Long-Term Neurological Sequelae Among Severe COVID-19 Patients: A Systematic Review and Meta-Analysis.

Few studies have thoroughly evaluated the neuro-invasive effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which may contribute to a wide range of sequelae from mild long-term effects like headaches and fatigue to severe events like stroke and arrhythmias. Our study aimed to evaluate the long-term neurological effects of coronavirus disease 2019 (COVID-19) among patients discharged from the hospital. In this systematic review and meta-analysis, we assessed the long-term neurocognitive effects of COVID-19. Post-COVID-19 neurological sequelae were defined as persistent symptoms of headache, fatigue, myalgia, anosmia, dysgeusia, sleep disturbance, issues with concentration, post-traumatic stress disorder (PTSD), suicidality, and depression long after the acute phase of COVID-19. Data from observational studies describing post-COVID-19 neurocognitive sequelae and severity of COVID-19 from September 1, 2019, to the present were extracted following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol with a consensus of three independent reviewers. A systematic review was performed for qualitative evaluation and a meta-analysis was performed for quantitative analysis by calculating log odds of COVID-19 neurocognitive sequelae. The odds ratio (OR) and 95% confidence interval (CI) were obtained and forest plots were created using random effects models.  We found seven studies, out of which three were used for quantitative synthesis of evidence. Of the 3,304 post-COVID-19 patients identified, 50.27% were male with a mean age of 56 years; 20.20% had post-COVID-19 symptoms more than two weeks after the acute phase of infection. Among persistence symptoms, neurocognitive symptoms like headache (27.8%), fatigue (26.7%), myalgia (23.14%), anosmia (22.8%), dysgeusia (12.1%), sleep disturbance (63.1%), confusion (32.6%), difficulty to concentrate (22%), and psychiatric symptoms like PTSD (31%), feeling depressed (20%), and suicidality (2%) had a higher prevalence. In meta-analysis, COVID-19 patients with severe symptoms had higher odds of headache (pooled OR: 4.53; 95% CI: 2.37-8.65; p<0.00001; I2: 0%) and myalgia (pooled OR: 3.36; 95% CI: 2.71-4.17; p<0.00001; I2: 0%). Anosmia, fatigue, and dysgeusia had higher but non-significant odds following COVID-19. Although we had sufficient data for headache and fatigue to identify higher rates and associations following COVID-19, we could not establish relationships with other post-COVID-19 neurocognitive séqueles. Long-term follow-up may mitigate the neurocognitive effects among COVID-19 patients as these symptoms are also associated with a poor quality of life.

Effect Comparison of E-Cigarette and Traditional Smoking and Association with Stroke-A Cross-Sectional Study of NHANES.

Introduction: Tobacco use is one of the most significant risk factors for stroke. Besides traditional cigarettes and combustible products, the use of e-cigarettes and electronic nicotine delivery products has been widespread among young adults in the recent era. Furthermore, the trend of vaping has increased over the last decade. However, the relationship between e-cigarettes and stroke is largely unknown. The aim of this study was to evaluate the prevalence and identify the relationship between e-cigarette smoking and stroke. Methods: A cross-sectional study was performed using the NHANES database of the US population. Adults with a history of smoking were considered in our study and divided into three groups, e-cigarette users, traditional, and dual smokers. The Chi-squared test, Wilcoxon rank-sum test, and multivariable logistic regression analysis were used to identify the prevalence and association of e-cigarette consumption and stroke. Results: Out of a total of 266,058 respondents from 2015 to 2018, we found 79,825 respondents who smoked e-cigarettes (9.72%) or traditional (29.37%) or dual smoking (60.91%). Stroke prevalence among e-cigarette smokers was 1.57%. Stroke was more prevalent among traditional smokers than among e-cigarette smokers. (6.75% vs. 1.09%; p < 0.0001) E-cigarette smokers had early onset of stroke in comparison with traditional smokers. (median age: 48 vs. 59 years; p < 0.0001). Among females with stroke, the prevalence of e-cigarette use was higher in comparison with traditional smoking (36.36% vs. 33.91%; p < 0.0001). Among the stroke population, the prevalence of e-cigarette use was higher among Mexican-Americans (21.21% vs. 6.02%) and other Hispanics (24.24% vs. 7.70%) compared with traditional smoking (p < 0.0001). The regression analysis found higher odds of stroke history among e-cigarette users than traditional smokers [aOR: 1.15; 95% CI: 1.15−1.16)]. Conclusion: Though stroke was more prevalent in traditional smokers, the incidence of stroke was early-in-onset and was strongly associated with e-cigarette use compared to traditional smokers. We have also identified vascular effects of e-cigarettes components as possible triggers for the stroke.

Timing of Antenatal Steroid Administration and Effects on the Newborn Infant: A Retrospective Study.

OBJECTIVE: The timing of antenatal steroids (ANS) on short- and long-term effects on newborn infants was evaluated. STUDY DESIGN: This study was conducted at the University of Cincinnati Medical Center Level-III Neonatal Intensive Care Unit by reviewing the medical records of all women with history of ANS exposure from January 2015 to December 2018. We compared outcomes of newborns delivered within the ideal therapeutic window of 24 hours to 7 days (within window [WW]) after administration to those exposed and delivered outside the therapeutic window (outside window primary group [OWP]). Outcomes included anthropometrics, blood sugars, thyroid hormone profile, and neonatal morbidities. RESULTS: A total of 669 patients were identified as having received at least two doses of ANS. Two-thirds of them delivered within the ideal therapeutic window. Significant differences were found in anthroprometrics including lower birth weight, shorter length, and smaller head circumferences in those born within the window compared with those outside the window. Derangements in glucose homeostasis requiring treatment and elevations of thyroid stimulating hormone (TSH) were seen in infants born outside the ideal therapeutic window compared with those born within the therapeutic window. No differences were found in neonatal morbidities including severe intraventricular hemorrhage (sIVH), necrotizing enterocolitis (NEC), need for resuscitation, exogenous surfactant administration, continuous positive airway pressure (CPAP), mechanical ventilation, bronchopulmonary dysplasia (BPD), or periventricular leukomalacia (PVL). After controlling for selected covariates, only birth length was different between the groups. CONCLUSION: Effects on anthropometrics, glucose homeostasis, and thyroid function support the need to develop new or refine existing risk stratification systems to time the administration of antenatal steroids. Better targeting of women and fetuses may confer the benefits of systemic corticosteroids while mitigating the risks of adverse effects. KEY POINTS: · The timing of antenatal steroids on short and long-term effects on newborn infants was evaluated.. · Differences were found in anthroprometrics, glucoses, and thyroid function.. · No differences were found in neonatal morbidities..

Stem Cell Therapies for Ischemic Stroke: A Systematic Review.

Stroke is one of the leading causes of death and disability worldwide. It is associated with a high economic burden, causing an increasing demand for highly effective, curative, and long-lasting therapies. Stem cells are unique human cells that have the capacity for developing into specialized cell types with the potential for facilitating regeneration and repair of damaged tissues. Therefore, many preclinical studies have shown the feasibility, safety, and efficacy of stem cell-based therapies; however, the evidence is still inadequate for their therapeutic use in humans. We employed a systematic approach to search published data from 2000 to 2020 on five main databases: PubMed, PubMed Central, Google Scholar, ScienceDirect, and Medline. Two research registries were also searched: the Cochrane Registry and clinicaltrial.gov. Data was collected after applying inclusion and exclusion criteria and studies were appraised critically. Both Medical Subject Headings (MeSH) and regular keyword search strategies were employed. The findings of this study are in line with previously reported studies in which stem cell-based therapies were found to be relatively safe, feasible, and effective.

Ocular manifestations of liver disease in children: Clinical aspects and implications.

Liver and eyes are interlinked to each other in various medical conditions. There are certain ocular findings which directly indicate specific liver disorders. Thus, it becomes critical to identify disorders of liver and eyes early in the course of illness, so that prompt management may be initiated before the commencement of complications. It is highly advantageous in metabolic liver disorders as it offers prognostic value and spares the patient of unnecessary invasive and detailed work up. However, due to its silent and heterogeneous presentation, it is often unrecognized and ignored. Eye abnormalities could be due to, either direct toxic effects of abnormal metabolites, excess of normal metabolites, or by deficient energy metabolism. A number of inherited liver conditions have associated ocular lesions such as Kayser-Fleischer rings in Wilson's disease, posterior embryotoxon or optic drusen in Alagille's syndrome, and cherry-red spot in Niemann-Pick's type A. A thorough eye examination is important in distinguishing between several different forms of familial intrahepatic cholestasis which are associated with anomalies of the heart, bones, or kidneys. Early diagnosis is important, as in most cases, dietary restriction and early therapy prevents the onset of disability. The aim of this review is to sensitize and make pediatricians, hepatologists and ophthalmologists aware of specific ocular findings, suggestive of certain hepatobiliary disorders, thus helping in early referral. The pediatric and adult literature was thoroughly reviewed to organize the present review.

Clinical Profile, Liver Dysfunction and Outcome of Dengue Infection in Children: A Prospective Observational Study.

BACKGROUND: Liver involvement in dengue illness is common and can lead to acute liver failure (ALF). No single method can effectively identify patients at risk for disease progression and bad outcome. We aimed to determine the relationship between liver dysfunction, kinetics of liver function tests (LFTs) and severity of hepatitis on the outcome in pediatric dengue illness. METHODS: We conducted a prospective observational study of hospitalized children (1-12 years) with dengue infection (July 2014-July 2015). Serial monitoring of LFTs was done in confirmed dengue cases. Patients were classified into non-severe (NSD) and severe dengue (SD). Severity of hepatitis was graded: mild, moderate and severe hepatitis. Events were noted during hospitalization. RESULTS: One hundred two children (66, boys), median age 72 (48-96) months, were analyzed (NSD, n = 41; SD, n = 61). Elevated transaminases (92%) was the most common abnormality; aspartate transaminase (AST) and alanine transaminase (ALT) in 87% and 82%, respectively. Maximum abnormalities in LFTs peaked at day 5 (AST, ALT) and day 7 (Alkaline Phosphatase [ALP], gamma-glutamyl transferase) of illness. Elevated transaminases was found to be higher in SD than NSD (100% vs. 80%, P = 0.006). Severe hepatitis developed organ dysfunction such as altered sensorium (P < 0.001), ALF (P < 0.001), acute kidney injury (P < 0.001) and shock (P < 0.001), more commonly than those with mild to moderate hepatitis. Fourteen patients died, two-thirds of whom had severe hepatitis (P < 0.001). Using binary logistic regression, presence of severe hepatitis and shock at presentation was an independent predictor for ALF (odds ratio: 77; 95% confidence interval : 13-457, P < 0.001) and mortality (odds ratio: 55; 95% confidence interval: 4.6-66, P < 0.001), respectively. CONCLUSIONS: Many children with dengue have liver involvement. Severe hepatitis in dengue is associated with significant organ dysfunction and poor outcome.

Blood Glucose Variability and Outcomes in Critically Ill Children.

OBJECTIVES: To find the incidence of hyperglycemia (blood glucose [BG] ≥150 mg/dl), hypoglycemia (BG ≤60 mg/dl), and variability (presence of hypoglycemia and hyperglycemia) in critically ill children in the 1st week of Intensive Care Unit (ICU) stay and their association with mortality, length of ICU stay, and organ dysfunction. MATERIALS AND METHODS: The design was a retrospective observational cohort study. Consecutive children ≤18 years of age admitted from March 2003 to April 2012 in a combined adult and pediatric closed ICU. Relevant data were collected from chart review and hospital database. RESULTS: Out of 258 patients included, isolated hyperglycemia was seen in 139 (53.9%) and was unrelated to mortality and morbidity. Isolated variability in BG was noted in 76 (29.5%) patients and hypoglycemia was seen in 9 (3.5%) patients. BG variability was independently associated with multiorgan dysfunction syndrome on multivariate analysis (adjusted odds ratio [OR]: 7.1; 95% confidence interval [CI]: 1.6-31.1). Those with BG variability had longer ICU stay (11 days vs. 4 days, on log-rank test, P = 0.001). Insulin use was associated with the occurrence of variability (adjusted OR: 3.6; 95% CI: 1.8-7.0). CONCLUSION: Glucose disorders were frequently observed in critically ill children. BG variability was associated with multiorgan dysfunction and increased ICU stay.