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OBJECTIVE The objective of this study was to compare clinical and patient-reported outcomes (PROs) between posterior foraminotomy and anterior cervical discectomy and fusion (ACDF) in patients presenting with cervical radiculopathy. METHODS The Quality Outcomes Database was queried for patients who had undergone ACDF or posterior foraminotomy for radiculopathy. To create two highly homogeneous groups, optimal individual matching was performed at a 5:1 ratio between the two groups on 29 baseline variables (including demographic characteristics, comorbidities, symptoms, patient-reported scores, underlying pathologies, and levels treated). Outcomes of interest were length of stay, reoperations, patient-reported satisfaction, increase in EQ-5D score, and decrease in Neck Disability Index (NDI) scores for arm and neck pain as long as 1 year after surgery. Noninferiority analysis of achieving patient satisfaction and minimal clinically important difference (MCID) in PROs was performed with an accepted risk difference of 5%. RESULTS A total of 7805 eligible patients were identified: 216 of these underwent posterior foraminotomy and were matched to 1080 patients who underwent ACDF. The patients who underwent ACDF had more underlying pathologies, lower EQ-5D scores, and higher NDI and neck pain scores at baseline. Posterior foraminotomy was associated with shorter hospitalization (0.5 vs 0.9 days, p < 0.001). Reoperations within 12 months were significantly more common among the posterior foraminotomy group (4.2% vs 1.9%, p = 0.04). The two groups performed similarly in PROs, with posterior foraminotomy being noninferior to ACDF in achieving MCID in EQ-5D and neck pain scores but also having lower rates of maximal satisfaction at 12 months (North American Spine Society score of 1 achieved by 65.2% posterior foraminotomy patients vs 74.6% of ACDF patients, p = 0.02). CONCLUSIONS The two procedures were found to be offered to different populations, with ACDF being selected for patients with more complicated pathologies and symptoms. After individual matching, posterior foraminotomy was associated with a higher reoperation risk within 1 year after surgery compared to ACDF (4.2% vs 1.9%). In terms of 12-month PROs, posterior foraminotomy was noninferior to ACDF in improving quality of life and neck pain. The two procedures also performed similarly in improving NDI scores and arm pain, but ACDF patients had higher maximal satisfaction rates.

Prescribed opioids are a mainstay pain treatment after traumatic injury, but a subgroup of patients may be at risk for continued opioid use. We evaluated the predictive utility of a traditional screening tool, the Opioid Risk Tool (ORT), and two other measures: average in-hospital milligram morphine equivalents (MME) per day and an assessment of opioid demand in predicting pain outcomes. Assessments of pain-related outcomes (pain intensity, interference, injury-related stress, and need for additional pain treatment) were administered at 2 weeks and 12 months post-discharge in a sample of 34 patients hospitalized for traumatic injury. Bayesian linear models were used to evaluate changes in responses over time as a function of predictors. High-risk ORT, higher MME per day, and greater opioid demand predicted less change in outcomes over time. This report provides first evidence that malleable factors of opioid and opioid demand have utility in predicting pain outcomes following traumatic injury.

Abstract Background Error analysis plays a crucial role in clinical concept extraction, a fundamental subtask within clinical natural language processing (NLP). The process typically involves a manual review of error types, such as contextual and linguistic factors contributing to their occurrence, and the identification of underlying causes to refine the NLP model and improve its performance. Conducting error analysis can be complex, requiring a combination of NLP expertise and domain-specific knowledge. Due to the high heterogeneity of electronic health record (EHR) settings across different institutions, challenges may arise when attempting to standardize and reproduce the error analysis process. Objectives This study aims to facilitate a collaborative effort to establish common definitions and taxonomies for capturing diverse error types, fostering community consensus on error analysis for clinical concept extraction tasks. Materials and Methods We iteratively developed and evaluated an error taxonomy based on existing literature, standards, real-world data, multisite case evaluations, and community feedback. The finalized taxonomy was released in both .dtd and .owl formats at the Open Health Natural Language Processing Consortium. The taxonomy is compatible with several different open-source annotation tools, including MAE, Brat, and MedTator. Results The resulting error taxonomy comprises 43 distinct error classes, organized into 6 error dimensions and 4 properties, including model type (symbolic and statistical machine learning), evaluation subject (model and human), evaluation level (patient, document, sentence, and concept), and annotation examples. Internal and external evaluations revealed strong variations in error types across methodological approaches, tasks, and EHR settings. Key points emerged from community feedback, including the need to enhancing clarity, generalizability, and usability of the taxonomy, along with dissemination strategies. Conclusion The proposed taxonomy can facilitate the acceleration and standardization of the error analysis process in multi-site settings, thus improving the provenance, interpretability, and portability of NLP models. Future researchers could explore the potential direction of developing automated or semi-automated methods to assist in the classification and standardization of error analysis.

AbstractThis joint ASGE-ESGE guideline provides an evidence-based summary and recommendations regarding the role of endoscopic bariatric and metabolic therapies (EBMTs) in the management of obesity. The document was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. It evaluates the efficacy and safety of EBMT devices and procedures that currently have CE mark or FDA-clearance/approval, or that had been approved within five years of document development. The guideline suggests the use of EBMTs plus lifestyle modification in patients with a BMI of ≥30 kg/m2, or with a BMI of 27.0–29.9 kg/m2 with at least 1 obesity-related comorbidity. Furthermore, it suggests the utilization of intragastric balloons and devices for endoscopic gastric remodeling (EGR) in conjunction with lifestyle modification for this patient population.

Abstract Three classes of BCMA-directed therapy (BDT) exist: antibody drug-conjugates (ADCs), CAR-T, and T-cell engagers (TCEs), each with distinct strengths and weaknesses. To aid clinicians in selecting between BDTs, we reviewed myeloma patients treated at Mayo Clinic with commercial or investigational BDT between 2018–2023. We identified 339 individuals (1-exposure = 297, 2-exposures = 38, 3-exposures = 4) who received 385 BDTs (ADC = 59, TCE = 134, CAR-T = 192), with median follow-up of 21-months. ADC recipients were older, with more lines of therapy (LOT), and penta-refractory disease. Compared to ADCs, CAR-T (aHR = 0.29, 95%CI = 0.20–0.43) and TCEs (aHR = 0.62, 95%CI = 0.43–0.91) had better progression-free survival (PFS) on analysis adjusted for age, the presence of extramedullary (EMD), penta-refractory disease, multi-hit high-risk cytogenetics, prior BDT, and the number of LOT in the preceding 1-year. Likewise, compared to ADCs, CAR-T (aHR = 0.28, 95%CI = 0.18–0.44) and TCEs (aHR = 0.60, 95%CI = 0.39–0.93) had superior overall survival. Prior BDT exposure negatively impacted all classes but was most striking in CAR-T, ORR 86% vs. 50% and median PFS 13-months vs. 3-months. Of relapses, 54% were extramedullary in nature, and a quarter of these cases had no history of EMD. CAR-T demonstrates superior efficacy and where feasible, should be the initial BDT. However, for patients with prior BDT or rapidly progressive disease, an alternative approach may be preferable.

Abstract Neuromuscular blocking agents (NMBAs) are commonly used to induce skeletal muscle relaxation during surgery. While muscle relaxation facilitates surgical procedures and tracheal intubation, adequate recovery of muscle function after surgery is required to support pulmonary function, and even mild residual neuromuscular block increases the risk of severe postoperative pulmonary complications. While recovery of muscle function after surgery involving NMBAs can be monitored and, in addition, be accelerated by use of current antagonists (reversal agents), there is a clear clinical need for a safe drug to antagonize all types of NMBAs. Here we show that inhibition of the skeletal muscle-specific chloride ion (Cl-) channel, the ClC-1 channel, markedly accelerates recovery of both single contraction (twitch) and physiologically important sustained contractions (tetanic) in a novel rat model mimicking NMBA-induced muscle block used during surgery. ClC-1 inhibition was found to reverse any NMBA with superior properties to existing reversal agents. This suggests ClC-1 inhibition as a novel mechanism for fast and efficacious reversal from neuromuscular block.

Abstract Background Alcohol is consumed by an estimated 137.4 million people in the United States 12 years of age and older, and, as a result, is estimated to have caused about 140 thousand deaths among people 20 to 64 years of age each year from 2015 up to and including 2019. Methods The proposed proposed review of the evidence on alcohol’s impact to health aims to produce conclusions to inform the Dietary Guidelines for Americans, 2026–2030. A multi-method approach will be utilized to formulate conclusions on (i) weekly (i.e., average) thresholds to minimize long-term and short-term risks of morbidity and mortality, (ii) daily thresholds to minimize the short-term risk of injury or acute illness due to per occasion drinking, (iii) alcohol use among vulnerable populations (e.g., pregnant women), and (iv) situations and circumstances that are hazardous for alcohol use. To inform expert discussions, this project will also include a systematic review of existing low-risk drinking guidelines, a systematic review of meta-analyses which examine alcohol’s impact on key attributable disease and mortality outcomes, and of estimates of the lifetime absolute risk of alcohol-attributable mortality and morbidity based on a person’s sex and average level of alcohol use. The preliminary conclusions produced as a result of this project will undergo public consultation, and data from these consultations will be analyzed using both quantitative and qualitative methods. The results of the public consultations will be used to further revise and refine the project’s conclusions. Discussion This project will establish a scientific consensus concerning alcohol’s impact on health. This consensus is imperative for informing the upcoming Dietary Guidelines for Americans, 2026–2030, and for better informing individuals about the health risks associated with alcohol use.

Abstract Ivosidenib is a first-in-class mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor with efficacy and tolerability in patients with advanced mIDH1 hematologic malignancies, leading to approval in frontline and relapsed/refractory (R/R) mIDH1 acute myeloid leukemia. We report final data from a phase 1 single-arm substudy of once-daily ivosidenib in patients with R/R mIDH1 myelodysplastic syndrome (MDS) after failure of standard-of-care therapies. Primary objectives were to determine safety, tolerability, and clinical activity. The primary efficacy end point was the complete remission (CR) + partial remission (PR) rate. Nineteen patients were enrolled; 18 were included in the efficacy analysis. Treatment-related adverse events occurred in 8 (42.1%) patients, including a grade 1 QT interval prolongation in 1 (5.3%) patient and grade 2 differentiation syndrome in 2 (10.5%) patients. Rates of CR + PR and objective response (CR + PR + marrow CR) were 38.9% (95% confidence interval [CI], 17.3-64.3) and 83.3% (95% CI, 58.6-96.4), respectively. Kaplan-Meier estimates showed a 68.6% probability of patients in CR achieving a remission duration of ≥5 years, and a median overall survival of 35.7 months. Of note, 71.4% and 75.0% baseline red blood cell (RBC)- and platelet-transfusion-dependent patients, respectively, became transfusion independent (TI; no transfusion for ≥56 days); 81.8% and 100% of baseline RBC and platelet TI patients, respectively, remained TI. One (5.3%) patient proceeded to a hematopoietic stem cell transplant. In conclusion, ivosidenib is clinically active, with durable remissions and a manageable safety profile observed in these patients. This trial was registered at www.ClinicalTrials.gov as #NCT02074839.

Background: Unicompartmental knee arthroplasty (UKA) is a reliable procedure to treat medial compartment knee osteoarthritis (OA). The reported survivorship of UKA has varied in the literature 3–7 . In part, the higher failure rates of UKA seen in registries could be related to the caseload and experience of the reporting surgeon 8 . The introduction of techniques that make procedures more reliable, especially in the hands of inexperienced surgeons, can decrease the rate of failure. With the Oxford UKA implant (Zimmer Biomet), the recommended surgical technique involves cutting the tibia first, followed by the femoral preparation. However, a technique that allows for preparation of the femur first, as well as the use of the femoral component as a reference for the tibial cut, may reduce the common technical errors seen with the procedure. We have utilized the femur-first technique in cases of medial Oxford UKA. Description: The femur-first method outlined in the present article does not require any unique instruments beyond what is supplied by the manufacturer. Before beginning, the femoral positional guide needs to be decoupled from its base. To start, the intramedullary guide is introduced approximately 1 cm anterior and medial to the intercondylar notch. Once the femoral osteophytes are removed, the surgeon identifies the center of the femoral condyle and marks it. The posterior tibial cartilage is then removed with a saw to facilitate the placement of the appropriately sized femoral spherical guide. The size of the femoral component is determined by selecting the implant that aligns best with the width of the femoral condyle. The femoral drill guide is detached from its base because there is not enough space for the base, as the tibia has not yet been resected. The decoupled femoral guide is connected to the intramedullary rod, allowing the precise positioning of the femoral component in approximately 10° of flexion relative to the femoral sagittal plane and drilling of the 2 peg holes. The posterior condylar resection guide is impacted into position, and the osteotomy of the posterior condyle is made. The distal femur is then milled with use of a number-0 spigot, and the femoral component trial is positioned into place. The femoral condyle is “resurfaced” with the femoral component, which restores joint obliquity and the natural height, a critical element of the femur-first technique. Following this, the 1-mm (size-dependent) spherical gauge is placed around the femoral component trial. The tibial guide is secured with the G-clamp and a number-0 resection block, and is pinned into place. We recommend swapping the number-0 cutting guide for a +2 when making the cut in order to avoid over-resection. Recutting is advised if a minimum 3-mm feeler gauge does not adequately occupy the flexion space. The final step is to balance the flexion and extension gaps in the usual fashion. Alternatives: The alternative technique is a traditional tibia-first approach, in which tibial resection is performed prior to femoral resection. As described in the original manufacturer’s manual, the tibial cut is accomplished with use of a number-0 cutting guide, and the tibial rotation is based on the axis formed by the anterior superior iliac spine and knee center, irrespective of the femoral condyle. Rationale: The femur-first technique is advantageous in several ways. When performing the femoral cut first, the surgeon can better align the drill guide at the center of medial femoral condyle. This will result in the femoral component being positioned more in line with the coronal plane of the femoral condyle. Additionally, the tibial resection is made with the femoral trial in place; therefore, the depth of resection can be more accurate, potentially avoiding excessive bone resection. Finally, with the femoral trial in place, the surgeon can judge the rotation and medial-lateral position of the tibial component more precisely, hence lowering the possibility of bearing spin-out, impingement, and dislocation or unexplained pain. Expected Outcomes: The femur-first technique is a bone-preserving procedure that results in thinner bearings when compared with a tibia-first approach 1 . The femur-first approach also improves radiographic outcomes, including femoral coronal, femoral sagittal, and tibial sagittal alignments, while tibial coronal alignment does not differ. There is an early trend toward improved 5-year survivorship with the femur-first (98%) versus tibia-first (94%, p = 0.35) techniques. There has been no significant difference reported in Knee Society Scores between techniques. Important Tips: Perform a preliminary cut of the posterior tibial cartilage in order to allow insertion of the femoral drill guide under the femoral condyle. Make sure the femoral drill guide lies in the center of the marked medial femoral condyle. Align the tibial sagittal cut with the femoral component trial in order to avoid bearing impingement. Be conservative in the tibial cutting by utilizing a +2 cutting guide (since the coupling is performed with the intramedullary guide in place, which drives the tibial guide distally). Acronyms and Abbreviations: UKA = unicompartmental knee arthroplasty FF = femur-first M-L = medial-lateral AP = anteroposterior PA = posteroanterior ASA = acetylsalicylic acid (aspirin) BID = bis in die, twice a day PT = physical therapy TF = tibia-first FCA = femoral coronal angle FSA = femoral sagittal angle TSA = tibial sagittal angle IM = intramedullary OA = osteoarthritis