Does obesity and varying body mass index affect the clinical outcomes and safety of biportal endoscopic lumbar decompression? A comparative cohort study.

BACKGROUND: Endoscopic spine surgery has recently grown in popularity due to the potential benefits of reduced pain and faster recovery time as compared to open surgery. Biportal spinal endoscopy has been successfully applied to lumbar disc herniations and lumbar spinal stenosis. Obesity is associated with increased risk of complications in spine surgery. Few prior studies have investigated the impact of obesity and associated medical comorbidities with biportal spinal endoscopy. METHODS: This study was a prospectively collected, retrospectively analyzed comparative cohort design. Patients were divided into cohorts of normal body weight (Bone Mass Index (BMI)18.0-24.9), overweight (BMI 25.0-29.9) and obese (BMI > 30.0) as defined by the World Health Organization (WHO). Patients underwent biportal spinal endoscopy by a single surgeon at a single institution for treatment of lumbar disc herniations and lumbar spinal stenosis. Demographic data, surgical complications, and patient-reported outcomes were analyzed. Statistics were calculated amongst treatment groups using analysis of variance and chi square where appropriate. Statistical significance was determined as p < 0.05. RESULTS: Eighty-four patients were followed. 26 (30.1%) were normal BMI, 35 (41.7%) were overweight and 23 (27.4%) were obese. Patients with increasing BMI had correspondingly greater American Society of Anesthesiologist (ASA) scores. There were no significant differences in VAS Back, VAS Leg, and ODI scores, or postoperative complications among the cohorts. There were no cases of surgical site infections in the cohort. All cohorts demonstrated significant improvement up to 1 year postoperatively. CONCLUSIONS: This study demonstrates that obesity is not a risk factor for increased perioperative complications with biportal spinal endoscopy and has similar clinical outcomes and safety profile as compared to patients with normal BMI. Biportal spinal endoscopy is a promising alternative to traditional techniques to treat common lumbar pathology.

Multi-disciplinary Insights from the First European Forum on Visceral Myopathy 2022 Meeting.

Visceral myopathy is a rare, life-threatening disease linked to identified genetic mutations in 60% of cases. Mostly due to the dearth of knowledge regarding its pathogenesis, effective treatments are lacking. The disease is most commonly diagnosed in children with recurrent or persistent disabling episodes of functional intestinal obstruction, which can be life threatening, often requiring long-term parenteral or specialized enteral nutritional support. Although these interventions are undisputedly life-saving as they allow affected individuals to avoid malnutrition and related complications, they also seriously compromise their quality of life and can carry the risk of sepsis and thrombosis. Animal models for visceral myopathy, which could be crucial for advancing the scientific knowledge of this condition, are scarce. Clearly, a collaborative network is needed to develop research plans to clarify genotype-phenotype correlations and unravel molecular mechanisms to provide targeted therapeutic strategies. This paper represents a summary report of the first 'European Forum on Visceral Myopathy'. This forum was attended by an international interdisciplinary working group that met to better understand visceral myopathy and foster interaction among scientists actively involved in the field and clinicians who specialize in care of people with visceral myopathy.

Visceral myopathy: clinical syndromes, genetics, pathophysiology, and fall of the cytoskeleton.

Visceral smooth muscle is a crucial component of the walls of hollow organs like the gut, bladder, and uterus. This specialized smooth muscle has unique properties that distinguish it from other muscle types and facilitate robust dilation and contraction. Visceral myopathies are diseases where severe visceral smooth muscle dysfunction prevents efficient movement of air and nutrients through the bowel, impairs bladder emptying, and affects normal uterine contraction and relaxation, particularly during pregnancy. Disease severity exists along a spectrum. The most debilitating defects cause highly dysfunctional bowel, reduced intrauterine colon growth (microcolon), and bladder-emptying defects requiring catheterization, a condition called megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS). People with MMIHS often die early in childhood. When the bowel is the main organ affected and microcolon is absent, the condition is known as myopathic chronic intestinal pseudo-obstruction (CIPO). Visceral myopathies like MMIHS and myopathic CIPO are most commonly caused by mutations in contractile apparatus cytoskeletal proteins. Here, we review visceral myopathy-causing mutations and normal functions of these disease-associated proteins. We propose molecular, cellular, and tissue-level models that may explain clinical and histopathological features of visceral myopathy and hope these observations prompt new mechanistic studies.

Pregnancy-Induced Sensitization Promotes Sex Disparity in Living Donor Kidney Transplantation.

The presence of sex disparity in living donor kidney transplantation (LDKT) remains controversial. To determine if women fall behind men in LDKT evaluation, we performed an intention to treat study of 2587 candidates listed for kidney transplant at a single transplant center over 7 years. We found that women and men kidney transplant candidates engaged an equivalent type and number of prospective living donors. However, sex-specific differences in sensitization history and histocompatibility reduced the rate of LDKT for women by 30%. Pregnancy-induced incompatibility with spouse donors was limiting given that spouses were among the individuals most likely to complete donation. Notably, participation in a kidney paired exchange program eliminated sex-based differences in LDKT. Collectively, these data suggest that pregnancy is a formidable biologic barrier for women and contributes uniquely to sex disparity in LDKT. Targeted efforts to improve transplant center participation in paired kidney exchanges may increase sex equity in LDKT.

What Demographic and Clinical Characteristics Correlate With Expectations With Trapeziometacarpal Arthritis?

BACKGROUND: Pretreatment variables have been shown to be associated with the fulfillment of patient expectations, yet in treating thumb trapeziometacarpal osteoarthritis (OA) it remains unclear how patient expectations correlate with the effectiveness of treatment. An increased understanding of the variables that affect patient expectations enables tailored patient education and patient-provider communication. QUESTIONS/PURPOSES: (1) Is there a correlation between patient demographics and clinical characteristics, and the expectations the patients have when seeking treatment for trapeziometacarpal OA? (2) What factors are independently associated with the total expectations score and frequency of expecting "back to normal" among patients treated for trapeziometacarpal OA? METHODS: Between March 2011 and October 2013, 89 patients of all 96 eligible patients seeking treatment for trapeziometacarpal OA were approached and agreed to participate in this study. Participants completed a validated expectations survey measuring the number of expectations and the degree of improvement expected. Comparative analysis of demographic and clinical characteristics and multivariate regression analysis against patients' expectations were performed to assess and identify factors that correlate with the number and degree of expectations. Sample size was determined with an a priori power analysis (with 80% power and statistical significance set at p < 0.05), which showed that 88 patients were needed to detect the minimal clinical difference of 12 points in the Michigan Hand Questionnaire; we then increased this by 10% to allow for potential dropouts. RESULTS: After controlling for potential confounding variables such as age, hand dominance, and work status, the following factors were associated with a higher expectations score: choice of surgery (ß = 11.5; 95% CI, 0.7-23.8; p = 0.044), female gender (ß = 19.0; 95% CI, 5.3-32.7; p = 0.007), and dominant side affected (ß = -41.6; 95% CI, -63.7 to -19.5; p < 0.001). For the frequency of "back to normal" responses, surgical treatment (ß = 7.4; 95% CI, 2.3-12.4; p = 0.005) and history of previous injury (ß = 8.2; 95% CI, 0.1-16.3; p = 0.047) were independently associated factors after controlling for confounding variables. There were no independent associations with age, marital status, work status, depression or anxiety, or prior contralateral surgery. CONCLUSIONS: Patients whose dominant side was affected, were female, and chose surgical treatment, had higher total expectations. Patients who reported an antecedent injury and chose surgical treatment more frequently expected a return to normal. With identification of these factors, orthopaedic surgeons can recognize patients who are prone to higher expectations, and, thus, have the opportunity to implement efficient pretreatment education. In addition, identification of specific factors enables a focused measure of the effect of these factors on the fulfillment of expectations. LEVEL OF EVIDENCE: Level II, prognostic study.

Patients With Thumb Carpometacarpal Arthritis Have Quantifiable Characteristic Expectations That Can Be Measured With a Survey.

BACKGROUND: Although patient expectations associated with major orthopaedic conditions have shown clinically relevant and variable effects on outcomes, expectations associated with thumb carpometacarpal (CMC) arthritis have not been identified, described, or analyzed before, to our knowledge. QUESTIONS/PURPOSES: We asked: (1) Do patients with thumb CMC arthritis express characteristic expectations that are quantifiable and have measurable frequency? (2) Can a survey on expectations developed from patient-derived data quantitate expectations in patients with thumb CMC arthritis? METHODS: The study was a prospective cohort study. The first phase was a 12-month-period involving interviews of 42 patients with thumb CMC arthritis to define their expectations of treatment. The interview process used techniques and principles of qualitative methodology including open-ended interview questions, unrestricted time, and study size determined by data saturation. Verbatim responses provided content for the draft survey. The second phase was a 12-month period assessing the survey for test-retest reliability with the recruitment of 36 participants who completed the survey twice. The survey was finalized from clinically relevant content, frequency of endorsement, weighted kappa values for concordance of responses, and intraclass coefficient and Cronbach's alpha for interrater reliability and internal consistency. RESULTS: Thirty-two patients volunteered 256 characteristic expectations, which consisted of 21 discrete categories. Expectations with similar concepts were combined by eliminating redundancy while maintaining original terminology. These were reduced to 19 items that comprised a one-page survey. This survey showed high concordance, interrater reliability, and internal consistency, with weighted kappa values between 0.58 and 0.78 (95% CI, 0.39-0.78; p < 0.001); intraclass correlation coefficient of 0.94 (95% CI, 0.94-0.98; p < 0.001), and Cronbach's alpha values of 0.94 and 0.95 (95% CI, 0.91-0.96; p < 0.001). The thumb CMC arthritis expectations survey score is convertible to an overall score between 0 to 100 points calculated on the basis of the number of expectations and the degree of improvement expected, with higher scores indicating higher expectations. CONCLUSIONS: Patients with thumb CMC arthritis volunteer a characteristic and quantifiable set of expectations. Using responses recorded verbatim from patient interviews, a clinically relevant, valid, and reliable expectations survey was developed that measures the physical and psychosocial expectations of patients seeking treatment for CMC arthritis. The survey provides a calculable score that can record patients' expectations. Clinical application of this survey includes identification of factors that influence fulfilment of these expectations. LEVEL OF EVIDENCE: Level II, prospective study.

The effect of rhBMP-2 in a novel, non-instrumented extremity nonunion model.

BACKGROUND: Pre-clinical models of bony nonunion typically employ critical-length defects. However, these models may not accurately reflect clinical practice since many nonunions are diagnosed without bone loss. We developed a non-displaced rat ulna fracture model in order to examine the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) with an absorbable collagen sponge (ACS) for nonunion treatment. METHODS: Transverse diaphyseal ulna fractures were created in 24 Sprague-Dawley rats. Eight animals (Group 1: Nonunion) received no further intervention. The remaining 16 animals were treated with 5 µg rhBMP-2/ACS at 8 weeks after the original intervention (Group 2: Nonunion + BMP) or at the time of initial injury (Group 3: Fresh fracture + BMP). RESULTS: In Group 1, 7 of 8 fractures demonstrated gross motion and a persistent radiographic gap (12.5% healing rate). In Groups 2 and 3, fractures healed at a rate of 75% (6 of 8 in each group) as determined by manual and radiographic evaluation. Biomechanical testing for torque load-to-failure and torsional stiffness demonstrated no significant difference between healed specimens treated with rhBMP-2. CONCLUSIONS: To our knowledge, this is the first description of a physiologic, non-stabilized, non-defect fracture nonunion model in a rodent. Furthermore, unlike previous nonunion models, the healing rates after treatment with rhBMP-2 are comparable to that of clinical data, suggesting that this model may provide an environment more representative of nonunions in humans.

Surgical Site Infections in Spinal Surgery.

Surgical site infections (SSIs) are a potentially devastating complication of spine surgery. SSIs are defined by the Centers for Disease Control and Prevention as occurring within 30 days of surgery or within 12 months of placement of foreign bodies, such as spinal instrumentation. SSIs are commonly categorized by the depth of surgical tissue involvement (ie, superficial, deep incisional, or organ and surrounding space). Postoperative infections result in increased costs and postoperative morbidity. Because continued research has improved the evaluation and management of spinal infections, spine surgeons must be aware of these modalities. The controversies in evaluation and management of SSIs in spine surgery will be reviewed.

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.

A Comparison of Short-Term Outcomes after Surgical Treatment of Multilevel Degenerative Cervical Myelopathy in the Geriatric Patient Population: An Analysis of the National Surgical Quality Improvement Program Database 2010-2020.

STUDY DESIGN: Retrospective review of the American College of Surgeons-National Surgical Quality Improvement Program database from 2010 to 2020. PURPOSE: To compare the short-term complication rates of anterior cervical decompression and fusion (ACDF), posterior cervical laminoplasty (LP), and posterior cervical laminectomy and fusion (PCF) in a geriatric population. OVERVIEW OF LITERATURE: The geriatric population in the United States has increased significantly. Degenerative cervical myelopathy (DCM) is caused by cervical spinal stenosis, and its prevalence increases with age. Therefore, the incidence of multilevel DCM requiring surgical intervention is likely to increase. ACDF, LP, and PCF are the most commonly used surgical techniques for treating multilevel DCM. However, there is uncertainty regarding the optimal surgical technique for the decompression of DCM in geriatric patients. METHODS: Patients aged 65 years who had undergone either multilevel ACDF, LP, or PCF for the treatment of DCM were analyzed. Additional analysis was performed by standardizing the data for the American Society of Anesthesiologists classification scores and preoperative functional status. RESULTS: A total of 23,129 patients were identified. Patients with ACDF were younger, more often female, and preoperatively healthier than those in the other two groups. The estimated postoperative mortality and morbidity, mean operation time, and length of hospital stay were the lowest for ACDF, second lowest for LP, and highest for PCF. The readmission and reoperation rates were comparable between ACDF and LP; however, both were significantly lower than PCF. CONCLUSIONS: PCF is associated with the highest risk of mortality, morbidity, unplanned reoperation, and unplanned readmission in the short-term postoperative period in patients aged 65 years. In contrast, ACDF carries the lowest risk. However, some disease-specific factors may require posterior treatment. For these cases, LP should be included in the preoperative discussion when determining the ideal surgical approach for geriatric patients.

Contemporary Trends in the Orthopaedic Surgery Residency Match and the Effects of COVID-19.

Objective: We aimed to elucidate associations between geographic location, size, and ranking of medical schools that orthopaedic surgery residents graduate from and the residencies that they match both pre-COVID-19 and post-COVID-19 pandemic by examining the 2017 to 2022 orthopaedic surgery residency cohorts. Methods: Demographics were extracted using Doximity Residency Navigator platform, the 2021 US News and World Report, and program websites. Medical schools were classified as large if they had >613 medical students. Postgraduate year 1 (PGY-1) (2021 match) and PGY-2 (2022 match) residents were classified as the COVID-19 cohort. Location was categorized as Northeast, Midwest, South, and West. Chi-square tests, Cohen's H value, and descriptive statistics were used for analysis with statistical significance set at p <0.05. Results: Four thousand two hundred forty-three residents from 160 accredited US orthopaedic residency programs (78.4%) were included. Northeastern applicants were most likely to match in the same region (p <0.01), and southern applicants were most likely to match at their home program (p <0.001). Applicants affected by the COVID-19 pandemic did not differ from their predecessors with regards to matching to the same region (p = 0.637) or home program (p = 0.489). Applicants from public medical schools were more likely to match in the same region and at their home program (p <0.001), whereas those from private medical schools were more likely to match at top-ranked residencies (p <0.001). Students from both top 25- and top 50-ranked medical schools were more likely to match at their home program (p <0.01) and attend top 20-ranked residency programs (p <0.0001). Conclusion: These results demonstrate significant associations between matched residencies and attended medical schools' geographic location, school type, and ranking. During the pandemic, geographic trends were overall unchanged, whereas residents from large or lower-ranked schools were more likely to match at home programs, and those from private or top-ranked schools were less likely to attend top residencies.

The Role of Perioperative Nutritional Status and Supplementation in Orthopaedic Surgery: A Review of Postoperative Outcomes.

¼ Identification of malnourished and at-risk patients should be a standardized part of the preoperative evaluation process for every patient.¼ Malnourishment is defined as a disorder of energy, protein, and nutrients based on the presence of insufficient energy intake, weight loss, muscle atrophy, loss of subcutaneous fat, localized or generalized fluid accumulation, or diminished functional status.¼ Malnutrition has been associated with worse outcomes postoperatively across a variety of orthopaedic procedures because malnourished patients do not have a robust metabolic reserve available for recovery after surgery.¼ Screening assessment and basic laboratory studies may indicate patients' nutritional risk; however, laboratory values are often not specific for malnutrition, necessitating the use of prognostic screening tools.¼ Nutrition consultation and perioperative supplementation with amino acids and micronutrients are 2 readily available interventions that orthopaedic surgeons can select for malnourished patients.

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.

Comparison of CT-Guided needle biopsy versus percutaneous endoscopic debridement and drainage in pathogen identification and pain outcomes for spondylodiscitis patients: A systematic review and literature review.

Introduction: Spondylodiscitis (SD) is an infection of the intervertebral disc with involvement of the adjacent vertebral bodies. Diagnostic tests with CT-guided biopsy only provide a positive yield in 14%-48% of cases. Percutaneous endoscopic debridement and drainage (PEDD) has recently shown promise in the treatment of spondylodiscitis. Research question: The purpose of this study is to determine differences in pathogen identification and clinical outcomes for PEDD versus CT-guided needle biopsy in SD patients. Materials and methods: We conducted a systematic review of the literature using PRISMA guidelines to determine differences in positive microbiology results, perioperative complications, pain control, and long-term clinical outcomes for PEDD vs. CT-guided needle biopsy in SD patients. Results: 1078 studies were evaluated, 87 of which underwent full review. 15 studies met the inclusion and exclusion criteria, including 7 PEDD, 7 CT-guided biopsy, and 1 CT-guided biopsy vs. PEDD article, for a total of 192 PEDD patients and 604 CT-guided biopsy patients. We found 36.59% of CT-guided biopsy patients had positive microbiology results, compared to 84.38% of PEDD patients. No major perioperative complications occurred as a result of the PEDD procedure. Of the five PEDD studies that reported pain outcomes, greater than 80% of patients experienced relief after intervention. Discussion and conclusion: These results suggest that PEDD may improve pathogen identification while simultaneously reducing pain compared to CT-guided needle biopsy in SD. Although current treatment guidelines recommend CT-guided biopsy, in patients with severe back pain and suspected SD, PEDD can be considered an alternative intervention.

Effect of the administration route on the hemostatic efficacy of tranexamic acid in patients undergoing short-segment posterior lumbar interbody fusion: a systematic review and meta-analysis.

OBJECTIVE: Tranexamic acid (TXA) is an FDA-approved antifibrinolytic that is seeing increased popularity in spine surgery owing to its ability to reduce intraoperative blood loss (IOBL) and allogeneic transfusion requirements. The present study aimed to summarize the current literature on these formulations in the context of short-segment instrumented lumbar fusion including ≥ 1-level posterior lumbar interbody fusion (PLIF). METHODS: The PubMed, Cochrane, and Web of Science databases were queried for all full-text English studies evaluating the use of topical TXA (tTXA), systemic TXA (sTXA), or combined tTXA+sTXA in patients undergoing PLIF. The primary endpoints of interest were operative time, IOBL, and total blood loss (TBL); secondary endpoints included venous thromboembolic complication occurrence, and allogeneic and autologous transfusion requirements. Outcomes were compared using random effects. Comparisons were made between the following treatment groups: sTXA, tTXA, and sTXA+tTXA. Given that sTXA is arguably the standard of care in the literature (i.e., the most common route of administration that to this point has been studied the most), the authors compared sTXA versus tTXA and sTXA versus sTXA+tTXA. Study heterogeneity was assessed with the I2 test, and grouped analysis using the Hedge's g test was performed for measurement of effect size. RESULTS: Forty-five articles were identified, of which 17 met the criteria for inclusion with an aggregate of 1008 patients. TXA regimens included sTXA only, tTXA only, and various combinations of sTXA and tTXA. There were no significant differences in operative time, TBL, or postoperative drainage between the sTXA and tTXA groups or between the sTXA and sTXA+tTXA groups. CONCLUSIONS: The present meta-analysis suggested clinical equipoise between isolated sTXA, isolated tTXA, and combinatorial tTXA+sTXA formulations as hemostatic adjuvants/neoadjuvants in short-segment fusion including ≥ 1-level PLIF. Given the theoretically lower venous thromboembolism risk associated with tTXA, additional investigations using large cohorts comparing these two formulations within the posterior fusion population are merited. Although TXA has been shown to be effective, there are insufficient data to support topical or systemic administration as superior within the open PLIF population.

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.

Generation of CHOPi012-A iPSC line from a patient with visceral myopathy-related chronic intestinal pseudo-obstruction.

Visceral myopathies are debilitating conditions characterized by dysfunction of smooth muscle in visceral organs (bowel, bladder, and uterus). Individuals affected by visceral myopathy experience feeding difficulties, growth failure, life-threatening abdominal distension, and may depend on intravenous nutrition for survival. Unfortunately, our limited understanding of the pathophysiology of visceral myopathies means that current therapies remain supportive, with no mechanism-based treatments. We developed a patient-derived iPSC line with a c.769C > T p.R257C/+ mutation, the most common genetic cause of visceral myopathy. This cell line will facilitate studies of how the ACTG2 R257C heterozygous variant affects smooth muscle development and function.

Generation of CHOPe003-A ESC line to study an ACTG2 variant affecting smooth muscle development and function.

Dysfunction of visceral smooth muscle ("visceral myopathy") impairs bowel, bladder, and uterine function. Symptoms of this life-threatening condition include massive intestinal distension with slow transit, vomiting, feeding intolerance, growth failure, poor bladder emptying, and difficult vaginal delivery. The most common genetic cause of visceral myopathy is a heterozygous point mutation (R257C) in gamma smooth muscle actin (ACTG2). We genetically modified the WAe0009-A human embryonic stem cell line to carry the c.769C>T p.R257C/+ mutation. This cell line will facilitate studies of how the ACTG2 R257C heterozygous variant affects smooth muscle development and function.

Single Nucleus Sequencing of Human Colon Myenteric Plexus-Associated Visceral Smooth Muscle Cells, Platelet Derived Growth Factor Receptor Alpha Cells, and Interstitial Cells of Cajal.

BACKGROUND AND AIMS: Smooth muscle cells (SMCs), interstitial cells of Cajal (ICCs), and platelet-derived growth factor receptor alpha (PDGFRα+) cells (PαCs) form a functional syncytium in the bowel known as the "SIP syncytium." The SIP syncytium works in concert with the enteric nervous system (ENS) to coordinate bowel motility. However, our understanding of individual cell types that form this syncytium and how they interact with each other remains limited, with no prior single-cell RNAseq analyses focused on human SIP syncytium cells. METHODS: We analyzed single-nucleus RNA sequencing data from 10,749 human colon SIP syncytium cells (5572 SMC, 372 ICC, and 4805 PαC nuclei) derived from 15 individuals. RESULTS: Consistent with critical contractile and pacemaker functions and with known enteric nervous system interactions, SIP syncytium cell types express many ion channels, including mechanosensitive channels in ICCs and PαCs. PαCs also prominently express extracellular matrix-associated genes and the inhibitory neurotransmitter receptor for vasoactive intestinal peptide (VIPR2), a novel finding. We identified 2 PαC clusters that differ in the expression of many ion channels and transcriptional regulators. Interestingly, SIP syncytium cells co-express 6 transcription factors (FOS, MEIS1, MEIS2, PBX1, SCMH1, and ZBTB16) that may be part of a combinatorial signature that specifies these cells. Bowel region-specific differences in SIP syncytium gene expression may correlate with regional differences in function, with right (ascending) colon SMCs and PαCs expressing more transcriptional regulators and ion channels than SMCs and PαCs in left (sigmoid) colon. CONCLUSION: These studies provide new insights into SIP syncytium biology that may be valuable for understanding bowel motility disorders and lead to future investigation of highlighted genes and pathways.