High Morbidity Research Articles

RAB37 suppresses the EMT, migration and invasion of gastric cancer cells by mediating autophagic degradation of β-catenin.

Gastric cancer, characterized by its high morbidity and mortality rates, exhibits low levels of RAB37. The role and molecular mechanisms of RAB37, a small GTPase, in the pathogenesis of gastric cancer are still unclear. We assessed RAB37 expression in gastric cancer cells using quantitative Polymerase Chain Reaction (qPCR), Western blot, and immunohistochemical staining (IHC), and analyzed EMT marker proteins and autophagy changes via Western blot, immunofluorescence (IF), and transmission electron microscopy (TEM). Co-immunoprecipitation (co-IP) was used to identify protein-protein interactions. We studied the migration and invasion of gastric cancer cells using wound healing and transwell assays in vitro and a mouse pulmonary metastasis model in vivo. Overexpression of RAB37 suppressed EMT, invasion, and migration while enhancing autophagy in gastric cancer cells, which was dependent on its GTPase activity. However, all these effects could be reversed by the autophagy inhibitor chloroquine. Regarding the molecular mechanism, RAB37 strengthened the interaction between p62 and β-catenin, which consequently enhanced the p62-mediated autophagic degradation of β-catenin. Furthermore, RAB37 curbed the pulmonary metastasis of both general and cisplatin-resistant gastric cancer cells. The low level of RAB37 reduces interaction between p62 and β-catenin and then the autophagic degradation of β-catenin, thereby promoting the EMT, invasion, and migration in gastric cancer cells. The low expression of RAB37 in gastric cancer suggests a potential therapeutic target, especially for cisplatin-resistant gastric cancer.

Risk factors and outcome of Pseudomonas aeruginosa bloodstream infections (PABSI) in hematological patients: a single center retrospective cohort study.

Bloodstream infections caused by Pseudomonas aeruginosa (PABSI) in hematological patients are associated with high morbidity and mortality. We investigated the epidemiology, risk factors, and outcomes of PABSI at our center. All adult hematological patients with PABSI between January 2013 and July 2023 were included. Demographic and clinical characteristics, antimicrobial susceptibilities, antibiotic therapy, fluoroquinolone-prophylaxis, source of infection, and 30-day outcome were recorded. Descriptive statistics, tests for difference, and logistic regression models were performed. Fifty patients with PABSI were identified with a median age of 58.5 years (range 24-78). 37 patients (74%) had severe neutropenia, 20 (40%) received allogeneic HSCT, and 29 (58%) had acute leukemia. A total of 34 (68%) had received timely appropriate anti-pseudomonal antibiotic therapy. The most common presumed cause of PABSI was mucositis (n = 16, 32%), followed by pneumonia (8, 16%) and skin and soft tissue infections (n = 6, 12%). Empirical combination therapy was used in 16 (32%) patients, while targeted combination therapies were used in 27 (54%) patients. P. aeruginosa detection led to treatment change in 31 (62%) cases. The overall 30-day survival rate was 78% (n = 39). Carbapenem-resistance occurred in 34% (n = 17), and multidrug-resistance (MDR) in 20% (n = 10). Prior antibiotic exposure was associated with resistance. Appropriate antibiotic therapy was associated with survival, whereas antibiotic resistance and organ infection were associated with a fatal outcome. Prior antibiotic exposure in hematological patients is associated with resistance in PABSI, which is a major risk factor for a fatal outcome. Antibiotic stewardship efforts should be intensified and fluoroquinolone prophylaxis needs to be reconsidered.

Isoliquiritigenin Exhibits Anti-Inflammatory Responses in Acute Lung Injury by Covalently Binding to the Myeloid Differentiation Protein-2 Domain.

Acute lung injury (ALI), a systemic inflammatory response with high morbidity, lacks effective pharmacological therapies. Myeloid differentiation protein-2 (MD2) has emerged as a promising therapeutic target for ALI. Herein, we aimed to evaluate the ability of isoliquiritigenin (ISL), a natural flavonoid found in licorice as a novel MD2 inhibitor, to inhibit lipopolysaccharide (LPS)-induced ALI. We established a mouse ALI model and a RAW 264.7 cell injury model through LPS administration. Then, lung injury was assessed through histopathological examination, and the effects of ISL were evaluated using immunofluorescence, western blotting, reverse transcription-quantitative polymerase chain reaction, flow cytometry, and enzyme-linked immunosorbent assays. In addition, the interaction between ISL and MD2 was investigated through co-immunoprecipitation and LPS displacement assays. Molecular docking and liquid chromatography/mass spectrometry analyses were employed to predict the ISL-binding domain of MD2. We found that ISL covalently bound to the Cysteine 133 residue of MD2, disrupting the formation of the LPS/MD2/toll-like receptor 4 complex, and ISL significantly suppressed proinflammatory cytokine production and reactive oxygen species generation in LPS-induced RAW264.7 cells. Moreover, ISL significantly alleviated lung injury in LPS-induced mice, reducing pulmonary microvascular permeability, inflammatory cell infiltration, and inflammatory cytokine expression. The underlying mechanism of ISL involved the inhibition of nuclear factor kappa B and the p38 mitogen-activated protein kinase pathway. Our findings supported that MD2 is the direct target of ISL in mediating its anti-inflammatory response invivo and invitro, and it holds potential as a therapeutic candidate for treating ALI and other inflammatory diseases.

Dexmedetomidine Regulates Macrophage Phenotype Remodeling Through AMPK/SIRT1 to Alleviate Inflammatory Mediators and Lung Injury.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality in the intensive care unit (ICU) and can cause excessive inflammation. Dexmedetomidine (DEX) is a drug that exerts anti-inflammatory effects. Identifying the anti-inflammatory mechanism of DEX in the context of ALI/ARDS possesses potential significance for the prevention and treatment of ARDS. In this study, DEX was used to treat mouse models of cecal ligation and puncture (CLP) and lipopolysaccharide (LPS)-stimulated cells. Immunofluorescence, western blot analysis, and flow cytometry were used to detect macrophage phenotypic markers in mice, and western blot analysis, real-time qPCR (RT-qPCR), ELISA, and immunofluorescence were used to detect macrophage phenotype markers in RAW264.7 cells. Flow cytometry was used to detect phenotypic markers of bone marrow-derived macrophages (BMDM). Culture medium collected from macrophages was used to cultivate human non-small cell adenocarcinoma epithelial cells (A549) to detect their aquaporins 1 (AQP1) expression and apoptosis status. Western blot analysis was used to detect the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1(SIRT1) signaling pathway both in vivo and in vitro. The regulatory effect of DEX on macrophage phenotype remodeling was detected by knocking down AMPK expression in cells using AMPK shRNA. The results showed that in both in vivo and in vitro experiments, DEX downregulated the expression of M1 markers (tumor necrosis factor-α [TNF-α], nitric oxide synthase [iNOS], and cluster of differentiation [CD]-86) and upregulated the expression of M2 markers (arginase-1 [ARG-1], interleukin [IL]-10, and CD206) in macrophages. The culture medium of macrophages treated with DEX alleviated the edema and apoptosis of A549 cells. DEX activates the AMPK/SIRT1 signaling pathway in macrophages. After AMPK knockdown, the ability of DEX to regulate macrophage phenotype remodeling decreased. Together, this study suggests that DEX regulates macrophage phenotype remodeling by activating the AMPK/SIRT1 pathway, thereby reducing ALI/ARDS.

CUL4B protects kidneys from acute injury by restraining p53/PAI-1 signaling

Acute kidney injury (AKI) caused by nephrotoxins, ischemia reperfusion (IR) or sepsis is associated with high morbidity and mortality. Unveiling new mechanisms underlying AKI can help develop new therapeutic strategy. Cullin 4B (CUL4B) is a scaffold protein in the CUL4B-RING E3 ubiquitin ligase (CRL4B) complex. Here, we demonstrate that CUL4B can protect kidneys from acute injury induced by cisplatin and IR. CUL4B is upregulated in mouse tubular epithelial cells (TECs) after cisplatin treatment or IR. Loss of CUL4B in kidneys exacerbates renal injury, inflammation, and apoptosis of TECs caused by cisplatin and IR. Transcriptome analysis reveals that Cul4b deficiency enhances injury-induced PAI-1 expression. CUL4B suppresses PAI-1 expression by promoting polyubiquitination and degradation of p53. Inhibition of either PAI-1 or p53 can prevent the aggravated renal injury and inflammation caused by loss of CUL4B. Our work has identified the kidney-protective role of CUL4B against acute injury.

Intestinal metaplasia key molecules and UPP1 activation via Helicobacter pylori /NF-kB: drivers of malignant progression in gastric cancer

Gastric cancer (GC) remains a significant global health challenge due to its high morbidity and mortality rates. The development of GC is a multi-hit process and the exploration of precancerous lesions is crucial. To elucidate the molecular and cellular dynamics underlying gastric carcinogenesis, we conducted an integrative single-cell RNA sequencing analysis of 26,028 high-quality cells from gastric antral mucosa biopsies across various stages, including non-atrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, and early gastric cancer. By constructing a detailed single-cell atlas, we identified distinct epithelial cell subpopulations and their corresponding molecular signatures. We focused on the biological link between gastric epithelial cells and cancer cells. Notably, we observed that gland mucous cells acquired an intestinal-like stem cell phenotype during metaplasia, with MUC6, MUC2 and OLFM4 emerging as the specific markers for unique endocrine cells in early malignant lesions. Additionally, our analysis highlighted UPP1 as a key oncogene, with its expression progressively increasing from normal epithelial cells to malignant cells. UPP1 upregulation was shown to promote GC cell proliferation and migration, implicating it in the oncogenic process. Further, we explored the impact of Helicobacter pylori infection on gene expression, revealing that Helicobacter pylori infection upregulates UPP1 via the NF-κB pathway. Our cell-cell communication analysis underscored the significant role of the Macrophage migration inhibitory factor pathway in the tumor microenvironment, contributing to GC progression. Various key molecules involved in intestinal metaplasia, along with UPP1 and the Macrophage migration inhibitory factor pathway, collectively illustrate the multifaceted nature and complexity of gastric cancer evolution, highlighting the cumulative impacts that drive tumorigenesis.

Psychological stress among hypertensive male patients in Jordan: prevalence and associated factors

BackgroundHypertension is a global, modifiable risk factor for cardiovascular and cerebrovascular disorders, imposing a significant burden due to its high mortality and morbidity rates. This study aimed to assess the prevalence and severity of psychological stress among hypertensive patients in Jordan and identify the factors associated with psychological stress.MethodsThis descriptive, cross-sectional study was conducted on hypertensive patients at three community healthcare clinics in Jordan from May to July 2024. A sample of 276 hypertensive male patients was randomly selected, representing 85% of the total patients in the selected clinics. Patients were selected via systematic random sampling. A self-administered questionnaire on psychological stress using the Depression, Anxiety, and Stress Scale (DASS-42) was employed. The data were collected through Google Forms and analyzed using SPSS statistical software (version 27).ResultsA total of 276 hypertensive males participated in the study, and the mean score of psychological stress was 16.02(± 7.59). The prevalence of psychological stress was 55.1%, with 60 (39.5%) experiencing mild stress and 57 (37.5%) experiencing moderate stress. Chronic diseases and inadequate exercise were significantly associated with psychological stress (p-values: 0.003 and < 0.001, respectively). Participants reporting stressful work were more than four times more likely to experience psychological stress than those who did not report work-related stress (OR = 4.06; 95% CI: 2.00–8.25; p < 0.001). A stressful home environment and insufficient sleep were also significantly associated with psychological stress (p = 0.026 and p < 0.001, respectively).ConclusionsThe results highlight a strong association between psychological stress and hypertension. Factors such as chronic diseases, insufficient exercise, occupational stress, a stressful home environment, and inadequate sleep contribute to psychological stress among hypertensive patients. These findings provide valuable insights for healthcare providers in developing tailored interventions to alleviate stress while managing hypertension.

Acupuncture for hypoxic ischemic encephalopathy in neonates.

Peripartum asphyxia affects three to five per 1000 live births, with moderate or severe hypoxic ischemic encephalopathy (HIE) occurring in 0.5 to 1 per 1000 live births, and is associated with high mortality and morbidity. Therapeutic hypothermia is an effective treatment, but alternative therapies such as acupuncture are also used. To determine the benefits and harms of acupuncture (e.g. needle acupuncture with or without electrical stimulation; laser acupuncture; non-penetrating types of manual or embedded acupressure) on mortality and morbidity in neonates with HIE, compared with 1) no treatment, 2) placebo or sham treatment, 3) any pharmacologic treatment, or 4) different types of acupuncture. We searched CENTRAL, PubMed, Embase, ClinicalTrials.gov, and the WHO ICTRP in March 2023. We conducted a search of the grey literature to identify reports of trials conducted by or referenced in research by CORDIS EU, National Institute for Health and Care Excellence (NICE), and NHSGGC Paediatrics for Health Professionals. We also checked the reference lists of relevant articles to identify additional studies. We included randomized controlled trials (RCTs) or quasi-RCTs and cluster-randomized trials. We included studies where participants were term infants (37 weeks or greater) and late preterm infants (34 + 0 to 36 + 6 weeks' gestation) 10 days of age or less, with evidence of peripartum asphyxia. We included studies on acupuncture (e.g. needle acupuncture with or without electrical stimulation; laser acupuncture; non-penetrating types of manual or embedded acupressure). We included studies where acupuncture was compared with: 1) no treatment; 2) placebo or sham treatment; 3) any pharmacologic treatment; or 4) different types of acupuncture. We used standard Cochrane methods. Our primary outcomes were all-cause mortality at the latest follow-up, major neurodevelopmental disability in children aged 18 to 24 months and aged 3 to 5 years, adverse events until hospital discharge, and length of hospital stay. We included four studies (enrolling 464 infants) that compared acupuncture with no treatment. The studies ranged in size from 60 to 200 infants. Three studies were conducted in China and one in Russia. None of the four studies reported on any of the prespecified outcomes of our review. We did not identify any ongoing studies. There is limited availability of studies addressing this specific population. The included studies did not assess mortality, long-term neurodevelopmental outcomes, or adverse effects of acupuncture. We are unable to draw any conclusions about the benefits and harms of acupuncture for HIE in neonates. In light of the current limitations, clinicians are urged to approach the use of acupuncture in neonates with HIE cautiously, as there is no evidence to support its routine application. The available trials assessed surrogate outcomes that have a relatively small impact on newborns, and failed to report important outcomes such as mortality and long-term neurodevelopmental outcomes. Other available trials were performed on older infants who had experienced neonatal HIE. Given the lack of available evidence, well-designed randomized controlled trials with relevant outcomes such as mortality and neurodevelopmental outcomes are essential to evaluate the efficacy and safety of acupuncture for HIE in neonates.

Hellp’s Syndrome – Maternal Morbimortality, Clinical Case Report

Introduction: HELLP syndrome is a hypertensive disorder of pregnancy associated with severe maternal-fetal complications and representing high morbidity and mortality. Objective: A clinical history of HELLP syndrome as a complication of severe preeclampsia was analyzed, highlighting the importance of early detection and appropriate treatment. Clinical case: A young 26-year-old multi-gestation patient from the city of Loja, with a family history of arterial hypertension, was diagnosed with HELLP syndrome and severe preeclampsia in the 33rd week of gestation after five prenatal check-ups and due to the severity of her condition, it was decided to terminate the pregnancy by cesarean section. Conclusion: The importance and urgency of early identification and treatment of HELLP syndrome and its complications, highlighting the need for an individualized approach based on the patient’s laboratory studies and the importance of management in primary care and the patient’s care.

EPIDEMIOLOGICAL TRENDS OF MENINGITIS IN BRAZIL FROM 2001 TO 2022

Introduction: Meningitis is a worldwide pathology that has a high morbidity and mortality rate. Its pathophysiology consists of an inflammation that affects the meninges, especially in the subarachnoid space, cranial and spinal segments. Materials and methods: Descriptive study that used secondary data to examine the disease "meningitis" that occurred between 2001 and 2022. The data were obtained from the Database of the Department of Information and Informatics of the SUS (DATASUS), accessible at https:/ /datasus.saude.gov.br/informacoes-de-saude-tabnet/. Results: In the years 2001-2022, 452,392 cases were reported in Brazil. The prevalence in the North region reached a total of 18,836 cases, in the Northeast 82,106, Southeast = 236,345, South = 93,353 and Central-West = 21,752, highlighting the Southeast region with the highest prevalence of cases. Discussion: The Southeast region has a higher number of meningitis cases due to the local health infrastructure and population growth in this region. Viral meningitis is one of the most relevant causes as it affects individuals of all ages, being the cause of large epidemic outbreaks and bacterial is a condition of great importance, due to its high mortality and morbidity compared to viral meningitis, the main bacterial agent is Neisseria meningitidis. Conclusion: Meningitis is a serious public health problem due to its intensity of spread and its high morbidity and mortality rate, especially in children. Therefore, it is necessary to highlight the importance of prophylactic methods such as vaccination, which are extremely effective in controlling and eradicating diseases. Keywords: Viral meningitis; Bacterial meningitis; Nursing; Epidemiology

SREBP1c-Mediated Transcriptional Repression of YME1L1 Contributes to Acute Kidney Injury by Inducing Mitochondrial Dysfunction in Tubular Epithelial Cells.

Acute kidney injury (AKI) is a prevalent clinical syndrome with high morbidity and mortality. Accumulating studies suggest mitochondrial dysfunction as the typical characteristics and key process of AKI, but the underlying mechanism remains elusive. The YME1-like 1 (YME1L1) ATPase, an inner mitochondrial membrane protein, is screened and identified to be downregulated in renal tubular epithelial cells of various mouse models and patients of AKI. Dramatically, restoration of YME1L1 expression significantly alleviates cisplatin-induced AKI and subsequent chronic kidney disease (CKD) through attenuating mitochondrial dysfunction via maintaining optic atrophy 1 (OPA1)-mediated mitochondrial energy metabolism homeostasis. Mechanistically, the upregulated expression of sterol regulatory element binding transcription factor 1c (SREBP1c) is demonstrated to be responsible for cisplatin-mediated transcriptional inhibition of YME1L1 via directly binding to its promoter region. Moreover, cisplatin-induced methyltransferase-like 3 (METTL3)-mediated m6A modification enhances SREBP1c mRNA stability, thereby upregulating its expression. Notably, both depletion of SREBP1c and renal tubule-specific overexpression of YME1L1 markedly ameliorate cisplatin-induced AKI and its transition to CKD. Taken together, these findings suggest that METTL3-mediated SREBP1c upregulation contributes to AKI and its progression to CKD through disrupting mitochondrial energy metabolism via transcriptionally suppressing YME1L1. Targeting the SREBP1c/YME1L1 signaling may serve as a novel therapeutic strategy against AKI.

Interpretable multimodal machine learning (IMML) framework reveals pathological signatures of distal sensorimotor polyneuropathy

BackgroundDistal sensorimotor polyneuropathy (DSPN) is a common neurological disorder in elderly adults and people with obesity, prediabetes and diabetes and is associated with high morbidity and premature mortality. DSPN is a multifactorial disease and not fully understood yet.MethodsHere, we developed the Interpretable Multimodal Machine Learning (IMML) framework for predicting DSPN prevalence and incidence based on sparse multimodal data. Exploiting IMMLs interpretability further empowered biomarker identification. We leveraged the population-based KORA F4/FF4 cohort including 1091 participants and their deep multimodal characterisation, i.e. clinical data, genomics, methylomics, transcriptomics, proteomics, inflammatory proteins and metabolomics.ResultsClinical data alone is sufficient to stratify individuals with and without DSPN (AUROC = 0.752), whilst predicting DSPN incidence 6.5 ± 0.2 years later strongly benefits from clinical data complemented with two or more molecular modalities (improved ΔAUROC > 0.1, achieved AUROC of 0.714). Important and interpretable features of incident DSPN prediction include up-regulation of proinflammatory cytokines, down-regulation of SUMOylation pathway and essential fatty acids, thus yielding novel insights in the disease pathophysiology.ConclusionsThese may become biomarkers for incident DSPN, guide prevention strategies and serve as proof of concept for the utility of IMML in studying complex diseases.

CLINICAL AND PATHOLOGIC PRESENTATIONS OF YERSINIOSIS IN VARIOUS NONDOMESTIC SPECIES: AN INVESTIGATION OF YERSINIA PSEUDOTUBERCULOSIS OUTBREAKS FROM FOUR NORTH AMERICAN ZOOLOGICAL INSTITUTIONS.

Yersiniosis due to Yersinia psuedotuberculosis can be associated with high morbidity and mortality in various species and has been a cosmopolitan management challenge in zoological institutions. This gram-negative, environmental bacterium thrives in cold, wet conditions and poses a risk to zoo species. Outbreaks can be costly and impact conservation efforts through loss of threatened and endangered species. Antemortem or clinical diagnosis can be challenging due to intermittent fecal shedding and nonspecific clinical signs. This case series describes common clinical presentations, typical postmortem findings, and response to treatment and prophylaxis at four North American zoological institutions. In total, five outbreaks occurred at four institutions during the winter months from 2013 to 2021. Artiodactyls were by far the most common species involved, and clinical signs included separation from the herd, lethargy, diarrhea, and unexpected death. Other species affected in these outbreaks included cheetahs (Acinonyx jubatus), a great-tailed grackle (Quiscalus mexicanus), a rainbow lorikeet (Trichoglossus moluccanus), and a squirrel monkey (Saimiri sciureus). Necrotizing enteritis with sepsis and pneumonia were common postmortem findings. Mortality rates were originally 76.7%, and herd prophylaxis with a third-generation cephalosporin reduced these rates. These data describe the observational and diagnostic tools to aid in timely diagnosis of a Yersinia outbreak across taxa. Aggressive treatment or prophylaxis were shown to improve survival rates.

An immunocompetent human kidney on-a-chip model to study renal inflammation and immune-mediated injury.

Kidney damage and dysfunction is an emerging health issue worldwide resulting in high morbidity and mortality rates. Numerous renal diseases are recognized to be driven by the immune system. Despite this recognition, the development of targeted therapies has been challenging as knowledge of the underlying mechanism and complex interactions remains insufficient. Recent advancements in the field offer promising avenues for exploring the interplay between renal cells and immune cells and their role in the development of renal inflammation and diseases. This study describes the establishment of a human immunocompetent 3D in vitro co-culture model of the proximal tubule in a high-throughput microfluidic platform that can be used to study renal functionality and inflammatory processes. &#xD;The model incorporated RPTEC in the top compartment and HUVECs in the bottom compartment cultured under flow and in direct contact with a collagen-I ECM gel resulting in the formation of polarized tubular structures. As an immune component, human primary monocytes of different donors were added to the lumen of the endothelium. Renal inflammation was successfully induced using complement activated serum (CAS) as evident by epithelial morphological changes, increased expression of adhesion molecules, release of pro-inflammatory cytokines, and reduced epithelial viability. Realtime migratory behavior of monocytes showed increased extravasation and migration towards the ECM and Renal compartment upon exposure to CAS with donor-to-donor differences observed. Finally, immune modulatory compounds showed efficacious inhibition of monocyte migration under inflammatory conditions in the microfluidic co-culture model. &#xD;A successful co-culture model was established and can be applied to study renal functionality in health and disease but also for drug screening due to the compatibility of the platform with automation and relatively high throughput. Overall, the described proximal tubule model has high potential to fill the gap that currently exists to study renal inflammation preclinically.&#xD.

Acute coronary syndrome rates by age and sex before and during the COVID-19 pandemic in Israel: nationwide study.

There have been reports of sharp declines in acute coronary syndrome (ACS) during the COVID-19 pandemic. The study aims to assess nationwide ACS emergency department (ED) visit rates across age and sex subgroups and the general population, with a comparison before and throughout the pandemic's various phases. A multiple interrupted time series analysis was used to assess 61 349 ACS nationwide hospital visits from January 2018 to December 2021 at monthly intervals. The study period was divided into three periods: January 2018-February 2020 (pre-pandemic period); March 2020-January 2021 (early-pandemic period); February 2021-December 2021 (late-pandemic period). Segmented regression with a seasonally adjusted autoregressive moving average structure was used to build predictive models with an estimated reference trendline (counterfactual). Over 11 months of the early-pandemic period (lockdowns), the largest decrease in visits was seen in women aged 65 and above, of 18.4% [incidence rate ratio (IRR) 0.82; 95% confidence interval (CI) 0.77-0.86]. The lowest decrease was observed in men aged 25-64, of 7.2% (IRR 0.93; 0.91-0.94). During the late-pandemic period, which included high vaccination coverage and no lockdowns, the largest further decrease was in women aged 25-64 of 20.1% (IRR 0.80; 0.75-0.84) on average. The pandemic influenced ACS ED visits variably, with substantial declines during phases of high COVID-19 morbidity and mortality. Older individuals, particularly women, demonstrated the largest decrease in ACS ED visits, highlighting the need for tailored public health strategies to maintain public confidence in access to critical care during future health emergencies.

Do current indices predict cardioversion success in patients with atrial fibrillation? A retrospective observational study

Abstract Objective Atrial fibrillation (AF) is one of the leading arrhythmias that causes serious complications. Our aim is to investigate the factors predicting the success of cardioversion in patients who underwent the procedure due to AF. Methods A total of 107 patients who underwent cardioversion were included in the study. Patients were divided into groups based on cardioversion success. Demographic, echocardiographic, and laboratory characteristics were compared between the groups. Results Hypertension and diabetes mellitus were more frequent in patients with successful cardioversion, but no statistically significant difference was found between the groups (p &gt; 0.05). The pre-procedure leukoglycemic index (LGI) was found to be higher in the successful cardioversion group. However, this difference was not statistically significant between the groups (p &gt; 0.05). Although the fibrosis-4 (FIB-4) index and systemic immune-inflammation index (SII) were numerically higher in the group with unsuccessful cardioversion, no statistically significant difference was observed between the groups (p &gt; 0.05). Echocardiographic parameters such as left atrial diameter and mitral regurgitation rate were higher in patients with successful cardioversion, but no significant difference was detected between the groups (p &gt; 0.05). Conclusion AF is a significant arrhythmia that may lead to high mortality and morbidity. Various scoring systems have been developed to predict cardioversion success. The LGI, FIB-4 index, and SII are potential predictors of cardioversion success. However, these parameters alone are insufficient to predict cardioversion success. Further large-scale randomized studies are needed to clarify the effectiveness of these parameters.

Treatment of Leptomeningeal Metastases from Breast Cancer: A Literature Review

Breast cancer (BC), owing to its high prevalence, represents one of the leading causes of women’s death worldwide. Due to remarkable progress in therapy directed against this malignant neoplasm, there was an increase in the survival of affected patients and, therefore, a rise in the number of central nervous system metastases (CNSM) – up to twenty percent, located in the leptomeninges. There is not enough evidence of the therapeutic options for treating leptomeningeal metastases (LM) from breast cancer in the medical literature, and the management of these patients is complex. Even with an aggressive approach, therapeutic outcomes are uniformly disappointing due to the relentless growth of the central nervous system and systemic cancer or their lethal complications. The development of management strategies for CNSM constitutes an important clinical challenge and more prospective trials are needed to better address the impact of the available treatment on overall survival and quality of life. This article aims to provide an overview of the current established treatment for LM from BC, a rare complication of metastatic breast cancer (MBC), with high morbidity and mortality rates.

Foot-and-Mouth Disease in Asia.

Foot-and-mouth disease (FMD) is a highly contagious transboundary disease prevalent across the Asian continent, affecting both wild and domestic artiodactyls. The disease is caused by a virus belonging to the Aphthovirus genus of the Picornaviridae family which is categorized into seven serotypes: C, O, A, SAT1, SAT2, SAT3, and Asia1. The virus spreads through direct and indirect contact, including semen, meat, fomites, ingestion, and aerosols. FMD has a severe economic impact due to the high morbidity and mortality, especially in young animals. Prevention of the disease relies on vaccination with the prevalent serotype(s) or the slaughter and destruction of affected animals. This review discusses the prevalence of various FMD virus (FMDV) serotypes across Asia, along with the transmission modes, pathogenesis, immune response, and immune suppression by FMDV. Additionally, the review explores FMD diagnosis, prevention, and control strategies, and highlights future opportunities for research aimed at developing strain-specific viral and bacterial combined vaccines.

Spinal Intramedullary Tumors.

Intramedullary tumors are a subgroup of spinal tumors and are associated with high morbidity and mortality. The estimated incidence of spinal tumors in general is 0.74 to 1.6 per 100 000 persons per year, with intramedullary tumors making up 10% to 30% of the total. The diagnosis is often delayed because of the insidious onset of symptoms, which are often nonspecific at first. This review is based on pertinent publications about intramedullary tumors that were retrieved by a selective search in the PubMed database. Intramedullary tumors often cause diffuse neurologic symptoms of gradually increasing severity, progressing, in advanced cases, to a complete spinal cord transection syndrome. Magnetic resonance imaging of the spine without and with intravenous contrast is the standard diagnostic technique. The histopathological origin of most intramedullary tumors is from glial cells, but other types of intramedullary tumor exist as well. The primary treatment of all intramedullary tumors is surgical resection. 9% to 34% of patients may experience a worse neurological deficit after surgery than before, but such problems resolve completely in 25% to 41% of cases. The extent of resection is the main factor affecting the risk of tumor recurrence and progression. The extent of resection also determines the possible indication for adjuvant treatment, which is needed, in particular, for high-grade and subtotally resected tumors, and for those that display progression. The treatment of intramedullary tumors is based on case series, retrospective analyses, and case reports, as randomized trials are lacking. Patients with intramedullary tumors should be cared for, as much as possible, in the setting of prospective, uniform studies of their spontaneous course and the outcomes after treatment. This will yield better evidence on the treatment of these tumors in the future.

The challenges and strategies of lung cancer screening in the era of precision medicine

Lung cancer is the malignant tumor with the highest morbidity and mortality in the world. The number of new cases and deaths of lung cancer in China ranked first in all malignant tumors. Lung cancer screening plays an important role in improving the survival rate and quality of life of patients. However, there are several challenges of lung cancer screening in China, including identifying the target population, selecting appropriate screening methods, managing screening results, and maintaining quality control. In the era of precision medicine, combining artificial intelligence (AI) and big data to develop predictive models can significantly enhance the accuracy and effectiveness of lung cancer screening. To develop a lung cancer screening strategy tailored to the Chinese population, further exploration of precision medicine is essential.