Concomitant Guillain-Barré Syndrome and COVID-19: A Meta-Analysis of Cases.

Background and Objectives: Recent findings demonstrate that the transmigration of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) to the nervous system implicates severe neurotropic pathologies, including the onset of the rare disease called Guillain-Barré syndrome (GBS) which is characterized by immune-mediated polyneuropathy. This study aimed to identify the predisposing factors and the clinical features of coronavirus disease 2019 (COVID-19)-induced GBS. Materials and Methods: We have performed an analysis of 147 cases. A systematic review of the published research work was performed per the PRISMA statement to obtain individual participant data (IPD) for the meta-analysis. The search was conducted through PubMed, using the combined search terms "Guillain-Barré syndrome" and "COVID-19". All case reports and series in the English language with accessed full text were included in the search. Results: A systematic database search led to the retrieval of 112 peer-reviewed articles published between 1 April 2020, and 8 February 2022. The articles comprised 16 case series and 96 case reports containing IPD for 147 patients. Our findings showed that 77.6% of all cases were 40 years or older. Males comprised most of the cases (65.3%; n = 96). The intensive care unit (ICU) admission was 44.9%, and the need for mechanical ventilation (MV) was 38.1%. The patients presented with hyporeflexia or areflexia (84.4%; n = 124), lower limb strength and sensation impairment (93.2%; n = 138), upper limb strength and sensation impairment (85.7; n = 126), and somatic sensation impairment (72.8%; n = 107). The patients presented with increased cerebral spinal fluid (CSF) protein levels (92%; n = 92) and the presence of CSF albuminocytological dissociation (83.5%; n = 71). The most common variant of GBS observed was acute inflammatory demyelinating polyneuropathy (AIDP). We found that predisposing factors concomitant with COVID-19 and GBS were male gender and older age. Among the cases, patient mortality was 10.9%. Conclusions: A gap of knowledge exists regarding the complete spectrum of clinical characteristics of COVID-19-related GBS. Recent findings suggest that SARS-CoV-2 triggers GBS, as it follows a similar para-infectious pattern as the other viral agents contributing to the onset of GBS.

Prevalence of hepatopancreatic injury and clinical outcomes in patients with COVID-19 in USA.

BACKGROUND: (1) To determine the prevalence of hepatopancreatic injury in coronavirus disease 2019 (COVID-19) patients. (2) To correlate hepatopancreatic injury in COVID-19 with mortality, disease severity, and length of stay in this cohort. RESULTS: Forty-five thousand three hundred sixty patients were included in the analysis, 62.82% of which had either hepatic or pancreatic injury. There was a significant upward trend in transaminases, alkaline phosphatase, prothrombin time, bilirubin, lactate dehydrogenase, and lipase and a downward trend in albumin with an increase in disease severity. COVID-19-positive patients with hepato-pancreatic injury have a significantly higher mortality (OR 3.39, 95%CI 3.15-3.65) after controlling for the differences in age, sex, race/ethnicity, liver cirrhosis, and medication exposures. They also have increased disease severity (OR 2.7, 95%CI 2.5-2.9 critical vs mild/moderate; OR 1.4, 95% CI 1.3-1.5 severe vs mild/moderate) and longer hospital length of stay (2 days). CONCLUSION: COVID-19 can cause liver injury. Mortality, disease severity, and hospital length of stay are increased in COVID-19 patients with hepatopancreatic injury.

Cerebrospinal fluid findings and hypernatremia in COVID-19 patients with altered mental status.

BACKGROUND: The objective of the study was to assess the cerebrospinal fluid (CSF) findings in COVID-19 patients. AIMS: This was an observational retrospective cohort from electronic medical records of hospitalized patients (n = 2655) with confirmed COVID-19 between February 15, 2020, and April 15, 2020, in 182 hospitals from a large health system in the USA. The review of data yielded to a total of 79 patients in 20 hospitals who had CSF analysis. METHODS: Outcomes during hospitalization, including hospital length of stay, disease severity, ventilator time, and in-hospital death were recorded. Independent variables collected included patient demographics, diagnoses, laboratory values, and procedures. RESULTS: A total of 79 patients underwent CSF analysis. Of these, antigen testing was performed in 73 patients. Ten patients had CSF analysis for general markers such as total protein, cell count, glucose, clarity, and color. Seven of the 10 cases (70%) had normal total cell count and normal white blood cell count in CSF. Sixty-three percent (5/8) had elevated total protein. Two patients had normal levels of lactate dehydrogenase (LDH) and 1 patient had significantly elevated (fourfold) neuron-specific enolase (NSE) level in CSF. CONCLUSION: Unlike bacterial infections, viral infections are less likely to cause remarkable changes in CSF glucose, cell count, or protein. Our observations showed no pleocytosis, but mild increase in protein in the CSF of the COVID-19 patients. The fourfold elevation of NSE may have diagnostic/prognostic value as a biomarker in CSF for COVID-19 patients who have altered mental status.

Can Neuron Specific Enolase Be a Diagnostic Biomarker for Neuronal Injury in COVID-19?

Neuron specific enolase (NSE) is a biomarker for neuronal injury. However, increased levels in cerebrospinal fluid (CSF) and serum is associated with the clinical outcome in patients with head injury, ischemic stroke, intracerebral hemorrhage, cardiac arrest, anoxic encephalopathy, encephalitis, brain metastasis, and status epilepticus. Recently, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which started in China, rapidly evolved into the coronavirus disease 2019 (COVID-19) pandemic. Patients with COVID-19 have a wide range of symptoms varying from mild upper respiratory symptoms to severe illness requiring mechanical ventilation. While coronaviruses primarily target the human respiratory system, neurological symptoms are also observed in some patients. These include symptoms such as loss of taste and olfaction and diseases like cerebrovascular disorders including ischemic stroke and hemorrhages, encephalopathies, Guillain-Barré syndrome and acute disseminated encephalomyelitis. Here we report an observation from a patient whose NSE levels increased approximately four-fold in CSF. This finding was accompanied by increased white blood cell count and elevated protein in CSF indicating neuroinflammation. Thus, we suggest that NSE may be used as a CSF biomarker in COVID-19 patients with encephalopathy.

Cosmetovigilance: A New Concept for the Residency Curriculum.

Description Primary care physicians need to incorporate "cosmetovigilance" into their post-graduate curriculum to increase their residents' awareness of the adverse reactions induced by the use of cosmetic products, as well as promoting good reporting behavior.

Early Aggressive Hydration Is Associated with Decreased Opioid Use and Readmission in Mild Acute Pancreatitis.

Background: Acute pancreatitis (AP) is one of the most common causes of hospital admissions due to gastrointestinal disorders. No pharmacologic agents have been proven to impact the prognosis, and the treatment still remains supportive with intravenous fluids for hydration. Although early hydration has been recommended for the management of mild AP, there is no consensus on the type, rate, and amount of the fluid replacement. Objective: In this study, we aimed to investigate the outcome of aggressive hydration in patients with AP. Methods: Retrospective data from patients admitted to 12 hospitals (2015-2017) was used for analysis. Five hundred patients who met the inclusion and exclusion criteria for mild AP were included. The subjects were classified into 3 groups based on the amount of intravenous fluids they received in the first 12 hours of admission: Hydration group A (0-1.5 ml/kg/h), Hydration group B (>1.5-3 ml/kg/h) and Hydration group C (>3 ml/kg/h). Laboratory test results on the second day of admission, length of stay (LOS) and opioid analgesic use on the last day were analyzed using a Chi-square test. A p-value of less than 0.05 was considered statistically significant. Results: Patients with aggressive hydration (>3 ml/kg/h) had a greater reduction in creatinine (mean difference = -0.05, p = 0.017) compared to those who received standard hydration (0-1.5 ml/kg/h). There was no significant difference in LOS among the three hydration groups. Patients with aggressive hydration were less likely to use opioid analgesics on the last day of hospitalization (23.9% vs. 35.3%, p = 0.044) compared to standard hydration. Patients with hydration were less likely to experience a readmission for any reason within 30 days (Odds ratio (OR) = 1.603, 95% CI, 1.064-2.414, p = 0.024) compared to those who received low hydration. Conclusions: Our findings showed that less narcotics were required for the patients receiving aggressive hydration in mild AP. On the other hand, early aggressive hydration is not widely implemented in community hospitals, despite beneficial effects.

A New Journal to Publish Houses of Bricks: Introducing the HCA Healthcare Journal of Medicine.

Description Welcome to the HCA Healthcare Journal of Medicine, a new peer-reviewed scientific periodical dedicated to the care and improvement of human life by publishing and disseminating scholarly work focusing on innovation and enhanced quality, developing new knowledge in clinical care, and contributing to research in medical education.

Research and Data Mining During the COVID-19 Pandemic.

Description With the recent advances in information and technology systems, most developed countries have invested in building advanced systems for the management of electronic medical records. If the infrastructure of these systems are well designed, they both serve as an information resource for routine patient care and also serve as the primary backbone for medical research. This evidence became clear during the recent coronavirus pandemic, which has been a worldwide challenge since the beginning of 2020. Rapid spread of SARS-CoV-2 infections all over the world has resulted in tremendous health, economic and social ramifications, including social distancing, travel restrictions and closing of schools and businesses. Medical educational activities have shifted towards telemedicine, online learning and web-based meetings and conferences to prevent virus spread. While experimental lab research slowed, research with electronic medical records and databases accelerated in order to investigate the risk factors associated with COVID-19 and clinical management strategies to combat the disease. The urgency for COVID-related research has also lead to inconsistent and sometimes inaccurate output.

Importance of Awareness of Adverse Drug Reaction Reporting During the COVID-19 Pandemic.

Description Health care professionals hold the responsibility of reporting any adverse drug reactions in order to learn about new therapy and how best to safely care for our patients. The information derived from case publications and FDA MedWatch reports are essential to accumulate information and increase awareness for the possible risks of new drugs.

Neurological Exam in Rats Following Stroke and Traumatic Brain Injury.

Using the appropriate model for testing neurological symptoms in rats is essential for the assessment of functional outcome. A number of tests have been developed to quantify the severity of neurological deficits. These tests should meet criteria such as validity, specificity, sensitivity, and utility. Although analysis of motor function shows homology in primates and rodents, the total neurological exam scores may not always reflect the clinical outcome. Therefore, the selection of the appropriate tests has critical importance when evaluating therapeutic strategies. This chapter describes Toklu's modified neurological exam score method which can be used practically to assess neurological symptoms following traumatic brain injury (TBI) and stroke. The method is a combination of balance, muscle strength, coordination, and reflex.

Cosmetovigilance: A review of the current literature.

The term "pharmacovigilance" defines the activities related to the collection, detection, assessment, monitoring, and prevention of adverse reactions occurring with medications. Recently, the spectrum of "-vigilance" has broadened to include safety of herbal products and cosmetic products as well. "Cosmetovigilance" was introduced as a new term used for defining surveillance carried out by industry to address the safety of cosmetic products. It was first used in literature by Vigan (1997) to refer to the monitoring of cosmetic product safety. Today, it is recognized globally as a concept of public health. For this systematic review, a PubMed search was conducted in July 2018 for the term "cosmetovigilance."

Factors associated with participation and completion of a survey-based study.

PURPOSE: The Healthy Work Place (HWP) study investigated methods to improve clinicians' dissatisfaction and burnout. The purpose of this paper is to identify factors that influenced study enrollment and completion and assess effects of initial clinic site enrollment rates on clinician outcomes, including satisfaction, burnout, stress and intent to leave practice. DESIGN/METHODOLOGY/APPROACH: In total, 144 primary care clinicians (general internists, family physicians, nurse practitioners and physician assistants) at 14 primary care clinics were analyzed. FINDINGS: In total, 72 clinicians enrolled in the study and completed the first survey (50 percent enrollment rate). Of these, 10 did not complete the second survey (86 percent completion rate). Gender, type, burnout, stress and intervention did not significantly affect survey completion. Hence, widespread agreement about most moral/ethical issues (72 percent vs 22 percent; p=0.0060) and general agreement on treatment methods (81 percent vs 50 percent; p=0.0490) were reported by providers that completed both surveys as opposed to just the initial survey. Providers with high initial clinic site enrollment rates (=50 percent providers) obtained better outcomes, including improvements in or no worsening of satisfaction (odds ratio (OR)=19.16; p=0.0217) and burnout (OR=6.24; p=0.0418). SOCIAL IMPLICATIONS: More providers experiencing workplace agreement completed the initial and final surveys, and providers at sites with higher initial enrollment rates obtained better outcomes including a higher rate of improvement or no worsening of job satisfaction and burnout. ORIGINALITY/VALUE: There is limited research on clinicians' workplace and other factors that influence their participation in survey-based studies. The findings help us to understand how these factors may affect quality of data collecting and outcome. Thus, the study provides us insight for improvement of quality in primary care.

Oestradiol and leptin have separate but additive anorexigenic effects and differentially target fat mass in rats.

We recently showed that male rats exhibit lower hypophagia and body weight loss compared to female rats following central leptin delivery, suggesting a role for oestradiol in leptin responsiveness. Accordingly, we delivered Ob (leptin) or GFP (control) gene into the brain of male rats that were simultaneously treated with oestradiol or vehicle. In a reciprocal approach, we compared oestradiol-deficient (OVX) with intact females (sham) that received leptin or control vector. Changes in food intake), body weight and body composition were examined. In males, oestradiol and leptin resulted in lower cumulative food intake (15%) and endpoint body weight (5%), although rats receiving dual treatment (oestradiol-leptin) ate 28% less and weighed 22% less than vehicle-control. Changes in food intake were unique to each treatment, with a rapid decrease in vehicle-leptin followed by gradual renormalisation. By contrast, hypophagia in oestradiol-control was of lower amplitude and sporadic. Leptin selectively targeted fat mass and endpoint abdominal fat mass was 65%-80% lower compared to their respective control groups. In females, both leptin groups had lower body weight (endpoint values 20% lower than control groups) with the highest extent in sham animals (endpoint value was 28% less in sham-leptin than in sham-control). OVX rats rapidly started regaining their lost body weight reminiscent of the pattern in males. Leptin rapidly and robustly reduced fat mass with endpoint values 30%-35% less than control treated animals. It appears that leptin and oestradiol decreased food intake and body weight via different mechanisms, with the pattern of oestradiol-leptin being reminiscent of that observed in females and the pattern of OVX-leptin reminiscent of that observed in males. Oestrogen status did not influence initial fat mass loss by leptin. It can be concluded that oestradiol modulates the long-term response to central leptin overexpression, although its actions on energy homeostasis are additive and independent of those of leptin.

ACE2 activator diminazene aceturate reduces adiposity but preserves lean mass in young and old rats.

The obesity epidemic is multi-generational and is particularly debilitating in the aging population, necessitating the use of pharmaceutical interventions. Recent evidence suggests that increasing the activity of the angiotensin converting enzyme-2 [ACE2]/angiotensin-(1-7)[Ang-(1-7)]/Mas receptor (MasR) axis in obese animal models leads to significant reductions in body weight. It was hypothesized that activation of ACE2 via diminazene aceturate (DIZE) will significantly reduce body weight of rats fed a high fat diet. Young and old (4 and 23 months, respectively) male Fisher 344 × Brown Norway rats were fed 60% high fat diet for one week, and subsequently given either 15 mg/kg/day DIZE s.c. or vehicle for three weeks. DIZE treatment resulted in a significant reduction of food intake and body weight in both young and old animals. However, that decrease was so dramatic in the older animals that they all nearly stopped eating. Interestingly, the TD-NMR assessments revealed that the weight-loss was primarily a result of decreased body fat percentage, with a relative preservation of lean mass. Tissue weights confirm the significant loss of white adipose tissue (WAT), with no change in muscle weights. Gene expression and serum ACE2 activity analyses implied that increased activation of the ACE2/Ang-(1-7)/MasR axis plays a role in reducing fat mass. Collectively, our results suggest that DIZE may be a useful tool in the study of obesity; however, caution is recommended when using this compound in older animals due to severe anorectic effects, although there is a mechanism by which muscle is preserved.

Limiting feeding to the active phase reduces blood pressure without the necessity of caloric reduction or fat mass loss.

Reducing body weight has been shown to lower blood pressure in obesity-related hypertension. However, success of those lifestyle interventions is limited due to poor long-term compliance. Emerging evidence indicates that feeding schedule plays a role on the regulation of blood pressure. With two studies, we examined the role of feeding schedule on energy homeostasis and blood pressure. In study 1, rats were fed a high-fat diet (HFD) ad libitum for 24 h (Control) or for 12 h during the dark phase (time-restricted feeding, TRF). In study 2, rats fed a HFD were administered a long-acting α-MSH analog at either light onset [melanotan II (MTII) light] or dark onset (MTII dark) or saline (Control). MTII light animals ate most of their calories during the active phase, similar to the TRF group. In study 1, Control and TRF rats consumed the same amount of food and gained the same amount of weight and fat mass. Interestingly, systolic and mean arterial pressure (MAP) was lower in the TRF group. In study 2, food intake was significantly lower in both MTII groups relative to Control. Although timing of injection affected light versus dark phase food consumption, neither body weight nor fat mass differed between MTII groups. Consistent with study 1, rats consuming their calories during the active phase displayed lower MAP. These data indicate that limiting feeding to the active phase reduces blood pressure without the necessity of reducing calories or fat mass, which could be relevant to obesity-related hypertension.

The Clinical Significance of Relative Bradycardia.

INTRODUCTION: Relative bradycardia is a poorly understood paradoxical phenomenon that refers to a clinical sign whereby the pulse rate is lower than expected for a given body temperature. OBJECTIVE: To provide an overview and describe infectious and noninfectious causes of relative bradycardia. METHODS: PubMed and Medline databases were searched using individual and Medical Subject Headings terms including relative bradycardia, fever, pulse-temperature dissociation and pulsetemperature deficit in human studies published from inception to October 2, 2016. The causes and incidence of relative bradycardia were reviewed. RESULTS: Relative bradycardia is found in a wide variety of infectious and noninfectious diseases. The pathogenesis remains poorly understood with proposed mechanisms including release of inflammatory cytokines, increased vagal tone, direct pathogenic effect on the myocardium, and electrolyte abnormalities. The incidence of this sign varies widely, which may be attributable to multiple factors, including population size, time course for measuring pulse and temperature, and lack of a consistent definition used. The fact that this sign is not consistently identified in case series suggests that relative bradycardia is caused by mechanisms presumably involving or influenced by pathogen and host factors. CONCLUSIONS: Relative bradycardia is a sensitive but nonspecific clinical sign that may be an important bedside tool for narrowing the differential diagnosis of potential infectious and noninfectious etiologies. Recognizing this relationship may assist the clinician by providing bedside clinical clues into potential etiologies of disease, particularly in the setting of infectious diseases and in circumstances when other stigma of disease is absent.

The effect of solifenacin on postvoid dribbling in women: results of a randomized, double-blind placebo-controlled trial.

INTRODUCTION AND HYPOTHESIS: To determine the effectiveness of the muscarinic receptor antagonist solifenacin (VESIcare®) in the treatment of postvoid dribbling (PVD). METHODS: We carried out a multicenter, 12-week, double-blind, randomized, placebo-controlled, parallel design study. Between 2012 and 2015, a total of 118 women (age 18-89 years) with PVD at least twice/weekly, were randomized to receive solifenacin (5 mg; n = 58) or placebo (n = 60) once daily. The primary outcome was the percentage reduction in PVD episodes. Secondary outcomes included the percentage of patients with ≥50% reduction in PVD episodes and changes in quality of life. RESULTS: There were no differences in either the primary or secondary outcome variables. Subgroup analysis, based on those with more severe disease (>10 PVD episodes/week), showed a greater and significant percentage reduction in the frequency of PVD episodes per day (60.3% vs 32.1%; p = 0.035) and a higher percentage of patients showing ≥50% reduction in the frequency of PVD episodes with solifenacin (68.1% vs 45.8%; p = 0.0476). A significant solifenacin effect occurred at week 2 and continued through week 12 for the subgroup. For solifenacin, PVD reduction was the same for the entire cohort and subgroup, whereas for placebo, it was 10% lower in the subgroup, declining from 42% to 32%. CONCLUSION: There were no differences in PVD outcomes between the solifenacin and placebo groups. Solifenacin may play a role in treating women with the most severe symptoms. Because of the powerful placebo response seen in this study, behavior-based interventions may be useful for treating PVD.

Overpressure blast injury-induced oxidative stress and neuroinflammation response in rat frontal cortex and cerebellum.

BACKGROUND & AIM: Overpressure blast-wave induced brain injury (OBI) and its long-term neurological outcome pose significant concerns for military personnel. Our aim is to investigate the mechanism of injury due to OBI. METHODS: Rats were divided into 3 groups: (1) Control, (2) OBI (exposed 30psi peak pressure, 2-2.5ms), (3) Repeated OBI (r-OBI) (three exposures over one-week period). Lung and brain (cortex and cerebellum) tissues were collected at 24h post injury. RESULTS: The neurological examination score was worse in OBI and r-OBI (4.2±0.6 and 3.7±0.5, respectively) versus controls (0.7±0.2). A significant positive correlation between lung and brain edema was found. Malondialdehyde (index for lipid peroxidation), significantly increased in OBI and r-OBI groups in cortex (p<0.05) and cerebellum (p<0.01-0.001). The glutathione (endogenous antioxidant) level decreased in cortex (p<0.01) and cerebellum (p<0.05) of r-OBI group when compared with the controls. Myeloperoxidase activity indicating neutrophil infiltration, was significantly (p<0.01-0.05) elevated in r-OBI. Additionally, tissue thromboplastin activity, a coagulation marker, was elevated, indicating a tendency to bleed. NGF and NF-κB proteins along with Iba-1 and GFAP immunoreactivity significantly augmented in the frontal cortex demonstrating microglial activation. Serum biomarkers of injury, NSE, TNF-alpha and leptin, were also elevated. CONCLUSION: OBI triggers both inflammation and oxidative injury in the brain. This data in conjunction with our previous observations suggests that OBI triggers a cascade of events beginning with impaired cerebral vascular function leading to ischemia and chronic neurological consequences.