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World Journal of Gastroenterology Jun 2024Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory... (Review)
Review
Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome, multiple organ failure, and death. Despite extensive studies on the pathogenicity of SARS-CoV-2, its impact on the hepatobiliary system remains unclear. While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels, the exact source of this damage is not fully understood. Proposed mechanisms for injury include direct cytotoxicity, collateral damage from inflammation, drug-induced liver injury, and ischemia/hypoxia. However, evidence often relies on blood tests with liver enzyme abnormalities. In this comprehensive review, we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients, drawing from liver biopsies, complete autopsies, and liver analyses. We present evidence of the direct impact of SARS-CoV-2 on the liver, substantiated by observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes, including mitochondrial swelling, endoplasmic reticulum dilatation, and hepatocyte apoptosis. Additionally, we describe the diverse liver pathology observed during COVID-19 infection, encompassing necrosis, steatosis, cholestasis, and lobular inflammation. We also discuss the emergence of long-term complications, notably COVID-19-related secondary sclerosing cholangitis. Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.
Topics: Humans; COVID-19; Liver; SARS-CoV-2; Liver Diseases; Hepatocytes
PubMed: 38947288
DOI: 10.3748/wjg.v30.i22.2866 -
Cureus Jun 2024Cushing's disease (CD) is a rare and serious condition characterized by a persistent increase in cortisol levels, resulting in various complications across multiple...
Cushing's disease (CD) is a rare and serious condition characterized by a persistent increase in cortisol levels, resulting in various complications across multiple bodily systems. Elderly individuals often face a multitude of chronic illnesses and geriatric syndromes, which can complicate the diagnosis and treatment of CD in this demographic. This case study details the presentation of an elderly patient with adrenocorticotropic hormone (ACTH)-dependent CD, who initially presented with an acute exacerbation of chronic obstructive pulmonary disease. The article delves into the unique onset characteristics and treatment strategies for CD in the elderly, providing valuable insights for the comprehensive management of similar clinical cases.
PubMed: 38947141
DOI: 10.7759/cureus.63277 -
MedRxiv : the Preprint Server For... Jun 2024Post-Acute Sequelae of SARS-CoV-2 infection (PASC), also known as Long-COVID, encompasses a variety of complex and varied outcomes following COVID-19 infection that are...
Post-Acute Sequelae of SARS-CoV-2 infection (PASC), also known as Long-COVID, encompasses a variety of complex and varied outcomes following COVID-19 infection that are still poorly understood. We clustered over 600 million condition diagnoses from 14 million patients available through the National COVID Cohort Collaborative (N3C), generating hundreds of highly detailed clinical phenotypes. Assessing patient clinical trajectories using these clusters allowed us to identify individual conditions and phenotypes strongly increased after acute infection. We found many conditions increased in COVID-19 patients compared to controls, and using a novel method to associate patients with clusters over time, we additionally found phenotypes specific to patient sex, age, wave of infection, and PASC diagnosis status. While many of these results reflect known PASC symptoms, the resolution provided by this unprecedented data scale suggests avenues for improved diagnostics and mechanistic understanding of this multifaceted disease.
PubMed: 38947087
DOI: 10.1101/2023.09.11.23295259 -
MedRxiv : the Preprint Server For... Jun 2024Clonal hematopoiesis of indeterminate potential (CHIP) is a common inflammatory condition of aging that causes myriad end-organ damage. We have recently shown...
BACKGROUND
Clonal hematopoiesis of indeterminate potential (CHIP) is a common inflammatory condition of aging that causes myriad end-organ damage. We have recently shown associations for CHIP with acute kidney injury and with kidney function decline in the general population, with stronger associations for CHIP driven by mutations in genes other than (non- CHIP). Longitudinal kidney function endpoints in individuals with pre-existing chronic kidney disease (CKD) and CHIP have been examined in two previous studies, which reported conflicting findings and were limited by small sample sizes.
METHODS
In this study, we examined the prospective associations between CHIP and CKD progression events in four cohorts of CKD patients (total N = 5,772). The primary outcome was a composite of 50% kidney function decline or kidney failure. The slope of eGFR decline was examined as a secondary outcome. Mendelian randomization techniques were then used to investigate potential causal effects of CHIP on eGFR decline. Finally, kidney function was assessed in adenine-fed CKD model mice having received a bone marrow transplant recapitulating -CHIP compared to controls transplanted wild-type bone marrow.
RESULTS
Across all cohorts, the average age was 66.4 years, the average baseline eGFR was 42.6 ml/min/1.73m , and 24% had CHIP. Upon meta-analysis, non- CHIP was associated with a 59% higher relative risk of incident CKD progression (HR 1.59, 95% CI: 1.02-2.47). This association was more pronounced among individuals with diabetes (HR 1.29, 95% CI: 1.03-1.62) and with baseline eGFR ≥ 30 ml/min/1.73m (HR 1.80, 95% CI: 1.11-2.90). Additionally, the annualized slope of eGFR decline was steeper among non- CHIP carriers, relative to non-carriers (β -0.61 ± 0.31 ml/min/1.73m , p = 0.04). Mendelian randomization analyses suggested a causal role for CHIP in eGFR decline among individuals with diabetes. In a dietary adenine mouse model of CKD, -CHIP was associated with lower GFR as well as greater kidney inflammation, tubular injury, and tubulointerstitial fibrosis.
CONCLUSION
Non- CHIP is a potentially targetable novel risk factor for CKD progression.
PubMed: 38946975
DOI: 10.1101/2024.06.19.24309181 -
The Pan African Medical Journal 2024as cholera, due to toxigenic bacteria Vibrio cholera (serogroups O1 and O139), is a major public health threat in Africa, the aim of this work was to investigate...
INTRODUCTION
as cholera, due to toxigenic bacteria Vibrio cholera (serogroups O1 and O139), is a major public health threat in Africa, the aim of this work was to investigate potentially pathogenic Vibrionaceae bacteria firstly from human stool samples, and secondly from various environmental water points of Saint-Louis city in Senegal.
METHODS
a hospital-based study was conducted between 2013 and 2015. Stool samples were taken and cultured from daily incoming patients or hospitalized for acute diarrhea at Saint-Louis´ regional hospital. For environment, a monthly longitudinal sampling from January to October 2016 was carried out at 10 sites in the city. We used total DNA extracted from APW (alkaline peptone water) broth solutions and on suspect bacterial colonies to run PCR Multiplex targeting specific DNA fragments to detect Vibrio genus and specific species. In case of positivity, a simplex PCR was performed to test for cholera toxins Ctx, and V. parahaemolyticus TRH and TDH.
RESULTS
for 43 patients screened, bacterial culture was positive in 6% of cases but no strain of V. cholerae or other Vibrio sp. was isolated. PCR on 90 APW solutions were positive for Vibrio sp.(n = 43), V. cholera(n = 27), V. mimicus(n = 16), V. parahaemolyticus(8), V. alginolyticus(n = 4), and V. vulnificus(n = 2). Unlike for those on suspected colonies which were positive for a majority of V. parahaemolyticus (n = 40) and V. cholerae non-O1 / O139 (n = 35). Six strains of V. parahaemolyticus carried TRH gene, 3 of which expressed simultaneously virulence TRH and TDH genes. For physicochemical parameters, all temperatures varied similarly according to a unimodal seasonality, as well as salinity.
CONCLUSION
despite the presence of natural populations of Vibrionaceae, even toxigenic ones, was noted in water environment, along with favorable habitat conditions that could play a role in transmission of Vibriosis in the Saint Louis population, we did not isolate any of them from patients screened at the hospital.
Topics: Humans; Senegal; Cholera; Feces; Polymerase Chain Reaction; Diarrhea; Water Microbiology; Vibrionaceae; Vibrio; DNA, Bacterial; Vibrio cholerae; Adult; Female; Male
PubMed: 38946740
DOI: 10.11604/pamj.2024.48.5.34685 -
Precision Clinical Medicine Jun 2024Myeloid differentiation factor 88 (MyD88) is the core adaptor for Toll-like receptors defending against microbial invasion and initiating a downstream immune response...
BACKGROUND
Myeloid differentiation factor 88 (MyD88) is the core adaptor for Toll-like receptors defending against microbial invasion and initiating a downstream immune response during microbiota-host interaction. However, the role of MyD88 in the pathogenesis of inflammatory bowel disease is controversial. This study aims to investigate the impact of MyD88 on intestinal inflammation and the underlying mechanism.
METHODS
MyD88 knockout (MyD88) mice and the MyD88 inhibitor (TJ-M2010-5) were used to investigate the impact of MyD88 on acute dextran sodium sulfate (DSS)-induced colitis. Disease activity index, colon length, histological score, and inflammatory cytokines were examined to evaluate the severity of colitis. RNA transcriptome analysis and 16S rDNA sequencing were used to detect the potential mechanism.
RESULTS
In an acute DSS-colitis model, the severity of colitis was not alleviated in MyD88 mice and TJ-M2010-5-treated mice, despite significantly lower levels of NF-κB activation being exhibited compared to control mice. Meanwhile, 16S rDNA sequencing and RNA transcriptome analysis revealed a higher abundance of intestinal and an up-regulation of the nucleotide oligomerization domain-like receptors (NLRs) signaling pathway in colitis mice following MyD88 suppression. Further blockade of the NLRs signaling pathway or elimination of gut microbiota with broad-spectrum antibiotics in DSS-induced colitis mice treated with TJ-M2010-5 ameliorated the disease severity, which was not improved solely by MyD88 inhibition. After treatment with broad-spectrum antibiotics, downregulation of the NLR signaling pathway was observed.
CONCLUSION
Our study suggests that the suppression of MyD88 might be associated with unfavorable changes in the composition of gut microbiota, leading to NLR-mediated immune activation and intestinal inflammation.
PubMed: 38946731
DOI: 10.1093/pcmedi/pbae013 -
Haematologica Jul 2024
Topics: Humans; Leukemia, Myeloid, Acute; Neoplasm, Residual; Child
PubMed: 38946650
DOI: 10.3324/haematol.2024.285153 -
Journal of the American Medical... Jul 2024Acute hepatic porphyria (AHP) is a group of rare but treatable conditions associated with diagnostic delays of 15 years on average. The advent of electronic health...
BACKGROUND
Acute hepatic porphyria (AHP) is a group of rare but treatable conditions associated with diagnostic delays of 15 years on average. The advent of electronic health records (EHR) data and machine learning (ML) may improve the timely recognition of rare diseases like AHP. However, prediction models can be difficult to train given the limited case numbers, unstructured EHR data, and selection biases intrinsic to healthcare delivery. We sought to train and characterize models for identifying patients with AHP.
METHODS
This diagnostic study used structured and notes-based EHR data from 2 centers at the University of California, UCSF (2012-2022) and UCLA (2019-2022). The data were split into 2 cohorts (referral and diagnosis) and used to develop models that predict (1) who will be referred for testing of acute porphyria, among those who presented with abdominal pain (a cardinal symptom of AHP), and (2) who will test positive, among those referred. The referral cohort consisted of 747 patients referred for testing and 99 849 contemporaneous patients who were not. The diagnosis cohort consisted of 72 confirmed AHP cases and 347 patients who tested negative. The case cohort was 81% female and 6-75 years old at the time of diagnosis. Candidate models used a range of architectures. Feature selection was semi-automated and incorporated publicly available data from knowledge graphs. Our primary outcome was the F-score on an outcome-stratified test set.
RESULTS
The best center-specific referral models achieved an F-score of 86%-91%. The best diagnosis model achieved an F-score of 92%. To further test our model, we contacted 372 current patients who lack an AHP diagnosis but were predicted by our models as potentially having it (≥10% probability of referral, ≥50% of testing positive). However, we were only able to recruit 10 of these patients for biochemical testing, all of whom were negative. Nonetheless, post hoc evaluations suggested that these models could identify 71% of cases earlier than their diagnosis date, saving 1.2 years.
CONCLUSIONS
ML can reduce diagnostic delays in AHP and other rare diseases. Robust recruitment strategies and multicenter coordination will be needed to validate these models before they can be deployed.
PubMed: 38946554
DOI: 10.1093/jamia/ocae141 -
Stroke Jul 2024GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089...
BACKGROUND
GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown.
METHODS
Ischemic stroke was induced in wild-type (WT) or GPR65 knockout (GPR65) mice by photothrombotic ischemia. Male mice were injected intraperitoneally with BTB09089 every other day at days 3, 7, or 14 poststroke. AAV-Syn-GPR65 (adenoassociated virus-synapsin-GPR65) was utilized to overexpress GPR65 in the peri-infarct cortical neurons of GPR65 and WT mice. Motor function was monitored by grid-walk and cylinder tests. The neurorestorative effects of BTB09089 were observed by immunohistochemistry, Golgi-Cox staining, and Western blotting.
RESULTS
BTB09089 significantly promoted motor outcomes in WT but not in GPR65 mice, even when BTB09089 was delayed for 3 to 7 days. BTB09089 inhibited the activation of microglia and glial scar progression in WT but not in GPR65 mice. Meanwhile, BTB09089 reduced the decrease in neuronal density in WT mice, but this benefit was abolished in GPR65 mice and reemerged by overexpressing GPR65 in peri-infarct cortical neurons. Furthermore, BTB09089 increased the GAP43 (growth-associated protein-43) and synaptophysin puncta density, dendritic spine density, dendritic branch length, and dendritic complexity by overexpressing GPR65 in the peri-infarct cortical neurons of GPR65 mice, which was accompanied by increased levels of p-CREB (phosphorylated cAMP-responsive element-binding protein). In addition, the therapeutic window of BTB09089 was extended to day 14 by overexpressing GPR65 in the peri-infarct cortical neurons of WT mice.
CONCLUSIONS
Our findings indicated that delayed BTB09089 treatment improved neurological functional recovery and brain tissue repair poststroke through activating neuronal GRP65. GPR65 overexpression may be a potential strategy to expand the therapeutic time window of GPR65 agonists for neurorehabilitation after ischemic stroke.
PubMed: 38946544
DOI: 10.1161/STROKEAHA.124.046954 -
Stroke Jul 2024There is a well-known association between low socioeconomic status (SES), poor survival, and clinician-reported outcomes after stroke. We aimed to assess socioeconomic...
BACKGROUND
There is a well-known association between low socioeconomic status (SES), poor survival, and clinician-reported outcomes after stroke. We aimed to assess socioeconomic differences in Patient Reported Outcome Measures 3 months after stroke.
METHODS
This nationwide cohort study included patients registered with acute stroke in the Swedish Stroke Register 2015-2017. Patient Reported Outcome Measures included activities of daily living (mobility, toileting, and dressing), and poststroke symptoms (low mood, fatigue, pain, and poor general health). Information on SES prestroke was retrieved from Statistics Sweden and defined by a composite measure based on education and income tertiles. Associations between SES and Patient Reported Outcome Measures were analyzed using logistic regression adjusting for confounders (sex and age) and additionally for potential mediators (stroke type, severity, cardiovascular disease risk factors, and living alone). Subgroup analyses were performed for stroke type, men and women, and younger and older patients.
RESULTS
The study included 44 511 patients. Of these, 31.1% required assistance with mobility, 18% with toileting, and 22.2% with dressing 3 months after stroke. For poststroke symptoms, 12.3% reported low mood, 39.1% fatigue, and 22.7% pain often/constantly, while 21.4% rated their general health as poor/very poor. Adjusted for confounders, the odds of needing assistance with activities of daily living were highest for patients with low income and primary school education, for example, for mobility, odds ratio was 2.06 (95% CI, 1.89-2.24) compared with patients with high income and university education. For poststroke symptoms, odds of poor outcome were highest for patients with low income and university education (eg, odds ratio, 1.79 [95% CI, 1.49-2.15] for low mood). Adjustments for potential mediators attenuated but did not remove associations. The associations were similar in ischemic and hemorrhagic strokes and more pronounced in men and patients <65 years old.
CONCLUSIONS
There are substantial SES-related differences in Patient Reported Outcome Measures poststroke. The more severe outcome associated with low SES is more pronounced in men and in patients of working age.
PubMed: 38946533
DOI: 10.1161/STROKEAHA.124.047172