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Background Type I interferons (IFNs) are essential antiviral cytokines induced upon respiratory exposure to coronaviruses. Defects in type I IFN signaling can result in severe disease upon exposure to respiratory viral infection and are associated with worse clinical outcomes. Neutralizing autoantibodies (auto‐Abs) to type I IFNs were reported as a risk factor for life‐threatening COVID‐19, but their presence has not been evaluated in patients with severe Middle East respiratory syndrome (MERS). Methods We evaluated the prevalence of type I IFN auto‐Abs in a cohort of hospitalized patients with MERS who were enrolled in a placebo‐controlled clinical trial for treatment with IFN‐β1b and lopinavir‐ritonavir (MIRACLE trial). Samples were tested for type I IFN auto‐Abs using a multiplex particle‐based assay. Results Among the 62 enrolled patients, 15 (24.2%) were positive for immunoglobulin G auto‐Abs for at least one subtype of type I IFNs. Auto‐Abs positive patients were not different from auto‐Abs negative patients in age, sex, or comorbidities. However, the majority (93.3%) of patients who were auto‐Abs positive were critically ill and admitted to the ICU at the time of enrollment compared to 66% in the auto‐Abs negative patients. The effect of treatment with IFN‐β1b and lopinavir‐ritonavir did not significantly differ between the two groups. Conclusion This study demonstrates the presence of type I IFN auto‐Abs in hospitalized patients with MERS.

Animal and human data indicate variable effects of interferons in treating coronavirus infections according to inflammatory status and timing of therapy. In this sub-study of the MIRACLE trial (MERS-CoV Infection Treated with a Combination of Lopinavir–Ritonavir and Interferon β-1b), we evaluated the heterogeneity of treatment effect of interferon-β1b and lopinavir–ritonavir versus placebo among hospitalized patients with MERS on 90-day mortality, according to cytokine levels and timing of therapy. We measured plasma levels of 17 cytokines at enrollment and tested the treatment effect on 90-day mortality according to cytokine levels (higher versus lower levels using the upper tertile (67%) as a cutoff point) and time to treatment (≤ 7 days versus > 7 days of symptom onset) using interaction tests. Among 70 included patients, 32 received interferon-β1b and lopinavir–ritonavir and 38 received placebo. Interferon-β1b and lopinavir–ritonavir reduced mortality in patients with lower IL-2, IL-8 and IL-13 plasma concentrations but not in patients with higher levels (p-value for interaction = 0.09, 0.07, and 0.05, respectively) and with early but not late therapy (p = 0.002). There was no statistically significant heterogeneity of treatment effect according to other cytokine levels. Further work is needed to evaluate whether the assessment of inflammatory status can help in identifying patients with MERS who may benefit from interferon-β1b and lopinavir–ritonavir. Trial registration: This is a sub-study of the MIRACLE trial (ClinicalTrials.gov number, NCT02845843).

The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-β1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-β1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. The MIRACLE trial is designed as a recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The aim of this article is to describe the statistical analysis plan for the MIRACLE trial. The primary outcome is 90-day mortality. The primary analysis will follow the intention-to-treat principle. The MIRACLE trial is the first randomized controlled trial for MERS treatment. Trial registration ClinicalTrials.gov, NCT02845843 . Registered on 27 July 2016.

In a double-blind, randomized, controlled trial, 95 patients with MERS in Saudi Arabia received recombinant interferon beta-1b plus lopinavir–ritonavir or placebo for 14 days. Active treatment led to improved survival at 90 days when initiated within 7 days after illness onset.

ObjectivesThe aim of this study was to first assess the knowledge and perception of first-year university students in Iraq about COVID-19 in general and SARS-CoV-2 latest variant of concern, and to evaluate the attitudes towards protection measures including vaccination.Study designA cross-sectional study was conducted among newly enrolled students at the American University of Iraq-Baghdad. Mann-Whitney U and Kruskal-Wallis tests were used to test an association between the outcomes measured on a 5-point Likert scale and the binary and the categorical independent variables, respectively. χ2 test was used to test the association between nominal categorical variables, while Kendall’s τ-b was used for ordinal variables.ParticipantsStudents (n=432) were invited to fill out a survey specifically tailored to assess their knowledge, perception and attitude towards Omicron variant and COVID-19 vaccines acceptance. 363 students enrolled in various majors participated in this study.ResultsAssessment of COVID-19 knowledge and perception revealed that students still lack reliable info and data about FDA-approved treatment options (70.5%), SARS-CoV-2 variants (96.5%) and approved vaccines. Students’ attitude and practices towards recommended safety measures should be reassessed to better manage the pandemic. Adherence level was shown to be associated with the belief in its capacity to effectively manage the new variant. Interestingly, 85% of the students have received at least one dose of approved vaccine. A significant positive correlation was detected between the level of adherence to recommended precautions and the intention to take a third booster shot if proven effective.ConclusionsStudents’ reliable knowledge about COVID-19 pandemic including the various strains and approved vaccines should be improved to better manage the pandemic and set foundations for a more appropriate approach when another pandemic occurs. Special workshops should be organised to ensure that students and the public have a more trusted source of information about COVID-19.

Introduction Neurofibromatosis type 1 (NF1) is a genetic disorder caused by a mutation in the NF1 gene. This disease presents with various system-based manifestations, including cardiac, musculoskeletal, and neuronal issues, which have been well-studied in previous research and have prompted the development of current and emerging treatments. These treatments, mainly medications targeting specific manifestations of NF1, aim to mitigate the negative impacts of the disease on patients’ lives. NF1 is associated with an increased risk of malignancy and a significant decrease in life expectancy. In this paper, we review the current and emerging treatments for NF1 in relation to its system-based manifestations.MethodsWe conducted an extensive literature search using specific keywords through databases such as PubMed, Scopus, and Cochrane. The articles we found were compiled and subjected to strict inclusion and exclusion criteria.ResultsPharmacological advances have led to the development of products that hold promise as future treatments for NF1. Given the diverse manifestations that can affect multiple organ systems in patients with NF1, it is important to consider a variety of treatment options to achieve optimal results. However, one of the major challenges in diagnosing and treating NF1 is that patients present asymptomatically, making it necessary to rely on clinical features for diagnosis.ConclusionIn conclusion, NF1 is a complex disease with varying manifestations and a growing field of pharmacologic treatments. The information presented in this article synthesizes current knowledge and available therapies for NF1.

Objective: The coronavirus disease (COVID-19) pandemic has disrupted healthcare systems worldwide, resulting in decreased and delayed hospital visits of patients with non-COVID-19-related acute emergencies. We evaluated the impact of the COVID-19 pandemic on the presentation and outcomes of patients with non-COVID-19-related medical and surgical emergencies. Method: All non-COVID-19-related patients hospitalized through emergency departments in three tertiary care hospitals in Saudi Arabia and Bahrain in June and July 2020 were enrolled and categorized into delayed and non-delayed groups (presentation ≥/=24 or <24 h after onset of symptom). Primary outcome was the prevalence and cause of delayed presentation; secondary outcomes included comparative 28-day clinical outcomes (i.e., 28-day mortality, intensive care unit (ICU) admission, invasive mechanical ventilation, and acute surgical interventions). Mean, median, and IQR were used to calculate the primary outcomes and inferential statistics including chi-square/Fisher exact test, t-test where appropriate were used for comparisons. Stepwise multivariate regression analysis was performed to identify the factors associated with delay in seeking medical attention. Results: In total, 24,129 patients visited emergency departments during the study period, compared to 48,734 patients in the year 2019. Of the 256 hospitalized patients with non-COVID-19-related diagnoses, 134 (52%) had delayed presentation. Fear of COVID-19 and curfew-related restrictions represented 46 (34%) and 25 (19%) of the reasons for delay. The 28-day mortality rates were significantly higher among delayed patients vs. non-delayed patients (n = 14, 10.4% vs. n = 3, 2.5%, OR: 4.628 (CI: 1.296–16.520), p = 0.038). Conclusion: More than half of hospitalized patients with non-COVID-19-related diagnoses had delayed presentation to the ED where mortality was found to be significantly higher in this group. Fear of COVID-19 and curfew restrictions were the main reasons for delaying hospital visit.

Capillary refill time (CRT) is a non-invasive marker of peripheral perfusion that plays a crucial role in the management of critically ill patients, particularly those with sepsis. This narrative review, adhering to PRISMA guidelines, investigates the reliability and clinical significance of CRT in sepsis care. CRT assessments are influenced by factors such as age, sex, temperature, lighting, and measurement techniques. Inconsistencies in CRT implementation and interpretation among healthcare professionals highlight the need for standardized protocols and comprehensive training to minimize variability and enhance reliability. While there is no universally accepted cutoff value for normal CRT, studies suggest that CRT > 2.5-3 seconds indicates impaired tissue perfusion and is associated with adverse outcomes in sepsis patients. CRT serves as a warning sign for severe infections, a triage tool for identifying patients at risk, and a marker of tissue hypoperfusion. It correlates with microcirculatory parameters and lactate levels, reflecting the presence and severity of shock. CRT-guided fluid resuscitation strategies have shown promise in reducing organ dysfunction and mortality compared to lactate-targeted approaches. Persistent abnormal CRT post-resuscitation signifies a severe clinical phenotype with greater organ dysfunction and lower survival rates. To optimize the clinical application of CRT, healthcare providers should use standardized measurement techniques in appropriate patient populations while considering ambient factors. As a qualitative and quantitative measure, CRT serves as a critical tool for early detection of tissue hypoperfusion, guiding resuscitation efforts, and predicting outcomes in sepsis management.

Mucopolysaccharidoses (MPS) are autosomal recessive disorders characterized by deficiency of lysosomal enzymes which break down the glycosaminoglycans (GAGs) which results in widespread intra and extra-cellular accumulations of GAGs. Early initiation of treatment, before the onset of irreversible tissue damage, clearly provides a favorable disease outcome. Early detection might be afforded by analysis of amniotic fluid. To report our experience of prenatal diagnosis of MPS over 14-year period for cases referred from medical centers throughout Egypt. Also to report the benefit of prenatal genetic testing in cases accompanied with genetic disorders. The present study included 33 pregnant women at risk of having a fetus with MPS. Of these cases, 3 women had more than one pregnancy evaluated. All cases had a detailed genetic ultrasound examination and a maternal serum alpha-fetoprotein (MSAFP) evaluation during the second trimester of pregnancy. Thirty-eight amniocentesis procedures were performed during the study for 2 dimensional electrophoresis (2-DEP) of GAGs. Positive consanguinity was present in near 70% (23/33) of the couples. Detailed genetic ultrasound examination revealed a case with anencephaly and another one with a twin pregnancy. One case had a MSAFP of 3.6 multiple of the normal median (open neural tube defect). Another 2 cases had a risk of having Down syndrome. Results of the 2-DEP of GAGs in amniotic fluid revealed 36.8% (14/33) affected fetuses. During the final counseling setting of the 14 cases with abnormal results, 43% (6/14) elected to continue their pregnancy while 57% (8/14) elected termination. Early prenatal screening and diagnosis, through a systematic multidisciplinary approach, to all cases of mucopolysaccharidoses are recommended, to improve the quality of life and to avoid the presence of other associated fetal developmental malformations.