Factors associated with severe infection in rheumatoid arthritis patients: lessons learned from the COVID-19 pandemic.

PURPOSE: This aimed to identify the factors associated with severe/critical coronavirus disease 2019 (COVID-19) infection in rheumatoid arthritis (RA) patients. METHODS: Two-hundred RA patients diagnosed according to the American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) classification criteria with proven COVID-19 infection were recruited and categorized according to the world health organization (WHO) COVID-19 severity grading into 2 groups: patients with mild/moderate COVID-19 (n = 164) and patients with severe/critical COVID-19 (n = 36). Comparison between both groups was done to identify the risk factors associated with severe/critical infection. Incidence of RA disease activity flare defined as increase in clinical disease activity index (CDAI) more than 10 points following infection was calculated. RESULTS: Multivariate analysis identified history of previous serious infection, age > 60 years, and diabetes as factors positively associated, whereas COVID-19 vaccination was negatively associated with severe/critical infection. Following COVID-19 infection, the number of patients with severe/critical COVID-19 who had high RA disease activity and the incidence of flares was significantly higher in comparison to patients with mild/moderate COVID-19 (P < 0.001 and 0.003; respectively). CONCLUSION: Age > 60 years, diabetes, and history of previous serious infections are risk factors for severe/critical COVID-19, while vaccination has a protective role in RA patients. Infection particularly when severe is associated with risk of disease flare.

Novel biomarkers for the assessment of disease activity in patients with sarcoidosis: a case-control study.

BACKGROUND AND AIM: The prognosis of sarcoidosis is challenging and largely depends on the persistence of disease activity and the degree of organ dysfunction. Various biomarkers have been evaluated for diagnosis, disease activity assessment, and prognosis. This study aimed to determine if the ratios of monocytes to high-density lipoprotein cholesterol (MHR), platelets to lymphocytes (PLR), neutrophils to lymphocytes (NLR), and lymphocytes to monocytes ratio (LMR) could be used as novel sarcoidosis activity markers. METHODS: In a case-control study, 54 patients with biopsy-confirmed sarcoidosis were divided into two groups; group 1: consisted of 27 patients with active sarcoidosis who were newly diagnosed and treatment-naive, and group 2: consisted of 27 patients with inactive sarcoidosis who had been on treatment for at least 6 months. All patients were subjected to a comprehensive history, physical examination, laboratory tests, chest imaging, spirometry, and screening for extrapulmonary organ involvement by means of electrocardiogram and eye examination. RESULTS: The mean age of the patients was 44 ± 11 years (79.6% were females & 20.4% were males). MHR, NLR, and LMR were significantly higher in patients with active sarcoidosis than in an inactive disease with a cut-off value of 8.6, a sensitivity of 81.5%, and a specificity of 70.4% (P-value < 0.001), a cut-off value of 1.95, sensitivity of 74% and specificity of 66.7% (P-value 0.007) and a cut-off value of < 4, a sensitivity of 81.5%, and a  specificity of 85.2% (P-value < 0.001), respectively. In contrast, PLR was not statistically significant between active and inactive sarcoidosis patients. CONCLUSIONS: The lymphocytes monocytes ratio is a highly sensitive and specific biomarker that could be used to assess the disease activity in sarcoidosis patients.

Study of nasal mucosa histopathological changes in patients with hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is an interstitial lung disease that develops after inhalation of a variety antigens in susceptible individuals. The nasal mucosa is constantly exposed to these antigens that can irritate the respiratory mucosa. So, the purpose of this study was to study nasal histopathological changes in order to identify any shared pathological changes between the upper airways and the well-known pathological features of HP. 40 HP patients diagnosed at the Chest Department, Kasr Alainy hospital following ATS/JRS/ALAT guidelines were included. Patients were subjected to thorough history, high-resolution computed tomography, spirometry, cough evaluation test (CET), sinonasal outcome test-22 (SNOT-22), sinonasal examination and nasal mucosal biopsy by an otolaryngologist under visualization by a rigid nasal endoscope. The mean age of the patients was 46.2 ± 13.5 (85% were females and 15% were males). 90% of patients presented with cough and the mean CET was 17.15 ± 5.59.77.5% of patients suffered from sinonasal symptoms and the mean SNOT-22 was 12.18 ± 3.8. There was a significant correlation between the burden of sinonasal symptoms represented by the SNOT-22 and the severity of the cough represented by CET (r 0.40, p 0.01). 87.5% of HP patients had chronic inflammation of the nasal mucosa with predominant lymphocytic infiltration in 72.5% of patients. 77.5% of HP patients had a high burden of sinonasal symptoms which is positively associated with cough severity. 72.5% of patients had predominately lymphocytic infiltration of the nasal mucosa.Trial registration: retrospectively registered, registration number is NCT05723796, date of registration 13/02/2023.

Neuropsychiatric post-acute sequelae of COVID-19: prevalence, severity, and impact of vaccination.

The potential long-term neuropsychiatric effects of COVID-19 are of global concern. This study aimed to determine the prevalence and predictors of neuropsychiatric post-acute sequelae of COVID-19 among Egyptian COVID-19 survivors and to study the impact of full vaccination before COVID-19 infection on the occurrence and severity of these manifestations. Three months after getting COVID-19 infection, 1638 COVID-19 survivors were screened by phone for possible neuropsychiatric sequelae. Subjects suspected to suffer from these sequelae were invited to a face-to-face interview for objective evaluation. They were requested to rate the severity of their symptoms using visual analogue scales (VAS). The mean age of participants was 38.28 ± 13 years. Only 18.6% were fully vaccinated before COVID-19 infection. Neuropsychiatric post-acute sequelae of COVID-19 were documented in 598 (36.5%) subjects, fatigue was the most frequent one (24.6%), followed by insomnia (16.4%), depression (15.3%), and anxiety (14.4%). Moderate and severe COVID-19 infection and non-vaccination increased the odds of developing post-COVID-19 neuropsychiatric manifestations by 2 times (OR 1.95, 95% CI = 1.415-2.683), 3.86 times (OR 3.86, 95% CI = 2.358-6.329), and 1.67 times (OR 1.67, 95% CI = 1.253-2.216), respectively. Fully vaccinated subjects before COVID-19 infection (n = 304) had significantly lesser severity of post-COVID-19 fatigue, ageusia/hypogeusia, dizziness, tinnitus, and insomnia (P value = 0.001, 0.008, < 0.001, 0.025, and 0.005, respectively) than non-vaccinated subjects. This report declared neuropsychiatric sequelae in 36.5% of Egyptian COVID-19 survivors, fatigue being the most prevalent. The effectiveness of COVID-19 vaccines in reducing the severity of some post-COVID-19 neuropsychiatric manifestations may improve general vaccine acceptance.

Serum interleukin 1ß and sP-selectin as biomarkers of inflammation and thrombosis, could they be predictors of disease severity in COVID 19 Egyptian patients? (a cross-sectional study).

BACKGROUND: Thromboembolism was a chief cause of mortality in 70% of patients with COVID-19. Our objective was to see if serum interleukins 1 beta (IL-1ß) and soluble platelets selectin (sP-selectin) could serve as novel markers of thromboembolism in COVID-19 patients. METHODS: This cross sectional study involved 89 COVID-19 patients who were recruited from 1st of February to 1st of May 2021. Clinical and laboratory data were collected, and chest imaging was performed. The levels of IL-1ß and sP-selectin were assessed in all cases through ELISA kits. Comparisons between groups were done using an unpaired t-test in normally distributed quantitative variables. In contrast, a non-parametric Mann-Whitney test was used for non-normally distributed quantitative variables. RESULTS: Severe COVID-19 infection was associated with higher serum levels of CRP, Ferritin, LDH, D dimer, IL-1ß and sP-selectin (P <  0.001) with significant correlation between levels of IL-1ß and sP-selectin (r 0.37, P <  0.001), D-dimer (r 0.29, P 0.006) and Ferritin (r 0.5, p <  0.001). Likewise, a positive correlation was also found between levels of sP-selectin, D-dimer and Ferritin (r 0.52, P <  0.001) (r 0.59, P <  0.001). Imaging studies revealed that 9 (10.1%) patients developed venous and 14 (15.7%) developed arterial thrombosis despite receiving anticoagulant therapy. Patients with thrombotic events had significantly higher levels of IL-1ß, sP-selectin and LDH serum levels. Meanwhile, there was no statistical significance between CRP, D-dimer or Ferritin levels and the development of thrombotic events. CONCLUSION: IL-1ß and sP-selectin levels can be promising predictors for severe COVID-19 infection and predictable thrombosis.

Dual-energy X-ray absorptiometry measures of lean body mass as a biomarker for progression in boys with Duchenne muscular dystrophy.

We evaluated whether whole-body dual-energy X-ray absorptiometry (DXA) measures of lean body mass can be used as biomarkers for disease progression and treatment effects in patients with Duchenne muscular dystrophy. This post hoc analysis utilized data from a randomized, 2-period study of domagrozumab versus placebo in 120 ambulatory boys with DMD. DXA measures of lean body mass were obtained from the whole body (excluding head), arms, legs and appendicular skeleton at baseline and every 16 weeks. Treatment effects on DXA measures for domagrozumab versus placebo were assessed at Week 49. At Week 49, domagrozumab statistically significantly increased lean body mass versus placebo in the appendicular skeleton (p = 0.050) and arms (p < 0.001). The relationship between lean body mass at Week 49 and functional endpoints at Week 97 was evaluated. Changes in lean body mass at Week 49 in all regions except arms were significantly correlated with percent change from baseline in 4-stair climb (4SC) at Week 97. DXA-derived percent lean mass at Week 49 also correlated with 4SC and North Star Ambulatory Assessment at Week 97. These data indicate that whole-body DXA measures can be used as biomarkers for treatment effects and disease progression in patients with DMD, and warrant further investigation.Trial registration: ClinicalTrials.gov, NCT02310763; registered 8 December 2014.

Post-COVID-19 neuropsychiatric manifestations among COVID-19 survivors suffering from migraine: a case-control study.

BACKGROUND: The burden of post-coronavirus disease (COVID)-19 symptoms has been increasing and is of great concern in patients with pre-existing chronic medical conditions.This study aimed to delineate the post-COVID-19 neuropsychiatric symptoms among migraine patients compared to the non-migraine control group. METHODS: Two groups, each of 204 COVID-19 survivors, were enrolled in the study after 3 months of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, one group fulfilling the episodic migraine criteria and the other serving as a matching control group. Subjects were evaluated through an in-person interview for post-COVID-19 neuropsychiatric symptoms, including detailed headache patterns and severity, using the visual analogue scale. RESULTS: The Frequency of headache during the acute phase of COVID-19 was more frequent in migraine patients (OR = 1.60, 95%CI = 1.04-2.45, P-value = 0.031). The reported significant post-COVID-19 neuropsychiatric symptoms in migraine patients compared to controls were fatigue (OR = 1.662, 95%CI = 1.064-2.596, P-value = 0.025), anosmia/hyposmia (OR = 2.06, 95%CI = 1.164- 3.645, P-value = 0.012), cacosmia (OR = 2.663, 95%CI = 1.145-6.195, P-value = 0.019), depression (OR = 2.259, 95%CI = 1.284- 3.975, P-value = 0.004), anxiety (OR = 3.267, 95%CI = 1.747- 6.108, P-value ≤ 0.001), insomnia (OR = 2.203, 95%CI = 1.298- 3.739, P-value = 0.003), and headache (OR = 3.148, 95%CI = 1.616-6.136, P-value = ≤ 0.001).While there was no statistically significant difference between migraine patients and controls regarding the post-COVID-19 functional status score (P-value = 0.102). The pattern of post-COVID-19 headache was reported as chronic headache transformation in 17.6% of the migraine group, with the median intensity rate being 5.5 and IQR (3-7). In the control group, 14% experienced chronic headache attributed to systemic viral infection with a median intensity rate of 2 and IQR (2-5), while 12% experienced a new daily persistent headache with a median intensity of 5 and IQR (1-6). CONCLUSION: The study highlighted the importance of follow-up migraine patients upon recovery from COVID-19 infection, being more vulnerable to post-COVID-19 symptoms.

Magnesium Sulfate for Prevention of Post-ERCP-Pancreatitis: A Randomized Controlled Trial.

BACKGROUND: Acute pancreatitis is one of the most common complications of endoscopic retrograde cholangiopancreatography (ERCP). Studies suggest that intrapancreatic calcium has an important role in activating pancreatic enzymes; in addition, elevated intraductal pressure is required for development of pancreatitis. Magnesium sulfate (MS), as a calcium antagonist and a muscle relaxant of the Oddi sphincter, is suggested to reduce the incidence and severity of post-ERCP-pancreatitis (PEP) in this article. METHODS: We included 270 patients who referred for ERCP between March 2017 and March 2018. They were enrolled into MS (2 g) and placebo (normal saline) groups, administered 1 hour before and 6 hours after the procedure. The ERCPs were done by fellows of gastroenterology under supervision of expert physicians. The incidence and severity of PEP were followed. RESULTS: PEP was seen in 12 (8.9%) patients in the MS group and 17 (12.6%) in the placebo group (P value=0.33). The incidence of PEP in high risk patients group (P value=0.017). CONCLUSION: Although the usage of MS was not able to prevent PEP in all patients enrolled in this study, but it could significantly reduce the incidence of PEP in high risk patients of intervention group in comparison with placebo group. The median length of hospital stay was also significantly lower in new drug group in contrast to placebo.

Quantitative magnetic resonance imaging measures as biomarkers of disease progression in boys with Duchenne muscular dystrophy: a phase 2 trial of domagrozumab.

Duchenne muscular dystrophy (DMD) is a progressive, neuromuscular disorder caused by mutations in the DMD gene that results in a lack of functional dystrophin protein. Herein, we report the use of quantitative magnetic resonance imaging (MRI) measures as biomarkers in the context of a multicenter phase 2, randomized, placebo-controlled clinical trial evaluating the myostatin inhibitor domagrozumab in ambulatory boys with DMD (n = 120 aged 6 to < 16 years). MRI scans of the thigh to measure muscle volume, muscle volume index (MVI), fat fraction, and T2 relaxation time were obtained at baseline and at weeks 17, 33, 49, and 97 as per protocol. These quantitative MRI measurements appeared to be sensitive and objective biomarkers for evaluating disease progression, with significant changes observed in muscle volume, MVI, and T2 mapping measures over time. To further explore the utility of quantitative MRI measures as biomarkers to inform longer term functional changes in this cohort, a regression analysis was performed and demonstrated that muscle volume, MVI, T2 mapping measures, and fat fraction assessment were significantly correlated with longer term changes in four-stair climb times and North Star Ambulatory Assessment functional scores. Finally, less favorable baseline measures of MVI, fat fraction of the muscle bundle, and fat fraction of lean muscle were significant risk factors for loss of ambulation over a 2-year monitoring period. These analyses suggest that MRI can be a valuable tool for use in clinical trials and may help inform future functional changes in DMD.Trial registration: ClinicalTrials.gov identifier, NCT02310763; registered December 2014.

Neurological Manifestations in a Cohort of Egyptian Patients with COVID-19: A Prospective, Multicenter, Observational Study.

BACKGROUND: The COVID-19 pandemic has reached over 276 million people globally with 5.3 million deaths as of 22nd December 2021. COVID-19-associated acute and long-term neurological manifestations are well recognized. The exact profile and the timing of neurological events in relation to the onset of infection are worth exploring. The aim of the current body of work was to determine the frequency, pattern, and temporal profile of neurological manifestations in a cohort of Egyptian patients with confirmed COVID-19 infection. METHODS: This was a prospective study conducted on 582 hospitalized COVID-19 patients within the first two weeks of the diagnosis of COVID-19 to detect any specific or non-specific neurological events. RESULTS: The patients' mean (SD) age was 46.74 (17.26) years, and 340 (58.42%) patients were females. The most commonly encountered COVID-19 symptoms were fever (90.72%), cough (82.99%), and fatigue (76.98%). Neurological events (NE) detected in 283 patients (48.63%) and were significantly associated with a severe COVID-19 at the onset (OR: 3.13; 95% CI: 2.18-4.51; p < 0.0001) and with a higher mortality (OR: 2.56; 95% CI: 1.48-5.46; p = 0.019). The most frequently reported NEs were headaches (n = 167) and myalgias (n = 126). Neurological syndromes included stroke (n = 14), encephalitis (n = 12), encephalopathy (n = 11), transverse myelitis (n = 6) and Guillain-Barré syndrome (n = 4). CONCLUSIONS: Neurological involvement is common (48.63%) in COVID-19 patients within the first two weeks of the illness. This includes neurological symptoms such as anosmia, headaches, as well as a constellation of neurological syndromes such as stroke, encephalitis, transverse myelitis, and Guillain-Barré syndrome. Severity of acute COVID-19 illness and older age are the main risk factors.

Beyond probiotic legend: ESSAP gut microbiota health score to delineate SARS-COV-2 infection severity.

COVID-19 pandemic continues to be a global health crisis. The gut microbiome critically affects the immune system, and some respiratory infections are associated with changes in the gut microbiome; here, we evaluated the role of nutritional and lifestyle habits that modulate gut microbiota on COVID-19 outcomes in a longitudinal cohort study that included 200 patients infected with COVID-19. Of these, 122 cases were mild and seventy-eight were moderate, according to WHO classification. After detailed explanation by a consultant in clinical nutrition, participants responded to a written questionnaire on daily sugar, prebiotic intake in food, sleeping hours, exercise duration and antibiotic prescription, during the past 1 year before infection. Daily consumption of prebiotic-containing foods, less sugar, regular exercise, adequate sleep and fewer antibiotic prescriptions led to a milder disease and rapid virus clearance. Additionally, data on these factors were compiled into a single score, the ESSAP score (Exercise, Sugar consumption, Sleeping hours, Antibiotics taken, and Prebiotics consumption; 0-11 points), median ESSAP score was 5 for both mild and moderate cases; however, the range was 4-8 in mild cases, but 1-6 in moderate (P = 0·001, OR: 4·2, 95 % CI 1·9, 9·1); our results showed a negative correlation between regular consumption of yogurt containing probiotics and disease severity (P = 0·007, OR: 1·6, 95 % CI 1·1, 2·1). Mild COVID-19 disease was associated with 10-20 min of daily exercise (P = 0·016), sleeping at least 8 h daily, prescribed antibiotics less than 5 times per year (P = 0·077) and ate plenty of prebiotic-containing food.

A homozygous CAP2 pathogenic variant in a neonate presenting with rapidly progressive cardiomyopathy and nemaline rods.

Nemaline Myopathy (NM) is a disorder of skeletal muscles caused by mutations in sarcomere proteins and characterized by accumulation of microscopic rod or thread-like structures (nemaline bodies) in skeletal muscles. Patients diagnosed with both NM and infantile cardiomyopathy are very rare. A male infant presented, within the first few hours of life, with severe dilated cardiomyopathy, biventricular dysfunction and left ventricular noncompaction. A muscle biopsy on the 8th day of life from the right sternocleidomastoid muscle identified nemaline rods. Whole exome sequencing identified a c.1288 delT (homozygous pathogenic variant) in the CAP2 gene (NM_006366), yielding a CAP2 protein (NP_006357.1) with a p.C430fs. Both parents were heterozygous for the same variant but have no history of heart or muscle disease. Analysis of patient derived fibroblasts and cardiomyocytes derived from induced pluripotent stem cells confirmed the p.C430fs mutation (pathogenic variant), which appears to cause loss of both CAP2 protein and mRNA. The CAP2 gene encodes cyclase associated protein 2, an actin monomer binding and filament depolymerizing protein and CAP2 knockout mice develop severe dilated cardiomyopathy and muscle weakness. The patient underwent a heart transplant at 1 year of age. Heart tissue explanted at that time also showed nemaline rods and additionally disintegration of the myofibrillar structure. Other extra cardiac concerns include mild hypotonia, atrophic and widened scarring. This is the first description of a patient presenting with nemaline myopathy associated with a pathogenic variant of CAP2.

A Combined Prospective and Retrospective Comparison of Long-Term Functional Outcomes Suggests Delayed Loss of Ambulation and Pulmonary Decline with Long-Term Eteplirsen Treatment.

BACKGROUND: Studies 4658-201/202 (201/202) evaluated treatment effects of eteplirsen over 4 years in patients with Duchenne muscular dystrophy and confirmed exon-51 amenable genetic mutations. Chart review Study 4658-405 (405) further followed these patients while receiving eteplirsen during usual clinical care. OBJECTIVE: To compare long-term clinical outcomes of eteplirsen-treated patients from Studies 201/202/405 with those of external controls. METHODS: Median total follow-up time was approximately 6 years of eteplirsen treatment. Outcomes included loss of ambulation (LOA) and percent-predicted forced vital capacity (FVC%p). Time to LOA was compared between eteplirsen-treated patients and standard of care (SOC) external controls and was measured from eteplirsen initiation in 201/202 or, in the SOC group, from the first study visit. Comparisons were conducted using univariate Kaplan-Meier analyses and log-rank tests, and multivariate Cox proportional hazards models with regression adjustment for baseline characteristics. Annual change in FVC%p was compared between eteplirsen-treated patients and natural history study patients using linear mixed models with repeated measures. RESULTS: Data were included from all 12 patients in Studies 201/202 and the 10 patients with available data from 405. Median age at LOA was 15.16 years. Eteplirsen-treated patients experienced a statistically significant longer median time to LOA by 2.09 years (5.09 vs. 3.00 years, p < 0.01) and significantly attenuated rates of pulmonary decline vs. natural history patients (FVC%p change: -3.3 vs. -6.0 percentage points annually, p < 0.0001). CONCLUSIONS: Study 405 highlights the functional benefits of eteplirsen on ambulatory and pulmonary function outcomes up to 7 years of follow-up in comparison to external controls.

Stigma, Uncertainty, and Coping at the Time of COVID-19 Pandemic Amid Health Care Professionals: How Far Have We Gone?

ABSTRACT: Stigma and uncertainty are noticed in global pandemics. Their impacts on health care providers tend to persist notably during and after the outbreaks. Our objective was to assess stigma, uncertainty, and coping among health care providers through an online survey using the Discrimination and Stigma Scale Version 12 (DISC-12) modified version to assess stigma related to treating COVID-19, the Intolerance of Uncertainty Scale, and the Brief Resilient Coping Scale (BRCS). Of the respondents (n = 65), 63.1% treated patients with COVID-19, and 21.5% worked in isolation hospitals. Physicians who treated patients with COVID-19 had significantly higher scores in all DISC subscales: unfair treatment (8.73 ± 6.39, p = 0.001), stopping self from doing things (2.05 ± 1.41, p = 0.019), overcoming stigma (1.17 ± 0.80, p = 0.035), and positive treatment (1.90 ± 1.65, p = 0.005). Unfair treatment was negatively correlated with BRCS (r = -0.279, p = 0.024). On the other hand, physicians who did not treat patients with COVID-19 had significantly higher BRCS scores. We concluded that frontline physicians experienced greater stigma associated with lower resilient coping strategies.

Occurrence of pulmonary residuals as one of the sequelae of COVID-19 and it's predictors among moderate and severe cases.

BACKGROUND: Moderate and severe COVID-19 patients typically present with pneumonia. In this study we aimed to detect the occurrence of pulmonary residuals as a late sequela of COVID-19 and to identify it's predictors among moderate and severe cases. METHODS: This observational prospective study involved 85 COVID-19 patients confirmed by real time polymerase chain reaction (RT-PCR) nasopharyngeal swab, patients were recruited in the period of 1 st of June to 1 st of July. Demographic and clinical data were obtained for each patient. Chest imaging was performed initially and after 3 weeks to detect post COVID pulmonary residuals. RESULTS: The study population included 74 (87.1%) moderate and 11 (12.9%) severe patients. Patients with older age, male gender, high BMI and initial chest CT of consolidation/mixed consolidation and ground glass opacities (GGOs) had more frequent post COVID-19 pulmonary residuals (P 0.003, 0.026, 0.031, 0.035) respectively. There was a statistically significant difference between patients who showed complete resolution and patients who developed pulmonary residuals regarding the lymphocyte count, serum CRP and ferritin levels (P 0.0001). After logistic regression, male gender, high BMI, initial chest CT of consolidation/mixed consolidation and GGOs, lymphocytopenia, high serum CRP and ferritin levels were the predictors of pulmonary residuals. While the age wasn't statistically significant. CONCLUSION: 38.5% of moderate and severe COVID-19 patients tend to have pulmonary residuals. Independent predictors of pulmonary residuals as a sequela of COVID-19 are male gender, high BMI, initial chest CT of consolidation and mixed consolidation/GGOs, lymphocytopenia, high serum CRP and ferritin levels.

Open-Label Evaluation of Eteplirsen in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: PROMOVI Trial.

BackgroundEteplirsen received accelerated FDA approval for treatment of Duchenne muscular dystrophy (DMD) with mutations amenable to exon 51 skipping, based on demonstrated dystrophin production.ObjectiveTo report results from PROMOVI, a phase 3, multicenter, open-label study evaluating efficacy and safety of eteplirsen in a larger cohort.MethodsAmbulatory patients aged 7-16 years, with confirmed mutations amenable to exon 51 skipping, received eteplirsen 30 mg/kg/week intravenously for 96 weeks. An untreated cohort with DMD not amenable to exon 51 skipping was also enrolled.Results78/79 eteplirsen-treated patients completed 96 weeks of treatment. 15/30 untreated patients completed the study; this cohort was considered an inappropriate control group because of genotype-driven differences in clinical trajectory. At Week 96, eteplirsen-treated patients showed increased exon skipping (18.7-fold) and dystrophin protein (7-fold) versus baseline. Post-hoc comparisons with patients from eteplirsen phase 2 studies (4658-201/202) and mutation-matched external natural history controls confirmed previous results, suggesting clinically notable attenuation of decline on the 6-minute walk test over 96 weeks (PROMOVI: -68.9 m; phase 2 studies: -67.3 m; external controls: -133.8 m) and significant attenuation of percent predicted forced vital capacity annual decline (PROMOVI: -3.3%, phase 2 studies: -2.2%, external controls: -6.0%; p < 0.001). Adverse events were generally mild to moderate and unrelated to eteplirsen. Most frequent treatment-related adverse events were headache and vomiting; none led to treatment discontinuation.ConclusionsThis large, multicenter study contributes to the growing body of evidence for eteplirsen, confirming a positive treatment effect, favorable safety profile, and slowing of disease progression versus natural history.

COVID-19 Disease Outcomes: Does Gastrointestinal Burden Play a Role?

BACKGROUND: The novel coronavirus disease 2019 presents an urgent threat to global health. As the epidemic grows, prognosis prediction is essential for monitoring risky patient. It is thus important to consider gastrointestinal manifestations and the duration of symptoms as predictors of prognosis. Our aim was to determine the correlation of gastrointestinal symptoms and laboratory markers with disease outcomes and whether symptom duration varies substantially between patients. We also undertook this study to determine the optimal time to predict COVID-19 outcome. PATIENTS AND METHODS: A total of 190 patients with polymerase chain reaction-confirmed COVID-19 were followed up until recovery. We proposed a correlation between gastrointestinal symptoms and disease severity (based on clinical data, and diagnostic investigations) to estimate the duration of symptoms as a predictor of COVID-19 prognosis. RESULTS: The prevalence of gastrointestinal symptoms was 49.5%, consisting mainly of diarrhea in 27.9% of patients. In addition, a longer disease duration and higher temperature were observed in patients with diarrhea. Symptom duration was variable, with a median of 12 days and a range of 1-55 days. Statistical analysis indicated that patients with a duration of symptoms ≥12 day had more severe symptoms and a worse prognosis. Patients who complained of diarrhea had 2.7 times the odds of a longer duration of symptoms, and those with a history of chronic lung disease have 7.2 times the odds of a longer duration of symptoms. CONCLUSION: GIT manifestations (mainly diarrhea) and the duration of symptoms of COVID-19 provide prognostic evidence of COVID-19 outcomes, irrespective of earlier categorization by the World Health Organization. Thus, patients with mild symptoms who present with diarrhea and a duration of symptoms longer than 12 days are expected to have a worse prognosis.

Relative Frequency and Risk Factors of COVID-19 Related Headache in a Sample of Egyptian Population: A Hospital-Based Study.

OBJECTIVES: Headache is considered one of the most frequent neurological manifestations of coronavirus disease 2019 (COVID-19). This work aimed to identify the relative frequency of COVID-19-related headache and to clarify the impact of clinical, laboratory findings of COVID-19 infection on headache occurrence and its response to analgesics. DESIGN: Cross-sectional study. SETTING: Recovered COVID-19 patients. SUBJECTS: In total, 782 patients with a confirmed diagnosis of COVID-19 infection. METHODS: Clinical, laboratory, and imaging data were obtained from the hospital medical records. Regarding patients who developed COVID-19 related headache, a trained neurologist performed an analysis of headache and its response to analgesics. RESULTS: The relative frequency of COVID-19 related headache among our sample was 55.1% with 95% confidence interval (CI) (.516-.586) for the estimated population prevalence. Female gender, malignancy, primary headache, fever, dehydration, lower levels of hemoglobin and platelets and higher levels of neutrophil/lymphocyte ratio (NLR) and CRP were significantly associated with COVID-19 related headache. Multivariate analysis revealed that female gender, fever, dehydration, primary headache, high NLR, and decreased platelet count were independent predictors of headache occurrence. By evaluating headache response to analgesics, old age, diabetes, hypertension, primary headache, severe COVID-19, steroid intake, higher CRP and ferritin and lower hemoglobin levels were associated with poor response to analgesics. Multivariate analysis revealed that primary headache, steroids intake, moderate and severe COVID-19 were independent predictors of non-response to analgesics. DISCUSSION: Headache occurs in 55.1% of patients with COVID-19. Female gender, fever, dehydration, primary headache, high NLR, and decreased platelet count are considered independent predictors of COVID-19 related headache.