Navigating Ankle Fracture Surgery in the Shadow of COVID-19.

BACKGROUND: This case control study aimed to evaluate the impact of preoperative COVID-19 diagnosis on postoperative complications in patients undergoing ankle fracture surgery using the National COVID-19 Cohort Collaborative (N3C) database. The investigation focused on the interplay between COVID-19 diagnosis timing, patient characteristics, and clinical outcomes, particularly considering the potential mechanisms by which COVID-19 may contribute to increased complications. METHODS: This case control study included patients who underwent ankle fracture surgery using the N3C database. The cohort was divided into two groups: patients without COVID-19 diagnosis within 12 weeks of surgery (n = 16 806) and those with a positive COVID-19 diagnosis within 12 weeks of surgery (n = 369). Demographic factors were analyzed. Clinical outcomes encompassed deep vein thrombosis (DVT), sepsis, surgical site infection, bleeding, acute kidney injury, 30-day mortality, and 365-day mortality. Multivariate logistic regression analyses were conducted. RESULTS: The COVID-19-positive cohort displayed a slightly higher mean age (52.95 ± 18.43 vs 51.62 ± 18.36, P = .169) and body mass index (34.88 ± 9.99 vs 33.86 ± 8.80, P = .028) compared to the negative cohort. Although some outcomes, such as DVT and sepsis, demonstrated slightly higher frequencies in the COVID-19-positive group, these differences were not statistically significant. Adjusted odds ratios (AORs) for various COVID-19 diagnosis periods were generally not significant, except for a heightened risk of 30-day all-cause mortality associated with COVID-19 positivity within 0 to 2 weeks of surgery (AOR = 6.29, P = .003). CONCLUSIONS: Preoperative COVID-19 diagnosis within 12 weeks did not exhibit a significant association with most postoperative complications. While this study did not unveil substantial COVID-19-related effects, acknowledging the broader context of the pandemic remains essential in guiding comprehensive patient care strategies. LEVEL OF EVIDENCE: Level III.

A brain microbiome in salmonids at homeostasis.

Ectotherms have peculiar relationships with microorganisms. For instance, bacteria are recovered from the blood and internal organs of healthy teleosts. However, the presence of microbial communities in the healthy teleost brain has not been proposed. Here, we report a living bacterial community in the brain of healthy salmonids with bacterial loads comparable to those of the spleen and 1000-fold lower than in the gut. Brain bacterial communities share >50% of their diversity with gut and blood bacterial communities. Using culturomics, we obtained 54 bacterial isolates from the brains of healthy trout. Comparative genomics suggests that brain bacteria may have adaptations for niche colonization and polyamine biosynthesis. In a natural system, Chinook salmon brain microbiomes shift from juveniles to reproductively mature adults. Our study redefines the physiological relationships between the brain and bacteria in teleosts. This symbiosis may endow salmonids with a direct mechanism to sense and respond to environmental microbes.

Erythrocytes of the common carp are immune sentinels that sense pathogen molecular patterns, engulf particles and secrete pro-inflammatory cytokines against bacterial infection.

Introduction: Red blood cells (RBCs), also known as erythrocytes, are underestimated in their role in the immune system. In mammals, erythrocytes undergo maturation that involves the loss of nuclei, resulting in limited transcription and protein synthesis capabilities. However, the nucleated nature of non-mammalian RBCs is challenging this conventional understanding of RBCs. Notably, in bony fishes, research indicates that RBCs are not only susceptible to pathogen attacks but express immune receptors and effector molecules. However, given the abundance of RBCs and their interaction with every physiological system, we postulate that they act in surveillance as sentinels, rapid responders, and messengers. Methods: We performed a series of in vitro experiments with Cyprinus carpio RBCs exposed to Aeromonas hydrophila, as well as in vivo laboratory infections using different concentrations of bacteria. Results: qPCR revealed that RBCs express genes of several inflammatory cytokines. Using cyprinid-specific antibodies, we confirmed that RBCs secreted tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). In contrast to these indirect immune mechanisms, we observed that RBCs produce reactive oxygen species and, through transmission electron and confocal microscopy, that RBCs can engulf particles. Finally, RBCs expressed and upregulated several putative toll-like receptors, including tlr4 and tlr9, in response to A. hydrophila infection in vivo. Discussion: Overall, the RBC repertoire of pattern recognition receptors, their secretion of effector molecules, and their swift response make them immune sentinels capable of rapidly detecting and signaling the presence of foreign pathogens. By studying the interaction between a bacterium and erythrocytes, we provide novel insights into how the latter may contribute to overall innate and adaptive immune responses of teleost fishes.

Saline suppression testing-induced hypocalcemia and implications for clinical interpretations.

BACKGROUND: Extracellular calcium critically regulates physiologic aldosterone production. Moreover, abnormal calcium flux and signaling are involved in the pathogenesis of the majority of primary aldosteronism cases. METHODS: We investigated the influence of the saline suppression test (SST) on calcium homeostasis in prospectively recruited participants (n = 86). RESULTS: During SST, 100% of participants had decreases in serum calcium, with 48% developing frank hypocalcemia. Serum calcium declined from 2.30 ± 0.08 mmol/L to 2.13 ± 0.08 mmol/L (P < .001) with parallel increases in parathyroid hormone from 6.06 ± 2.39 pmol/L to 8.13 ± 2.42 pmol/L (P < .001). In contrast, serum potassium and bicarbonate did not change, whereas eGFR increased and serum glucose decreased (P < .001). Lower body surface area (translating to greater effective circulating volume expansion during SST) was associated with greater reductions in (ß = .33, P = .001), and absolutely lower, serum calcium levels (ß = .25, P = .001). When evaluating clinically-relevant diagnostic thresholds, participants with post-SST aldosterone levels <138 pmol/L had lower post-SST calcium and 25-hydroxyvitamin D levels (P < .05), and higher post-SST parathyroid hormone levels (P < .05) compared with those with post-SST aldosterone levels >277 pmol/L. CONCLUSION: SST uniformly decreases serum calcium, which is likely to be due to the combination of variable dilution, increased renal clearance, and vitamin D status. These acute reductions in bioavailable calcium are associated with lower post-SST aldosterone. Given the critical role of extracellular calcium in regulating aldosterone production, these findings warrant renewed inquiry into the validity of SST interpretations for excluding primary aldosteronism.

Breaking barriers: Innovative approaches for skin delivery of RNA therapeutics.

RNA therapeutics represent a rapidly expanding platform with game-changing prospects in personalized medicine. The disruptive potential of this technology will overhaul the standard of care with reference to both primary and specialty care. To date, RNA therapeutics have mostly been delivered parenterally via injection, but topical administration followed by intradermal or transdermal delivery represents an attractive method that is convenient to patients and minimally invasive. The skin barrier, particularly the lipid-rich stratum corneum, presents a significant hurdle to the uptake of large, charged oligonucleotide drugs. Therapeutic oligonucleotides need to be engineered for stability and specificity and formulated with state-of-the-art delivery strategies for efficient uptake. This review will cover various passive and active strategies deployed to enhance permeation through the stratum corneum and achieve effective delivery of RNA therapeutics to treat both local skin disorders and systemic diseases. Some strategies to achieve selectivity between local and systemic administration will also be discussed.

Evaluation of a Transitional Patient Navigation Protocol for People Living With Hepatitis C Virus in the New York City Jail System.

We evaluated outcomes from a telephone-based transitional patient navigation (TPN) service for people living with hepatitis C virus (HCV) upon returning to the community after incarceration in New York City (NYC) jails. NYC Health + Hospitals/Correctional Health Services offered referrals for TPN services provided by the NYC local health department patient navigation staff. We compared rates of connection to care among people referred for TPN services with those who were not referred. People living with HIV had a higher connection to care rate at three months (65.0% vs 39.8%, p≤.05) and people with opioid use disorder had a higher connection rate at six months (55.1% vs 36.1%, p≤.05) compared with people without these conditions. However, there was not an improved connection to HCV care associated with referral to TPN services for the overall cohort. Further research, including qualitative studies, may inform improved strategies for connection to HCV care after incarceration.

Severe Mpox Among People With Advanced Human Immunodeficiency Virus Receiving Prolonged Tecovirimat in New York City.

Severe mpox has been observed in people with advanced human immunodeficiency virus (HIV). We describe clinical outcomes of 13 patients with advanced HIV (CD4 <200 cells/µL), severe mpox, and multiorgan involvement. Despite extended tecovirimat courses and additional agents, including vaccinia immune globulin, cidofovir, and brincidofovir, this group experienced prolonged hospitalizations and high mortality.

Elevated Serum Alkaline Phosphatase is an Independent Predictor of Complications After Lumbar Spinal Fusion.

BACKGROUND: Alkaline phosphatase (ALP) is an enzyme which has been proven useful as a biomarker for bone turnover and inflammation. We hypothesized that high serum ALP levels are associated with increased complication rates following lumbar spinal fusion. METHODS: Lumbar spinal fusion procedures from 2005 to 2019 were queried from the National Surgical Quality Improvement Program (NSQIP) database. Serum alkaline phosphatase levels were stratified into low <44 IU/L, normal 44-147 IU/L, and high >147 IU/L. A risk-adjusted multivariate logistic regression was used to analyze ALP as an independent risk factor for complications. RESULTS: A total of 16,441 patients who underwent lumbar fusion procedures were included. Adjusted multivariate logistic regression analysis demonstrated that patients with a high serum ALP level had a significantly increased risk for developing septic shock (OR 4.68, 95% CI 1.83-11.97), pneumonia (OR 2.89, 95% CI 1.59-5.25), requiring a transfusion (OR 2.09, 95% CI 1.68-2.59), reoperation within 30 days (OR 1.68, 95% CI 1.12-2.52), readmission within 30 days (OR 1.60, 95% CI 1.16-2.21), increased length of stay (OR 1.87, 95% CI 1.49-2.36), and nonhome discharge (OR 2.18, 95% CI 1.80-2.66). CONCLUSIONS: Elevated serum ALP in patients undergoing lumbar fusion procedures is associated with increased risk for multiple in-hospital complications as well as higher rates of readmission and reoperation.

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.

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.

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

Rationale: Acute cellular rejection (ACR) after lung transplant 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. Objectives: 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 time points. Measurements and Main Results: Among 103 lung transplant recipients, 25 (24.3%) developed ACR. In comparing samples acquired 1 month after transplant, subjects who never developed ACR demonstrated lower airway enrichment with several oral commensals (e.g., Prevotella and Veillonella spp.) than those with current or future (beyond 1 mo) ACR. However, a subgroup analysis of those who developed ACR beyond 1 month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared with baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in α-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. Conclusions: 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.

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.

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.

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.