Cause Of Death Research Articles

Clinical outcomes prediction in kidney transplantation by use of biomarkers from hypothermic machine perfusion.

The clinical outcomes of kidney transplantation from deceased donors have seen significant improvements with the use of machine perfusion (MP), now a standard practice in transplant centers. However, the use of perfusate biomarkers for assessing organ quality remains a subject of debate. Despite this, some centers incorporate them into their decision-making process for donor kidney acceptance. Recent studies have indicated that lactate dehydrogenase (LDH), glutathione S-transferase, interleukin-18, and neutrophil gelatinase-associated lipocalin (NGAL) could predict post-transplant outcomes. Between August 2016 and June 2017, 31 deceased-donor after brain death were included and stroke was the main cause of death. Pediatric patients, hypersensitized recipients were excluded. 43 kidneys were subjected to machine perfusion. Perfusate samples were collected just before the transplantation and stored at -80ºC. Kidney transplant recipients have an average age of 52 years, 34,9% female, with a BMI 24,6±3,7. We employed receiver operating characteristic analysis to investigate associations between these perfusate biomarkers and two key clinical outcomes: delayed graft function and primary non-function. The incidence of delayed graft function was 23.3% and primary non-function was 14%. A strong association was found between NGAL concentration and DGF (AUC=0.766, 95% CI, P=0.012), and between LDH concentration and PNF (AUC=0.84, 95% CI, P=0.027). Other perfusate biomarkers did not show significant correlations with these clinical outcomes. The concentrations of NGAL and LDH during machine perfusion could assist transplant physicians in improving the allocation of donated organs and making challenging decisions regarding organ discarding. Further, larger-scale studies are required.

Plasma and interstitial fluid antibiotic levels of subcutaneously implanted compounded florfenicol calcium sulfate beads in New Zealand White rabbits (Oryctolagus cuniculus).

To determine antibiotic levels in plasma and interstitial fluid (ISF) after SC placement of compounded florfenicol (FF) calcium sulfate beads (CSBs) in New Zealand White rabbits (Oryctolagus cuniculus). 6 juvenile female rabbits (n = 5 treatment and 1 control). An ultrafiltration probe and CSBs were placed SC in 6 rabbits (n = 5 for FF CSBs and 1 for control CSBs). Plasma (3, 6, 12, 24, and 48 hours and 7, 14, and 21 days) and ISF (daily for 21 days) samples were collected, and FF was measured by HPLC for pharmacokinetic analysis. Hematology, biochemistry, and histopathology were assessed. Means ± SD for the area under the curve, maximum concentration, time of maximum concentration, terminal half-life, and mean residence time to the last data point for plasma and ISF were 16.63 ± 8.16 and 17,902 ± 7,564 h·µg/mL, 0.79 ± 0.38 and 245 ± 223 µg/mL, 2.90 ± 0.3 and 59 ± 40 hours, 30.81 ± 16.9 and 27.3 ± 9.39 hours, 23.4 ± 10 and 73.7 ± 13 hours, respectively. Plasma FF was < 2 µg/mL at all time points. The ISF FF remained > 8 μg/mL for 109.98 to 231.58 hours. One rabbit death occurred during treatment, but the cause of death was undetermined. Local tissue inflammation was present, but no clinically significant systemic adverse effects were found on hematology, biochemistry, or histopathology in the remaining rabbits. Florfenicol CSBs maintained antibiotic concentrations in ISF at levels likely to be effective against bacteria sensitive to > 8 µg/mL for 5 to 10 days while maintaining low (< 2 µg/mL) plasma levels. Florfenicol CSBs may be effective for local antibiotic treatment in rabbit abscesses.

Using portable X-ray fluorescence elemental analysis to explore porous skeletal lesions: Interplay of sex, age at death, and cause of death.

Search for possible associations between bone elemental concentration and the presence of porous skeletal lesions (PSLs), considering the sex, age, and cause of death (COD) of the individuals. The sample comprised 107 non-adult individuals (56 females, 51 males) aged 0-20 (x̄ = 13.2, SD = 5.8) from the Coimbra and Lisbon Identified Skeletal Collections. Cribra cranii, orbitalia, humeralis, and femoralis were recorded as present/absent, and elemental concentrations were assessed by portable x-ray fluorescence (pXRF). A multivariate statistical approach was applied. Well-preserved skeletons with minimal diagenesis showed no sex-related elemental variations or PSL associations. In contrast, age-at-death correlated with elevated Ca, P, Sr, and Pb levels. Cribra cranii increased with age while other cribra declined post-adolescence. Higher concentrations of Fe and lower of S were linked to cribra cranii. Respiratory infections as COD increased the odds of expressing cribra femoralis (OR = 5.25, CI = 1.25-15.14), cribra cranii (OR = 2.91, CI = 0.97-8.69), and cribra orbitalia (OR = 2.76, CI = 1.06-7.24). Feasible pXRF results and low cribra intraobserver error assure replicability. Elevated Ca, P, and Sr in older individuals may relate to skeletal growth, while increased Pb suggests bioaccumulation. Cribra's increase with age reflects different rates of marrow conversion and bone remodeling. Higher Fe and lower S in individuals with cribra cranii possibly reflects poor nutrition, early alcohol use, and sideroblastic anemia, aligning with 19th-20th-century Portugal's living conditions. Respiratory infections increased cribra expression, revealing intricate interplays among inflammation, anemia(s), marrow expansion, and diet. This research highlights a complex scenario and blazes a new path for cribra interpretation.

Maternal deaths among Brazilian indigenous women-Analysis from 2015 to 2021.

This study examines maternal mortality among Brazilian indigenous women from 2015 to 2021, contrasting their causes of death with non-indigenous women. An observational study utilizing Ministry of Health data analyzed maternal deaths' characteristics, comparing indigenous and non-indigenous groups based on death certificates and live-birth records. Variables included age, region, location, time, and cause of death. Maternal mortality ratios (MMR) were calculated with linear regression and outliers identified with Grubbs test. Prevalence ratios compared MMR and causes of death. Between 2015 to 2021, Brazil recorded 13 023 maternal deaths. Among these, with 205 among indigenous women (1.60% of total). Indigenous women had higher MMR (115.14/100 000), than non- indigenous women (66.92/100 000), consistently across years. Hemorrhagic causes notably contributed to the indigenous women's elevated MMR. Indigenous Brazilian women face elevated maternal mortality rates across all causes, primarily due to hemorrhage, contrasting wih national trends.

Diagnosis of pneumonia in paediatric age group by comparing two modalities chest x-ray versus ultrasonography at tertiary care hospital

: Up to 20 million cases of pneumonia in children ages 0 to 5 years require hospitalization each year, from total 150 million cases of pneumonia. The most common cause of death in children worldwide is pneumonia. Due to the general non-specificity of the signs and symptoms, clinical history and physical examination cannot reliably distinguish between the causes of respiratory cases. As a result, accurate diagnosis frequently requires medical imaging, but two-thirds of the world's population lack access to diagnostic imaging, which lead to increasing the consequences of respiratory illnesses. : To know the characteristic of pneumonia in x-ray and ultrasonography. To compare X-ray chest and USG for early diagnosis. : A Prospective observational study was conducted among 100 paediatric patients diagnosed with pneumonia and admitted in paediatric ward, at New Civil Hospital, Surat. : Out of total, 52.7% and 47.3% patients were Males and Females, respectively. 87.2% cases were fully immunized, while remaining were partially immunized. Sensitivity and specificity of chest X-ray is 83.4 % and 86.8 % respectively. Sensitivity and specificity of USG thorax is 96.8 % and 90.5 % respectively. Young children are at least four times more susceptible to radiation damage than adults.: In comparison to chest radiography, lung ultrasound has the potential advantages of being more sensitive and specific, radiation-free, subject to less regulatory constraints, relatively less expensive so it can be used in diagnosis in patients with pneumonia.

Global status and trends of metabolomics in diabetes: A literature visualization knowledge graph study

BACKGROUND Diabetes is a metabolic disease characterized by hyperglycemia, which has increased the global medical burden and is also the main cause of death in most countries. AIM To understand the knowledge structure of global development status, research focus, and future trend of the relationship between diabetes and metabolomics in the past 20 years. METHODS The articles about the relationship between diabetes and metabolomics in the Web of Science Core Collection were retrieved from 2002 to October 23, 2023, and the relevant information was analyzed using CiteSpace6.2.2R (CiteSpace), VOSviewer6.1.18 (VOSviewer), and Bibliometrix software under R language. RESULTS A total of 3123 publications were included from 2002 to 2022. In the past two decades, the number of publications and citations in this field has continued to increase. The United States, China, Germany, the United Kingdom, and other relevant funds, institutions, and authors have significantly contributed to this field. Scientific Reports and PLoS One are the journals with the most publications and the most citations. Through keyword co-occurrence and cluster analysis, the closely related keywords are "insulin resistance", "risk", "obesity", "oxidative stress", "metabolomics", "metabolites" and "biomarkers". Keyword clustering included cardiovascular disease, gut microbiota, metabonomics, diabetic nephropathy, molecular docking, gestational diabetes mellitus, oxidative stress, and insulin resistance. Burst detection analysis of keyword depicted that "Gene", "microbiota", "validation", "kidney disease", "antioxidant activity", "untargeted metabolomics", "management", and "accumulation" are knowledge frontiers in recent years. CONCLUSION The relationship between metabolomics and diabetes is receiving extensive attention. Diabetic nephropathy, diabetic cardiovascular disease, and kidney disease are key diseases for future research in this field. Gut microbiota, molecular docking, and untargeted metabolomics are key research directions in the future. Antioxidant activity, gene, validation, mass spectrometry, management, and accumulation are at the forefront of knowledge frontiers in this field.

Predictive value of Systematic Coronary Risk Evaluation 2-Diabetes risk model and arterial stiffness for cardiovascular events in the Asian population with type 2 diabetes mellitus.

Individuals with diabetes are at high risk of developing cardiovascular events. The present study investigated the predictive value of the cardio-ankle vascular index (CAVI) when added to the Systematic Coronary Risk Evaluation 2-Diabetes (SCORE2-Diabetes) risk algorithm to predict cardiovascular events in the Asian population. The SCORE2-Diabetes risk was assessed in 1,502 patients with diabetes, aged 40-69 years. Then, we further stratified each 10-year risk category with a CAVI value of 9.0. The primary outcomes (composite of all causes of death, myocardial infarction, stroke and hospitalization for heart failure) were assessed over 5 years. The mean age of the population was 59.8 ± 6.4 years. The proportion of 10-year risk according to the SCORE2-Diabetes risk of low, moderate, high and very high risk identified at 7.2, 30.0, 27.2 and 35.6%, respectively. The mean CAVI value was 8.4 ± 1.4, and approximately 35.4% of the patients had CAVI ≥9.0. The SCORE2-Diabetes risk algorithm independently predicted the primary outcomes in patients with diabetes (hazard ratio 1.18, 95% confidence interval [CI] 1.13-1.22), whereas CAVI did not (hazard ratio 1.03, 95% CI 0.89-1.18). The C-index for the primary outcomes of the SCORE2-Diabetes risk algorithm alone was 0.72 (95% CI 0.67-0.77). The combination of SCORE2-Diabetes and CAVI, both in the continuous value and risk groups, did not improve discrimination (C-index 0.72, 95% CI 0.67-0.77 and 0.68, 95% CI 0.64-0.74, respectively). Adding the CAVI to the SCORE2-Diabetes risk algorithm did not improve individual risk stratification in patients with diabetes.

Tuberculosis-diabetes comorbidities: Mechanistic insights for clinical considerations and treatment challenges

Tuberculosis (TB) remains a leading cause of death among infectious diseases, particularly in poor countries. Viral infections, multidrug-resistant and ex-tensively drug-resistant TB strains, as well as the coexistence of chronic illnesses such as diabetes mellitus (DM) greatly aggravate TB morbidity and mortality. DM [particularly type 2 DM (T2DM)] and TB have converged making their control even more challenging. Two contemporary global epidemics, TB-DM behaves like a syndemic, a synergistic confluence of two highly prevalent diseases. T2DM is a risk factor for developing more severe forms of multi-drug resistant-TB and TB recurrence after preventive treatment. Since a bidirectional relationship exists between TB and DM, it is necessary to concurrently treat both, and promote recommendations for the joint management of both diseases. There are also some drug-drug interactions resulting in adverse treatment outcomes in TB-DM patients including treatment failure, and reinfection. In addition, autophagy may play a role in these comorbidities. Therefore, the TB-DM comorbidities present several health challenges, requiring a focus on multidisciplinary collaboration and integrated strategies, to effectively deal with this double burden. To effectively manage the comorbidity, further screening in affected countries, more suitable drugs, and better treatment strategies are required.

Efficacy of Huangma Ding or autologous platelet-rich gel for the diabetic lower extremity arterial disease patients with foot ulcers

BACKGROUND Diabetes foot is one of the most serious complications of diabetes and an important cause of death and disability, traditional treatment has poor efficacy and there is an urgent need to develop a practical treatment method. AIM To investigate whether Huangma Ding or autologous platelet-rich gel (APG) treatment would benefit diabetic lower extremity arterial disease (LEAD) patients with foot ulcers. METHODS A total of 155 diabetic LEAD patients with foot ulcers were enrolled and divided into three groups: Group A (62 patients; basal treatment), Group B (38 patients; basal treatment and APG), and Group C (55 patients; basal treatment and Huangma Ding). All patients underwent routine follow-up visits for six months. After follow-up, we calculated the changes in all variables from baseline and determined the differences between groups and the relationships between parameters. RESULTS The infection status of the three groups before treatment was the same. Procalcitonin (PCT) improved after APG and Huangma Ding treatment more than after traditional treatment and was significantly greater in Group C than in Group B. Logistic regression analysis revealed that PCT was positively correlated with total amputation, primary amputation, and minor amputation rates. The ankle-brachial pressure and the transcutaneous oxygen pressure in Groups B and C were greater than those in Group A. The major amputation rate, minor amputation rate, and total amputation times in Groups B and C were lower than those in Group A. CONCLUSION Our research indicated that diabetic foot ulcers (DFUs) lead to major amputation, minor amputation, and total amputation through local infection and poor microcirculation and macrocirculation. Huangma Ding and APG were effective attreating DFUs. The clinical efficacy of Huangma Ding was better than that of autologous platelet gel, which may be related to the better control of local infection by Huangma Ding. This finding suggested that in patients with DFUs combined with coinfection, controlling infection is as important as improving circulation.

Colorectal cancer outcomes among Hispanic/Latino patients in the United States: a scoping review protocol.

This scoping review will identify the patterns of survival, treatment, and recurrence among Hispanic and/or Latino/a/x (H/L) patients with colorectal cancer (CRC) living in the United States (US) and Puerto Rico. Additionally, population- and individual-level determinants of cancer outcomes among H/L CRC patients will be mapped to highlight under-reported/under-investigated research areas. CRC is the third most common cancer excluding skin cancers in the US. Unlike non-Hispanic White populations, cancer is the number one cause of death in H/L populations and currently represents 21% of total deaths. Despite this, a lack of consensus exists on CRC outcomes for H/L patients. Most research on H/L individuals has examined incidence and screening of CRC, with fewer studies focusing on cancer outcomes. All epidemiological study designs and systematic reviews will be considered. The review will only include peer-reviewed studies that report on survival, treatment, and/or recurrence patterns for H/L patients with CRC residing in the US and Puerto Rico. A 3-step search with a 2-stage study selection process will be followed, as recommended by JBI and Arksey and O'Malley. Databases to be searched will include MEDLINE (PubMed), Embase (Ovid), and Scopus. A data extraction tool will be designed based on JBI recommendations. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRSIMA-ScR) will be used, with the results presented in a PRISMA diagram. Publications in English from database inception to the present will be considered.

From rare events to systematic data collection: the RESCUED registry for sudden cardiac death in the young in Germany.

Approximately one-third of sudden cardiac deaths in the young (SCDY) occur due to a structural cardiac disease. Forty to fifty percent of SCDY cases remain unexplained after autopsy (including microscopic and forensic-toxicological analyses), suggesting arrhythmia syndromes as a possible cause of death. Due to the possible inheritability of these diseases, blood relatives of the deceased may equally be carriers of the causative genetic variations and therefore may have an increased cardiac risk profile. A better understanding of the forensic, clinical, and genetic data might help identify a subset of the general population that is at increased risk of sudden cardiac death. The German registry RESCUED (REgistry for Sudden Cardiac and UnExpected Death) comprises information about SCDY fatalities and clinical and genetic data of both the deceased and their biological relatives. The datasets collected in the RESCUED registry will allow for the identification of leading causes of SCDY in Germany and offer unique possibilities of scientific analyses with the aim of detecting unrecognized trends, risk factors, and clinical warning signs of SCDY. In a pilot phase of 24months, approximately 180 SCDY cases (< 50years of age) and 500 family members and clinical patients will be included. RESCUED is the first registry in Germany collecting comprehensive data of SCDY cases and clinical data of the biological relatives reviewed by cardiac experts. RESCUED aims to improve individual risk assessment and public health approaches by directing resources towards early diagnosis and evidence-based, personalized therapy and prevention in affected families. Trial registration number (TRN): DRKS00033543.

The double burden of severe mental illness and cancer: a population-based study on colorectal cancer care pathways from screening to end-of-life care.

Cancer is one of the main causes of death in persons with severe mental illness (SMI). Although their cancer incidence is similar, or sometimes even potentially lower compared to the general population, their cancer mortality remains higher. The role of healthcare provision and care equity in this mortality is increasingly being addressed in research, but available studies are limited in their scope. In this context, our aim was to compare colorectal cancer (CRC) care pathways from screening to end-of-life care in patients with and without pre-existing SMI on a national scale. This research leverages real-world data from the French national health claims database, covering the entire population, to assess cancer screening, diagnosis, treatment and post-treatment follow-up as well as quality of care (QOC) pathways among patients with incident CRC in 2015-2018, considering whether they had pre-existing SMI. We matched patients with SMI with three patients without - on age, sex, region of residence, year of cancer incidence and cancer type and location at presentation - as well as nationally established quality of CRC care indicators and regression models adjusting for relevant socio-economic, clinical and care provider-related covariates. Among patients with incident CRC, 1,532 individuals with pre-existing SMI were matched with individuals without SMI. After adjusting for covariates, both colon and rectal cancer patients with SMI were less likely to participate in the national CRC screening programme and to receive advanced diagnostic examinations (e.g., colonoscopies and several complementary diagnostic examinations). They also had lower odds of receiving combined treatments (e.g., neoadjuvant chemotherapy, radiotherapy and excision) and of having access to targeted therapy or capecitabine but higher odds for invasive care (e.g., stoma). Colon cancer patients with SMI were also more likely to have no treatment at all, and rectal cancer patients with SMI were less likely to receive post-treatment follow-up. Suboptimal QOC was observed for both groups of patients, but to a higher extent for patients with SMI, with statistically significant differences for indicators focusing on diagnosis and post-treatment follow-up. Our findings reveal discrepancies across the care continuum of CRC between individuals with and without SMI and provide initial avenues on where to focus future efforts to address them, notably at the entry and exit stages of cancer care pathways, while calling for further research on the mechanisms preventing equity of physical healthcare for individuals with SMI.

Histopathological study of lungs, kidney and spleen in death due to burns

Burn injuries occur universally and have plagued mankind ever since antiquity till the present day. As burns continue to be a major problem, a prospective study of demographic and pathological profile in deaths due to burns was conducted at the Department of Pathology Karnataka Institute of Medical Sciences Hubballi. To study the demographic profile, histopathological changes in lungs, kidney and spleen and to find the cause of death in cases due to burns. : The present study was carried out in the Department of Pathology, Karnataka institute of medical sciences, Hubballi, during the period of one year from 1-11-2014 to 31-10-2015. Total of 44 cases with burn injuries were used as material for study purpose and the collection of tissues were done for histopathology examination. This study includes 44 autopsy cases of death due to burn, of which majority were females. The age of the subjects ranged from 13 years to 65 years. Maximum numbers of victims were found in the age group of 21-30 years were 22 cases (50.00%).Most of the female victims were married and housewives. Most common manner of the burn were said accidental burns in 27 cases (61.36%) and 13 cases (29.54%) were due to suicidal burns, 4 cases (9.09%) were homicidal burns.Burns were more common in females most were married. Age group most commonly found was between 21-30 years of age probably related to dowry related issues, inexperience in cooking styles, house hold works, and inability to bear stress. Most common place of burns were kitchen. Most common manner of burns were said accidental. Most common cause of burns was due to said kerosene spill over or self pouring. TBSA involved more than 76%, in maximum number of cases. Maximum finding were seen in lung. Most common findings were diffuse alveolar damage, acute tubular injury and congested splenomegaly.

Enhanced tuberculosis diagnosis with computer-aided chest X-ray and urine LAM in adults with HIV admitted to hospital (CASTLE study): A cluster randomised trial.

People with HIV (PHIV) admitted to hospital have high mortality, with tuberculosis (TB) being the major cause of death. Systematic use of new TB diagnostics could improve TB diagnosis and might improve outcomes. We conducted a cluster randomised trial among adult PHIV admitted to Zomba Central Hospital, Malawi. Admission-days were randomly assigned to: enhanced TB diagnostics using urine lipoarabinomannan (LAM) antigen tests (SILVAMP-LAM, Fujifilm, Japan and Determine-LAM, Alere/Abbot, USA), digital chest X-ray with computer aided diagnosis (dCXR-CAD, CAD4TBv6, Delft, Netherlands), plus usual care ("enhanced TB diagnostics"); or usual care alone ("usual care"). The primary outcome was TB treatment initiation during admission. Secondary outcomes were 56-day mortality, TB diagnosis within 24-hours, and undiagnosed TB at discharge, ascertained by culture of one admission sputum sample. Between 2 September 2020 and 15 February 2022, we recruited 419 people. Four people were excluded post-recruitment, leaving 415 adults recruited during 207 randomly assigned admission-days in modified intention-to-treat analysis. At admission, 90.8% (377/415) were taking antiretroviral therapy (ART) with median (IQR) CD4 cell count 240 cells/mm3. In the enhanced diagnostic arm, median CAD4TBv6 score was 60 (IQR: 51-71), 4.4% (9/207) had SILVAMP-LAM-positive and 14.4% (29/201) had Determine-LAM positive urine with three samples positive by both urine tests. TB treatment was initiated in 46/208 (22%) in enhanced TB diagnostics arm and 24/207 (12%) in usual care arm (risk ratio [RR] 1.92, 95% CI 1.20-3.08). There was no difference in mortality by 56 days (enhanced TB diagnosis: 54/208, 26%; usual care: 52/207, 25%; hazard ratio 1.05, 95% CI 0.72-1.53); TB treatment initiation within 24 hours (enhanced TB diagnosis: 8/207, 3.9%; usual care: 5/208, 2.4%; RR 1.61, 95% CI 0.53-4.71); or undiagnosed microbiological-confirmed TB at discharge (enhanced TB diagnosis, 0/207 (0.0%), usual care arm 2/208 (1.0%) (p = 0.50). Urine SILVAMP-LAM/Determine-LAM plus dCXR-CAD diagnostics identified more hospitalised PHIV with TB than usual care. The increase in TB treatment appeared mainly due to greater use of Determine-LAM, rather than SILVAMP-LAM or dCXR-CAD. Poor concordance between Determine-LAM and SILVAMP-LAM urine tests requires further investigation. Inpatient mortality for adults with HIV remains unacceptability high.

Causes and attributable fraction of death from ARDS in inflammatory phenotypes of sepsis

BackgroundHypoinflammatory and hyperinflammatory phenotypes have been identified in both Acute Respiratory Distress Syndrome (ARDS) and sepsis. Attributable mortality of ARDS in each phenotype of sepsis is yet to be determined. We aimed to estimate the population attributable fraction of death from ARDS (PAFARDS) in hypoinflammatory and hyperinflammatory sepsis, and to determine the primary cause of death within each phenotype.MethodsWe studied 1737 patients with sepsis from two prospective cohorts. Patients were previously assigned to the hyperinflammatory or hypoinflammatory phenotype using latent class analysis. The PAFARDS in patients with sepsis was estimated separately in the hypo and hyperinflammatory phenotypes. Organ dysfunction, severe comorbidities, and withdrawal of life support were abstracted from the medical record in a subset of patients from the EARLI cohort who died (n = 130/179). Primary cause of death was defined as the organ system that most directly contributed to death or withdrawal of life support.ResultsThe PAFARDS was 19% (95%CI 10,28%) in hypoinflammatory sepsis and, 14% (95%CI 6,20%) in hyperinflammatory sepsis. Cause of death differed between the two phenotypes (p < 0.001). Respiratory failure was the most common cause of death in hypoinflammatory sepsis, whereas circulatory shock was the most common cause in hyperinflammatory sepsis. Death with severe underlying comorbidities was more frequent in hypoinflammatory sepsis (81% vs. 67%, p = 0.004).ConclusionsThe PAFARDS is modest in both phenotypes whereas primary cause of death among patients with sepsis differed substantially by phenotype. This study identifies challenges in powering future clinical trials to detect changes in mortality outcomes among patients with sepsis and ARDS.

Current perspectives of viral hepatitis

Viral hepatitis represents a major danger to public health, and is a globally leading cause of death. The five liver-specific viruses: Hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, and hepatitis E virus, each have their own unique epidemiology, structural biology, transmission, endemic patterns, risk of liver complications, and response to antiviral therapies. There remain few options for treatment, in spite of the increasing prevalence of viral-hepatitis-caused liver disease. Furthermore, chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality, even though effective treatments are available that could reduce or prevent most patients’ complications. In 2016, the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030, along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis. Today, treatment is sufficiently able to prevent the disease from reaching advanced phases. However, future therapies must be extremely safe, and should ideally limit the period of treatment necessary. A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis. This review aims to summarize the current state of knowledge on each type of viral hepatitis, together with major innovations.

Proteogenomic characterization of difficult-to-treat breast cancer with tumor cells enriched through laser microdissection

BackgroundBreast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women globally. Despite advances, there is considerable variation in clinical outcomes for patients with non-luminal A tumors, classified as difficult-to-treat breast cancers (DTBC). This study aims to delineate the proteogenomic landscape of DTBC tumors compared to luminal A (LumA) tumors.MethodsWe retrospectively collected a total of 117 untreated primary breast tumor specimens, focusing on DTBC subtypes. Breast tumors were processed by laser microdissection (LMD) to enrich tumor cells. DNA, RNA, and protein were simultaneously extracted from each tumor preparation, followed by whole genome sequencing, paired-end RNA sequencing, global proteomics and phosphoproteomics. Differential feature analysis, pathway analysis and survival analysis were performed to better understand DTBC and investigate biomarkers.ResultsWe observed distinct variations in gene mutations, structural variations, and chromosomal alterations between DTBC and LumA breast tumors. DTBC tumors predominantly had more mutations in TP53, PLXNB3, Zinc finger genes, and fewer mutations in SDC2, CDH1, PIK3CA, SVIL, and PTEN. Notably, Cytoband 1q21, which contains numerous cell proliferation-related genes, was significantly amplified in the DTBC tumors. LMD successfully minimized stromal components and increased RNA–protein concordance, as evidenced by stromal score comparisons and proteomic analysis. Distinct DTBC and LumA-enriched clusters were observed by proteomic and phosphoproteomic clustering analysis, some with survival differences. Phosphoproteomics identified two distinct phosphoproteomic profiles for high relapse-risk and low relapse-risk basal-like tumors, involving several genes known to be associated with breast cancer oncogenesis and progression, including KIAA1522, DCK, FOXO3, MYO9B, ARID1A, EPRS, ZC3HAV1, and RBM14. Lastly, an integrated pathway analysis of multi-omics data highlighted a robust enrichment of proliferation pathways in DTBC tumors.ConclusionsThis study provides an integrated proteogenomic characterization of DTBC vs LumA with tumor cells enriched through laser microdissection. We identified many common features of DTBC tumors and the phosphopeptides that could serve as potential biomarkers for high/low relapse-risk basal-like BC and possibly guide treatment selections.

WDR1 promotes prostate cancer progression through Wnt/β-catenin signaling.

Prostate cancer (PCa) is the second most common cancer and the fifth leading cause of cancer-related death among men. A comprehensive understanding of PCa progression is crucial for the development of innovative therapeutic strategies for its treatment. While WDR1 (WD-repeat domain 1) serves as a significant cofactor of actin-depolymerizing factor/cofilin, its role in PCa progression remains unknown. In this study, we demonstrated that knockdown of WDR1 in various PCa cells substantially inhibited cell proliferation, migration, and invasion in vitro, as confirmed at both the cellular and molecular levels. Moreover, the overexpression of WDR1 promoted PCa cell proliferation and metastasis in vitro. Mechanistically, we showed that the application of lithium chloride, an activator of the Wnt/β-Catenin signaling pathway, restored the suppressive effects of WDR1 deficiency on cell proliferation and migration in PCa cells. Our findings suggest that the WDR1-β-Catenin axis functions as an activator of the malignant phenotype and represents a promising therapeutic target for PCa treatment.

Risk of prostate cancer death in men diagnosed with prostate cancer at cystoprostat-ectomy. A nationwide population-based study.

One out of three men who undergo cystoprostatectomy for bladder cancer is diagnosed with incidental prostate cancer (PCa) at histopathological examination. Many of these men are PSA tested as part of their follow-up, but it is unclear if this is needed. The aim of this study was to assess the risk of PCa death in these men and the need of PSA-testing during follow-up. Between 2002 and 2020, 1,554 men were diagnosed with PCa after cystoprostatectomy performed for non-metastatic bladder cancer and registered in the National Prostate Cancer Register (NPCR) of Sweden. We assessed their risk of death from PCa, bladder cancer and other causes up to 15 years after diagnosis by use of data in The Cause of Death Register. The use of androgen deprivation therapy (ADT) as a proxy for PCa progression was assessed by fillings in The Prescribed Drug Register. Fifteen years after diagnosis, cumulative incidence of death from PCa was 2.6% (95% CI 2.3%-2.9%), from bladder cancer 32% (95% CI: 30%-34%) and from other causes 40% (95% CI: 36%-44%). Only 35% of men with PCa recorded as primary cause of death in The Cause of Death Register had started ADT before date of death, indicating sticky-diagnosis bias with inflated risk of PCa death. For a large majority of men diagnosed with incidental PCa at cystoprostatectomy performed for bladder cancer, the risk of PCa death is very small so there is no rationale for PSA testing during follow-up.

A Comphrensive Review on Amoebiasis

With its wide range of dissemination, Entamoeba histolytica poses a serious threat in practically any nation where there is a regular barrier between human waste, food, and water sources. Except E. histolytica, at least eight distinct amoebas are thought to be commensals in the human intestinal lumen. As the second biggest cause of death from parasitic disease globally, the parasite poses a serious threat to public health in most regions of the world and has reemerged in several previously inactive locations. The majority of E. histolytica infections have very minor or no symptoms, however, colitis and liver abscesses brought on by amoebic infections are the most common clinical manifestations. Typically, a laboratory's diagnosis of amoebiasis is based on a microscope.