Citations

Ventricular arrhythmias after electrical cardioversion for AF are rare. Most of these arrhythmias are related to QT prolongation, resulting from marked and sudden slowing of heart rates, treatment with Class III antiarrhythmic drugs or other QT-prolonging medications, and the ventricular repolarisation remodelling effect of electrical cardioversion. A case of polymorphic ventricular tachycardia post-cardioversion of rapid AF in a patient with tachycardia-induced cardiomyopathy and the use of amiodarone is reported.

Abstract Description Cholangiocarcinoma (CCA) is an aggressive epithelial malignancy of the bile duct, with rising global incidence and poor prognosis. Current treatments achieve only 20-30% response rates in advanced cases, highlighting the need for novel therapeutic approaches. The tumor microenvironment (TME) has emerged as a critical focus for innovative therapies. Sulfatase 2 (SULF2) is a heparan sulfate (HS)-editing enzyme that alters HS chain affinity for growth factors and receptors, modulating heparan sulfate proteoglycans (HSPG) in cell signaling pathways. Specific sulfatases in HSPGs have been implicated as therapeutic targets in CCA. This study investigates the potential of anti-SULF2 antibodies to modulate immune cells within the TME using a C57BL6 syngeneic mouse model. Anti-SULF2-treated mice were compared to untreated controls, with tumors analyzed via CyTOF. Treatment resulted in reduced immunosuppressive cells and increased anti-tumor immune cells, suggesting that SULF2 inhibition shifts the TME toward an anti-tumorigenic state. These findings highlight SULF2 as a promising target for therapeutic intervention. Future studies will explore spatial transcriptomic and proteomics to elucidate the interplay between SULF2 expression in the TME makeup. We will also explore the molecular mechanisms of SULF2 suppression and its influence on cytokine signaling pathways within the TME. Funding Sources Supported by CTSA Grant Number TL1 TR002380 from the National Center for Advancing Translational Science (NCATS). Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

OBJECTIVE Patient-reported outcome measures (PROMs) are standardized questionnaires used to evaluate patients’ quality of life and health status before and after medical procedures. While worse preoperative health is often associated with worse postoperative outcomes, the role of baseline PROMs in predicting postoperative dysphagia following cervical surgery has been unexplored with Eating Assessment Tool–10 (EAT-10) scores. This study aimed to investigate the relationship between baseline PROMs and the incidence of postoperative dysphagia. METHODS A prospectively collected multi-institutional quality registry of patients undergoing anterior cervical spine surgery was retrospectively reviewed. Eight baseline PROMs were assessed: Neck Disability Index (NDI), modified Japanese Orthopaedic Association scale, EQ-5D questionnaire, EuroQol visual analog scale, visual analog scales for neck pain (NP-VAS) and arm pain, and 10-item Patient-Reported Outcomes Measurement Information System Global Physical Health and Global Mental Health. Including baseline dysphagia as a fixed effect, multivariable logistic regressions were performed to examine the impact of patient-reported baseline PROMs on the incidence of dysphagia. RESULTS Baseline PROMs were collected from 1706 patients. When assessing baseline PROMs independently in multivariable analyses, worse baseline NDI score (OR 1.04, p = 0.001) was a significant predictor of dysphagia at 12 months after surgery, while other PROMs were not. When assessing baseline PROMs together in multivariable analysis, worse baseline NDI score (OR 1.07, p < 0.001) and better NP-VAS score (OR 0.88, p = 0.006) were significant predictors of dysphagia at 12 months, while other PROMs were not. Patients in the severe or complete disability NDI categories (NDI score ≥ 25; 465/1466 patients without baseline dysphagia) experienced significantly more new dysphagia at 1 month (65% vs 50%, p < 0.001), 3 months (30% vs 21%, p < 0.001), and 12 months (32% vs 14%, p < 0.001) after anterior cervical spine surgery. These patients also had no significant difference in baseline EAT-10 scores (0.103 ± 0.386 vs 0.115 ± 0.405, p = 0.6), yet experienced significantly worse EAT-10 score changes between baseline and 12 months (3.369 ± 5.954 vs 1.208 ± 3.332, p < 0.001). CONCLUSIONS Baseline NDI score appears to be the strongest independent predictor of the 8 PROMs in determining whether patients have dysphagia at 12 months after anterior cervical surgery.

OBJECTIVE This study examined the extent to which preoperative depression predicts dysphagia after cervical spine surgery. METHODS A prospectively collected multi-institutional quality registry was retrospectively reviewed. Patients undergoing cervical surgery were categorized based on preoperative depression, and correlations with pre- and postoperative Eating Assessment Tool-10 (EAT-10) dysphagia questionnaire scores were assessed. Mixed-effects logistic regressions were performed to assess the impact of preoperative depression on the incidence of dysphagia. RESULTS Of 2002 patients meeting inclusion criteria, 524 (26%) reported having preoperative depression. Depression was associated with a higher incidence of dysphagia at baseline (25% vs 12%, p < 0.001) and at 1 (62% vs 54%, p = 0.038), 3 (36% vs 26%, p < 0.001), and 12 months (36% vs 22%, p < 0.001) postoperatively. Including baseline dysphagia as a fixed effect, multivariable analysis revealed that depression is not a significant independent predictor of postoperative dysphagia at 1 (OR 1.14, p = 0.5), 3 (OR 1.09, p = 0.6), or 12 months (OR 1.27, p = 0.2). Patients with depression and no baseline dysphagia (395 of 524) were significantly more likely to report new dysphagia at 12 months (26% vs 18%, p = 0.006), but not at 1 (53% vs 52%, p = 0.7) or 3 months (28% vs 22%, p = 0.06). The average change in EAT-10 scores between baseline and 12 months was significantly worse in patients with preoperative depression and no baseline dysphagia (2.552 [SD 5.041] vs 1.634 [SD 4.095], p < 0.001). Post hoc multivariable analyses excluding those with baseline dysphagia did not significantly affect the results. CONCLUSIONS Although patients with preoperative depression report dysphagia more often at baseline and at 1, 3, and 12 months after cervical surgery, preoperative depression is not an independent predictor of postoperative dysphagia. Preoperative depression may be valuable to consider as a risk factor for developing dysphagia after cervical surgery, but the heightened dysphagia risk in patients with depression may be attributed to secondary factors associated with depression such as comorbid conditions.

Importance Total pancreatectomy (TP) is indicated for advanced pancreatic cancer or multifocal tumors. Furthermore, TP may be performed to avoid the risk of pancreatic fistula in selected patients to improve the perioperative risk profile. Objective To define reference values for TP based on a low-risk cohort treated at expert centers. Design, Setting, and Participants This multicenter study analyzed outcomes from patients undergoing primary TP for malignant or benign lesions from 25 international expert centers from January 2017 to November 2023. Low-risk patients undergoing TP (LR-TP) were without vascular resections or significant comorbidities. Exposures TP. Main Outcomes and Measures Twenty reference values were derived from the 75th or the 25th percentile of the median values of all centers. Outcomes of LR-TP were compared with a cohort of TP with vascular resection, TP due to high-risk pancreatic anastomosis, and the benchmark values for low-risk pancreatoduodenectomy. Results Of 994 patients, 333 (33.5%; median [IQR] age, 66 [58-72] years; 171 male [51.4%]) qualified as the LR-TP cohort. Reference values included blood loss (≤1000 mL), major complications (≤37%), 3-month postoperative mortality (&amp;lt;6%), and retrieved lymph nodes (≥29). Compared with TP with vascular resections, reference cutoffs were not met for major complications (51% vs LR-TP ≤37%) and 90-day mortality (11% vs LR-TP ≤6%). For TP due to high-risk anastomosis, failure to rescue rate (38% vs ≤6%) and 90-day mortality (11% vs LR-TP ≤6%) were not met. Compared with pancreatoduodenectomy, reference values for postoperative mortality were 3 times higher for LR-TP (≤2% vs ≤6%) and less for resected lymph nodes (≥16 vs ≥29). Conclusions and Relevance This case-control study provided global reference values for TP, indicating significantly higher postoperative morbidity and mortality compared with pancreatoduodenectomy. Perioperative morbidity of TP was especially increased in patients with vascular resections. These reference values can serve for quality control of pancreatic surgery.

Abstract Background Allowable total error (ATE) is a quality concept that defines acceptable analytical performance for a clinical laboratory assay. ATE will vary in terms of the amount of error permissible not only between assays but also based on the test setting and the assay’s clinical use. In the clinical laboratory, ATE limits are routinely applied, for example, when evaluating new analytical methodology or equipment for patient testing, troubleshooting unacceptable quality control, or in evaluating instrument comparability. Content Currently, there are no universally applicable standards for defining the maximum magnitude of allowable error. However, there are several resources available for users to consider when setting ATE limits. Examples include clinical outcomes studies, biological variation of the measurand, state-of-the-art, professional organizations, and requirements set by regulatory agencies and proficiency testing/external quality assessment scheme organizers. Each of these approaches varies in terms of the resulting magnitude of allowable error for the same assay. This review describes these resources in more detail and discusses the strengths and weaknesses of each approach. Summary ATE users should be aware of different resources and their limitations before defining acceptance criteria for an assay in their clinical laboratory.

Multiple myeloma (MM) is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). While these precursor conditions are asymptomatic, they are not entirely benign and carry a lifelong risk of progression to MM. Unlike other cancers defined by pathology, malignant transformation from MGUS or SMM to MM has so far relied on demonstration of clinical end-organ damage as morphology and cytogenetics cannot reliably distinguish them. In this study, using genomic data from 374 patients with MGUS or SMM (277 training, 97 validation), to our knowledge, we demonstrate for the first time the ability to identify malignant transformation in MGUS and SMM. We introduce the concept of genomic MM and genomic MGUS to differentiate the subsets of MGUS and SMM that are biologically malignant with genomic features indistinguishable from MM from the subset that is premalignant and unlikely to progress to malignancy. Importantly, we find that most SMM has biological features of malignant transformation indistinguishable from MM. As expected, this subset that we consider having genomic MM is associated with a high risk of progression to MM although some patients remained progression-free beyond 5 years. Conversely, 60% of MGUS and 10% of SMM have no evidence of malignant transformation (genomic MGUS), with no progression during follow-up. Integration of genomic features with the 2/20/20 International Myeloma Working Group model significantly improved the prediction of progression among genomic MM. These findings support the use of genomic criteria to refine the classification and the risk stratification in myeloma precursor conditions.

Abstract Background Physical activity is associated with lower colorectal cancer (CRC) risk, but its association with molecular subtypes defined by genetic and epigenetic alterations of the disease is unclear. Such information may enhance the understanding of the mechanisms related to the benefits of physical activity. Methods Pooled observational (cases: n = 5386; controls: n = 6798; studies n = 5) and genome-wide association data (cases: n = 8178; controls: n = 10 472; studies n = 5) were used. We used multivariable logistic regression models and Mendelian randomization to assess the association between physical activity and the risk of CRC subtypes defined by individual tumor markers (and marker combinations), namely microsatellite instability status, CpG island methylator phenotype status, and BRAF and KRAS mutations. We used case-only analysis to test for differences between molecular subtypes. We applied Bonferroni correction to account for multiple tests. Results In the pooled observational analysis, higher levels of physical activity were associated with lower CRC risk (Obs-per 1SD, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.90 to 0.97), with an association that was stronger in males (Obs-per 1SD, OR = 0.91, 95% CI = 0.87 to 0.96) than in females (Obs-per 1SD, OR = 0.97, 95% CI = 0.91 to 1.03; Pinteraction = .04). Higher physical activity was associated with a lower risk of CRC across all molecular subtypes, especially in males. There was no difference in the associations by subtypes by pooled observational or Mendelian randomization analyses. The findings did not differ by study design, anatomical site, and early or late age onset of CRC. Conclusions Our findings suggest that physical activity is not differentially associated with the 4 major molecular subtypes involved in colorectal carcinogenesis, indicating that its benefits extend broadly across colorectal cancer pathogenesis.

Abstract OBJECTIVES: · To determine if patients with knee flexion contracture after distal femur fracture have poorer outcomes than patients who regain full knee extension. · To determine if factors such as patient age, gender, open fracture or implant used favors knee flexion contracture. METHODS: Design: Prospective, multicenter trial Setting: Twenty academic level I trauma centers Patient Selection Criteria: Patients with a distal femur fracture. Patients were evaluated for knee flexion contracture at 3, 6 and 12 months post-operatively. Outcome Measures and Comparisons: SMFA, Bother Index and EQ Health Index scores were recorded. Walking and stair climbing ability were assessed. RESULTS: · 126 patients had radiographic follow up for 12 months. There was clinical follow-up for 99 patients at 3 months, 90 patients at 6 months and 74 pts at 12 months. · Patients with full knee extension had better SMFA scores at 12 months than patients with knee flexion contracture (p = 0.308). · Bother Index (p = 0.29) and EQ Health State (p = 0.12) scores did not demonstrate a difference between patients with or without knee flexion contracture at any time point. · Patients with full knee extension had improved walking ability compared to patients with flexion contracture (p = 0.008). Patients with full knee extension had better stair climbing ability than patients with flexion contracture (p = 0.02). · Only older patient age showed a difference in likelihood of flexion contracture (p = 0.01) The rates of flexion contracture in women versus men (p = 0.51), RIMN versus LLP (p = 0.74) and open versus closed fracture (p = 0.24) were not statistically different. CONCLUSIONS: · Patients with knee flexion contractures after distal femur fracture do worse than patients who regain full extension. · Older patients with distal femur fractures are at greater risk for knee flexion contracture. LEVEL OF EVIDENCE: Level I