A systematic review of trials currently investigating therapeutic modalities for post-acute COVID-19 syndrome and registered on WHO International Clinical Trials Platform.

BACKGROUND: Post-acute COVID-19 syndrome (PACS) is a well-recognized, complex, systemic disease which is associated with substantial morbidity. There is a paucity of established interventions for the treatment of patients with this syndrome. OBJECTIVES: To systematically review registered trials currently investigating therapeutic modalities for PACS. DATA SOURCES: A search was conducted up to the 16 September, 2022, using the COVID-19 section of the WHO Internal Clinical Trials Registry Platform. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: Interventional clinical trials of any sample size examining any therapeutic modality targeting persistent symptoms among individuals after diagnosis with COVID-19. METHODS: Data on trial characteristics and intervention characteristics were collected and summarized. RESULTS: After screening 17 125 trials, 388 trials, from 42 countries, were eligible. In total, we had 406 interventions, of which 368 were mono-therapeutic strategies, whereas 38 were intervention combinations. Among 824 primary outcomes identified, there were >300 different outcomes. Rehabilitation was the most employed class of intervention in 169 trials. We encountered 76 trials examining the pharmacological agents of various classes, with the most common agent being colchicine. Complementary and alternative medicine encompassed 64 trials exploring traditional Chinese medicine, Ayurveda, homeopathic medications, naturopathic medications, vitamins, dietary supplements, and botanicals. Psychotherapeutic and educational interventions were also employed in 12 and 4 trials, respectively. Other interventions, including transcranial direct current stimulation, transcutaneous auricular vagus nerve stimulation, general electrical stimulation, cranial electrotherapy stimulation, various stem cell interventions, and oxygen therapy interventions, were also employed. CONCLUSION: We identified 388 registered trials, with a high degree of heterogeneity, exploring 144 unique mono-therapeutic interventions for PACS. Most studies target general alleviation of symptoms. There is a need for further high-quality and methodologically robust PACS treatment trials to be conducted with standardization of outcomes while following WHO's recommendation for uniform evaluation and treatment.

The initial experience with the Embotrap III stent-retriever in a real world setting.

MATERIALS AND METHODS: We performed a retrospective review of our prospectively maintained database to identify all patients treated with the Embotrap 3 stent-retriever between January 2021 and January 2022. We recorded the baseline demographics, NIHSS, ASPECT score and clot characteristics, first pass and final eTICI scores, complications and 90 day mRS. RESULTS: One hundred and ten patients met the inclusion criteria, average age 69 ± 14 years, 50% were male (n = 55). The median NIHSS at presentation was 18 (range 3-30) and 58.2% received IV tPA prior to MT. The median ASPECT score on plain CT was 8 with average clot length 20.2 ± 14.8 mm (n = 93). The first pass effect (FPE) was seen in 41.8% of cases with modified FPE seen in 59.1%. A 24-hour CT scan (n = 97) showed median ASPECTs of 7. 43.8% of patients achieve mRS ≤ 2 at 90-day mRS (n = 64). CONCLUSION: The Embotrap 3 stent-retriever has a high rate of FPE and final recanalization in this real world cohort of patients.

COVID-19-Associated cardiac pathology at the postmortem evaluation: a collaborative systematic review.

BACKGROUND: Many postmortem studies address the cardiovascular effects of COVID-19 and provide valuable information, but are limited by their small sample size. OBJECTIVES: The aim of this systematic review is to better understand the various aspects of the cardiovascular complications of COVID-19 by pooling data from a large number of autopsy studies. DATA SOURCES: We searched the online databases Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science for concepts of autopsy or histopathology combined with COVID-19, published between database inception and February 2021. We also searched for unpublished manuscripts using the medRxiv services operated by Cold Spring Harbor Laboratory. STUDY ELIGIBILITY CRITERIA: Articles were considered eligible for inclusion if they reported human postmortem cardiovascular findings among individuals with a confirmed SARS coronavirus type 2 (CoV-2) infection. PARTICIPANTS: Confirmed COVID-19 patients with post-mortem cardiovascular findings. INTERVENTIONS: None. METHODS: Studies were individually assessed for risk of selection, detection, and reporting biases. The median prevalence of different autopsy findings with associated interquartile ranges (IQRs). RESULTS: This review cohort contained 50 studies including 548 hearts. The median age of the deceased was 69 years. The most prevalent acute cardiovascular findings were myocardial necrosis (median: 100.0%; IQR, 20%-100%; number of studies = 9; number of patients = 64) and myocardial oedema (median: 55.5%; IQR, 19.5%-92.5%; number of studies = 4; number of patients = 46). The median reported prevalence of extensive, focal active, and multifocal myocarditis were all 0.0%. The most prevalent chronic changes were myocyte hypertrophy (median: 69.0%; IQR, 46.8%-92.1%) and fibrosis (median: 35.0%; IQR, 35.0%-90.5%). SARS-CoV-2 was detected in the myocardium with median prevalence of 60.8% (IQR 40.4-95.6%). CONCLUSIONS: Our systematic review confirmed the high prevalence of acute and chronic cardiac pathologies in COVID-19 and SARS-CoV-2 cardiac tropism, as well as the low prevalence of myocarditis in COVID-19.

Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: a systematic review and meta-analysis.

BACKGROUND: Post-acute coronavirus 2019 (COVID-19) syndrome is now recognized as a complex systemic disease that is associated with substantial morbidity. OBJECTIVES: To estimate the prevalence of persistent symptoms and signs at least 12 weeks after acute COVID-19 at different follow-up periods. DATA SOURCES: Searches were conducted up to October 2021 in Ovid Embase, Ovid Medline, and PubMed. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Articles in English that reported the prevalence of persistent symptoms among individuals with confirmed severe acute respiratory syndrome coronavirus 2 infection and included at least 50 patients with a follow-up of at least 12 weeks after acute illness. METHODS: Random-effect meta-analysis was performed to produce a pooled prevalence for each symptom at four different follow-up time intervals. Between-study heterogeneity was evaluated using the I2 statistic and was explored via meta-regression, considering several a priori study-level variables. Risk of bias was assessed using the Joanna Briggs Institute tool and the Newcastle-Ottawa Scale for prevalence studies and comparative studies, respectively. RESULTS: After screening 3209 studies, a total of 63 studies were eligible, with a total COVID-19 population of 257 348. The most commonly reported symptoms were fatigue, dyspnea, sleep disorder, and difficulty concentrating (32%, 25%, 24%, and 22%, respectively, at 3- to <6-month follow-up); effort intolerance, fatigue, sleep disorder, and dyspnea (45%, 36%, 29%, and 25%, respectively, at 6- to <9-month follow-up); fatigue (37%) and dyspnea (21%) at 9 to <12 months; and fatigue, dyspnea, sleep disorder, and myalgia (41%, 31%, 30%, and 22%, respectively, at >12-month follow-up). There was substantial between-study heterogeneity for all reported symptom prevalences. Meta-regressions identified statistically significant effect modifiers: world region, male sex, diabetes mellitus, disease severity, and overall study quality score. Five of six studies including a comparator group consisting of COVID-19-negative cases observed significant adjusted associations between COVID-19 and several long-term symptoms. CONCLUSIONS: This systematic review found that a large proportion of patients experience post-acute COVID-19 syndrome 3 to 12 months after recovery from the acute phase of COVID-19. However, available studies of post-acute COVID-19 syndrome are highly heterogeneous. Future studies need to have appropriate comparator groups, standardized symptom definitions and measurements, and longer follow-up.

Effect of introduction of a standardised peri-operative protocol on CSF shunt infection rate: a single-centre cohort study of 809 procedures.

PURPOSE: Shunt infection is a major problem in paediatric neurosurgery. Our institution introduced a mandatory shunt protocol with the aim of reducing infection rate. METHODS: A retrospective cohort study including consecutive patients undergoing permanent shunt operations (primary insertion and revision) across two study periods: 3 years immediately prior (2009-2012) and 3 years immediately after (2012-2015) protocol introduction. Absolute and relative risk reductions (ARR/RRR) and Chi-square statistical analysis was used alongside logistic regression, where any single factor with p ≤ 0.20 included in the multivariate model, producing an odds ratio (OR). RESULTS: Eight hundred nine operations in 504 children were identified (442 pre-protocol, 367 post). Overall infection rate decreased from 5.43% (24/442) pre-protocol to 3.27% (12/367) post-protocol (ARR = 2.16%, RRR = 39.8%, NNT = 46.3, p = 0.138), which did not reach statistical significance. For primary shunt insertions, infection rate reduced from 3.63 to 2.55% (ARR = 1.08%, RRR = 29.8%, NNT = 92.6, p = 0.565), whilst for revisions, it reduced from 6.83 to 3.81% (ARR = 3.02%, RRR 44.2%, NNT = 33.1, p = 0.156). Multivariate logistic regression showed that surgeon experience was a statistically significant predictor of infection, whilst responsible pathogens and latency were similar across the pre- and post-protocol groups. CONCLUSION: The protocol reduced overall infection rate in primary and revision shunt operations and we recommend paediatric units consider introducing a similar protocol for these procedures.

Donor-specific HLA-DQ antibodies may contribute to poor graft outcome after heart transplantation.

BACKGROUND: HLA-DQ donor-specific antibodies (DSA) are implicated in allograft dysfunction after renal and lung transplantation. Limited data exists on the impact of HLA-DQ antibodies on heart transplant patients. OBJECTIVE: To investigate the impact of DSA formation on allograft function and outcomes in heart transplant patients. DESIGN: Retrospective cohort study. SETTING: Collating post-transplantation patient data from computerized database in a tertiary hospital in Riyadh, Saudi Arabia from January 2006 to October 2014. PATIENTS AND METHODS: We excluded recipients with positive preoperative complement-dependent-cytotoxicity crossmatch grafts and those with preformed DSA. Anti-HLA antibodies were identified using Luminex-based assay in sera collected before transplantation with a routine endomyocardial biopsy the first year and then annually. MAIN OUTCOME MEASURES: Primary outcome measures were all-cause mortality, development of antibody mediated rejection, treated acute cellular rejection (ACR) and cardiac allograft vasculopathy (CAV). SAMPLE SIZE: 127 patients. RESULTS: DSA formation occurred in 43/127 (34%), with 33/43 (77%) targeting HLA-DQ antigens alone (n=7) or in combination with -DR, -A or B antibodies (n=26). Most (76%) were male and the mean (SD) age was 36 (14) years. Ten patients developed -A, -B or -DR antibodies without -DQ antibodies also present. Treated ACR (P=.011), reduced left ventricular ejection fraction (P less than .001), CAV development (P=.003), and all-cause mortality (P=.01) were all significantly more prevalent in the DSA-positive cohort. CONCLUSION: HLA-DQ donor-specific antibodies were the most common type detected and may play a significant role in poor outcomes post-cardiac transplantation. This emphasizes the importance of HLA-DQ matching and monitoring for DSA formation in order to minimize post-transplantation immunological risk. LIMITATIONS: Retrospective design comes with inherent biases, results from single institute, with a particularly young cohort. CONFLICT OF INTEREST: None.