Background. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that currently lacks reliable diagnostic biomarkers. The meta-analysis is performed with an aim to evaluate the diagnostic potential of cerebrospinal fluid (CSF) total tau (t-tau), phosphorylated-tau (p-tau), and their ratio in ALS patients. Methods. A comprehensive search for literature published between the 1^st of January 2000 and the 15^th of May 2022 was performed in databases PubMed, medRxiv, and Google Scholar. The retrieved articles were first screened by title and abstract, and later, full-text screening was performed based on the eligibility criteria. Data on p-tau and t-tau levels and p-tau/t-tau ratio in ALS patients and controls were extracted, and a meta-analysis was performed using random-effects models in Review Manager version 5.4. Results. Data were analyzed from seven studies reporting p-tau and t-tau levels and their ratio among ALS patients and controls. The number of total study participants was 1,100. In ALS patients, the levels of p-tau didn’t differ significantly with controls (standardized mean difference (SMD): 0.14 (95% CI: -0.41 to 0.70); ). In contrast, there were significantly elevated levels of t-tau and significantly lowered p-tau/t-tau ratio in ALS (SMD: 1.76 (95% CI: 0.53 to 2.98); and SMD: -3.09 (95% CI: -5.33 to -0.86); , respectively). Conclusion. Our meta-analysis study supports the role of core CSF biomarkers of neurodegeneration: t-tau and p-tau/t-tau ratio as a diagnostic biomarker of amyotrophic lateral sclerosis. This study found that t-tau is elevated while p-tau/t-tau ratio is lowered in ALS.

Bleeding disorders are a major group of hematological disorders, which are highly prevalent in the world. Excessive bleeding can result in serious consequences including hypoperfusion and cardiac arrest. The body has its selfmechanism to control excessive bleeding which is termed hemostasis. Hemostasis is achieved in two major steps, the formation of the primary and secondary hemostatic plugs. Endothelium, platelets, and coagulation factors are three components involved in hemostasis. Endothelium and platelets have a major role in forming the primary hemostatic plug. Consequently, the first step in investigating a bleeding disorder is platelet count. Despite normal platelet count, abnormality in the primary hemostatic plug may arise due to functional defects of the platelets including adhesion, activation, and aggregation. Von Willebrand disease (VWD) is an endothelial defect and the most prevalent inherited defect in coagulation. Abnormalities in the secondary hemostatic plug are largely due to coagulation factor deficiencies, and, to a lesser extent, the presence of inhibitors. Techniques involving viscoelastics have been aiding in rapid diagnosis and are useful in point‐of‐care testing. This article discusses the investigation of bleeding disorders from the perspective of the endothelium, platelet, and coagulation factor physiology. These three components should be properly investigated to achieve the definitive diagnosis of bleeding disorders.

Background: Sepsis syndromes are a major burden in the ICU with very high mortality. Vasopressin and copeptin are released in response to hypovolemia and have shown potential significance in diagnosing sepsis. Objective: To investigate the levels of copeptin in patients with sepsis syndromes and evaluate its relation with patient prognosis and mortality. Methods: Four databases were searched for literature published from inception to the 8th of November 2022. Original research articles where copeptin was measured in sepsis patients and compared with controls were included. Data extraction and synthesis: study characteristics, levels of copeptin in the participants, and copeptin assay description were extracted. Levels of copeptin in patients were pooled and compared with controls in terms of the standard mean difference (SMD) generated using a random-effects model. Results: Fifteen studies met the selection criteria. Copeptin levels were significantly higher in patients with sepsis, severe sepsis, and septic shock as compared to controls [(SMD: 1.49, 95% CI: 0.81–2.16, P<0.0001), (SMD: 1.94, 95% CI: 0.34–3.54, P=0.02), and (SMD: 2.17, 95% CI: 0.68–3.66, P=0.004), respectively]. The highest copeptin levels were noted in septic shock patients. The admission copeptin levels were significantly lower in survivors as compared to nonsurvivors (SMD: −1.73; 95% CI: −2.41 to −1.06, P<0.001). Conclusion and Relevance: Copeptin was significantly elevated in sepsis, severe sepsis, and septic shock. Survivors had a significantly lower copeptin during admission. Copeptin offered an excellent predictability to predict 1-month mortality. Measuring the copeptin in sepsis patients can aid treating physicians to foresee patients’ prognosis.

Background and Aims: According to the previous studies, herpes zoster (HZ) has been associated with cognitive function and dementia. There is a hypothesis claiming that dementia risk may be reduced by receiving the antiviral treatment for HZ. The purpose of this systematic review and meta‐analysis was to shed light on the association between dementia and HZ in individuals receiving and not receiving antiviral medications.Methods: Studies investigating the association between HZ and dementia were identified through a systematic search in PubMed/MEDLINE, Scopus, Embase, Google Scholar, and Cochrane Library databases from January, 2000 to April, 2022. Data on the risk of dementia in HZ‐infected patients under and not under antiviral treatment were extracted. The meta‐analysis was conducted using a random‐effects model. The modified ROBIN‐I tool was used to evaluate the risk of bias assessment. By utilizing the funnel plots, publication bias was investigated.Results: Six cohort studies on 538,531 patients were included. The overall risk of bias assessment was moderate. According to evidence‐based cohort studies, there was a significant direct association between HZ and risk of dementia in patients with HZ, who did not receive antiviral treatments (hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.03 to 1.28, p = 0.01). On the other hand, there was an inverse relationship between HZ and risk of dementia among patients with HZ, who received antiviral treatments (HR: 0.68, 95% CI: 0.59 to 0.77, p < 0.001).Conclusions: This study demonstrated that antiviral therapies may significantly lower the risk of dementia in patients with HZ. This study also confirmed that patients with HZ, without receiving antiviral therapies, may have an increased risk of developing dementia. Further longitudinal research is warranted in this area.

Background: Antimicrobial‐resistant Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacter (ESKAPE) species pathogens pose a threat to global health by limiting available treatments, escalating the burden of disease, and raising mortality rates. This study investigated the prevalence of ESKAPE pathogens in different infections in a Nepalese hospital and studied their antibiotic resistance pattern. Methodology: The study was performed from September 2022 to February 2023 at Tribhuvan University Teaching Hospital (TUTH), Kathmandu, Nepal. ESKAPE pathogens were isolated in accordance with standard procedures and subjected to antimicrobial susceptibility testing (AST). Identification was done via biochemical testing. The rates of multidrug resistance (MDR), production of extended‐spectrum beta‐lactamase (ESBL), and methicillin resistance were studied and statistically compared in terms of the type of pathogen, infection, and hospital admission. Result: Altogether, 7429 different clinical samples were cultured and ESKAPE pathogens were isolated from 503/1564 (32.1%) positive samples. The prevalence of these pathogens was significantly higher in admitted patients ( p < 0.001). Higher rates of isolation were from urine and sputum samples. Klebsiella pneumoniae was the most prevalent organism while Enterobacter was the least. A total of 52.3% and 7.4% of the isolates were MDR and ESBL producers, respectively. A significant proportion of MDR isolates were from patients admitted to the Intensive Care Unit (ICU). The prevalence of methicillin‐resistant Staphylococcus aureus (MRSA) was 36.8%. AST revealed comparatively lower resistance of Gram‐negative rods to tigecycline, polymyxin B, and colistin sulfate. Likewise, lower resistance rates to vancomycin and teicoplanin were observed in S. aureus. Conclusion: In various clinical samples, we discovered that ESKAPE pathogens were more prevalent. In order to escape the ESKAPE’s torment of antibiotic resistance, our findings urge the urgent implementation of sensible antibiotic use, training healthcare professionals in antibiotic stewardship, developing effective infection control strategies, and conducting effective surveillance.