Cervical Spine Surgery Following COVID-19 Infection: When is it Safe to Proceed?

STUDY DESIGN: Retrospective. OBJECTIVE: We utilized the NIH National COVID Cohort Collaborative (N3C) database to characterize the risk profile of patients undergoing spine surgery during multiple time windows following the COVID-19 infection. SUMMARY OF BACKGROUND DATA: While the impact of COVID-19 on various organ systems is well documented, there is limited knowledge regarding its effect on perioperative complications following spine surgery or the optimal timing of surgery after an infection. METHODS: We asked the National COVID Cohort Collaborative for patients who underwent cervical spine surgery. Patients were stratified into those with an initial documented COVID-19 infection within 3 time periods: 0-2 weeks, 2-6 weeks, or 6-12 weeks before surgery. RESULTS: A total of 29,449 patients who underwent anterior approach cervical spine surgery and 46,379 patients who underwent posterior approach cervical spine surgery were included. Patients who underwent surgery within 2 weeks of their COVID-19 diagnosis had a significantly increased risk for venous thromboembolic events, sepsis, 30-day mortality, and 1-year mortality, irrespective of the anterior or posterior approach. Among patients undergoing surgery between 2 and 6 weeks after COVID-19 infection, the 30-day mortality risk remained elevated in patients undergoing a posterior approach only. Patients undergoing surgery between 6 and 12 weeks from the date of the COVID-19 infection did not show significantly elevated rates of any complications analyzed. CONCLUSIONS: Patients undergoing either anterior or posterior cervical spine surgery within 2 weeks from the initial COVID-19 diagnosis are at increased risk for perioperative venous thromboembolic events, sepsis, and mortality. Elevated perioperative complication risk does not persist beyond 2 weeks, except for 30-day mortality in posterior approach surgeries. On the basis of these results, it may be warranted to postpone nonurgent spine surgeries for at least 2 weeks following a COVID-19 infection and advise patients of the increased perioperative complication risk when urgent surgery is required.

Advances in Imaging (Intraop Cone-Beam Computed Tomography, Synthetic Computed Tomography, Bone Scan, Low-Dose Protocols).

Spine surgery has seen a rapid advance in the refinement and development of 3-dimensional and nuclear imaging modalities in recent years. Cone-beam CT has proven to be a valuable tool for improving the accuracy of pedicle screw placement. The use of synthetic CT and low-dose CT have also emerged as modalities which allow for little to no radiation while streamlining imaging workflows. Bone scans also serve to provide functional information about bone metabolism in both the preoperative and postoperative monitoring phases.

Longitudinal Lower Airway Microbial Signatures of Acute Cellular Rejection in Lung Transplantation.

Rationale: Acute cellular rejection (ACR) after lung transplantation is a leading risk factor for chronic lung allograft dysfunction. Prior studies have demonstrated dynamic microbial changes occurring within the allograft and gut that influence local adaptive and innate immune responses. However, the lung microbiome's overall impact on ACR risk remains poorly understood. Objective: To evaluate whether temporal changes in microbial signatures were associated with the development of ACR. Methods: We performed cross-sectional and longitudinal analyses (joint modeling of longitudinal and time-to-event data and trajectory comparisons) of 16S rRNA gene sequencing results derived from lung transplant recipient lower airway samples collected at multiple timepoints. Measurements and Main Results: Among 103 lung transplant recipients, 25 (24.3%) developed ACR. In comparing samples acquired one month after transplant, subjects who never developed ACR demonstrated lower airway enrichment with several oral commensals (e.g., Prevotella and Veillonella spp.) compared to those with current or future (beyond one month) ACR. However, a subgroup analysis of those who developed ACR beyond one month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared to baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in alpha diversity (characterized by an initial decrease and a subsequent increase) and in the taxonomic trajectories of numerous oral commensals were more commonly observed in subjects with ACR. Conclusion: Dynamic changes in the lower airway microbiota are associated with the development of ACR, supporting its potential role as a useful biomarker or in ACR pathogenesis.

Treating Hepatitis C Virus Infection in Jails as an Offset to Declines in Treatment Activity in the Community, New York City, NY, 2014-2020.

Introduction: There are scant data on implementation of large-scale direct-acting antiviral treatment for hepatitis C virus in jails in the U.S. New York City Health + Hospitals/Correctional Health Services aimed to scale up hepatitis C virus treatment in the New York City jail system. This study describes the trends in annual hepatitis C virus treatment in New York City jails compared with those in Medicaid-funded treatment in the New York City community from 2014 to 2020. Methods: In this observational study, we extracted annual counts of direct-acting antiviral prescriptions for hepatitis C virus for those (1) in the New York City community who were covered by Medicaid and (2) those detained in New York City jails for 2014-2020. Data sources were New York City Department of Health and Mental Hygiene annual reports and Correctional Health Services treatment records, respectively. We used linear regression analysis to test for significant trends in annual treatment in these 2 cohorts during 2015-2019. Results: From 2015 to 2019, treatments started in New York City jails increased annually (p=0.001), whereas Medicaid-funded prescriptions in the New York City community declined since a peak in 2015 (p<0.001). In 2019, New York City jail-based treatment initiations totaled the equivalent of 10% of treatment covered by Medicaid in New York City, up from 0.3% in 2015. Conclusions: Scale up of jail-based hepatitis C virus treatment is an important strategy to offset declines observed in the community. Addressing barriers to care in jail, such as improving testing, linkage to care, and affordability of direct-acting antivirals for jail-based health services, can help sustain high levels of treatment in U.S. jails and other carceral facilities.

Sensorineural hearing loss after cardiac surgery: a systematic review.

BACKGROUND: Sensorineural hearing loss (SNHL) may occur following cardiac surgery. Although preventing post-operative complications is vitally important in cardiac surgery, there are few guidelines regarding this issue. This review aimed to characterize SNHL after cardiac surgery. METHOD: This systematic review was registered on PROSPERO and conducted in accordance with PRISMA guidelines. A systematic search of the PubMed, Embase and Cochrane Library were conducted from inception. Eligibility determination, data extraction and methodological quality analysis were conducted in duplicate. RESULTS: There were 23 studies included in the review. In the adult population, there were six cohort studies, which included 36 cases of hearing loss in a total of 7135 patients (5.05 cases per 1000 operations). In seven cohort studies including paediatric patients, there were 88 cases of hearing loss in a total of 1342 operations. The majority of cases of hearing loss were mild in the adult population (56.6%). In the paediatric population 59.2% of hearing loss cases had moderate or worse hearing loss. The hearing loss most often affected the higher frequencies, over 6000 Hz. There have been studies indicating an association between hearing loss and extracorporeal circulation, but cases have also occurred without this intervention. CONCLUSION: SNHL is a rare but potentially serious complication after cardiac surgery. This hearing loss affects both paediatric and adult populations and may have significant long-term impacts. Further research is required, particularly with respect to the consideration of screening for SNHL in children after cardiac surgery.

Kidney function and transplants in prune belly syndrome: a scoping review.

BACKGROUND: Children with prune belly syndrome (PBS) are at higher risk of developing kidney dysfunction and requiring kidney replacement therapy (KRT). While studies have described surgical and survival outcomes in these populations, there has yet to be a focused synthesis of evidence regarding kidney outcomes in this population. Here, the focus of this scoping review was to highlight knowledge gaps and report standards on kidney outcomes in PBS of all ages. METHODS: Following scoping review methodology, EMBASE, MEDLINE, and Scopus were searched for peer-reviewed literature that describe kidney outcomes in PBS. All studies with a broad set of kidney outcomes (such as kidney function measures, chronic kidney disease (CKD), KRT and associated outcomes) were included. Findings were summarized and qualitatively synthesized. RESULTS: Of the 436 unique records identified, 25 were included for synthesis. A total of 17 studies (441 patients) reported on kidney insufficiency outcomes, with an estimated prevalence of CKD ranging from 8 to 66%. A total of 15 studies (314 patients) described KRT, primary kidney transplant, and outcomes. Of these, the age for KRT ranged from 4 to 21 years, and graft survival ranged from 22 to 87% by last follow-up (range 1.3-27 years). CONCLUSIONS: There is significant variability in studies reporting kidney outcomes in PBS which limits meaningful synthesis. There is a need for future studies with comprehensive reporting of confounders and drivers for kidney insufficiency in PBS.

Interventional Techniques for the Management of Knee Osteoarthritis: A Literature Review.

Osteoarthritis of the knee is a prevalent condition that causes pain, discomfort, and disability that can severely impact the quality of life. This literature review aims to review the various interventional pain management techniques available to treat knee osteoarthritis. It analyzes the efficacy of various interventions such as intra-articular corticosteroids, prolotherapy, viscosupplementation, platelet-rich plasma, and genicular nerve blocks with radiofrequency ablation or cryoneurolysis. We searched databases for studies published in the past 20 years. A total of 37 articles were included. The literature supports the idea that a comprehensive treatment plan consisting of the various aforementioned techniques can provide relief for patients while delaying or avoiding joint replacement surgery.

Transcriptional repression by a secondary DNA binding surface of DNA topoisomerase I safeguards against hypertranscription.

Regulation of global transcription output is important for normal development and disease, but little is known about the mechanisms involved. DNA topoisomerase I (TOP1) is an enzyme well-known for its role in relieving DNA supercoils for enabling transcription. Here, we report a non-enzymatic function of TOP1 that downregulates RNA synthesis. This function is dependent on specific DNA-interacting residues located on a conserved protein surface. A loss-of-function knock-in mutation on this surface, R548Q, is sufficient to cause hypertranscription and alter differentiation outcomes in mouse embryonic stem cells (mESCs). Hypertranscription in mESCs is accompanied by reduced TOP1 chromatin binding and change in genomic supercoiling. Notably, the mutation does not impact TOP1 enzymatic activity; rather, it diminishes TOP1-DNA binding and formation of compact protein-DNA structures. Thus, TOP1 exhibits opposing influences on transcription through distinct activities which are likely to be coordinated. This highlights TOP1 as a safeguard of appropriate total transcription levels in cells.

Safety and efficacy of biological agents in the treatment of Systemic Lupus Erythematosus (SLE).

BACKGROUND: To determine the safety and efficacy of biological agents used in the treatment of systemic lupus erythematosus (SLE) in adults. METHODS: Systematic review and meta-analysis following PRISMA guidelines. DATA SOURCES: MEDLINE (through Pubmed), EMBASE, Cochrane library, Clinicaltrials.gov, Australianclinicaltrials.gov.au, ANZCTR.org.au and WHO International Clinical Trials Registry Platform for studies published from 20 May 2021 and 15 years prior. A grey literature search was performed and completed on 31 May 2021. STUDY CRITERIA: Phase II, III or quasi randomised controlled trials, studies with only cerebral or cutaneous lupus were excluded. DATA EXTRACTION: Two authors independently screened studies for eligibility, extracted, reviewed data for accuracy, and used the Cochrane tool to assess risk of bias. RESULTS: Forty-four studies were identified, consisting of 15 groups of drugs and 25 different biological agents, totalling 16,889 patients. The main outcomes assessed included Systemic Lupus Erythematosus Responder Index (SRI), BILAG-Based Composite Lupus Assessment (BICLA) and combined combined/partial renal remission (CRR/PRR). Four groups of biologics were found to improve outcomes. Anti-interferons: Anifrolumab increased BICLA response and SRI 5 to 8, decreased prednisone dosages, with increased herpes zoster infections, but fewer serious adverse events. Sifalimumab improved SRI but also increased herpes zoster infections. Anti BAFF/BLyS and/or APRIL: Belimumab consistently improved SRI 4, decreased prednisone dosages, increased combined CRR/PRR, and had no adverse safety outcomes. Tabalumab increased SRI 5 at 52 weeks with no steroid sparing effect but was associated with increased infusion related adverse events. Telitacicept improved SRI 4 at 52 weeks, with no increased adverse events, though data was rather sparse. Anti CD-20 monoclonal antibody, Obinutuzumab increased combined CRR/PRR at 1 and 2 years. Anti IL12/23 monoclonal antibody, Ustekinumab, increased SRI 4 to 6, but not BICLA at 24 weeks, with no concerning safety outcomes. CONCLUSION: Multiple biologic agents are shown in high quality studies to have a significant therapeutic impact on outcomes in SLE.

Pain Management Interventions in Lumbar Spinal Stenosis: A Literature Review.

Lumbar spinal stenosis (LSS) occurs due to the narrowing of the space within the vertebral canal and or intervertebral foramina. This results in the compression of the spinal cord and possibly the roots of the spinal nerves. Lower back pain and neurogenic claudication (NC) are major symptoms of spinal stenosis. This is a literature review that summarizes the important findings pertaining to pain management of spinal stenosis. Twenty-four original articles were assessed. Pain can be treated through non-invasive or surgical methods. Conservative techniques include physical exercises, epidural corticosteroid injection, local anesthetic injection therapy, and oral analgesics. Surgical intervention deals with the decompression of the affected spinal region, with or without vertebral fusion surgery. Other novel surgical techniques include implantation of specific equipment, known as interspinous spacer devices and minimally invasive lumbar decompression (MILD). Most studies offering a comparative analysis have demonstrated that surgical intervention is more efficacious than non-surgical interventions to manage pain associated with spinal stenosis.

A temporal analysis of perioperative complications following COVID-19 infection in patients undergoing lumbar spinal fusion: When is it safe to proceed?

Background Context: COVID-19 has been shown to adversely affect multiple organ systems, yet little is known about its effect on perioperative complications after spine surgery or the optimal timing of surgery after an infection. We used the NIH National COVID Cohort Collaborative (N3C) database to characterize the risk profile in patients undergoing spine surgery during multiple time windows following COVID-19 infection. Methods: We queried the National COVID Cohort Collaborative, a database of 17.4 million persons with 6.9 million COVID-19 cases, for patients undergoing lumbar spinal fusion surgery. Patients were stratified into those with an initial documented COVID-19 infection within 3 time periods: 0 to 2 weeks, 2 to 6 weeks, or 6 to 12 weeks before surgery. Results: A total of 60,541 patients who underwent lumbar spinal fusion procedures were included. Patients who underwent surgery within 2 weeks of their COVID-19 diagnosis had a significantly increased risk for venous thromboembolic events (OR 2.29, 95% CI 1.58-3.32), sepsis (OR 1.56, 95% CI 1.03-2.36), 30-day mortality (OR 5.55, 95% CI 3.53-8.71), and 1-year mortality (OR 2.70, 95% CI 1.91-3.82) compared with patients who were COVID negative during the same period. There was no significant difference in the rates of acute kidney injury or surgical site infection. Patients undergoing surgery between 2 and 6 weeks or between 6 and 12 weeks from the date of COVID-19 infection did not show significantly elevated rates of any complication analyzed. Conclusions: Patients undergoing lumbar spinal fusion within 2 weeks from initial COVID-19 diagnosis are at increased risk for perioperative venous thromboembolic events and sepsis. This effect does not persist beyond 2 weeks, however, so it may be warranted to postpone non-urgent spine surgeries for at least 2 weeks following a COVID-19 infection or to consider a more aggressive VTE chemoprophylaxis regimen for urgent surgery in COVID-19 patients.

The 2023 Impact of Inflammatory Bowel Disease in Canada: Special Populations-Children and Adolescents with IBD.

Rates of inflammatory bowel disease (IBD) in Canadian children and adolescents are among the highest in the world, and the incidence is rising most rapidly in children under five years of age. These young children may have either a typical form of IBD with multi-factorial aetiology, or they may have a monogenic form. Despite the growing number of children in Canada living with this important chronic disease, there are few available medical therapies approved by Health Canada due to the omission of children from most clinical trials of newly developed biologics. As a result, off-label use of medications is common, and physicians have learned to use existing therapies more effectively. In addition, most Canadian children are treated in multidisciplinary, specialty clinics by physicians with extra training or experience in IBD, as well as specialist nurses, dietitians, mental health care providers and other allied health professionals. This specialized clinic approach has facilitated cutting edge research, led by Canadian clinicians and scientists, to understand the causes of IBD, the optimal use of therapies, and the best ways to treat children from a biopsychosocial perspective. Canadians are engaged in work to understand the monogenic causes of IBD; the interaction between genes, the environment, and the microbiome; and how to address the mental health concerns and medical needs of adolescents and young adults transitioning from paediatric to adult care.

Statistical Fragility of Randomized Controlled Trials Evaluating Platelet-Rich Plasma Use for Knee Osteoarthritis: A Systematic Review.

Background: Numerous studies have been published on the use of platelet-rich plasma (PRP) for knee osteoarthritis (OA), with conflicting results. Purpose: To determine the fragility index (FI) and fragility quotient (FQ) of randomized controlled trials (RCTs) that evaluated the use of PRP to treat knee OA. Study Design: Systematic review. Methods: RCTs evaluating the efficacy of PRP injections for knee OA from 2000 to 2020 were included for analysis according to PRISMA guidelines. The FI was determined by calculating the number of outcome event reversals required to change the statistical significance. The associated FQ was determined by dividing the FI by the sample size. Results: Our initial search resulted in 41,149 studies, of which 8 RCTs (678 patients, 72 outcome events) were included in the analysis. One study failed to report PRP formulation details, whereas 87.5% of studies reported using either leukocyte-rich or leukocyte-poor PRP. The platelet concentration was reported in 25% of the included trials. The overall FI of the 72 outcome events was 8.5. Accounting for sample size, the associated FQ was determined to be 0.14, suggesting that the reversal of 14% of outcome events was required to change outcome significance. There were 51 statistically significant outcomes, of which the FI and FQ were 12 and 0.164, respectively. Conclusion: Comprehensive fragility analysis suggested that the published literature evaluating the efficacy of PRP use for knee OA may lack statistical stability. We recommend the reporting of both an FI and FQ in addition to P value analysis to provide a clear and thorough understanding of the statistical integrity of studies reporting on PRP use for knee OA.

The role of circumcision in preventing urinary tract infections in children with antenatal hydronephrosis: Systematic review and meta-analysis.

INTRODUCTION: Circumcision has been reported to reduce the risk of urinary tract infections (UTIs) in boys with antenatal hydronephrosis (HN). Our aim was to compare the incidence of UTIs in circumcised vs. uncircumcised boys with antenatal HN by conducting a systematic review and meta-analysis. STUDY DESIGN: A comprehensive search was performed until December 2022. Comparative studies were evaluated according to Cochrane collaboration recommendations. Assessed measures included: UTIs, continuous antibiotic prophylaxis (CAP) use, renal outcomes, and circumcision complications. Odds ratios (OR) and mean difference with 95% confidence interval (CI) were extrapolated from available data. Random-effects meta-analysis were performed. RESULTS: Twenty-three studies describing 9093 boys with antenatal HN were identified, including 4677 uncircumcised and 4416 circumcised boys. Overall effect estimates demonstrate that circumcised boys have significantly reduced odds of developing any UTI [OR 0.26, 95%CI 0.21, 0.32; p < 0.001]]. In addition, there a significantly reduced odds of developing UTI when circumcised and on CAP [OR 0.19, 95% CI 0.13, 0.30; p < 0.001]. When stratifying by etiology, circumcision reduced the odds of UTI in boys with isolated HN [OR 0.33, 95% CI 0.16, 0.68; p = 0.003], vesicoureteral reflux [OR 0.23, 95% CI 0.13, 0.42; P < 0.00001], or with posterior urethral valves [OR 0.29, 95% CI 0.13, 0.64; p = 0.002]. DISCUSSION: Circumcision reduces the incidence of UTIs in boys with antenatal HN. This review is limited by the varied definitions of UTIs and inconsistent reporting on HN etiology, renal outcomes, and circumcision complications. CONCLUSIONS: Circumcision should be considered in boys with antenatal HN to prevent the risk of developing UTI. Further research is warranted to individualize the prophylactic role of circumcision for patients with HN.

Implementation and early outcomes of a telehealth visit model to deliver tecovirimat for mpox infection in New York City.

The 2022 mpox outbreak in New York City posed challenges to rapidly scaling up treatment capacity. We describe a telehealth treatment model launched during this outbreak that facilitated healthcare provider treatment capacity, and was able to adhere to a Centers for Disease Control and Prevention (CDC)-sponsored expanded access investigational new drug (EA-IND) protocol for tecovirimat. Sixty-nine patients were evaluated and prescribed tecovirimat for mpox through telehealth visits at NYC Health + Hospitals/Bellevue and NYU Langone Health from June to August 2022. Thirty-two (46.4%) were previously diagnosed with HIV. Forty-four (63.8%) reported full recovery, with the remainder lost to follow-up. Most patients (n = 60, 87.0%) attended at least one follow-up visit (either in person or through telehealth) after starting treatment. We observed favorable treatment outcomes, with no serious adverse events, hospitalizations, or deaths related to mpox. While equitable access to telehealth remains a limitation that needs to be addressed, this telehealth model enabled a rapid scale-up of tecovirimat prescription during the mpox outbreak, and should be considered as an important tool used to respond to future infectious disease outbreaks.

High level of HIV viral suppression in a cross-sectional study of Ugandan men with urethritis and bacterial STI.

BACKGROUND: Urethritis associated with non-viral sexually transmitted infections (STI) increases the risk of HIV acquisition and transmission in those living with HIV (LWH) without viral load suppression (VLS). Compared to women, men typically have lower rates of HIV VLS. We assessed the prevalence of VLS and drug resistance mutations in men LWH and urethral discharge syndrome (UDS) in Kampala, Uganda. METHODS: Men with UDS were recruited in Kampala October 2019-November 2020. Medical, demographic, and behavioural data were collected with biological samples. All reactive HIV results (rapid, sequential algorithm) underwent confirmatory HIV antibody- and HIV incidence-testing, and viral load (VL) measurement. The pol and gp41 regions were sequenced on samples with VLs >1000 cpm, phylogenetic trees were generated, and resistance mutations were investigated. RESULTS: 50 of 250 participants (20%) had reactive HIV rapid tests and 48/50 (96%) were aware of their HIV status and using antiretroviral therapy (ART). The median age was 38 years (IQR 32-45), 27/50 (54%) had engaged in transactional sex, and 30/50 (60%) reported alcohol before sex. VLS was present in 46/50 (92%). There were no major resistance mutations present in any samples analyzed. CONCLUSIONS: The prevalence of HIV and VLS was greater in these men than in the general Ugandan adult population. Most men LWH were on ART and thus less likely to transmit HIV despite demonstrating sexual behaviours associated with high-risk of STIs. These data emphasize that high levels of ART coverage and VLS are achievable among men with UDS in urban Kampala.

A quantitative analysis of voiding cystourethrogram features confirms the association between high-grade vesicoureteral reflux with male sex, younger age, and hydronephrosis.

INTRODUCTION: Vesicoureteral reflux (VUR) is commonly diagnosed in the workup of urinary tract infections or hydronephrosis in children. Traditionally, VUR severity is graded subjectively based on voiding cystourethrogram (VCUG) imaging. Herein, we characterized the association between age, sex, and indication for VCUG, by employing standardized quantitative features. METHODS: We included renal units with a high certainty in VUR grade (>80% consensus) from the qVUR model validation study at our institution between 2013 and 2019. We abstracted the following variables: age, sex, laterality, indication for VCUG, and qVUR parameters (tortuosity, ureter widths on VCUG). High-grade VUR was defined as grade 4 or 5 The association between each variable and VUR grade was assessed. RESULTS: A total of 443 patients (523 renal units) were included, consisting of a 48:52 male/female ratio. The median age at VCUG was 13 months. Younger age at VCUG (<6 months) was associated with greater odds of severe VUR (odds ratio [OR] 2.0), and there was a weak correlation between age and VUR grade (ρ=-0.17). Male sex was associated with increased odds of high-grade VUR (OR 2.7). VCUGs indicated for hydronephrosis were associated with high-grade VUR (OR 4.1) compared to those indicated for UTI only. Ureter tortuosity and width were significantly associated with each clinical variable and VUR severity. CONCLUSIONS: Male sex, younger age (<6 months), and history of hydronephrosis are associated with both high-grade VUR and standardized quantitative measures, including greater ureter tortuosity and increased ureteral width. This lends support to quantitative assessment to improve reliability in VUR grading.