The incidence of COVID-19-related hospitalisation in migrants in the UK: Findings from the Virus Watch prospective community cohort study.

Background: Migrants in the United Kingdom (UK) may be at higher risk of SARS-CoV-2 exposure; however, little is known about their risk of COVID-19-related hospitalisation during waves 1-3 of the pandemic. Methods: We analysed secondary care data linked to Virus Watch study data for adults and estimated COVID-19-related hospitalisation incidence rates by migration status. To estimate the total effect of migration status on COVID-19 hospitalisation rates, we ran mixed-effect Poisson regression for wave 1 (01/03/2020-31/08/2020; wildtype), and mixed-effect negative binomial regressions for waves 2 (01/09/2020-31/05/2021; Alpha) and 3 (01/06/2020-31/11/2021; Delta). Results of all models were then meta-analysed. Results: Of 30,276 adults in the analyses, 26,492 (87.5 %) were UK-born and 3,784 (12.5 %) were migrants. COVID-19-related hospitalisation incidence rates for UK-born and migrant individuals across waves 1-3 were 2.7 [95 % CI 2.2-3.2], and 4.6 [3.1-6.7] per 1,000 person-years, respectively. Pooled incidence rate ratios across waves suggested increased rate of COVID-19-related hospitalisation in migrants compared to UK-born individuals in unadjusted 1.68 [1.08-2.60] and adjusted analyses 1.35 [0.71-2.60]. Conclusion: Our findings suggest migration populations in the UK have excess risk of COVID-19-related hospitalisations and underscore the need for more equitable interventions particularly aimed at COVID-19 vaccination uptake among migrants.

Enhanced mucosal mitochondrial function corrects dysbiosis and OXPHOS metabolism in IBD.

Background: Mitochondrial (Mito) dysfunction in IBD reduces mucosal O2 consumption and increases O2 delivery to the microbiome. Increased enteric O2 promotes blooms of facultative anaerobes (eg. Proteobacteria ) and restricts obligate anaerobes (eg. Firmicutes ). Dysbiotic metabolites negatively affect host metabolism and immunity. Our novel compound (AuPhos) upregulates intestinal epithelial cell (IEC) mito function, attenuates colitis and corrects dysbiosis in humanized Il10-/- mice. We posit that AuPhos corrects IBD-associated dysbiotic metabolism. Methods: Primary effect of AuPhos on mucosal Mito respiration and healing process was studied in ex vivo treated human colonic biopsies and piroxicam-accelerated (Px) Il10-/- mice. Secondary effect on microbiome was tested in DSS-colitis WT B6 and germ-free 129.SvEv WT or Il10-/- mice reconstituted with human IBD stool (Hu- Il10-/- ). Mice were treated orally with AuPhos (10- or 25- mg/kg; q3d) or vehicle, stool samples collected for fecal lipocalin-2 (f-LCN2) assay and microbiome analyses using 16S rRNA sequencing. AuPhos effect on microbial metabolites was determined using untargeted global metabolomics. AuPhos-induced hypoxia in IECs was assessed by Hypoxyprobe-1 staining in sections from pimonidazole HCl-infused DSS-mice. Effect of AuPhos on enteric oxygenation was assessed by E. coli Nissle 1917 WT (aerobic respiration-proficient) and cytochrome oxidase (cydA) mutant (aerobic respiration-deficient). Results: Metagenomic (16S) analysis revealed AuPhos reduced relative abundances of Proteobacteria and increased blooms of Firmicutes in uninflamed B6 WT, DSS-colitis, Hu-WT and Hu- Il10-/- mice. AuPhos also increased hypoxyprobe-1 staining in surface IECs suggesting enhanced O2 utilization. AuPhos-induced anaerobiosis was confirmed by a significant increase in cydA mutant compared to WT (O2-utlizing) E.coli . Ex vivo treatment of human biopsies with AuPhos showed significant increase in Mito mass, and complexes I and IV. Further, gene expression analysis of AuPhos-treated biopsies showed increase in stem cell markers (Lgr4, Lgr5, Lrig1), with concomitant decreases in pro-inflammatory markers (IL1ß,MCP1, RankL). Histological investigation of AuPhos-fed Px- Il10-/- mice showed significantly decreased colitis score in AuPhos-treated Px- Il10-/- mice, with decrease in mRNA of pro-inflammatory cytokines and increase in Mito complexes ( ND5 , ATP6 ). AuPhos significantly altered microbial metabolites associated with SCFA synthesis, FAO, TCA cycle, tryptophan and polyamine biosynthesis pathways. AuPhos increased pyruvate, 4-hydroxybutyrate, 2-hydroxyglutarate and succinate, suggesting an upregulation of pyruvate and glutarate pathways of butyrate production. AuPhos reduced IBD-associated primary bile acids (BA) with concomitant increase in secondary BA (SBA). AuPhos treatment significantly decreased acylcarnitines and increased L-carnitine reflective of enhanced FAO. AuPhos increases TCA cycle intermediates and creatine, energy reservoir substrates indicating enhanced OxPHOS. Besides, AuPhos also upregulates tryptophan metabolism, decreases Kynurenine and its derivatives, and increases polyamine biosynthesis pathway (Putresceine and Spermine). Conclusion: These findings indicate that AuPhos-enhanced IEC mitochondrial function reduces enteric O2 delivery, which corrects disease-associated metabolomics by restoring short-chain fatty acids, SBA, AA and IEC energy metabolism.

Association between chronic liver disease and adverse in-hospital outcomes in patients undergoing CABG: A propensity score-matched analysis of a 5-year national inpatient sample data from 2016-2020.

Despite a 30% decline in the rate over the last decade, coronary artery bypass graft (CABG) surgery remains a common major surgical procedure with significant morbidity and mortality. Chronic liver disease (CLD) patients, with increased survival rates due to medical advancements, are now frequently being considered for CABG, bearing higher perioperative risks. This study investigates the association between CLD and in-hospital outcomes in CABG patients using retrospective data from the National Inpatient Sample (NIS) database (2016-2020) including 7,945 CLD patients undergoing CABG that were propensity score matched with an equivalent number of patients with no CLD undergoing CABG. Clinical variables were extracted using corresponding ICD-10 codes and multivariable logistic and linear regression models were used to assess in-hospital mortality, complications, and length of stay. The overall mortality rate was 5.5% (8.6% in the CLD group with cirrhosis, 5.9% CLD group without cirrhosis, and 2.8% in the non-CLD group, p<0.001). CLD with cirrhosis was associated with higher odds of mortality (AOR= 4.21, 95% CI [3.61, 4.94]) and length of stay (ß = 1.03, 95% CI [1.01, 1.05]). CLD patients with cirrhosis demonstrated higher odds of perioperative cardiac complications (cardiac arrest, ventricular arrhythmias, tamponade, and shock), thromboembolic events, gastrointestinal bleeding, bowel ischemia, acute kidney injury, pneumonia, and sepsis. This study reveals a substantial impact of CLD on adverse outcomes in CABG patients, emphasizing the need for tailored preoperative assessments and postoperative care.

Chest Pain Redefined: Atypical Presentation of Superior Mesenteric Artery Syndrome.

Superior mesenteric artery (SMA) syndrome is a rare cause of small bowel obstruction characterized by duodenal compression due to the narrowing of the SMA-aorta angle. We present a case of a 43-year-old male with postprandial chest pain, severe weight loss, and a narrowed aortomesenteric angle evident on computed tomography. Conservative management, including hydration, positioning, and weight gain, was initiated, leading to symptom resolution. SMA syndrome diagnosis requires clinical suspicion and radiological confirmation. Understanding this syndrome's varied presentations, diagnostic challenges, and therapeutic approaches is crucial for prompt management, especially when atypical symptoms like chest pain manifest, as seen in our case.

The Impact of an Intern's Clinical Guidebook on Easing the Transition of New Interns Into the United States Healthcare System.

This study explores the efficacy of an intern's clinical guidebook in facilitating the transition of categorical internal medicine interns into the United States healthcare system. New interns, particularly foreign medical graduates, face multifaceted challenges during their initial year of residency. The research, conducted at Ascension Saint Joseph Hospital in Chicago, employed a quasi-experimental pre-post design involving 20 interns. Participants were provided with an intern's clinical guidebook, and their knowledge was assessed through pre and post exams. Results demonstrated a statistically significant improvement in overall knowledge, with mean scores increasing from 65% to 77.37%. Subgroup analysis revealed similar improvements among both male and female interns. Data confidentiality and ethical considerations were prioritized, with participant data anonymized and stored securely. Despite limitations, this study highlights the guidebook's potential to enhance intern education and improve the quality of care provided during the crucial transition period. Further research is recommended to validate and extend these findings.

Granular Insights: Neutrophil Predominance and Elastase Release in Severe Asthma Exacerbations in a Pediatric Cohort.

The chronic inflammatory component of asthma is propagated by granulocytes, including neutrophils and eosinophils, in the peripheral circulation and airway. Previous studies have suggested that these cells have an altered expression of adhesion-related molecules and a propensity for the release of granule contents that may contribute to tissue damage and enhance inflammatory complications in patients with status asthmaticus. The goal of this prospective cohort study at a tertiary care pediatric hospital with a large population of asthma patients was to assess the role of granulocyte-based inflammation in the development of asthma exacerbation. Subjects were enrolled from two patient populations: those with mild-to-moderate asthma exacerbations seen in the emergency department and those with severe asthma admitted to the intensive care unit (PICU). Clinical data were collected, and blood was drawn. Granulocytes were immediately purified, and the phenotype was assessed, including the expression of cell surface markers, elastase release, and cytokine production. Severe asthmatics admitted to the PICU displayed a significantly higher total neutrophil count when compared with healthy donors. Moreover, little to no eosinophils were found in granulocyte preparations from severe asthmatics. Circulating neutrophils from severe asthmatics admitted to the PICU displayed significantly increased elastase release ex vivo when compared with the PMN from healthy donors. These data suggest that the neutrophil-based activation and release of inflammatory products displayed by severe asthmatics may contribute to the propagation of asthma exacerbations.

Optimal Medical Therapy for Chronic Coronary Disease in 2024: Focus on Antithrombotic Therapy.

Antiplatelet therapy is the cornerstone of the secondary prevention of cardiovascular disease. Aspirin is indicated for all patients with chronic coronary disease to prevent recurrent ischemic events. A more potent antithrombotic therapy-including P2Y12 inhibitor monotherapy, dual antiplatelet therapy, or vascular dose anticoagulation-reduces the risk of ischemic events but also increases bleeding risk. Clinicians must weigh both ischemic risks and bleeding risks when determining an optimal antithrombotic therapy for patients with chronic coronary disease, and soliciting patient involvement in shared decision-making is critical.

Identification of Achalasia Within Absent Contractility Phenotypes on High-Resolution Manometry: Prevalence, Predictive Factors, and Treatment Outcome.

INTRODUCTION: Absent contractility on high-resolution manometry (HRM) defines severe hypomotility but needs distinction from achalasia. We retrospectively identified achalasia within absent contractility using HRM provocative maneuvers, barium esophagography, and functional lumen imaging probe (FLIP). METHODS: Adult patients with absent contractility on HRM during the 4-year study period were eligible for inclusion. Inadequate studies, achalasia after therapy, or prior foregut surgery were exclusions. Upright integrated relaxation pressure (IRP) >12 mm Hg, panesophageal pressurization, and/or elevated IRP on multiple rapid swallows and rapid drink challenge (RDC) were considered abnormal. Esophageal barium retention and abnormal esophagogastric junction distensibility index (<2.0 mm 2 /mm Hg) on FLIP defined achalasia. Clinical, endoscopic, and motor characteristics of patients with achalasia were compared with absent contractility without obstruction. RESULTS: Of 164 patients, 20 (12.2%) had achalasia (17.9% of 112 patients with adjunctive testing), while 92 did not, and 52 did not undergo adjunctive tests. Achalasia was diagnosed regardless of IRP value, but the median supine IRP was higher (odds ratio 1.196, 95% confidence interval 1.041-1.375, P = 0.012). Patients with achalasia were more likely to present with dysphagia (80.0% vs 35.9%, P < 0.001), with obstructive features on HRM maneuvers (83.3% vs 48.9%, P = 0.039), but lower likelihood of GERD evidence (20.0% vs 47.3%, P = 0.027) or large hiatus hernia (15.0% vs 43.8%, P = 0.002). On multivariable analysis, dysphagia presentation ( P = 0.006) and pressurization on RDC ( P = 0.027) predicted achalasia, while reflux and presurgical evaluations and lack of RDC obstruction predicted absent contractility without obstruction. DISCUSSION: Despite HRM diagnosis of absent contractility, achalasia is identified in more than 1 in 10 patients regardless of IRP value.

Novel ligand decorated theranostic zein nanoparticles coloaded with paclitaxel and carbon quantum dots: formulation and optimization.

Aim: The present research focused on development and optimization of ligand decorated theranostic nanocarrier encapsulating paclitaxel and carbon quantum dots (CQDs). Methods: CQDs were prepared by microwave-assisted pyrolysis and were characterized for particle size and fluorescence behavior. Ligand decorated zein nanoparticles, coloaded with paclitaxel and CQDs, were formulated using a one-step nanoprecipitation method and optimized for various process parameters. Results: Particle size for coated and uncoated nanoparticles was 90.16 ± 1.65 and 179.26 ± 3.61 nm, respectively, and entrapment efficiency was >80%. The circular dichroism spectroscopy showed zein retained its secondary structure and release study showed biphasic release behavior. Conclusion: The prepared theranostic nanocarrier showed optimal fluorescence and desired release behavior without altering the secondary structure of zein.

A Case Report of Primary Melanoma of the Urethra.

We illustrate a notable case of an 83-year-old male who presents to a community hospital with abdominal pain and hematuria. A few days after admission, an ulcerated lesion was found to be visible toward the ventral aspect of the penis, as well as bright red blood at the urethral meatus. An excisional biopsy of the urethral meatus, mid-urethra, and urethral tissue was done, and immunohistochemistry helped support the diagnosis of primary melanoma of the urethra. The pathophysiology and guidelines for treatment are discussed. Our purpose in putting forward this case is to present a rare diagnosis of primary melanoma of the male urethra and to emphasize the importance of early recognition to reduce the occurrence of invasive malignancy.

Safety and Efficacy of Highly Selective 5-Hydroxytryptamine Receptor 4 Agonists for Diabetic and Idiopathic Gastroparesis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Gastroparesis significantly affects quality of life and healthcare expenditure. Effective treatment options are limited, and the utility of current prokinetic agents is inhibited by serious adverse effects. There exists an unmet need for prokinetic agents demonstrating both efficacy and an acceptable adverse effect profile. Highly selective 5-Hydroxytryptamine receptor 4 (5-HT4) agonists have exhibited clinical efficacy and safety in randomized controlled trials (RCTs). Consequently, we conducted a meta-analysis to comprehensively assess the safety and efficacy of these highly selective agents. Multiple databases, including PubMed, Scopus, and Embase, were systematically screened from inception until September 2023. Only RCTs evaluating the efficacy and safety of highly selective 5-HT4 agonists for gastroparesis were included. Key outcomes of interest included the pooled rates of Gastroparesis Cardinal Symptom Index (GCSI) scores, gastric emptying time (GET), and adverse event rates in each group. We adhered to standard meta-analysis methodology utilizing the random-effects model, with heterogeneity assessed by I2 statistics. Our analysis identified six RCTs, comprising 570 patients with diabetic (48%) or idiopathic (51%) gastroparesis, with mean ages of 46 and 45.9 years in the intervention and placebo groups, respectively. In the meta-analysis, highly selective 5-HT4 agonists demonstrated significantly superior pooled GCSI scores compared to placebo (mean difference: 4.283, (1.380, 7.186), p<0.05). Pooled GET was also significantly improved with 5-HT4 agonists compared to placebo (mean difference: 2.534, (1.695, 3.373), p<0.05). Although pooled rates of total adverse events were higher with 5-HT4 agonists (mean difference: 6.975, (1.042, 46.684), p<0.05), rates of specific adverse events such as diarrhea, abdominal pain, and headaches were comparable. In conclusion, this meta-analysis underscores a statistically significant improvement in GET and GCSI scores among patients receiving highly selective 5-HT4 agonists (Velusetrag, Felcisetrag, Prucalopride) for both diabetic and idiopathic gastroparesis. While the overall adverse effect profile is deemed acceptable, larger studies with extended follow-up periods are needed to investigate rare and/or serious adverse events. Moreover, future high-quality RCTs comparing the efficacy and safety of these novel agents with currently available agents are essential to further validate these findings.

Angiomyolipoma With Epithelial Cysts: A Rare but Distinct Variant of Angiomyolipoma.

Renal angiomyolipomas, common benign tumors, can exhibit slow growth in sporadic cases or have aggressive tendencies when linked to genetic conditions like tuberous sclerosis. This case report focuses on the exceptionally rare angiomyolipoma with epithelial cysts (AMLEC) variant, particularly challenging to diagnose due to its scarcity. Describing a 41-year-old woman's case, initially suspected to be renal cell carcinoma during an infertility evaluation, subsequent partial nephrectomy revealed a tumor comprising smooth muscle, blood vessels, and fat, with cystic regions featuring cuboidal linings and a layer devoid of abnormal cell activity. Immunohistochemistry confirmed specific markers within different tumor components, highlighting the diagnostic complexities of AMLEC and emphasizing the crucial role of histopathological examinations in accurate characterizations.

Increased Oxidative Stress and Decreased Sirtuin-3 and FOXO3 Expression Following Carotid Artery Intimal Injury in Hyperlipidemic Yucatan Microswine.

Hypercholesterolemia is a major risk factor for atherosclerosis as oxidized-low-density lipoproteins (ox-LDL) contribute to the formation of foam cells and inflammation. Increased immune cell infiltration and oxidative stress induce instability of a plaque. Rupture of the unstable plaque precipitates adverse ischemic events. Since reactive oxygen species (ROS) play a critical role in plaque formation and vulnerability, regulating ROS generation may have therapeutic potential. Sirtuins, specifically sirtuin-3 (SIRT3), are antigenic molecules that can reduce oxidative stress by reducing mitochondrial ROS production through epigenetic modulation. Lack of SIRT3 expression is associated with dysregulation of ROS and endothelial function following high-fat high-cholesterol diet. SIRT3 deacetylates FOXO3a (Forkhead transcription factor O subfamily member 3a) and protects mitochondria against oxidative stress which can lead to even further protective anti-oxidizing properties. This study was designed to investigate the association between hyperlipidemia, intimal injury, chronic inflammation, and the expression of NAD-dependent deacetylase SIRT-3, FOXO3, antioxidant genes, and oxidative stress in carotid arteries of hypercholesterolemic Yucatan microswine. We found that intimal injury in hypercholesterolemic state led to increased expression of oxidative stress, inflammation, neointimal hyperplasia, and plaque size and vulnerability, while decreasing anti-oxidative regulatory genes and mediators. The findings suggest that targeting the SIRT3-FOXO3a-oxidative stress pathway will have therapeutic significance.

reguloGPT: Harnessing GPT for Knowledge Graph Construction of Molecular Regulatory Pathways.

Motivation: Molecular Regulatory Pathways (MRPs) are crucial for understanding biological functions. Knowledge Graphs (KGs) have become vital in organizing and analyzing MRPs, providing structured representations of complex biological interactions. Current tools for mining KGs from biomedical literature are inadequate in capturing complex, hierarchical relationships and contextual information about MRPs. Large Language Models (LLMs) like GPT-4 offer a promising solution, with advanced capabilities to decipher the intricate nuances of language. However, their potential for end-to-end KG construction, particularly for MRPs, remains largely unexplored. Results: We present reguloGPT, a novel GPT-4 based in-context learning prompt, designed for the end-to-end joint name entity recognition, N-ary relationship extraction, and context predictions from a sentence that describes regulatory interactions with MRPs. Our reguloGPT approach introduces a context-aware relational graph that effectively embodies the hierarchical structure of MRPs and resolves semantic inconsistencies by embedding context directly within relational edges. We created a benchmark dataset including 400 annotated PubMed titles on N6-methyladenosine (m6A) regulations. Rigorous evaluation of reguloGPT on the benchmark dataset demonstrated marked improvement over existing algorithms. We further developed a novel G-Eval scheme, leveraging GPT-4 for annotation-free performance evaluation and demonstrated its agreement with traditional annotation-based evaluations. Utilizing reguloGPT predictions on m6A-related titles, we constructed the m6A-KG and demonstrated its utility in elucidating m6A's regulatory mechanisms in cancer phenotypes across various cancers. These results underscore reguloGPT's transformative potential for extracting biological knowledge from the literature. Availability and implementation: The source code of reguloGPT, the m6A title and benchmark datasets, and m6A-KG are available at: https://github.com/Huang-AI4Medicine-Lab/reguloGPT.

Artificial Intelligence as a Triage Tool during the Perioperative Period: Pilot Study of Accuracy and Accessibility for Clinical Application.

Background: Given the dialogistic properties of ChatGPT, we hypothesized that this artificial intelligence (AI) function can be used as a self-service tool where clinical questions can be directly answered by AI. Our objective was to assess the content, accuracy, and accessibility of AI-generated content regarding common perioperative questions for reduction mammaplasty. Methods: ChatGPT (OpenAI, February Version, San Francisco, Calif.) was used to query 20 common patient concerns that arise in the perioperative period of a reduction mammaplasty. Searches were performed in duplicate for both a general term and a specific clinical question. Query outputs were analyzed both objectively and subjectively. Descriptive statistics, t tests, and chi-square tests were performed where appropriate with a predetermined level of significance of P less than 0.05. Results: From a total of 40 AI-generated outputs, mean word length was 191.8 words. Readability was at the thirteenth grade level. Regarding content, of all query outputs, 97.5% were on the appropriate topic. Medical advice was deemed to be reasonable in 100% of cases. General queries more frequently reported overarching background information, whereas specific queries more frequently reported prescriptive information (P < 0.0001). AI outputs specifically recommended following surgeon provided postoperative instructions in 82.5% of instances. Conclusions: Currently available AI tools, in their nascent form, can provide recommendations for common perioperative questions and concerns for reduction mammaplasty. With further calibration, AI interfaces may serve as a tool for fielding patient queries in the future; however, patients must always retain the ability to bypass technology and be able to contact their surgeon.

Thermography of the superfluid transition in a strongly interacting Fermi gas.

Heat transport can serve as a fingerprint identifying different states of matter. In a normal liquid, a hotspot diffuses, whereas in a superfluid, heat propagates as a wave called "second sound." Direct imaging of heat transport is challenging, and one usually resorts to detecting secondary effects. In this study, we establish thermography of a strongly interacting atomic Fermi gas, whose radio-frequency spectrum provides spatially resolved thermometry with subnanokelvin resolution. The superfluid phase transition was directly observed as the sudden change from thermal diffusion to second-sound propagation and is accompanied by a peak in the second-sound diffusivity. This method yields the full heat and density response of the strongly interacting Fermi gas and therefore all defining properties of Landau's two-fluid hydrodynamics.

Acute type A aortic syndromes: outcomes are independent of aortic root/valve management.

Purpose: Clinical outcomes following various surgical intervention strategies for aortic root and valve pathology during repair of acute type A aortic syndromes were studied and compared. Methods: From 2004 to 2019, 634 patients underwent acute type A aortic repair. Patients were divided into 4 groups: Valve Resuspension (n = 456), Isolated Valve Replacement (AVR) (n = 24), Valve and Root Replacement (ROOT) (n = 97), and Valve Sparing Root Replacement (VSRR) (n = 57). The primary endpoint was midterm survival and multivariable risk factor analysis was performed. Results: The mean age was 55.4 ± 13 years, 424 (67%) were male, and overall early mortality was 12%. Early mortality was 13%, 8%, 11%, and 7% for the Valve Resuspension, AVR, ROOT, and VSRR groups respectively, p = 0.43. Five-year survival was 74%, 86%, 73%, and 84% for the Valve Resuspension, AVR, ROOT, and VSRR groups respectively, p = 0.46. There was no difference in late stroke, renal failure, heart block, and late bleeding (p > 0.05 for all). At late follow-up, AVR and ROOT patients had a higher mean gradient versus Valve Resuspension and VSRR patients, p < 0.0001. For the total cohort, risk factors for late mortality included preoperative peripheral vascular disease (hazard ratio (HR) 2.3, 95% confidence interval (CI) 1.2-4.4, p = 0.009) and preoperative dialysis (HR 2.8, 95% CI 1.3-6.1, p = 0.01). Conclusion: Mid-term survival following repair of acute type A aortic dissection is not independently associated with a specific type of aortic valve intervention. Native valve preservation leads to acceptable mid-term valve hemodynamics and should be the preferred therapy in this emergent clinical setting. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-023-01602-8.