Endothelial biomarkers (Von willebrand factor, BDCA3, urokinase) as predictors of mortality in COVID-19 patients: cohort study.

BACKGROUND: SARS-CoV-2 is a systemic disease that affects endothelial function and leads to coagulation disorders, increasing the risk of mortality. Blood levels of endothelial biomarkers such as Von Willebrand Factor (VWF), Thrombomodulin or Blood Dendritic Cell Antigen-3 (BDCA3), and uUokinase (uPA) increase in patients with severe disease and can be prognostic indicators for mortality. Therefore, the aim of this study was to determine the effect of VWF, BDCA3, and uPA levels on mortality. METHODS: From May 2020 to January 2021, we studied a prospective cohort of hospitalized adult patients with polymerase chain reaction (PCR)-confirmed COVID-19 with a SaO2 ≤ 93% and a PaO2/FiO2 ratio < 300. In-hospital survival was evaluated from admission to death or to a maximum of 60 days of follow-up with Kaplan-Meier survival curves and Cox proportional hazard models as independent predictor measures of endothelial dysfunction. RESULTS: We recruited a total of 165 subjects (73% men) with a median age of 57.3 ± 12.9 years. The most common comorbidities were obesity (39.7%), hypertension (35.4%) and diabetes (30.3%). Endothelial biomarkers were increased in non-survivors compared to survivors. According to the multivariate Cox proportional hazard model, those with an elevated VWF concentration ≥ 4870 pg/ml had a hazard ratio (HR) of 4.06 (95% CI: 1.32-12.5) compared to those with a lower VWF concentration adjusted for age, cerebrovascular events, enoxaparin dose, lactate dehydrogenase (LDH) level, and bilirubin level. uPA and BDCA3 also increased mortality in patients with levels ≥ 460 pg/ml and ≥ 3600 pg/ml, respectively. CONCLUSION: The risk of mortality in those with elevated levels of endothelial biomarkers was observable in this study.

Impact of Body Composition and Sarcopenia on Mortality in Chronic Obstructive Pulmonary Disease Patients.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have alterations in body composition, such as low cell integrity, body cell mass, and disturbances in water distribution evidenced by higher impedance ratio (IR), low phase angle (PhA), as well as low strength, low muscle mass, and sarcopenia. Body composition alterations are associated with adverse outcomes. However, according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), the impact of these alterations on mortality in COPD patients is not well-established. Our aims were to evaluate whether low strength, low muscle mass, and sarcopenia impacted mortality in COPD patients. METHODS: A prospective cohort study performance was conducted with COPD patients. Patients with cancer, and asthma were excluded. Body composition was assessed by bioelectrical impedance analysis. Low strength and muscle mass, and sarcopenia were defined according to EWGSOP2. RESULTS: 240 patients were evaluated, of whom 32% had sarcopenia. The mean age was 72.32 ± 8.24 years. The factors associated with lower risk of mortality were handgrip strength (HR:0.91, CI 95%; 0.85 to 0.96, p = 0.002), PhA (HR:0.59, CI 95%; 0.37 to 0.94, p = 0.026) and exercise tolerance (HR:0.99, CI 95%; 0.992 to 0.999, p = 0.021), while PhA below the 50th percentile (HR:3.47, CI 95%; 1.45 to 8.29, p = 0.005), low muscle strength (HR:3.49, CI 95%; 1.41 to 8.64, p = 0.007) and sarcopenia (HR:2.10, CI 95%; 1.02 to 4.33, p = 0.022) were associated with a higher risk of mortality. CONCLUSION: Low PhA, low muscle strength, and sarcopenia are independently associated with poor prognosis in COPD patients.

Short-Term Effect of Epley Maneuver as Treatment for Subjective Benign Paroxysmal Positional Vertigo.

Subjective Benign Paroxysmal Positional Vertigo (S-BPPV) is an atypical form of BPPV, its treatment is not well characterized and is not well known among otolaryngologists. The main aim of this study was to estimate the short-term efficacy of Epley maneuver as treatment for S-BPPV. This was a prospective study in a secondary care center. We included patients with unilateral S-BPPV demonstrated by negative nystagmus on Dix-Hallpike Maneuver (DHM) but with unilateral vestibular symptoms (dizziness or vertigo). Epley maneuver to the affected side was performed. Patients underwent Dizziness Handicap Inventory (DHI) and at 1-week follow-up, DHI and DHM were repeated. Outcome measures were resolution of symptoms during DHM and improvement of DHI scores. Patients were divided into resolved and unresolved groups according to the absence or presence of symptoms during the 1 week DHM. Wilcoxon-Mann-Whitney and Kruskal-Wallis tests were used, quantitative values were reported as mean and standard deviation. The results included thirteen participants, 12 females and 1 male, mean age 53.31 years (SD ± 15.71). Right ear was involved in 46.15% and left in 53.84%. A total of 46.15% patients (n = 6) had resolution of symptoms. DHI initial score for the resolved group was 34.66 ± 22 and for the unresolved group was 39.71 ± 19.61 (p = 0.568). At 1-week evaluation scores were 19.66 ± 25.05 for the resolved group and 30.28 ± 21.42 for the unresolved group (p = 0.252). DHI improvement was 15.00 ± 23.21 and 9.42 ± 10.17 for each group, respectively (p = 0.943). We concluded the Epley maneuver is an effective short-term treatment for S-BPPV. Half of the patients would need further diagnostic tests.

Multiple Audiometric Analysis in the Screening of Vestibular Schwannoma.

Introduction Asymmetric sensorineural hearing loss is the main early symptom of retrocochlear lesions, hence its importance in screening for vestibular schwannomas. Currently, there is no consensus regarding its definition. The objective was to identify the audiometric pattern that would serve as a predictor for vestibular schwannoma in patients with asymmetric hearing loss. Materials and methods A cross-sectional study was conducted that included patients with asymmetric hearing loss attending a secondary care center and a tertiary care center. Clinical, audiometric and imaging (MRI with gadolinium) variables were collected. Asymmetric hearing loss was defined as a difference of 15 dB in one or more frequencies between both ears. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of different audiometric patterns were analyzed. Results A total of 107 patients were studied and divided into two groups: group 1 without vestibular schwannoma (n=98); and group 2 with vestibular schwannoma (n=9). No significant difference in demographic characteristics or audiometric patterns was found in patients with and without vestibular schwannoma. The audiometric pattern with the best sensitivity as a screening test was a difference >20 dB in the 4,000 Hz frequency, with a sensitivity of 77.78%, specificity of 30.61%, PPV of 8.33%, NPV of 93.75% and accuracy of 34.50%. Conclusion The audiometric pattern with the best results was a difference >20 dB in the 4,000 Hz frequency range; however, patients with asymmetric hearing loss could not be differentiated from patients with retrocochlear lesions based only on audiometry. Asymmetrical hearing loss must be studied with MRI.

On-Demand and Low Dose Intratympanic Gentamicin for Meniere's Disease: A Customized Approach.

OBJECTIVE: To evaluate the efficacy of on demand and low dose intratympanic gentamicin (ITG) in patients with intractable Meniere's disease (MD). STUDY DESIGN: Clinical chart review. SETTING: Secondary care center. PATIENTS: Subjects with MD who failed conventional treatment and underwent on demand ITG infiltration from June 2013 to December 2018. INTERVENTION: 0.4 to 0.5 ml of buffered gentamicin were administered through an intratympanic route. A total of 5 mg in case of low dose and 20 mg as a standard dose. MAIN OUTCOME MEASURES: Vertigo control, Meniere's Disease Functional Level Scale (MDFLS), Dizziness Handicap Inventory (DHI), and pure tone audiometry pre and posttreatment. RESULTS: Thirty-one patients, 16 women and 15 men with a mean age of 52.81 (22-79) years were included. The number of ITG injections ranged from 1 to 7, with a mean of 2.52 applications per patient. Mean interval between doses was 212.15 (21-1442) days. Average follow-up was 24.03 months. An improvement on MDFLS was seen on 77.4% (n = 24) patients. DHI score improved after gentamicin treatment (mean 55.23 versus 24.06, p ≤ 0.001). Thirty patients (96.8%) reached complete or substantial vertigo control. Only one patient did not achieve control. Hearing was preserved in 43.5% (n = 10) of analyzed audiograms, whereas 17.4% (n = 4) developed hearing loss greater than 20 dB, which was not statistically significant (p = 0.099). CONCLUSIONS: In our study, on demand and low dose ITG was effective for vertigo control in patients with intractable MD. Individualized therapy is recommended in all patients to minimize vestibular and cochlear toxicity.

Stakeholder cooperation to overcome challenges in orphan medicine development: the example of Duchenne muscular dystrophy.

Duchenne muscular dystrophy is a rare, progressive, muscle-wasting disease leading to severe disability and premature death. Treatment is currently symptomatic, but several experimental therapies are in development. Implemented care standards, validated outcome measures correlating with clinical benefit, and comprehensive information about the natural history of the disease are essential for regulatory approval of any treatment. However, for Duchenne muscular dystrophy and other rare diseases, these requirements are not always in place when potential therapies enter the clinical trial phase. A cooperative effort of stakeholders in Duchenne muscular dystrophy-including representatives from patients' groups, academia, industry, and regulatory agencies-is aimed at addressing this shortfall by identifying strategies to overcome challenges, developing the tools needed, and collecting relevant data. An open and constructive dialogue among European stakeholders has positively affected development of treatments for Duchenne muscular dystrophy; this approach could serve as a paradigm for development of treatments for rare diseases in general.