be seen as well in immortalized cells and their in vivo counterparts SCOUTs and STINs. Thus, a whole-genome transcriptome analysis comparing FTSCs, immortalized FTSCs, and transformed FTSCs showed a clear molecular progression sequence that is recapitulated by the spectrum of accumulated perturbations characterizing the range of proliferations seen in vivo. Biomarkers unique to STIC relative to normal tubal epithelium provide a basis for novel detection approaches to early HGSC, but must be viewed critically given their potential expression in lesser proliferations. Perturbations shared by both immortalized and transformed FTSCs may provide unique early targets for prevention strategies. Central to these efforts has been the ability to clone and perpetuate multipotent FTSCs.

Epidemiological associations between iron and cardiovascular disease and diabetes.

Disruptions in iron homeostasis are linked to a broad spectrum of chronic conditions including cardiovascular, malignant, metabolic, and neurodegenerative disease. Evidence supporting this contention derives from a variety of analytical approaches, ranging from molecular to population-based studies. This review focuses on key epidemiological studies that assess the relationship between body iron status and chronic diseases, with particular emphasis on atherosclerosis ,metabolic syndrome and diabetes. Multiple surrogates have been used to measure body iron status, including serum ferritin, transferrin saturation, serum iron, and dietary iron intake. The lack of a uniform and standardized means of assessing body iron status has limited the precision of epidemiological associations. Intervention studies using depletion of iron to alter risk have been conducted. Genetic and molecular techniques have helped to explicate the biochemistry of iron metabolism at the molecular level. Plausible explanations for how iron contributes to the pathogenesis of these chronic diseases are beginning to be elucidated. Most evidence supports the hypothesis that excess iron contributes to chronic disease by fostering excess production of free radicals. Overall, epidemiological studies, reinforced by basic science experiments, provide a strong line of evidence supporting the association between iron and elevated risk of cardiovascular disease and diabetes. In this narrative review we attempt to condense the information from existing literature on this topic.