COVID-19 Stroke Apical Lung Examination Study 2: a national prospective CTA biomarker study of the lung apices, in patients presenting with suspected acute stroke (COVID SALES 2).

BACKGROUND: Apical ground-glass opacification (GGO) identified on CT angiography (CTA) performed for suspected acute stroke was developed in 2020 as a coronavirus-disease-2019 (COVID-19) diagnostic and prognostic biomarker in a retrospective study during the first wave of COVID-19. OBJECTIVE: To prospectively validate whether GGO on CTA performed for suspected acute stroke is a reliable COVID-19 diagnostic and prognostic biomarker and whether it is reliable for COVID-19 vaccinated patients. METHODS: In this prospective, pragmatic, national, multi-center validation study performed at 13 sites, we captured study data consecutively in patients undergoing CTA for suspected acute stroke from January-March 2021. Demographic and clinical features associated with stroke and COVID-19 were incorporated. The primary outcome was the likelihood of reverse-transcriptase-polymerase-chain-reaction swab-test-confirmed COVID-19 using the GGO biomarker. Secondary outcomes investigated were functional status at discharge and survival analyses at 30 and 90 days. Univariate and multivariable statistical analyses were employed. RESULTS: CTAs from 1,111 patients were analyzed, with apical GGO identified in 8.5 % during a period of high COVID-19 prevalence. GGO showed good inter-rater reliability (Fleiss κ = 0.77); and high COVID-19 specificity (93.7 %, 91.8-95.2) and negative predictive value (NPV; 97.8 %, 96.5-98.6). In subgroup analysis of vaccinated patients, GGO remained a good diagnostic biomarker (specificity 93.1 %, 89.8-95.5; NPV 99.7 %, 98.3-100.0). Patients with COVID-19 were more likely to have higher stroke score (NIHSS (mean +/- SD) 6.9 +/- 6.9, COVID-19 negative, 9.7 +/- 9.0, COVID-19 positive; p = 0.01), carotid occlusions (6.2 % negative, 14.9 % positive; p = 0.02), and larger infarcts on presentation CT (ASPECTS 9.4 +/- 1.5, COVID-19 negative, 8.6 +/- 2.4, COVID-19 positive; p = 0.00). After multivariable logistic regression, GGO (odds ratio 15.7, 6.2-40.1), myalgia (8.9, 2.1-38.2) and higher core body temperature (1.9, 1.1-3.2) were independent COVID-19 predictors. GGO was associated with worse functional outcome on discharge and worse survival after univariate analysis. However, after adjustment for factors including stroke severity, GGO was not independently predictive of functional outcome or mortality. CONCLUSION: Apical GGO on CTA performed for patients with suspected acute stroke is a reliable diagnostic biomarker for COVID-19, which in combination with clinical features may be useful in COVID-19 triage.

The Effect of Surgical Weight Loss on Cognition in Individuals with Class II/III Obesity.

BACKGROUND: Obesity is a global epidemic and is associated with cognitive impairment and dementia. It remains unknown whether weight loss interventions, such as bariatric surgery, can mitigate cognitive impairment. OBJECTIVES: We aimed to determine the effect of surgical weight loss on cognition in individuals with class II/III obesity. DESIGN: We performed a prospective cohort study of participants who underwent bariatric surgery. At baseline and two years following surgery, participants completed metabolic risk factor and neuropsychological assessments. SETTING: Participants were enrolled from an academic suburban bariatric surgery clinic. PARTICIPANTS: There were 113 participants who completed baseline assessments and 87 completed two-year follow-up assessments (66 in-person and 21 virtual) after bariatric surgery. The mean (SD) age was 46.8 (12.5) years and 64 (73.6%) were female. INTERVENTION: Bariatric surgery. There were 77 (88.5%) participants that underwent sleeve gastrectomy and 10 (11.5%) that underwent gastric bypass surgery. MEASUREMENTS: Cognition was assessed using the NIH toolbox cognitive battery (NIHTB-CB) and the Rey Auditory Verbal Learning Test (AVLT). The primary outcome was the change in NIHTB-CB fluid composite score before and after surgery. RESULTS: The primary outcome, NIHTB-CB composite score, was stable following bariatric surgery (-0.4 (13.9), p=0.81,n=66). Among secondary outcomes, the NIHTB-CB dimensional card sorting test (executive function assessment), improved (+6.5 (19.9),p=0.01,n=66) while the Rey AVLT delayed recall test (memory assessment) declined (-0.24 (0.83),p=0.01,n=87) following surgery. Improvements to metabolic risk factors and diabetes complications were not associated with improvements to NIHTB-CB composite score. The other 4 NIHTB-CB subtests and Rey AVLT assessments of auditory learning and recognition were stable at follow-up. CONCLUSIONS: Following bariatric surgery, the age-adjusted composite cognitive outcome did not change, but an executive subtest score improved. These results suggest that bariatric surgery may mitigate the natural history of cognitive decline in individuals with obesity, which is expected to be faster than normal aging, but confirmatory randomized controlled trials are needed. The decline in delayed recall also warrants further studies to determine potential differential effects on cognitive subtests.

Potential drug-drug interactions among hospitalised TB patients.

BACKGROUND: Hospitalised TB patients are at heightened risk for developing drug-drug interactions (DDIs) due to overlapping CYP450 enzyme and/or drug transporter biotransformation of anti-TB drugs and co-medications given for treating TB-associated comorbidities. We aimed to compare the occurrence, characterisation and determinants of database identified potential DDIs (pDDIs) associated with first-line anti-TB drugs and other co-medications using a subscription and free access drug information database.METHOD: This was a single-centre retrospective study to assess pDDIs between first-line anti-TB drugs and other medications for comorbidities among hospitalised TB patients using IBM Micromedex® and Drugs.com.RESULTS: On multivariate regression analysis, hospitalised TB patients with comorbidities such as diabetes mellitus, HIV infection and hypertension, longer hospitalisation, and patients administered with more than seven drugs during their hospital stay were associated with increased risk for the occurrence of pDDIs. Significant discrepancies were observed in the detection and severity of pDDIs between IBM Micromedex and Drugs.com.CONCLUSION: We recommend using free access drug information database to a subscription drug information database in drug interaction screening protocols in clinics for enhanced identification of pDDIs and reducing monetary burden in resource-limited settings.

Nonlocal Reaction-Diffusion Equations in Biomedical Applications.

Nonlocal reaction-diffusion equations describe various biological and biomedical applications. Their mathematical properties are essentially different in comparison with the local equations, and this difference can lead to important biological implications. This review will present the state of the art in the investigation of nonlocal reaction-diffusion models in biomedical applications. We will consider various models arising in mathematical immunology, neuroscience, cancer modelling, and we will discuss their mathematical properties, nonlinear dynamics, resulting spatiotemporal patterns and biological significance.

The influence of persistent bleeding after supracervical hysterectomy on depressive and anxious symptoms: a prospective bicenter study.

PURPOSE: Postoperative spotting is a frequent adverse symptom after laparoscopic supracervical hysterectomy (LSH). The conical excision (eLSH) reduces the postoperative spotting rate, but data in a larger collective are still rare and inconsistent. The influence of persistent bleeding on the anxious and depressive symptoms has not been analyzed yet. METHODS: 311 patients, who underwent a laparoscopic supracervical hysterectomy with conical excision (n = 163), or with straight cervical resection (n = 148) were included. Anxious and depressive symptoms and postoperative spotting were recorded before operation, at 3 month follow-up and at 1 year follow-up in both operative groups using a validated questionnaire (German version of Hospital Anxiety and Depression Scale, HADS-D) and additional questions concerning the frequency and impact of bleeding. Statistical analysis included the impairment of bleeding as well as its impact on depressive and anxious symptoms for both groups. RESULTS: 11.5% after eLSH and 15.5% after LSH reported spotting after 1 year. Supracervical hysterectomy significantly improves depressive and anxious symptoms at 3 and at 12 month follow-up for both groups (p < 0.001) independent on residual spotting. Patients with a preoperative continuous bleeding showed a maximum benefit independent on operative method. CONCLUSION: Laparoscopic supracervical hysterectomy has a positive effect on anxious and depressive symptoms in the short-term and intermediate-term follow-up. The conical excision of the cervical stump reduces postoperative spotting rate, but has no explicit advantage on symptoms of depression or anxiety, irrespective of residual postoperative spotting.

The influence of conventional and extended supracervical hysterectomy on sexuality and quality of life parameters: a prospective bi-center study with a special focus on postoperative spotting.

PURPOSE: Supracervical as well as total hysterectomy are considered to improve postoperative sexuality as well as quality of life, but the benefit of supracervical hysterectomy (LSH) is impaired in up to 20 percent by postoperative spotting. The aim of this study was to analyze the influence of a conical excision of the cervical stump during supracervical hysterectomy on the postoperative spotting rate and its influence on sexuality and in turn quality of life. METHODS: 321 Patients who underwent a laparoscopic supracervical hysterectomy with conical excision (extended laparoscopic supracervical hysterectomy, eLSH, n = 166, Dormagen hospital) or with straight cervical resection (laparoscopic supracervical hysterectomy, LSH, n = 133, MIC Clinics Berlin) were included. Sexual matters, quality of life parameters and additional questions were recorded before operation, at three months of follow up, and at one year of follow up in both groups using a validated questionnaire (German version of International Consultation on Incontinence Questionnaire Vaginal Symptoms Module, ICIQ_VS). Statistical analysis included the impact and impairment of bleeding on sexuality, quality of life in both groups and co-factors such as vaginal symptoms. RESULTS: 11.3% after eLSH and 15.5% after LSH reported spotting after 1 year. Supracervical hysterectomy significantly improves quality of life and sexuality and a conical excision of the remaining stump is associated with a lower but insignificantly reduced spotting rates. Postoperative spotting has no negative influence on sexual matter score of ICIQ_VS, but reduces the postoperative quality of life focusing on vaginal symptoms in a significant way. CONCLUSION: The improvement of ICIQ_VS scores after supracervical hysterectomy is independent of postoperative spotting, but the quality-of-life score is positively influenced by a reduction in the postoperative spotting rate.

Vitamin D supplementation and clinical outcomes in COVID-19: a systematic review and meta-analysis.

PURPOSE: To provide a precise summary and collate the hitherto available clinical evidence on the effect of vitamin D supplementation on clinical outcomes in COVID-19 patients. METHODS: PubMed/MEDLINE, Scopus, and Web of Science databases were systematically searched using appropriate keywords till June 8, 2021, to identify observational studies and randomized controlled trials (RCTs) reporting adverse clinical outcomes (ICU admission and/or mortality) in COVID-19 patients receiving vitamin D supplementation vs. those not receiving the same. Both prior use and use of vitamin D after COVID-19 diagnosis were considered. Unadjusted/adjusted pooled odds ratio (OR) with 95% confidence intervals (CI) were calculated (PROSPERO registration number CRD42021248488). RESULTS: We identified 13 studies (10 observational, 3 RCTs) pooling data retrieved from 2933 COVID-19 patients. Pooled analysis of unadjusted data showed that vitamin D use in COVID-19 was significantly associated with reduced ICU admission/mortality (OR 0.41, 95% CI: 0.20, 0.81, p = 0.01, I2 = 66%, random-effects model). Similarly, on pooling adjusted risk estimates, vitamin D was also found to reduce the risk of adverse outcomes (pooled OR 0.27, 95% CI: 0.08, 0.91, p = 0.03, I2 = 80%, random-effects model). Subgroup analysis showed that vitamin D supplementation was associated with improved clinical outcomes only in patients receiving the drug post-COVID-19 diagnosis and not in those who had received vitamin D before diagnosis. CONCLUSIONS: Vitamin D supplementation might be associated with improved clinical outcomes, especially when administered after the diagnosis of COVID-19. However, issues regarding the appropriate dose, duration, and mode of administration of vitamin D remain unanswered and need further research.

Fracture risk in hypoparathyroidism: a systematic review and meta-analysis.

In this meta-analysis, we analyzed 7 observational studies for assessing the fracture risk in patients with hypoparathyroidism (hypoPT). We found that the risk of vertebral fractures is increased by almost 2-fold, especially those with nonsurgical hypoPT. PURPOSE: Patients with hypoPT have higher bone mineral density than age- and sex-matched controls. This would theoretically translate into a lower risk of fractures, although available clinical evidence is contradictory. Hence, the present systematic review and meta-analysis was undertaken to collate and provide a precise summary of fracture risk in hypoPT. METHODS: PubMed, Scopus, and Web of Science databases were systematically searched using appropriate keywords till March 8, 2021, to identify observational studies reporting the rate of occurrence of fractures among hypoPT patients (nonsurgical and/or postsurgical) compared to non-hypoPT subjects (controls). Study quality was assessed using Newcastle-Ottawa Scale. Pooled odds ratio (OR) with 95% confidence intervals (CI) was calculated. Subgroup analyses of nonsurgical and postsurgical hypoPT patients were also conducted. RESULTS: We identified 7 observational studies of high-quality pooling data retrieved from 1470 patients with hypoPT. When stratified based on the skeletal site, pooled analyses showed that hypoPT patients were at an increased risk of vertebral fractures compared to non-hypoPT controls (OR 2.22, 95% CI: 1.23, 4.03, p = 0.009, I2 = 49%, random-effects model). The increased risk of vertebral fractures was seen only in patients with nonsurgical hypoPT (OR 2.31, 95% CI: 1.32, 4.03, p = 0.003, I2 = 3%, random-effects model) but not in those with postsurgical hypoPT. hypoPT patients were not at an increased or decreased risk of any, humerus, or proximal femur/hip fractures than controls. CONCLUSIONS: Nonsurgical hypoPT patients are at an almost 2-fold increased risk of vertebral fractures and thus need to be actively screened irrespective of the underlying BMD.

Signatures for chronic obstructive pulmonary disease (COPD) and asthma: a comparative genetic analysis.

Background: Chronic obstructive pulmonary disease (COPD) and asthma are obstructive lung diseases which progress in severity with time. Environmental causes and genetic makeup of individuals play important roles in disease manifestation. The aim of present study was to search for diagnostic/prognostic biomarkers to differentiate COPD and asthma.Materials and methods: Seven ADAM33 and two AQP5 single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism method. The association of genotypes, haplotypes and allelic combination of variants in different genes was analyzed in 194 COPD, 150 asthma patients and 220 controls.Results: The genotype frequencies of SNPs V4(C/G), T1(T/C), S2(G/C) of ADAM33 and AQP5 A/G (rs3736309) were associated with COPD and asthma (P=0.038 to P<0.001), while S1(A/G) and F+1(C/T) were associated with asthma (both P<0.001) and V1(G/T) with 20 COPD (P<0.001). The allele frequencies of V4(C/G) (both P<0.001), V1(G/T) (both P<0.05), S2(G/C) (both P<0.01) and S1(A/G) (both P<0.05) were associated with COPD and asthma, while F+1(C/T) was associated only with asthma (P=0.005). Haplotypes of ADAM33 'GGTGGGT' (P=0.027), 'CGTCGGC' (P<0.001) and AQP5 'GA' and 'AG' (both P<0.001) were significant only in COPD.Conclusion: ADAM33 F+1(C/T) variant and allele combination 'GGTGGGTGA' may be specific markers for asthma, while AQP5 'AG' appeared as a haplotype associated only with COPD. These specific genetic biomarkers may be exploited to predict individual predisposition to COPD and asthma.