Infected Patients Research Articles

Programmed DNA tile response system enabled accurate detection of ATP for clinical diagnosis

Adenosine triphosphate (ATP), as a crucial signaling molecule, is of high potential diagnosis value for multiple diseases. However, current technologies for ATP detection struggle to satisfy the harsh conditions required for biospecimen tests, existing several limitations for clinical practical application. In this study, the DNA tile response system was designed and constructed by integrating nucleic acid aptamer, hybrid chain reaction (HCR), and DNA tile self-assembly technology to achieve accurate detection of ATP in body fluid specimens. The DNA tile response system, possessing high-order structure characteristic, could remove HCR false-positive products and conquer the high noise background to enhance the detection sensitivity. Under the optimal reaction parameters, this system achieved the low limit of detection (LOD) of 189.23 nM over a wide linear range and splendid detection specificity faced with multiple interference terms. Furthermore, this system, possessing simple storage conditions, long-term detection stability, and superior anti-interference performance, was sufficient to satisfy the detection requirements for complicated biological specimens in multi-scenarios. Ultimately, the DNA tile response system showed excellent diagnostic efficiency that could easily distinguish urinary tract infection patients and healthy controls through ATP quantification, as well as hypertension patients and healthy ones. This system provides a high-potential rapid detection tool for early diagnosis and dynamic monitoring of urinary tract infections and hypertension, holding enormous potential for clinical translation due to the superiorities of simple operation, general applicability, and low instrument requirements.

National Early Warning Score 2 to Predict ICU Admission of COVID-19 Patients in Bangladeshi Cohort

Objective: To assess the predictive accuracy of the National Early Warning Score 2 (NEWS 2) for early prediction of clinical deterioration (ICU admission) of COVID-19- infected patients in Bangladesh. Methods: Data from 244 patients with COVID-19 infection admitted from July 2021- September 2021, to the Aichi Hospital Ltd, Bangladesh, were retrospectively reviewed. Consecutive adult patients with laboratory-confirmed COVID-19 initially admitted to non- ICU wards were included. Categorical and quantitative variables were expressed as numbers (percentages) and median (interquartile range, IQR). We evaluated the predictive performance of NEWS2 to predict ICU admission by comparing the area under the receiver operating characteristics curve (AUROC) at thresholds 5 and 7 and assessed its association with ICU admission by performing multivariate logistic analyses. STATA conducted all the statistical analyses. Results: Among the included 218 patients, 68 patients were transferred to ICU. The AUROC was 0.96 (Standard error 0.01, 95% confidence interval 0.93-0.98), revealing that NEWS2 at hospital admission was a good predictor of ICU admission. A NEWS2 threshold of 5 had higher sensitivity than a threshold of 7 (72.06% and 29.41%). A point of 7 also had high specificity (99.33% and 63.33%) and a high positive predictive value than a threshold of 5 (95.24% vs. 47.12%). The NEWS2 entries 5 and 7 were related to ICU admission found in multivariate logistic regression analysis. Conclusion: Our results suggest that NEWS2 at hospital admission is a good predictor for ICU admission of COVID-19 patients in Bangladesh. Screening patients at admission with this tool may identify patients at risk of clinical deterioration and help in better management. EWMCJ Vol. 12, No. 1&2, January-July 2024: 60-65

Metabolomic alterations in the plasma of patients with various clinical manifestations of COVID-19

BackgroundThe metabolomic profiles of individuals with different clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have not been clearly characterized.MethodsWe performed metabolomics analysis of 166 individuals, including 62 healthy controls, 16 individuals with asymptomatic SARS-CoV-2 infection, and 88 patients with moderate (n = 42) and severe (n = 46) symptomatic 2019 coronavirus disease (COVID-19; 17 with short-term and 34 with long-term nucleic-acid test positivity). By examining differential expression, we identified candidate metabolites associated with different SARS-CoV-2 infection presentations. Functional and machine learning analyses were performed to explore the metabolites’ functions and verify their candidacy as biomarkers.ResultsA total of 417 metabolites were detected. We discovered 70 differentially expressed metabolites that may help differentiate asymptomatic infections from healthy controls and COVID-19 patients with different disease severity. Cyclamic acid and N-Acetylneuraminic Acid were identified to distinguish symptomatic infected patients and asymptomatic infected patients. Shikimic Acid, Glycyrrhetinic acid and 3-Hydroxybutyrate can supply significant insights for distinguishing short-term and long-term nucleic-acid test positivity.ConclusionMetabolomic profiling may highlight novel biomarkers for the identification of individuals with asymptomatic SARS-CoV-2 infection and further our understanding of the molecular pathogenesis of COVID-19.

STING-dependent induction of neutrophilic asthma exacerbation in response to house dust mite.

Severe refractory, neutrophilic asthma remains an unsolved clinical problem. STING agonists induce a neutrophilic response in the airways, suggesting that STING activation may contribute to the triggering of neutrophilic exacerbations. We aim to determine whether STING-induced neutrophilic lung inflammation mimics severe asthma. We developed new models of neutrophilic lung inflammation induced by house dust mite (HDM) plus STING agonists diamidobenzimidazole (diABZI) or cGAMP in wild-type, and conditional-STING-deficient mice. We measured DNA damage, cell death, NETs, cGAS/STING pathway activation by immunoblots, N1/N2 balance by flow cytometry, lung function by plethysmography, and Th1/Th2 cytokines by multiplex. We evaluated diABZI effects on human airway epithelial cells from healthy or patients with asthma, and validated the results by transcriptomic analyses of rhinovirus infected healthy controls vs patients with asthma. DiABZI administration during HDM challenge increased airway hyperresponsiveness, neutrophil recruitment with prominent NOS2+ARG1- type 1 neutrophils, protein extravasation, cell death by PANoptosis, NETs formation, extracellular dsDNA release, DNA sensors activation, IFNγ, IL-6 and CXCL10 release. Functionally, STING agonists exacerbated airway hyperresponsiveness. DiABZI caused DNA and epithelial barrier damage, STING pathway activation in human airway epithelial cells exposed to HDM, in line with DNA-sensing and PANoptosis pathways upregulation and tight-junction downregulation induced by rhinovirus challenge in patients with asthma. Our study identifies that triggering STING in the context of asthma induces cell death by PANoptosis, fueling the flame of inflammation through a mixed Th1/Th2 immune response recapitulating the features of severe asthma with a prognostic signature of type 1 neutrophils.

Successful management of infection and macrophage activation syndrome patient using low-dose etoposide: A case report

Successful management of infection and macrophage activation syndrome patient using low-dose etoposide: A case report

Cell binding tropism of rat hepatitis E virus is a pivotal determinant of its zoonotic transmission to humans

Classically, all hepatitis E virus (HEV) variants causing human infection belong to the genus Paslahepevirus (HEV-A). However, the increasing cases of rat HEV infection in humans since 2018 challenged this dogma, posing increasing health threats. Herein, we investigated the underlying mechanisms dictating the zoonotic potentials of different HEV species and their possible cross-protection relationships. We found that rat HEV virus-like particles (HEVVLPs) bound to human liver and intestinal cells/tissues with high efficiency. Moreover, rat HEVVLPs and infectious rat HEV particles penetrated the cell membrane and entered human target cells postbinding. In contrast, ferret HEVVLPs showed marginal cell binding and entry ability, bat HEVVLPs and avian HEVVLPs exhibited no binding and entry potency. Structure-based three-dimensional mapping identified that the surface spike domain of rat HEV is crucial for cell binding. Antigenic cartography indicated that rat HEV exhibited partial cross-reaction with HEV-A. Intriguingly, sera of HEV-A infected patients or human HEV vaccine Hecolin® immunized individuals provided partial cross-protection against the binding of rat HEVVLPs to human target cells. In summary, the interactions between the viral capsid and cellular receptor(s) regulate the distinct zoonotic potentials of different HEV species. The systematic characterization of antigenic cartography and serological cross-reactivity of different HEV species provide valuable insights for the development of species-specific diagnosis and protective vaccines against zoonotic HEV infection.

The Impact of COVID-19 Vaccination and Infection on the Exacerbation of Myasthenia Gravis

Objectives: Myasthenia Gravis (MG) is an autoimmune disorder that can exacerbate for various reasons, including vaccination and infection. This study aimed to investigate the safety of COVID-19 vaccines for MG patients, factors influencing MG exacerbation after COVID-19 infection (MECI), the course and prognosis of MECI, and the impact of COVID-19 vaccine on infected MG patients. Methods: Patients were enrolled from the MG database in the Department of Neurology, Xuanwu Hospital, Capital Medical University. Two questionnaires were administered to collect data concerning COVID-19 vaccination (questionnaire 1, Q1) and infection (questionnaire 2, Q2) during two distinct periods. MG exacerbation was defined as an increase of at least two points in the MG activity of daily living (MG-ADL) score. COVID-19 severity was categorized as “hospitalization” or “home management”; Results: During the first data-collecting period, our database registered 1013 adult patients: 273 (26.9%) had received COVID-19 vaccinations and completed Q1, and 8 (2.9%) experienced MG exacerbation after vaccination. During the second data-collecting period, among the newly registered patients, 366 patients completed Q2. Of these, 244 were infected, with 39 (16.0%) experiencing MECI and 21 (8.6%) requiring hospitalization. Multivariate analysis showed that generalized myasthenia gravis was associated with MECI (OR 3.354, 95% CI: 1.423–7.908, p = 0.006). Among the 244 infected patients, 143 had received COVID-19 vaccinations, including 14 who received their booster dose within 6 months before COVID-19 and 129 who were vaccinated more than 6 months before COVID-19. The remaining 101 were unvaccinated. No significant associations were found between COVID-19 vaccination and COVID-19 severity (p = 0.292) or MECI incidence (p = 0.478); Conclusions: COVID-19 vaccines were found to be safe for MG patients in stable condition. Patients with gMG were more susceptible to experiencing MECI. No significant impact of the vaccine on COVID-19 severity or MECI incidence was observed.

Effect of Statins and Renin–Angiotensin–Aldosterone System Inhibitors on IL-6 Levels in COVID-19 Patients

Background/Objectives: Severe clinical course and mortality from COVID-19 are mostly associated with increased concentrations of IL-6 and IL-10. Findings from clinical trials suggest that both statins and renin–angiotensin–aldosterone system inhibitors (RAASI) might have the potential to reduce unfavorable outcomes in patients with COVID-19. The aim of this study was to evaluate the effect of statins and RAASI on the cytokine concentrations in COVID-19 patients. Methods: SARS-CoV-2 infected patients were enrolled in this study, and demographic, clinical, and routine laboratory data were evaluated. Plasma cytokine levels were measured by multiplex assay. Results: COVID-19 patients with chronic cardiovascular diseases (CVD) had significantly lower median plasma IL-6 levels than COVID-19 patients with no co-morbidities (26 vs. 53 pg/mL, p = 0.021). COVID-19 patients with CVD who were taking statins had significantly lower median concentrations of IL-6 (21 vs. 44 pg/mL, p = 0.027), TNFα (21 vs. 39.5 pg/mL, p = 0.036), and IL-10 (19 vs. 25.5 pg/mL, p = 0.025) compared to COVID-19 patients with no CVD. In a binary logistic regression model, IL-6 was a significant variable, with an odds ratio value of 0.961 (95% CI 0.929–0.995). Regarding RAASI, only plasma IL-6 (22 vs. 44 pg/mL, p = 0.012) levels were found to be significantly lower in COVID-19 patients with CVD consuming these medications compared to patients who did not have any CVD. Conclusions: COVID-19 patients who had chronic cardiovascular co-morbidities and who were administered statins or RAASI had significantly lower concentrations of IL-6 than COVID-19 patients who did not have any co-morbidities. These findings suggest that the use of statins or RAASI may be of value in COVID-19 patients.

Single-cell Sequencing of Circulating Human Plasmablasts during Staphylococcus aureus Bacteremia.

Staphylococcus aureus is the major cause of healthcare-associated infections, including life-threatening conditions as bacteremia, endocarditis, and implant-associated infections. Despite adequate antibiotic treatment, the mortality of S. aureus bacteremia remains high. This calls for different strategies to treat this infection. In past years, sequencing of Ab repertoires from individuals previously exposed to a pathogen emerged as a successful method to discover novel therapeutic monoclonal Abs and understand circulating B cell diversity during infection. In this paper, we collected peripheral blood from 17 S. aureus bacteremia patients to study circulating plasmablast responses. Using single-cell transcriptome gene expression combined with sequencing of variable heavy and light Ig genes, we retrieved sequences from >400 plasmablasts revealing a high diversity with >300 unique variable heavy and light sequences. More than 200 variable sequences were synthesized to produce recombinant IgGs that were analyzed for binding to S. aureus whole bacterial cells. This revealed four novel monoclonal Abs that could specifically bind to the surface of S. aureus in the absence of Ig-binding surface SpA. Interestingly, three of four mAbs showed cross-reactivity with Staphylococcus epidermidis. Target identification revealed that the S. aureus-specific mAb BC153 targets wall teichoic acid, whereas cross-reactive mAbs BC019, BC020, and BC021 target lipoteichoic acid. All mAbs could induce Fc-dependent phagocytosis of staphylococci by human neutrophils. Altogether, we characterize the active B cell responses to S. aureus in infected patients and identify four functional mAbs against the S. aureus surface, of which three cross-react with S. epidermidis.

Antibodies to HIV-1 gp120 in an experimental model of atherosclerosis caused by immunization with native high-density lipoproteins

Antibodies to bacterial and viral antigens are detected in some systematic autoimmune diseases in the absence of infection. Autoimmune MRL mice and patients with mixed connective tissue disease produce antibodies to gp120 HIV-1, despite the fact that they had never been exposed to HIV-1. Conversely, viral infections may be accompanied by pathological autoimmune reactions. Reactivity to viral antigens in autoimmune diseases and autoimmune reactions in viral diseases are caused by the induction of antibodies via idiotype-anti-idiotype interactions between autoclones and lymphocyte clones against foreign antigens or homology of foreign antigens and autoantigens. Cardiovascular diseases caused by atherosclerosis are currently one of the main causes of mortality in HIV infected patients. It is assumed that HIV infection accelerates atherogenesis. The mechanisms of the association between HIV infection and atherosclerosis are not completely clear. Chronic activation of the immune system, disturbance of cytokine regulation caused by HIV infection, induction of autoantibodies against oxidized low-density lipoproteins (LDL) and antibodies to ApoB-D are considered as possible factors of atherogenesis in HIV infection. The aim of this research was to determine whether an atherogenic immune response against native human high-density lipoproteins (nHDL) could induce antibodies to gp120 HIV-1. Studies were conducted on model of autoimmune atherosclerosis caused by immunization with native human HDL in rabbits. Rabbits (n = 6) were one-time intradermally immunized with human nHDL at a dose of 200 μg of protein per animal in incomplete Freund’s adjuvant. Antibodies to gp120 HIV-1 were measured before immunization of rabbits and on the 28th and 42th day after immunization with HDL, and antibodies to HDL were weekly measured within 42 days after immunization. Histological analysis of the aorta was conducted after eight months after immunization. Transient anti-gp120 HIV-1 antibody production was detected in rabbits immunized with native HDL. The appearance of antibodies to gp120 HIV-1 in response to immunization with native HDL which causes atherosclerosis suggests that the immune response to gp120 HIV-1 during HIV infection may be accompanied by the production of atherogenic antibodies to HDL. Consequently, the antibodies to native lipoproteins caused by an immune response against gp120 HIV-1 may be a factor in atherogenesis during HIV-1 infection.

CT-based sarcopenia assessment: Predicting outcomes in acute infection patients.

In this retrospective cohort study, we investigated the prognostic value of sarcopenia evaluated by Computed Tomography (CT)-based indices for adverse hospitalization outcomes in patients with acute infections. We analyzed data from 225 patients admitted to the hospital for acute infections between 2019 and 2020. Patients who had undergone an abdominal CT scan either up to 1 month before or within the first 3 days of hospitalization were included. CT image analysis was used to evaluate skeletal muscle mass (by skeletal muscle index (SMI)) and muscle quality (by psoas muscle density, pMD). Low pMD was associated with higher in-hospital mortality (31% vs 11.4% p < 0.001) as well as higher longer-term mortality rates (p = 0.008 for 30 days and <0.001 for 90- and 1-year mortality). Low pMD remained an independent poor prognostic factor after controlling for confounders, with an adjusted odds ratio (aOR) of 2.74, (95% CI 1.33-5.67, p = 0.006) for 1-year mortality, and aOR of 2.61, (95% CI 1.23-5.55) for a prolonged hospital stay. Low SMI was associated with adverse outcomes, although this association was not independent after controlling for confounders. Notably, patients with both low SMI and pMD exhibited the poorest hospitalization outcomes: aOR for 1-year mortality 5.015 (95% CI 1.767-14.23, p = 0.002), and prolonged length of stay aOR 3.197, (95% CI 1.159-8.821, p = 0.025). CT-based muscle indices serve as independent prognostic factors in medical patients admitted with acute infection. Incorporating radiological assessments of sarcopenia into routine care for hospitalized patients with acute infection may enable risk stratification and early intervention in reversible conditions.

Epidemiology of human metapneumovirus in Taiwan from 2013 to 2023

Human metapneumovirus (HMPV) is a member of the genus Metapneumovirus in the family Pneumoviridae of the order Mononegavirales that can cause upper and lower respiratory tract disease. This retrospective study describes the epidemiology of hMPV based on community viral surveillance results from sentinel sites across Taiwan from 2013 to 2023. A total of 114 hMPV strains were isolated and analyzed to assess viral evolution through sequencing of their fusion protein genes. This study revealed that hMPV cases occur almost year-round in Taiwan, with a peak occurring during spring (March to May). Of the 114 infected patients, 68.4% were children under 4 years old. The geographical distribution of hMPV positivity was highest in Penghu County, followed by Changhua County and Hsinchu County. The clinical symptoms of hMPV infection are nonspecific, with fever (56.1%), cough (44.7%), rhinorrhea (21.1%), and sore throat (14.9%) being the most common. However, a few patients also developed severe central nervous system symptoms (1.8%) or dyspnea (0.9%). Phylogenetic analysis revealed genetic diversity among the 114 isolated hMPV strains, with the A2 lineage (57.9%) being the most frequently observed, followed by the B2 lineage (33.3%), in the Taiwanese community from 2013 to 2023. In conclusion, hMPV causes a serious acute respiratory disease in Taiwan that should not be neglected. Further epidemiological surveillance and investigations of the clinical characteristics of hMPV should be performed continually for prevention and control of this virus.

Taeniasis impacts human gut microbiome composition and function.

Human taeniasis, caused by Taenia tapeworms, is a global parasitic disease with significant implications for public health and food safety. These tapeworms can grow to considerable sizes and potentially impact the microecology of the host gut. Despite their importance, the effects of Taenia infection on host gut microbiota haven't been thoroughly investigated. In this study, we conducted a cross-sectional analysis of the gut microbiome in patients infected with Taenia asiatica (n = 87) compared to healthy controls (n = 79) in the Dali cohort, China. We also performed a longitudinal assessment of microbial changes following deworming in a subset of patients (n = 24). Our findings reveal a significant shift in gut microbial composition, characterized by increased alpha-diversity and an enrichment of Prevotella-driven enterotypes in infected patients compared to healthy controls. The stability of these microbial features post-deworming varied widely among individuals and was lower in those with lower initial alpha diversity and Prevotella-enterotype before deworming. We observed a significant depletion of Bifidobacterium species in infected individuals, regardless of enterotypes, and these prebiotics did not recover post-deworming. Metabolic network analysis and in vitro experiments suggest that the reduction of Bifidobacterium was linked to metabolic competition for ecological niches or nutrients, particularly stachyose, from other microbes rather than the parasitism itself. Furthermore, our machine learning analysis demonstrated that taxa associated with Bifidobacterium in stachyose metabolism could robustly predict infection but could not predict deworming. This study highlights the substantial impact of taeniasis on the human gut microbiome and overall gut health.

Interleukin-1 Beta rs16944 and rs1143634 and Interleukin-6 Receptor rs12083537 Single Nucleotide Polymorphisms as Potential Predictors of COVID-19 Severity.

Host genetic variation has been recognized as a key predictor of diverse clinical sequelae among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients. Insights into the link between the Interleukin-6 receptor (IL-6R) and Interleukin-1 beta (IL-1β) genetic variation and severe coronavirus disease 2019 (COVID-19) are crucial for developing new predictors and therapeutic targets. We aimed to investigate the association of IL-6R rs12083537, IL-1β rs16944, and IL-1β rs1143634 SNPs with the severity of COVID-19. Our study was conducted on 300 COVID-19-negative individuals (control group) and 299 COVID-19-positive cases, classified into mild, moderate, and severe subgroups. Analyses of IL-1β (rs16944, rs1143634) and IL-6R (rs12083537) SNPs' genotypes were performed using qPCR genotyping assays. The IL-1β (rs16944) CC genotype and IL-6R (rs12083537) GG genotype were substantially related to COVID-19 severity, which was also associated with comorbidities and some laboratory parameters (p < 0.001). The IL-1β (rs1143634) TT genotype was found to be protective. Likewise, the IL-1β (rs16944) CC genotype was associated with increased mortality. IL-1β rs16944 and IL-6R rs12083537 SNPs are promising potential predictors of SARS-CoV-2 disease severity. Meanwhile, the rs1143634 SNP T allele was protective against severity and mortality risk.

Disease progression associated cytokines in COVID-19 patients with deteriorating and recovering health conditions.

Understanding the immune response to COVID-19 is challenging due to its high variability among individuals. To identify differentially expressed cytokines between the deteriorating and recovering phases, we analyzed the Electronic Health Records (EHR) and cytokine profile data in a COVID-19 cohort of 444 infected patients and 145 non-infected healthy individuals. We categorized each patient's progression into Deterioration Phase (DP) and Recovery Phase (RP) using longitudinal neutrophil, lymphocyte and lactate dehydrogenase levels. A random forest model was built using healthy and severe patients to compute the contribution of each cytokine toward disease progression using Shapley Additive Explanations (SHAP). SHAP values were used for supervised clustering to identify DP and RP-related samples and their associated cytokines. The identified clusters effectively discriminated DP and RP samples, suggesting that the cytokine profiles differed between deteriorating and recovering health conditions. Especially, CXCL10, GDF15, PTX3, and TNFSF10 were differentially expressed between the DP and RP samples, which are involved in the JAK-STAT, NF- B, and MAPK signaling pathways contributing to the inflammatory response. Collectively, we characterized the immune response in terms of disease progression of COVID-19 with deteriorating and recovering health conditions.

Predicting the effect of nosocomial infection prevention on neonatal mortality and hospital stay in Ethiopia: a prospective longitudinal study

BackgroundNeonatal Nosocomial infections (NNIs) are a significant cause of morbidity and mortality for neonates in an intensive care unit. Neonatal causes of death in healthcare facilities are attributed to different factors. We aimed to investigate factors associated with NNIs, estimate the burden of NNIs, and assess how the prediction effects help to save medical mortality and length of hospital stay.MethodA prospective longitudinal study was conducted and data were collected from January 2022 to June 2022 from Jimma University Medical Center (JUMC). The data were gathered in a variety of ways, including an in-person interview with the patient’s caregiver, direct observations of neonatal patients, and a review of the study participants’ charts. This study includes patients aged 3 to 28 days who were admitted to the JUMC neonatal ward and stayed for at least 48 h. Multi-state model formulation and multivariate logistic regression were used for data analysis.ResultsA total of 545 neonates were included out of 688, and 30% (n = 164) of them acquired nosocomial infections (NIs); 98 (33%) of infected patients were born prematurely; and 71 (31.4%) were underweight at birth. NIs were higher in neonates with long hospital stay (AOR: 1.16, 95%CI: 1.13–1.20), use of urinary catheters (AOR: 3.09, 95%CI: 1.55–6.15), and undergoing surgical procedures (AOR: 2.42, 95%CI: 1.13–5.17). Patients who developed NIs had a higher risk of death (HR: 2, 95% CI: 1.31, 3.04). The burden of neonatal NIs was determined to have a risk of 0.3, a mortality rate of 9.6%, and an average duration of hospital stay of 14.6 days. Competing risk regression suggests that neonates with NIs have a significantly higher risk of death than those who are not infected (HR: 16.42, 95% CI: 8.70-30.98, p < 0.001). Assumed prevention that decreases the NIs rate in half would result in 101 lives and 1357 patient days saved from 10,000 neonatal inpatients.ConclusionUrinary catheterization and surgical procedure increased neonatal NIs. Longer hospital stay can increase the risk of NIs and can also result from the NIs. Our finding indicated that effective prevention of NIs could help reduce neonatal deaths and their hospital stays.

Hepatic Bone Morphogenetic Protein and Activin Membrane-Bound Inhibitor Levels Decline in Hepatitis C but Are Not Associated with Progression of Hepatocellular Carcinoma.

Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) is an antagonist of transforming growth factor (TGF)-β type 1 signaling. BAMBI functions as an anti-fibrotic protein and exerts pro- as well as anti-cancerogenic activities. Our study aimed to correlate hepatocyte BAMBI protein levels in hepatocellular carcinoma (HCC) with T stage, lymph node invasion, vessel invasion, grading, tumor size and Union for International Cancer Control (UICC) stage, as well as with liver inflammation and fibrosis stages. Hepatocyte BAMBI protein expression was assessed by immunohistochemistry in HCC tissues of 320 patients and non-tumor tissues of 51 patients. In the HCC tissues of the whole cohort and sex-specific analysis, BAMBI protein was not related to T stage, vessel invasion, lymph node invasion, histologic grade, UICC stage and tumor size. Accordingly, BAMBI was not associated with overall survival, recurrence-free and metastasis-free survival. BAMBI protein levels in tumor and non-tumor tissues were not related to inflammation and fibrosis grade. BAMBI protein levels in HCC tissues and non-tumor tissues from HCC patients, which were analyzed by immunoblot in a small cohort and by immunohistochemistry in the tissues of patients described above, were similar. Notably, BAMBI protein was low-abundant in HCC tissues of hepatitis C virus (HCV) compared to hepatitis B virus (HBV)-infected patients with comparable disease severity. Immunoblot analysis revealed reduced BAMBI protein in non-tumor tissues of patients with HCV in comparison to patients with HBV and normal human liver tissues. In summary, this analysis showed that hepatocyte BAMBI protein levels of patients with HCC are related to HCV infection rather than the severity of the underlying liver disease and cancer staging.

Effect of leucine on mitochondria and oxidative stress to reduce virulence and pathogenicity of Acinetobacter baumannii

Elucidating the virulence mechanisms of A. baumannii is essential for developing strategies to mitigate pathogenicity. Although high-virulent strains are associated with increased mortality rate in severely infected patients, the underlying mechanisms remains not well understood. Our analysis revealed leucine as a pivotal biomarker, with the 11dP and paaK being significant contributors to virulence. The ATP-dependent activity and antioxidant activity were identified as the most important pathways in distinguishing the virulence of A. baumannii. Exogenous leucine was found to modulate mitochondria dysfunction and oxidative stress, thereby diminishing the pathogenicity of A. baumannii towards Beas 2B cells. Moreover, leucine reduced the virulence of A. baumannii to Galleria mellonella (G. mellonella) and alleviated pathological damage to lung tissues in mice. Our study offers a novel treatment strategy based on metabolomics, which may assist in the exploration and management of infections caused by highly virulent pathogens. It sets a new course for reducing the impact of highly virulent A. baumannii infections and has significant implications for the development of future therapeutic interventions.

The unusual location of primary hydatid cyst: A case series study.

Cystic echinococcosis mainly affects the liver and lungs, in which the larvae from the microvascular wall in the liver pass to the lungs and then to the blood circulation and settle in any tissue or organ. The objective of this study was to report the unusual location of hydatid cysts in infected patients in Sulaimaniyah City, Iraq. This retrospective case series study enrolled 13 patients. They underwent a surgical operation to excise their cyst after confirmed diagnosis with blood investigations, electrocardiogram, chest X-ray, computed tomography scan, and magnetic resonance imaging (when needed). After the operation, the cyst was confirmed with histopathological examination, and patients were advised to take an Albendazole tablet. Most patients were females from rural areas, with a mean age of 38.93 ± 14.4 years. Patients presented with cysts on the skin of the anterior abdominal wall, gluteal region, mesenteric area, pericardium, tibia bone meta diaphysis, right inguinal region, right thigh, skin of the anterior neck, spleen, left suprarenal gland, right breast, and the iliopsoas muscle. The hydatid cyst can affect any body part with no site immune and often produces nonspecific symptoms.

The Influence of Prone Positioning on Energy and Protein Delivery in COVID-19 Patients Requiring ECMO Support

Background: Gastrointestinal dysfunction is a common complication of medical nutrition therapy in critically ill patients. Whether prone positioning leads to a deterioration in gastrointestinal function has not been fully clarified. Thus, we aimed to analyze the influence of prone positioning on the tolerance of medical nutrition therapy. Methods: We conducted a retrospective analysis of 102 SARS-CoV-2 infected patients with venovenous extracorporeal membrane oxygenation support (VV ECMO). Gastric residual volume (GRV) was used to assess the tolerance of enteral nutrition. Results: Nutritional data were collected for 2344 days. Undernutrition was observed in 40.8%, with a significantly higher incidence on days in prone position (48.4% versus 38.6%, p &lt; 0.001). On days in supine position, significantly more calories were administered enterally than on days in prone position (p &lt; 0.001). The mean GRV/24 h was 111.1 mL on days in supine position and 187.3 mL on days in prone position (p &lt; 0.001). Prone positioning was associated with higher rates of GRV of ≥500 mL/24 h independent of age, disease severity at ECMO start, ECMO runtime and ICU length of stay (adjusted hazard ratio: 4.06; 95%CI: 3.0–5.5; p &lt; 0.001). Conclusions: Prone position was associated with lower tolerance of enteral nutrition, as indicated by an increased GRV. As a result, reduced enteral nutritional support was administered.