Warfarin, not direct oral anticoagulants nor antiplatelet therapy, is associated with increased bleeding risk in emergency general surgery patients: implications in this new era of novel anticoagulants: An EAST Multicenter study.

INTRODUCTION: To assess perioperative bleeding complications & in-hospital mortality in patients requiring emergency general surgery (EGS) presenting with a history of antiplatelet (AP) vs. direct oral anticoagulant (DOAC) vs warfarin use. METHODS: Prospective observational study across 21 centers between 2019-2022. Inclusion criteria were age ≥ 18 years, & DOAC, warfarin or AP use within 24 hours of an EGSP. Outcomes included perioperative bleeding and in-hospital mortality. The study was conducted using ANOVA, Chi-square, and multivariable regression models. RESULTS: Of the 413 patients, 221 (53.5%) reported AP use, 152 (36.8%) DOAC use, & 40 (9.7%) warfarin use. Most common indications for surgery were obstruction (23% (AP), 45% (DOAC), 28% (warfarin)), intestinal ischemia (13%, 17%, 23%), & diverticulitis/peptic ulcers (7%, 7%, 15%). Compared to DOAC use, warfarin use was associated with significantly higher perioperative bleeding complication (OR 4.4 [2.0, 9.9]). There was no significant difference in perioperative bleeding complication between DOAC & AP use (OR 0.7 [0.4, 1.1]). Compared to DOAC use, there was no significant difference in mortality between warfarin use (0.7 [0.2, 2.5]) or AP use (OR 0.5 [0.2, 1.2]). After adjusting for confounders, warfarin use (OR 6.3 [2.8, 13.9]), medical history and operative indication were associated with an increase in perioperative bleeding complications. However, warfarin was not independently associated with risk of mortality (OR 1.3 [0.39, 4.7]), whereas intraoperative vasopressor use (OR 4.7 [1.7, 12.8)), medical history & postoperative bleeding (OR 5.5 [2.4, 12.8]) were. CONCLUSIONS: Despite ongoing concerns about the increase in DOAC use & lack of readily available reversal agents, this study suggests that warfarin, rather than DOACs, is associated with higher perioperative bleeding complications. However, that risk does not result in an increase in mortality, suggesting that perioperative decisions should be dictated by patient disease & comorbidities rather than type of antiplatelet or anticoagulant use.

Shoulder terminal sensory articular nerve radiofrequency ablation for non-surgical refractory shoulder pain due to rotator cuff pathology and osteoarthritis: A technical note.

BACKGROUND: Given the high prevalence of chronic shoulder pain and encouraging early results of terminal sensory articular branch (TSAB) radiofrequency ablation to treat shoulder pain, research is warranted to refine the procedural technique based on updated neuroanatomical knowledge with the goal of further improving patient outcomes. OBJECTIVE: We describe an updated radiofrequency ablation protocol that accounts for varied locations of the TSABs of suprascapular, axillary, subscapular and lateral pectoral nerves within individual patients. DESIGN: Technical note. METHODS: Cadaveric studies delineating the sensory innervation of the shoulder joint were reviewed, and a more comprehensive radiofrequency ablation (RFA) protocol is proposed relative to historical descriptions. CONCLUSIONS: Based on neuroanatomical dissections of the shoulder joint, the proposed RFA protocol will provide a safe means of more complete sensory denervation and potentially improve clinical outcomes compared to historical descriptions, which must be confirmed in prospective studies.

Low back pain-related healthcare utilization following intraosseous basivertebral nerve radiofrequency ablation: a pooled analysis from three prospective clinical trials.

BACKGROUND: The effectiveness and safety of intraosseous basivertebral nerve ablation (BVNA) for treating vertebrogenic pain is established, but low back pain-related healthcare utilization (LBPr-HU) following BVNA continues to be defined. METHODS: LBPr-HU data were pooled from 3 prospective studies. LBPr-HU categories of interest included non-invasive conservative care, opioid utilization, lumbosacral spinal injection (LSI), lumbosacral radiofrequency ablation (LRFA), and lumbosacral spinal surgery. Pre- and post-BVNA LBPr-HU were compared at both 1- and 5-years using McNemar's test for proportions and paired t-tests for means. RESULTS: Two hundred forty-seven patients received BVNA and had 1-year follow-up; 205 had long-term follow-up (mean of 5.3 ± 1.33 years). Twenty-seven percent fewer participants initiated conservative care in the year post-BVNA compared to the year preceding BVNA (P < .001; 95% CI 19.8-34.5). Of 77/247 participants taking opioids at baseline, 40.3% and 61.7% fewer were taking them at one-year and 5.3 ± 1.33 years post-BVNA, respectively (P < .001). Of participants receiving LSIs in the year preceding BVNA, 81.2% fewer received LSI(s) in the year post-BVNA (P < .001; 95% CI 70.7-90.7); a 76.4% reduction in LSIs was maintained through a mean of 5.3 ± 1.33 years post-BVNA. LRFA rates were 1.6% at 1-year post-BVNA and 8.3% at 5.3 ± 1.33 years post-BVNA. Lumbar fusion surgery was 0.8% at 1-year post-BVNA and 6.5% at 5.3 ± 1.33 years post-BVNA. CONCLUSIONS: In this aggregate analysis of patients with vertebrogenic pain, utilization of conservative care, opioids, LSIs, and LRFA were substantially reduced through 5 years post-BVNA compared to baseline. Lumbar fusion rates were less than half the published value at 5 years in similar populations.

The effectiveness of intradiscal corticosteroid injection for the treatment of chronic discovertebral low back pain: a systematic review.

OBJECTIVE: Determine the effectiveness of intradiscal corticosteroid injection (IDCI) for the treatment of discovertebral low back pain. DESIGN: Systematic review. POPULATION: Adults with chronic low back pain attributed to disc or vertebral end plate pain, as evidenced by positive provocation discography or Modic 1 or 2 changes on magnetic resonance imaging. INTERVENTION: Fluoroscopically guided or computed tomography-guided IDCI. COMPARISON: Sham/placebo procedure including intradiscal saline, anesthetic, discography alone, or other active treatment. OUTCOMES: Reduction in chronic low back pain reported on a visual analog scale or numeric rating scale and reduction in disability reported by a validated scale such as the Oswestry Disability Index. METHODS: Four reviewers independently assessed articles published before January 31, 2023, in Medline, Embase, CENTRAL, and CINAHL. The quality of evidence was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The risk of bias in randomized trials was evaluated with the Cochrane Risk of Bias tool (version 2). RESULTS: Of the 7806 unique records screened, 6 randomized controlled trials featuring 603 total participants ultimately met the inclusion criteria. In multiple randomized controlled trials, IDCI was found to reduce pain and disability for 1-6 months in those with Modic 1 and 2 changes but not in those selected by provocation discography. CONCLUSION: According to GRADE, there is low-quality evidence that IDCI reduces pain and disability for up to 6 months in individuals with chronic discovertebral low back pain as evidenced by Modic 1 and 2 changes but not in individuals selected by provocation discography. STUDY REGISTRATION: PROSPERO (CRD42021287421).

A pragmatic randomized prospective trial of cooled radiofrequency ablation of the medial branch nerves versus facet joint injection of corticosteroid for the treatment of lumbar facet syndrome: 12 month outcomes.

BACKGROUND: Lumbar medial branch radiofrequency ablation (LRFA) and intraarticular facet steroid injections (FJI) are commonly performed for recalcitrant facet joint-mediated pain. However, no study has compared clinical outcomes of the two treatments in patients selected using dual medial branch blocks (MBBs) with an 80% relief threshold. OBJECTIVE: Compare the effectiveness of cooled LRFA (C-LRFA) to FIJ as assessed by pain and functional improvements. DESIGN: Prospective randomized comparative trial. METHODS: Patients with dual MBB-confirmed facet joint-mediated pain were randomized to receive C-LRFA or FIJ. Outcomes were assessed at 1, 3, 6, and 12 months. The primary outcome was ≥50% improvement in numerical pain rating scale (NPRS) score at 3 months. Secondary outcomes included ≥30% Oswestry Disability Index (ODI) improvement and Patient Global Impression of Chance (PGIC) ≥6 points, among others. Data were analyzed using contingency tables and mixed-effects logistic regression models. RESULTS: Of 1128 patients screened, 32 met eligibility criteria, were randomized, and received their allocated study treatment. In total, 20 (62.5%) and 12 (37.5%) participants received C-LRFA and FIJ, respectively. In the C-LRFA group, 70% (95% CI 48-85), 55% (95% CI 34-74), and 45% (95% CI 26-66) of participants met the NPRS responder definition, compared to 25% (95%CI 9-53), 25% (95% CI 9-53), and 17% (95% CI 5-45) in the FJI group at 3, 6, and 12 months, respectively (P = .014 at 3 months). The PGIC responder proportion was higher in the C-LRFA compared to FJI group at 3 and 6 months (P < .05). CONCLUSIONS: C-LRFA demonstrated superior success rates compared to FJI across pain and functional outcome domains. TRIAL REGISTRATION DETAILS: ClinicalTrials.gov (NCT03614793); August 3, 2018.

Genicular nerve radiofrequency ablation for the treatment of chronic knee joint pain: a real-world cohort study with evaluation of prognostic factors.

BACKGROUND: Genicular nerve radiofrequency ablation (GNRFA) is an effective treatment for chronic knee pain. However, there has been minimal investigation of real-world, long-term outcomes and factors that predict treatment success after GNRFA. OBJECTIVES: To evaluate the effectiveness of GNRFA for chronic knee pain in a real-world population and identify predictive factors. METHODS: Consecutive patients who underwent GNRFA at a tertiary academic center were identified. Demographic, clinical, and procedural characteristics were collected from the medical record. Outcome data were numeric rating scale (NRS) pain reduction and Patient Global Impression of Change (PGIC). Data were collected by standardized telephone survey. Predictors of success were evaluated with logistic and Poisson regression analyses. RESULTS: Of the 226 total patients identified, 134 (65.6 ± 12.7; 59.7% female) were successfully contacted and analyzed, with a mean follow-up time of 23.3 ± 11.0 months. Of those, 47.8% (n = 64; 95% CI: 39.5%-56.2%) and 61.2% (n = 82; 95% CI: 52.7%-69.0%) reported ≥50% NRS score reduction and ≥2-point NRS score reduction, respectively, and 59.0% (n = 79; 95% CI: 50.5%-66.9%) reported "much improved" on the PGIC questionnaire. Factors associated with a greater likelihood of treatment success (P < .05) were higher Kellgren-Lawrence osteoarthritis grade (2-4 vs 0-1); no baseline opioid, antidepressant, or anxiolytic medication use; and >3 nerves targeted. CONCLUSION: In this real-world cohort, approximately half of the participants experienced clinically meaningful improvements in knee pain after GNRFA at an average follow-up time of nearly 2 years. Factors associated with higher likelihood of treatment success were more advanced osteoarthritis (Kellgren-Lawrence Grade 2-4); no opioid, antidepressant, or anxiolytic medication use; and >3 nerves targeted.

Anticoagulation in emergency general surgery: Who bleeds more? The EAST multicenter trials ACES study.

BACKGROUND: While direct oral anticoagulant (DOAC) use is increasing in the Emergency General Surgery (EGS) patient population, our understanding of their bleeding risk in the acute setting remains limited. Therefore, the objective of this study was to determine the prevalence of perioperative bleeding complications in patients using DOACs versus warfarin and AP therapy requiring urgent/emergent EGS procedures (EGSPs). METHODS: This was a prospective observational trial, conducted between 2019 and 2022, across 21 centers. Inclusion criteria were 18 years or older, DOAC, warfarin/AP use within 24 hours of requiring an urgent/emergent EGSP. Demographics, preoperative, intraoperative, and postoperative data were collected. ANOVA, χ 2 , and multivariable regression models were used to conduct the analysis. RESULTS: Of the 413 patients enrolled in the study, 261 (63%) reported warfarin/AP use and 152 (37%) reported DOAC use. Appendicitis and cholecystitis were the most frequent indication for operative intervention in the warfarin/AP group (43.4% vs. 25%, p = 0.001). Small bowel obstruction/abdominal wall hernias were the main indication for operative intervention in the DOAC group (44.7% vs. 23.8%, p = 0.001). Intraoperative, postoperative, and perioperative bleeding complications and in-hospital mortality were similar between the two groups. After adjusting for confounders, a history of chemotherapy (odds ratio [OR], 4.3; p = 0.015) and indication for operative intervention including occlusive mesenteric ischemia (OR, 4.27; p = 0.016), nonocclusive mesenteric ischemia (OR, 3.13; p = 0.001), and diverticulitis (OR, 3.72; p = 0.019) were associated with increased perioperative bleeding complications. The need for an intraoperative transfusion (OR, 4.87; p < 0.001), and intraoperative vasopressors (OR, 4.35; p = 0.003) were associated with increased in-hospital mortality. CONCLUSION: Perioperative bleeding complications and mortality are impacted by the indication for EGSPs and patient's severity of illness rather than a history of DOAC or warfarin/AP use. Therefore, perioperative management should be guided by patient physiology and indication for surgery rather than the concern for recent antiplatelet or anticoagulant use. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level III.

A genetically engineered, stem-cell-derived cellular vaccine.

Despite rapid clinical translation of COVID-19 vaccines in response to the global pandemic, an opportunity remains for vaccine technology innovation to address current limitations and meet challenges of inevitable future pandemics. We describe a universal vaccine cell (UVC) genetically engineered to mimic natural physiological immunity induced upon viral infection of host cells. Cells engineered to express the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike as a representative viral antigen induce robust neutralizing antibodies in immunized non-human primates. Similar titers generated in this established non-human primate (NHP) model have translated into protective human neutralizing antibody levels in SARS-CoV-2-vaccinated individuals. Animals vaccinated with ancestral spike antigens and subsequently challenged with SARS-CoV-2 Delta variant in a heterologous challenge have an approximately 3 log decrease in viral subgenomic RNA in the lungs. This cellular vaccine is designed as a scalable cell line with a modular poly-antigenic payload, allowing for rapid, large-scale clinical manufacturing and use in an evolving viral variant environment.

Does the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) accurately predict mortality for patients with elevated MELD scores?

BACKGROUND: The Model for End Stage Liver Disease (MELD) predicts mortality for liver disease patients. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) estimates mortality risk for surgical patients; however, NSQIP does not collect data regarding liver disease. This study's aim was to examine the accuracy of NSQIP mortality estimates for patients with elevated MELD scores. METHODS: NSQIP participant user files from 2005 to 2016 were queried. MELD scores were calculated and patients with scores ≥10 included. NSQIP-predicted mortality was compared to actual mortality. RESULTS: 268,873 patients met inclusion criteria. Predicted and observed number of 30-day postoperative deaths were 20,644 (7.7%) and 21,764 (8.1%). For patients with MELD ≥24, NSQIP-predicted 30-day mortality underestimated actual mortality. For patients with MELD ≤22, predicted and actual risks were similar. CONCLUSION: NSQIP predicts 30-day mortality risk well for patients with MELD scores from 10 to 22, but underestimates risk for patients with higher MELD scores.

Great power comes at a high (locomotor) cost: the role of muscle fascicle length in the power versus economy performance trade-off.

Muscle design constraints preclude simultaneous specialization of the vertebrate locomotor system for explosive and economical force generation. The resulting performance trade-off between power and economy has been attributed primarily to individual differences in muscle fiber type composition. While certainly crucial for performance specialization, fiber type likely interacts with muscle architectural parameters, such as fascicle length, to produce this trade-off. Longer fascicles composed of more serial sarcomeres can achieve faster shortening velocities, allowing for greater power production. Long fascicles likely reduce economy, however, because more energy-consuming contractile units are activated for a given force production. We hypothesized that longer fascicles are associated with both increased power production and locomotor cost. In 11 power-trained and 13 endurance-trained recreational athletes, we measured (1) muscle fascicle length via ultrasound in the gastrocnemius lateralis, gastrocnemius medialis and vastus lateralis, (2) maximal power during cycling and countermovement jumps, and (3) running cost of transport. We estimated muscle fiber type non-invasively based on the pedaling rate at which maximal cycling power occurred. As predicted, longer gastrocnemius muscle fascicles were correlated with greater lower-body power production and cost of transport. Multiple regression analyses revealed that variability in maximal power was explained by fiber type (46% for cycling, 24% for jumping) and average fascicle length (20% for cycling, 13% for jumping), while average fascicle length accounted for 15% of the variation in cost of transport. These results suggest that, at least for certain muscles, fascicle length plays an important role in the power versus economy performance trade-off.

Contrasting effects of the alkaloid ricinine on the capacity of Anopheles gambiae and Anopheles coluzzii to transmit Plasmodium falciparum.

BACKGROUND: Besides feeding on blood, females of the malaria vector Anopheles gambiae sensu lato readily feed on natural sources of plant sugars. The impact of toxic secondary phytochemicals contained in plant-derived sugars on mosquito physiology and the development of Plasmodium parasites remains elusive. The focus of this study was to explore the influence of the alkaloid ricinine, found in the nectar of the castor bean Ricinus communis, on the ability of mosquitoes to transmit Plasmodium falciparum. METHODS: Females of Anopheles gambiae and its sibling species Anopheles coluzzii were exposed to ricinine through sugar feeding assays to assess the effect of this phytochemical on mosquito survival, level of P. falciparum infection and growth rate of the parasite. RESULTS: Ricinine induced a significant reduction in the longevity of both Anopheles species. Ricinine caused acceleration in the parasite growth rate with an earlier invasion of the salivary glands in both species. At a concentration of 0.04 g l-1 in An. coluzzii, ricinine had no effect on mosquito infection, while 0.08 g l-1 ricinine-5% glucose solution induced a 14% increase in An. gambiae infection rate. CONCLUSIONS: Overall, our findings reveal that consumption of certain nectar phytochemicals can have unexpected and contrasting effects on key phenotypic traits that govern the intensity of malaria transmission. Further studies will be required before concluding on the putative role of ricinine as a novel control agent, including the development of ricinine-based toxic and transmission-blocking sugar baits. Testing other secondary phytochemicals in plant nectar will provide a broader understanding of the impact which plants can have on the transmission of vector-borne diseases.

Relationship between burnout and mistreatment: Who plays a role?

INTRODUCTION: Surgery residents have high burnout rates and mistreatment occurs during training. We hypothesized that residents who reported mistreatment would be more likely to experience burnout. METHODS: A multi-institutional observational study asked residents to complete the Maslach Burnout Inventory and to rate how often they experienced mistreatment. Scores in the high-risk range for emotional exhaustion or depersonalization were classified as burnout. Associations between mistreatment behaviors, program, sex, post graduate year(PGY), and clinical status were measured by Spearman's correlation, linear regression, and logistic regression. RESULTS: We invited 398 residents to participate; 180 responded(45%). 52%(n = 93) were female, there was an even distribution among PGY, and seven programs were represented. Almost half of the cohort (48%) reported high risk for burnout and 68% reported experiencing mistreatment. Mistreatment by senior physician team members were correlated with EE(rho = 0.184,p = 0.016) and DP(rho = 0.181,p = 0.016). CONCLUSION: While overall burnout was not significantly associated with mistreatment behaviors, both burnout and mistreatment were commonly reported.

The Impacts of COVID-19 on Early Childhood Education: Capturing the Unique Challenges Associated with Remote Teaching and Learning in K-2.

Due to the COVID-19 pandemic, schools across North America closed to in person learning in March 2020. Since then, it has becoming increasingly clear that physical distancing will need to be prolonged in the 2020/2021 school year and possibly resumed in the future. In response, education ministries shifted teaching and learning online. Research is urgently needed to mitigate the effects of COVID-19 on teaching and learning, particularly in the foundational early primary years. This research directly responds to this concern by examining the unique challenges associated with remote teaching and learning in early primary contexts. Given that learning in kindergarten and early primary grades is largely play- and inquiry- based, there is a particular need to investigate the impacts of this move for teachers, parents, and children in K-2. As such, the purpose of this research is twofold: (1) to capture the unique challenges and unanticipated successes associated with remote teaching and learning, and (2) to utilize findings to provide recommendations for remote learning as well as strategies for supporting in-person learning in the COVID-19 era (and post COVID-19 era). Data collection included 45-min semi-structured interviews with K-2 teachers (n = 25) and parents (n =11). All participants were from Ontario Canada. Data were collected from April-June 2020. The sample size was chosen to ensure saturation while uncovering a variety of perspectives. Data were analyzed in NVivo using an emergent thematic approach (Patton, 2016). The emergent thematic approach to analysis revealed five themes: equity considerations, synchronous versus asynchronous teaching and learning, social and emotional effects on students, academic impacts, and effects on parents/families.

General practitioner perspectives on barriers and enablers to bowel cancer screening in rural Tasmania: A thematic analysis of face-to-face interviews.

BACKGROUND AND OBJECTIVES: When detected early, nine in 10 Australians with bowel cancer can be successfully treated, yet participation in the National Bowel Cancer Screening Program (NBCSP) remains low. The aim of this study was to identify enablers and barriers to bowel cancer screening in rural Tasmanian communities from the perspective of general practitioners (GPs). METHOD: Qualitative analysis of face-to-face interviews with eight GPs was used to determine factors that influence NBCSP uptake in four rural Tasmanian Local Government Areas. RESULTS: High workloads, competing priorities and not knowing when a patient received an NBCSP kit were identified as barriers to supporting the program, while practice reminder systems were seen to improve the likelihood of GPs recommending the program to patients. DISCUSSION: GPs are important for improving participation in the NBCSP. Incorporating GPs' views of barriers and enablers for screening is key to improving NBCSP participation in rural Tasmania and Australia more broadly.