Northwell Health Orthopaedic Institute

Background: The novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is responsible for the global coronavirus disease 2019 pandemic. Small studies have shown a potential benefit of chloroquine/hydroxychloroquine±azithromycin for the treatment of coronavirus disease 2019. Use of these medications alone, or in combination, can lead to a prolongation of the QT interval, possibly increasing the risk of Torsade de pointes and sudden cardiac death. Methods: Hospitalized patients treated with chloroquine/hydroxychloroquine±azithromycin from March 1 to the 23 at 3 hospitals within the Northwell Health system were included in this prospective, observational study. Serial assessments of the QT interval were performed. The primary outcome was QT prolongation resulting in Torsade de pointes. Secondary outcomes included QT prolongation, the need to prematurely discontinue any of the medications due to QT prolongation, and arrhythmogenic death. Results: Two hundred one patients were treated for coronavirus disease 2019 with chloroquine/hydroxychloroquine. Ten patients (5.0%) received chloroquine, 191 (95.0%) received hydroxychloroquine, and 119 (59.2%) also received azithromycin. The primary outcome of torsade de pointes was not observed in the entire population. Baseline corrected QT interval intervals did not differ between patients treated with chloroquine/hydroxychloroquine (monotherapy group) versus those treated with combination group (chloroquine/hydroxychloroquine and azithromycin; 440.6±24.9 versus 439.9±24.7 ms, P =0.834). The maximum corrected QT interval during treatment was significantly longer in the combination group versus the monotherapy group (470.4±45.0 ms versus 453.3±37.0 ms, P =0.004). Seven patients (3.5%) required discontinuation of these medications due to corrected QT interval prolongation. No arrhythmogenic deaths were reported. Conclusions: In the largest reported cohort of coronavirus disease 2019 patients to date treated with chloroquine/hydroxychloroquine±azithromycin, no instances of Torsade de pointes, or arrhythmogenic death were reported. Although use of these medications resulted in QT prolongation, clinicians seldomly needed to discontinue therapy. Further study of the need for QT interval monitoring is needed before final recommendations can be made.

Abstract Older patients with melanoma have lower rates of sentinel lymph node (LN) metastases yet paradoxically have inferior survival. Patient age correlated with an inability to retain Technetium radiotracer during sentinel LN biopsy in more than 1,000 patients, and high Technetium counts correlated to better survival. We hypothesized that loss of integrity in the lymphatic vasculature due to extracellular matrix (ECM) degradation might play a role. We have implicated HAPLN1 in age-dependent ECM degradation in the dermis. Here, we queried whether HAPLN1 could be altered in the lymphatic ECM. Lymphatic HAPLN1 expression was prognostic of long-term patient survival. Adding recombinant HAPLN1 to aged fibroblast ECMs in vitro reduced endothelial permeability via modulation of VE-cadherin junctions, whereas endothelial permeability was increased following HAPLN1 knockdown in young fibroblasts. In vivo, reconstitution of HAPLN1 in aged mice increased the number of LN metastases, but reduced visceral metastases. These data suggest that age-related changes in ECM can contribute to impaired lymphatics. Significance: Our studies reveal that changes in the stroma during aging may influence the way tumor cells traffic through the lymphatic vasculature. Aging may dictate the route of metastatic dissemination of tumor cells, and understanding these changes may help to reveal targetable moieties in the aging tumor microenvironment. See related commentary by Marie and Merlino, p. 19. This article is highlighted in the In This Issue feature, p. 1

BACKGROUND: The primary purposes of this interdisciplinary consensus statement were to review the relevant indications for central neck dissection (CND) in patients with papillary thyroid cancer (PTC) and to outline the appropriate extent and relevant techniques required to accomplish a safe and effective CND. METHODS: A writing group convened by the American Head and Neck Society (AHNS) Endocrine Committee was tasked with identifying the important clinical elements to consider when managing the central neck compartment in patients with PTC based on available evidence in the literature, and the group's collective experience. The position statement paper was then submitted to the full Endocrine Committee, Education Committee, and AHNS Council. RESULTS: This consensus statement was developed to inform the clinical decision-making process when managing the central neck compartment in patients with PTC from the AHNS. This document is intended to provide clarity through definitions as well as a basic guideline from which to manage the central neck. It is our hope that this improves the quality and reduces variation in management of the central neck, facilitates communication, and furthers research for patients with thyroid cancer. CONCLUSION: This represents, in our opinion, contemporary optimal surgical care for this patient population and is endorsed by the American Head and Neck Society. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1269-1279, 2017.

Abstract Purpose: Platinum resistance in ovarian cancer is associated with epigenetic modifications. Hypomethylating agents (HMA) have been studied as carboplatin resensitizing agents in ovarian cancer. This randomized phase II trial compared guadecitabine, a second-generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer. Patients and Methods: Patients received either G+C (guadecitabine 30 mg/m2 s.c. once-daily for 5 days and carboplatin) or treatment of choice (TC; topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) in 28-day cycles until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were RECIST v1.1 and CA-125 response rate, 6-month PFS, and overall survival (OS). Results: Of 100 patients treated, 51 received G+C and 49 received TC, of which 27 crossed over to G+C. The study did not meet its primary endpoint as the median PFS was not statistically different between arms (16.3 weeks vs. 9.1 weeks in the G+C and TC groups, respectively; P = 0.07). However, the 6-month PFS rate was significantly higher in the G+C group (37% vs. 11% in TC group; P = 0.003). The incidence of grade 3 or higher toxicity was similar in G+C and TC groups (51% and 49%, respectively), with neutropenia and leukopenia being more frequent in the G+C group. Conclusions: Although this trial did not show superiority for PFS of G+C versus TC, the 6-month PFS increased in G+C treated patients. Further refinement of this strategy should focus on identification of predictive markers for patient selection.

BACKGROUND: Despite descriptions of various cardiovascular manifestations in patients with coronavirus disease 2019 (COVID-19), there is a paucity of reports of new onset bradyarrhythmias, and the clinical implications of these events are unknown. METHODS: Seven patients presented with or developed severe bradyarrhythmias requiring pacing support during the course of their COVID-19 illness over a 6-week period of peak COVID-19 incidence. A retrospective review of their presentations and clinical course was performed. RESULTS: Symptomatic high-degree heart block was present on initial presentation in three of seven patients (43%), and four patients developed sinus arrest or paroxysmal high-degree atrioventricular block. No patients in this series demonstrated left ventricular systolic dysfunction or acute cardiac injury, whereas all patients had elevated inflammatory markers. In some patients, bradyarrhythmias occurred prior to the onset of respiratory symptoms. Death from complications of COVID-19 infection occurred in 57% (4/7) patients during the initial hospitalization and in 71% (5/7) patients within 3 months of presentation. CONCLUSIONS: Despite management of bradycardia with temporary (3/7) or permanent leadless pacemakers (4/7), there was a high rate of short-term morbidity and death due to complications of COVID-19. The association between new-onset bradyarrhythmias and poor outcomes may influence management strategies for acutely ill patients with COVID-19.

PURPOSE: To determine whether needle arthroscopy (NA) compared with magnetic resonance imaging (MRI) in the diagnosis and treatment of meniscal tears is cost-effective when evaluated over a 2-year period via patient-reported outcomes. The hypothesis is that improved diagnostic accuracy with NA would lead to less costly care and similar outcomes. METHODS: A Markov model/decision tree analysis was performed using TreeAge Pro 2017 software. Patients were evaluated for degenerative and traumatic damage to the lateral/medial meniscus. Assumed sensitivities and specificities were derived from the medical literature. The direct costs for care were derived from the 2017 Medicare fee schedule and from private payer reimbursement rates. Costs for care included procedures performed for false-positive findings and for care for false-negative findings. Effectiveness was examined using the global knee injury and osteoarthritis outcome score (KOOS). Patients were evaluated over 2 years for costs and outcomes, including complications. Dominance and incremental cost-effectiveness were evaluated, and 1- to 2-way sensitivity analysis was performed to determine those variables that had the greatest effect. The consolidated economics evaluation and reporting standards checklist for reporting economic evaluations was used. RESULTS: NA was less costly and had similar KOOS versus MRI for both the medial/lateral meniscus with private pay. Costs were less for both Medicare and private pay for medial meniscus, $780 to $1,862, and lateral meniscus, $314 to $1,256, respectively. CONCLUSIONS: Based on the reported MRI incidence of false positives with the medial meniscus and false negatives with the lateral meniscus and based on assumed standards of care, more costly care is provided when using MRI compared with NA. Outcomes were similar with NA compared with MRI. LEVEL OF EVIDENCE: Level II, economic and decision analysis.

BACKGROUND: Restorative neurostimulation is a rehabilitative treatment for patients with refractory chronic low back pain (CLBP) associated with dysfunction of the lumbar multifidus muscle resulting in impaired neuromuscular control. The ReActiv8-B randomized, sham-controlled trial provided evidence of the effectiveness and safety of an implanted, restorative neurostimulator. The two-year analysis previously published in this journal demonstrated accrual of clinical benefits and long-term durability. OBJECTIVE: Evaluation of three-year effectiveness and safety in patients with refractory, disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery. MATERIALS AND METHODS: Prospective, observational follow-up of the 204 implanted trial participants. Low back pain visual analog scale (VAS), Oswestry Disability Index (ODI), EuroQol quality of life survey, and opioid intake were assessed at baseline, six months, and one, two, and three years after activation. The mixed-effects model repeated measures approach was used to provide implicit imputations of missing data for continuous outcomes and multiple imputation for proportion estimates. RESULTS: Data were collected from 133 participants, and 16 patients missed their three-year follow-up because of coronavirus disease restrictions but remain available for future follow-up. A total of 62% of participants had a ≥ 70% VAS reduction, and 67% reported CLBP resolution (VAS ≤ 2.5cm); 63% had a reduction in ODI of ≥ 20 points; 83% had improvements of ≥ 50% in VAS and/or ≥ 20 points in ODI, and 56% had these substantial improvements in both VAS and ODI. A total of 71% (36/51) participants on opioids at baseline had voluntarily discontinued (49%) or reduced (22%) opioid intake. The attenuation of effectiveness in the imputed (N = 204) analyses was relatively small and did not affect the statistical significance and clinical relevance of these results. The safety profile remains favorable, and no lead migrations have been observed to date. CONCLUSION: At three years, 83% of participants experienced clinically substantial improvements in pain, disability, or both. The results confirm the long-term effectiveness, durability, and safety of restorative neurostimulation in patients with disabling CLBP associated with multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02577354.

Gaining a better understanding of the change process holds promise to improve alcohol treatment. Ecological momentary assessment (EMA) coupled with intensive longitudinal data (ILD) approaches have been proposed as promising methods that can advance change process research but have been used infrequently in alcohol use disorder (AUD) treatment research. The current study used these approaches to examine the within-person associations of motivation and self-efficacy and drinking among treatment-seeking problem drinkers. Participants (N = 96) received daily EMA surveys before, during, and after treatment for 7 weeks spread over a 9-month period. Multilevel modeling was used to test the within-person relationships between the change processes and drinking, controlling for between-person associations and prior drinking. Results indicated that daily fluctuations in motivation and self-efficacy significantly predicted drinking over the next 24 hours; however, several theory-driven hypotheses regarding factors that might moderate that relationship were not supported. Overall, results support the advantages of EMA and ILD as methods that can advance AUD treatment research. (PsycINFO Database Record

BACKGROUND: Revision total knee arthroplasty (rTKA) is associated with significant risk of wound-related morbidity. The present study aimed to evaluate the 1) efficacy of closed-incision negative-pressure therapy (ciNPT) vs silver-impregnated antimicrobial dressing (AMD) in mitigating postoperative surgical site complications (SSCs), 2) the effect of ciNPT vs AMD on certain postoperative health utilization parameters, and on 3) patient-reported outcomes (PROs) improvement at 90-day postoperative follow-up. METHODS: This multicenter randomized controlled trial was conducted between December 2017 and August 2019. Patients ≥22 years, at high risk for SSC, and receiving rTKA with full exchange and reimplantation of new prosthetic components or open reduction and internal fixation of periprosthetic fractures were screened for inclusion. Eligible patients were randomized to receive a commercially available ciNPT system or a silver-impregnated AMD (n = 147, each) for minimum of 5-day duration. Primary outcome was the 90-day incidence of SSCs with stratification in accordance with revision type (aseptic/septic). Secondary outcomes were the 90-day health care utilization parameters (readmission, reoperation, dressing changes, and visits) and PROs. RESULTS: Of 294 patients randomized (age: 64.9 ± 9.0 years, female: 59.6%), 242 (82.0%) patients completed the study (ciNPT: n = 124; AMD: n = 118). The incidence of 90-day SSCs was lower for the ciNPT cohort (ciNPT: 3.4% vs AMD: 14.3%; odds ratio (OR): 0.22, 95% confidence interval (0.08, 0.59); P = .0013). Readmission rates (3.4% vs 10.2%, OR: 0.30(0.11, 0.86); P = .0208) and mean dressing changes (1.1 ± 0.3 vs 1.3 ± 1.0; P = .0003) were lower with ciNPT. The differences in reoperation rates, number of visits, and PRO improvement between both arms were not statistically significant (P > .05). CONCLUSION: ciNPT is effective in reducing the 90-day postoperative SSCs, readmission, and number of dressing changes after rTKA. Recommending routine implementation would require true-cost analyses.

Motivational interviewing (MI) is an efficacious treatment for alcohol use disorders. MI is thought to enhance motivation via a combination of 2 therapeutic strategies or active ingredients: 1 relational and 1 directional. The primary aim of this study was to examine MI's hypothesized active ingredients using a dismantling design. Problem drinkers (N = 139) seeking treatment were randomized to 1 of 3 conditions: MI, relational MI without the directional elements labeled spirit-only MI (SOMI), or a nontherapy control condition and followed for 8 weeks. Those assigned to MI or SOMI received 4 sessions of treatment over 8 weeks. All participants significantly reduced their drinking by Week 8, but reductions were equivalent across conditions. The hypothesis that baseline motivation would significantly moderate condition effects on outcome was generally not supported. Failure to find support for MI's hypothesized active ingredients is discussed in the context of the strengths and limitations of the study design. (PsycINFO Database Record

PURPOSE: Partial meniscectomy is a common orthopedic procedure intended to improve knee pain and function in patients with irreparable meniscal tears. However, 6-25% of partial meniscectomy patients experience persistent knee pain after surgery. In this randomized controlled trial (RCT) involving subjects with knee pain following partial meniscectomy, it was hypothesized that treatment with a synthetic medial meniscus replacement (MMR) implant provides significantly greater improvements in knee pain and function compared to non-surgical care alone. METHODS: In this prospective, multicenter RCT, subjects with persistent knee pain following one or more previous partial meniscectomies were randomized to receive either MMR or non-surgical care. This analysis evaluated the 1-year outcomes of this 2-year clinical trial. Patient-reported knee pain, function, and quality of life were measured using nine separate patient-reported outcomes. The primary outcomes were the pain subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS) and the average of all five KOOS subscales (KOOS Overall). Treatment cessation was defined as permanent device removal in the MMR group and any surgical procedure to the index knee in the non-surgical care group. RESULTS: Treated subjects had a median age of 52 years old (range 30-69 years) and one or more previous partial meniscectomies at a median of 34 months (range 5-430 months) before trial entry. Among 127 subjects treated with either MMR (n = 61) or non-surgical care (n = 66), 11 withdrew from the trial or were lost to follow-up (MMR, n = 0; non-surgical care, n = 11). The magnitude of improvement from baseline to 1 year was significantly greater in subjects who received MMR in both primary outcomes of KOOS Pain (P = 0.013) and KOOS Overall (P = 0.027). Treatment cessation was reported in 14.5% of non-surgical care subjects and only 4.9% of MMR subjects (n.s.). CONCLUSION: Treatment with the synthetic MMR implant resulted in significantly greater improvements in knee pain, function, and quality of life at 1 year of follow-up compared to treatment with non-surgical care alone. LEVEL OF EVIDENCE: I.

Abstract Immunotherapies like immune checkpoint inhibitors (ICI) have changed the standard of care for patients with cancer, often leading to durable responses. However, many patients remain or become refractory to ICIs owing to factors such as a lack of primed neoantigen-reactive T cells. We developed a peptide-based vaccination platform that utilizes fully personalized genome vaccines (PGV) and targets neoantigens predicted by our OpenVax computational pipeline. In this study, we report results from the PGV001 study (NCT02721043) targeting up to 10 neoantigens, administered in the adjuvant setting to patients with both solid and hematologic malignancies who have high risk of recurrence. Our data indicate that PGV001 is feasible and safe, with 13 of 14 enrolled patients receiving the vaccine and 11 completing the treatment. 100% of vaccinated patients developed targeted T-cell and B-cell responses, highlighting the capacity of OpenVax to predict immunogenic neoantigens and the potential of PGV001 for safely inducing targeted immunity. Significance: The PGV001 platform is feasible, safe, and immunogenic. The OpenVax pipeline predicted immunogenic neoantigens in tumors with wide-ranging mutational burdens. Data from this study prompted three additional PGV001 trials, one in newly diagnosed glioblastoma, one in urothelial cancer in combination with an ICI, and another in prostate cancer.

Introduction This study analyzed the number of peer-reviewed publications submitted by matriculants prior to applying for the orthopedic surgery residency. The graduating residency classes of 2023 and 2027 were included in the study to understand the trend of publications, to inform aspiring orthopedic surgeons. Methods The top, middle, and bottom 10 orthopedic surgery residency programs were identified on the Doximity online website. Matriculants were searched on PubMed and Google Scholar for publication contributions. Variables including number of publications, orthopedic publications, first-author authorship, and H-index were analyzed. A logistic regression model was created, and a t-test was conducted to statistically compare the 2027 and 2023 graduating classes. Results Matriculants of the 2023 match had higher numbers of publications, orthopedic surgery-specific publications, first authorships, and h-indices than the matriculants of the 2018 match. Conclusion The average number of publications has been observed to increase over four years, indicating an increase in competition to match into orthopedic surgery residency. Publishing in higher numbers may be a good indicator of an applicant's success in not only matching but also matching into a higher-tier program.

BACKGROUND AND OBJECTIVES: The prevalence of opioid-induced hyperalgesia (OIH) among patients maintained on opioids for chronic non-malignant pain has not been estimated. As a contribution toward establishing its prevalence, we report a case series of opioid maintained patients whose pain tolerance was measured by the cold pressor test at baseline. METHODS: A case series of 117 patients who had undergone detoxification was reviewed retrospectively. Most patients (n = 108) and selected non-addicted support persons who accompanied them (controls; n = 37) had cold pressor time (CPT) assessments at baseline. Twenty patients had a repeat CPT after 1 month. RESULTS: When 61 patients completed one month abstinent reported pain was improved (51%), unchanged (46%), or worse (3%). Baseline CPT was 48 sec for patients and 102 sec for controls, suggesting that opioid maintained patients were more pain sensitive than opioid naïve controls. CPT increased for 90% of 1-month completers, suggesting improved pain tolerance. Ameliorative response to detoxification, psychotherapy, and medical management, as defined as the absence of worsening pain with removal of opioids, was 97% in this population. CONCLUSION: The difference in CPT between opioid maintained patients and controls, and the response to detoxification, psychotherapy and medical management suggest the possibility that the prevalence of OIH may be high. SCIENTIFIC SIGNIFICANCE: This study adds to the growing evidence that chronic opioid treatment contributes little to the management of chronic pain and in fact appears to frequently make it worse. (Am J Addict 2017;26:738-743).

Many interventional strategies are commonly used to treat chronic low back pain (CLBP), though few are specifically intended to target the distinct underlying pathomechanisms causing low back pain. Restorative neurostimulation has been suggested as a specific treatment for mechanical CLBP resulting from multifidus dysfunction. In this randomized controlled trial, we report outcomes from a cohort of patients with CLBP associated with multifidus dysfunction treated with restorative neurostimulation compared to those randomized to a control group receiving optimal medical management (OMM) over 1 year. RESTORE is a multicenter, open-label randomized controlled trial. Candidates were assessed for CLBP associated with multifidus dysfunction, with no indication for or history of lumbar spine surgery. Participants were randomized to either restorative neurostimulation with the ReActiv8 system or OMM. The primary endpoint was a comparison of the mean change in the Oswestry Disability Index (ODI) between the treatment and control arms at 1 year, and secondary endpoints included pain (numeric rating scale [NRS]) and health-related quality of life (EuroQol Five-Dimension [EQ-5D-5L]). A total of 203 patients, average age 47 years, and with an average 11-year history of low back pain, were included in the analysis. The primary endpoint was a statistically significant demonstration of a clinically relevant mean improvement in the Oswestry Disability Index (ODI) between restorative neurostimulation and OMM arms: ODI (−19.7 ± 1.4 vs. −2.9 ± 1.4; p < 0.001). Additionally, improvements in both the numeric rating scale (NRS) (−3.6 ± 0.2 vs. −0.6 ± 0.2; p < 0.001) and EuroQol Five-Dimension (EQ-5D-5L) (0.155 ± 0.012 vs. 0.008 ± 0.012; p < 0.001) were statistically and clinically significant in the restorative neurostimulation arm compared to the OMM arm. The RESTORE trial demonstrates that restorative neurostimulation is a safe, reversible, clinically effective, and highly durable option for patients suffering with nonoperative CLBP associated with multifidus dysfunction. This demonstration of treatment superiority over OMM through 1 year is a significant milestone in addressing a major health burden and unmet clinical need. ClinicalTrials.gov Identifier: NCT04803214. Chronic low back pain can occur as a consequence of dysfunction in the key stabilizing muscles of the spine, the multifidi. This type of low back pain is difficult to treat, with many interventions resulting in limited improvement or short-term relief for a significant proportion of patients. Despite this limitation, these approaches still represent the best available care in most practices. Restorative neurostimulation is a technique that stimulates dysfunctional multifidi, overriding muscle inhibition to improve spinal function, reduce disability, and alleviate pain. The hypothesis was that this treatment is appropriate for a specific subset of patients who have failed to respond to best available conservative and interventional care. The goal of this study was to compare the effect of restorative neurostimulation to standard-of-care interventions (optimal medical management) for patients with chronic mechanical low back pain. Patients with an average 11-year history of chronic low back pain and diagnosed with multifidus dysfunction were randomly assigned to either ongoing optimal medical management or restorative neurostimulation. At 1 year, disability, pain, and healthcare-related quality of life were assessed. Patients treated with restorative neurostimulation demonstrated significant improvements in their clinical outcomes compared to those receiving optimal medical management alone. Device-related adverse events were rare, reinforcing the safety profile of this technique. This study demonstrated that without restorative neurostimulation, patients with chronic low back pain and multifidus dysfunction have very few effective options and obtained little clinical benefit from ongoing optimal medical management. Restorative neurostimulation is an important advancement for this difficult-to-treat population.

Two of the more common potential complications after arthroplasty are venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolus (PE), and excess bleeding. Appropriate chemoprophylaxis choices are essential to prevent some of these adverse events and from exacerbating others. Risk stratification to prescribe safe and effective medications in the prevention of postoperative VTE has shown benefit in this regard. The Department of Orthopaedic Surgery at Syosset Hospital/Northwell Health, which performs over 1200 arthroplasties annually, has validated and is using the 2013 version of the Caprini Risk Assessment Model (RAM) to stratify each patient for risk of postoperative VTE. This tool results in a culling of information, past and present, personal and familial, that provides a truly thorough evaluation of the patient's risk for postoperative VTE. The Caprini score then guides the medication choices for thromboprophylaxis. The Caprini score is only valuable if the data is properly collected, and we have learned numerous lessons after applying it for 18 months. Risk stratification requires practice and experience to achieve expertise in perioperative patient evaluation. Having access to pertinent patient information, while gaining proficiency in completing the Caprini RAM, is vital to its efficacy. Ongoing, real time analyses of patient outcomes, with subsequent change in process, is key to improving patient care.

PURPOSE: To evaluate the proximity to the radial nerve on cadaveric specimens of 2 modified anterolateral portals used for elbow arthroscopy. METHODS: Ten fresh cadaveric elbow specimens were prepared. Four-millimeter Steinman pins were inserted into 3 anterolateral portal sites in relation to the lateral epicondyle: (1) the standard distal anterolateral portal, (2) a modified direct anterolateral portal, and (3) a modified proximal anterolateral portal. These were defined as follows: direct portals 2 cm directly anterior to the lateral epicondyle, and proximal portals 2 cm proximal and 2 cm directly anterior to the lateral epicondyle. Each elbow was then dissected to reveal the course of the radial nerve. Digital photographs were taken of each specimen, and the distance from the Steinman pin to the radial nerve was measured. RESULTS: The modified proximal anterolateral and direct anterolateral portals were found to be a statistically significant distance from the radial nerve compare to the distal portal site (P = .011 and P = .0011, respectively). No significant difference was found in the proximity of the radial nerve between the modified proximal and direct anterolateral portals (P = .25). Inadequate imaging was found at a single portal site for the proximal site; 9 specimens were used for analysis of this portal with 10 complete specimens for the other 2 sites. CONCLUSIONS: In cadaveric analysis, both the modified proximal and direct lateral portals provide adequate distance from the radial nerve and may be safe for clinical use. In this study, the distal anterolateral portal was in close proximity of the radial nerve and may result in iatrogenic injury in the clinical setting. CLINICAL RELEVANCE: This is a cadaveric analysis of 2 modified portal locations at the anterolateral elbow for use in elbow arthroscopy. Further clinical studies are needed prior to determining their absolute safety in comparison to previously identified portal sites.

This article aims to give a brief outline of the pathogenesis and transmission of SARS-CoV-2 and how to safely navigate an arthroplasty practice during and after the pandemic.

IMPORTANCE: Cesarean birth rate among nulliparous, term, singleton, vertex (NTSV) pregnancies is a standard quality measure in obstetrical care. There are limited data on how the number and type of preexisting conditions affect mode of delivery among primigravidae, and it is also uncertain how maternal comorbidity burden differs across racial and ethnic groups and whether this helps to explain disparities in the NTSV cesarean birth rate. OBJECTIVE: To determine the association between obstetric comorbidity index (OB-CMI) score and cesarean delivery among NTSV pregnancies and to evaluate whether disparities in mode of delivery exist based on race and ethnicity group after adjusting for covariate factors. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study of deliveries between January 2019 and December 2021 took place across 7 hospitals within a large academic health system in New York and included all NTSV pregnancies identified in the electronic medical record system. Exclusion criteria were fetal demise and contraindication to labor. EXPOSURE: The OB-CMI score. Covariate factors assessed included race and ethnicity group (American Indian or Alaska Native, Asian or Pacific Islander, Hispanic, non-Hispanic Black, non-Hispanic White, other or multiracial, and declined or unknown), public health insurance, and preferred language. MAIN OUTCOME AND MEASURES: Cesarean delivery. RESULTS: A total of 30 253 patients (mean [SD] age, 29.8 [5.4] years; 100% female) were included. Non-Hispanic White patients constituted the largest race and ethnicity group (43.7%), followed by Hispanic patients (16.2%), Asian or Pacific Islander patients (14.6%), and non-Hispanic Black patients (12.2%). The overall NTSV cesarean birth rate was 28.5% (n = 8632); the rate increased from 22.1% among patients with an OB-CMI score of 0 to greater than 55.0% when OB-CMI scores were 7 or higher. On multivariable mixed-effects logistic regression modeling, there was a statistically significant association between OB-CMI score group and cesarean delivery; each successive OB-CMI score group had an increased risk. Patients with an OB-CMI score of 4 or higher had more than 3 times greater odds of a cesarean birth (adjusted odds ratio, 3.14; 95% CI, 2.90-3.40) than those with an OB-CMI score of 0. Compared with non-Hispanic White patients, nearly all other race and ethnicity groups were at increased risk for cesarean delivery, and non-Hispanic Black patients were at highest risk (adjusted odds ratio, 1.43; 95% CI, 1.31-1.55). CONCLUSIONS AND RELEVANCE: In this cross-sectional study of patients with NTSV pregnancies, OB-CMI score was positively associated with cesarean birth. Racial and ethnic disparities in this metric were observed. Although differences in the prevalence of preexisting conditions were seen across groups, this did not fully explain variation in cesarean delivery rates, suggesting that unmeasured clinical or nonclinical factors may have influenced the outcome.

Nongenetic predisposition to colorectal cancer continues to be difficult to measure precisely, hampering efforts in targeted prevention and screening. Epigenetic changes in the normal mucosa of patients with colorectal cancer can serve as a tool in predicting colorectal cancer outcomes. We identified epigenetic changes affecting the normal mucosa of patients with colorectal cancer. DNA methylation profiling on normal colon mucosa from 77 patients with colorectal cancer and 68 controls identified a distinct subgroup of normally-appearing mucosa with markedly disrupted DNA methylation at a large number of CpGs, termed as "Outlier Methylation Phenotype" (OMP) and are present in 15 of 77 patients with cancer versus 0 of 68 controls (P < 0.001). Similar findings were also seen in publicly available datasets. Comparison of normal colon mucosa transcription profiles of patients with OMP cancer with those of patients with non-OMP cancer indicates genes whose promoters are hypermethylated in the OMP patients are also transcriptionally downregulated, and that many of the genes most affected are involved in interactions between epithelial cells, the mucus layer, and the microbiome. Analysis of 16S rRNA profiles suggests that normal colon mucosa of OMPs are enriched in bacterial genera associated with colorectal cancer risk, advanced tumor stage, chronic intestinal inflammation, malignant transformation, nosocomial infections, and KRAS mutations. In conclusion, our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Prospective studies are needed to determine whether OMP could serve as a biomarker for an elevated epigenetic risk for colorectal cancer development. PREVENTION RELEVANCE: Our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Identification of OMPs in healthy controls and patients with colorectal cancer will lead to prevention and better prognosis, respectively.