Citations

Abstract Introduction/Objective: To assess the clinical utility of the FM/a® chemokine-cytokine assay in diagnosing fibromyalgia at an academic medical center. Methods: We performed a cross-sectional study on 50 patients diagnosed with fibromyalgia at a specialty fibromyalgia clinic between January 1, 2021 through July 31, 2021. Patients completed questionnaires and provided a venous blood sample sent to EpicGenetics, to complete the FM/a® test. Demographic, symptom, and historical data was obtained from chart review. Statistical analysis was performed. Results: Of 50 patients with a clinical diagnosis of fibromyalgia, the FM/a® test was positive in 45 (90%). Performance of the FM/a® test compared to the 2016 ACR criteria yielded an odds ratio of 3.5 with sensitivity of 0.91, specificity of 0.25. Univariate regression demonstrated an area under the curve (AUC) of 0.7337, which improved to 0.89 when adjusted for age, gender, and race. When compared to the 1990 ACR criteria, a positive FM/a® test had an odds ratio of 2.33 with sensitivity 0.92 and specificity 0.17. Univariate regression analysis demonstrated an AUC of 0.571, when adjusted for age, gender and race, AUC was similar at 0.585. Conclusion: The FM/a® test performed well overall, though inferiorly compared to the 1990 and 2016 ACR diagnostic criteria. When adjusted for age, gender, and race the test performed almost equivalently to the 2016 ACR criteria. The FM/a® test may be useful in general clinical practices to differentiate patients who are more likely to have FM.

Context.— Title 45, section 164.524 of the Code of Federal Regulations states that health care systems must provide patient health records upon that patient’s request. For complex testing, such as next-generation sequencing (NGS), this raises questions related to what data should be released and the laboratory considerations regarding the release of this data. Objective.— To describe the laboratory implications of releasing different NGS data files and the limitations for the clinical use of different NGS data files. Design.— The College of American Pathologists workgroup, composed of laboratorians with expertise regarding NGS testing, reviewed pertinent literature, including title 45, section 164.524, and the Health and Human Services “Guidance on Individuals’ Right to Access Health Information.” Results.— From an accreditation standpoint, validation of NGS includes both the wet bench and data processing (bioinformatics) portions, and appropriately validated laboratory testing is required to ensure quality patient results. NGS testing generates intermediate data files that have not completed the fully validated process but are often kept by the laboratory. These files may be requested by patients, but most patients will not be aware of the test validation process and the limitations of data that have not gone through a fully validated process. Conclusions.— Laboratories should encourage patients to receive their health data and to help individuals understand the content, uses, and limitations of laboratory data they have requested or received. NGS data used in a nonvalidated manner should not be used for clinical purposes without confirmation by a clinically validated method.

Abstract Background and study aims Biliary sphincterotomy is a crucial step in endoscopic retrograde cholangiopancreatography (ERCP), a procedure known to carry a 5% to 10% risk of complications. The relationship between Pure cut, Endocut, post-ERCP pancreatitis (PEP) and bleeding is unclear. This systematic review and meta-analysis compared these two current types and their relationships with adverse events. Patients and methods This systematic review involved searching articles in multiple databases until August 2023 comparing pure cut versus Endocut in biliary sphincterotomy. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Results A total of 987 patients from four randomized controlled trials were included. Overall pancreatitis: A higher risk of pancreatitis was found in the Endocut group than in the Pure cut group (P=0.001, RD=0.04 [range, 0.01 to 0.06]; I2=29%). Overall immediate bleeding: Statistical significance was found to favor Endocut, (P=0.05; RD=–0.15 [range, –0.29 to –0.00]; I2=93%). No statistical significance between current modes was found in immediate bleeding without endoscopic intervention (P=0.10; RD=–0.13 [range, –0.29 to 0.02]; I2=88%), immediate bleeding with endoscopic intervention (P=0.06; RD=–0.07 [range, –0.14 to 0.00]; I2=76%), delayed bleeding (P=0.40; RD=0.01 [range, –0.02 to 0.05]; I2=72%), zipper cut (P=0.58; RD=–0.03 [range, –0.16 to 0.09]; I2=97%), perforation (P=1.00; RD=0.00 [range, –0.01 to 0.01]; I2=0%) and cholangitis (P=0.77; RD=0.00 [range, –0.01 to 0.02]; I2=29%). Conclusions The available data in the literature show that Endocut carries an increased risk for PEP and does not prevent delayed or clinically significant bleeding, although it prevents intraprocedural bleeding. Based on such findings, Pure cut should be the preferred electric current mode for biliary sphincterotomy.

Abstract Severe mitral annular calcification (MAC) presents a surgical challenge due to the complexity of disease and the risk of valve replacement. There have been a variety of techniques to combat this risk including edge-to-edge repair, collar-enforced prosthesis, and pericardial patch techniques. This report highlights a case in which a novel reproducible surgical technique was used to prevent perivalvular leak with mitral valve replacement. This technique may add to surgeons' repertoire in addressing patients with MAC concentrated on the posterior annulus.

Abstract Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions. After exclusion of leukemic and most cutaneous forms of MTNKNs, patients were pooled with non-CNS relapse control patients from a single institution to create a CNS relapse–enriched training set. Using a complete case analysis (n = 182), including 91 with CNS relapse, we applied a least absolute shrinkage and selection operator Cox regression model to select weighted clinicopathologic variables for the CITI score, which we validated in an external cohort from the Swedish Lymphoma Registry (n = 566). CNS relapse was most frequently observed in patients with peripheral T-cell lymphoma, not otherwise specified (25%). Median time to CNS relapse and median overall survival after CNS relapse were 8.0 and 4.7 months, respectively. We calculated unique CITI risk scores for individual training set patients and stratified them into risk terciles. Validation set patients with low-risk (n = 158) and high-risk (n = 188) CITI scores had a 10-year cumulative risk of CNS relapse of 2.2% and 13.4%, respectively (hazard ratio, 5.24; 95% confidence interval, 1.50-18.26; P = .018). We developed an open-access web-based CITI calculator (https://redcap.link/citicalc) to provide an easy tool for clinical practice. The CITI score is a validated model to predict patients with MTNKN at the highest risk of developing CNS relapse.

Abstract In a previous study, we observed decreased 1,25-dihydroxyvitamin D levels, secondary hyperparathyroidism, and increased bone turnover markers in living kidney donors (LKDs) at 3 months and 36 months after kidney donation. In our recent survey-based study, we found no increased risk of fractures of all types but observed significantly more vertebral fractures in LKDs compared with matched controls. To elucidate the long-term effects of kidney donation on bone health, we recruited 139 LKDs and 139 age and sex matched controls from the survey-based participants for further mechanistic analyses. Specifically, we assessed whether LKDs had persistent abnormalities in calcium- and phosphorus-regulating hormones and related factors, in bone formation and resorption markers, and in density and microstructure of bone compared with controls. We measured serum markers, bone mineral density (BMD), bone microstructure and strength (via high-resolution peripheral quantitative computed tomography and micro-finite element analysis [HRpQCT]), and advanced glycation end-products in donors and controls. LKDs had decreased 1,25-dihydroxyvitamin D concentrations (donors mean 33.89 pg/mL vs. controls 38.79 pg/mL, percent difference = -12.6%; P < .001), increases in both parathyroid hormone (when corrected for ionized calcium; donors mean 52.98 pg/mL vs. controls 46.89 pg/mL,% difference 13%; P = .03) and ionized calcium levels (donors mean 5.13 mg/dL vs. controls 5.04 mg/dL; P < .001), and increases in several bone resorption and formation markers versus controls. LKDs and controls had similar measures of BMD; however, HRpQCT suggested that LKDs have a statistically insignificant tendency toward thinner cortical bone and lower failure loads as measured by micro-finite element analysis. Our findings suggest that changes in the hormonal mileu after kidney donation and the long-term cumulative effects of these changes on bone health persist for decades after kidney donation and may explain later-life increased rates of vertebral fractures.

Abstract Despite advances in understanding the cellular and molecular processes underlying memory and cognition, and recent successful modulation of cognitive performance in brain disorders, the neurophysiological mechanisms remain underexplored. High frequency oscillations beyond the classic electroencephalogram spectrum have emerged as a potential neural correlate of fundamental cognitive processes. High frequency oscillations are detected in the human mesial temporal lobe and neocortical intracranial recordings spanning gamma/epsilon (60–150 Hz), ripple (80–250 Hz) and higher frequency ranges. Separate from other non-oscillatory activities, these brief electrophysiological oscillations of distinct duration, frequency and amplitude are thought to be generated by coordinated spiking of neuronal ensembles within volumes as small as a single cortical column. Although the exact origins, mechanisms and physiological roles in health and disease remain elusive, they have been associated with human memory consolidation and cognitive processing. Recent studies suggest their involvement in encoding and recall of episodic memory with a possible role in the formation and reactivation of memory traces. High frequency oscillations are detected during encoding, throughout maintenance, and right before recall of remembered items, meeting a basic definition for an engram activity. The temporal coordination of high frequency oscillations reactivated across cortical and subcortical neural networks is ideally suited for integrating multimodal memory representations, which can be replayed and consolidated during states of wakefulness and sleep. High frequency oscillations have been shown to reflect coordinated bursts of neuronal assembly firing and offer a promising substrate for tracking and modulation of the hypothetical electrophysiological engram.

Abstract The Centers for Medicare & Medicaid Services (CMS) relies on public comments submitted in response to proposed national coverage determinations to assist the agency in determining the coverage of items and services for Medicare beneficiaries. In a cross-sectional study, we characterized the cited evidence and what funding supported the cited evidence submitted in public comments to CMS for all therapeutic medical device national coverage determinations finalized between June 2019 and June 2022. Of 681 public comments, 159 (23%) cited at least 1 identifiable published scientific journal article. Within these 159 public comments, 198 unique articles were cited, 170 (86%) of which included funding statements or author disclosures. Among these, 96 (56%) disclosed funding from manufacturers that would benefit from Medicare coverage and/or were written by author(s) who received funding from these manufacturers. In summary, most public commenters for national coverage determinations did not cite published scientific journal articles to support their positions. Among those who did, more than half of articles were directly funded by manufacturers that would benefit from coverage. Greater funding of independent, non–industry-supported research may help provide unbiased evaluations of benefits and harms to support Medicare coverage decisions.

Abstract Background and Aims In the STEP-HFpEF trial programme, treatment with semaglutide resulted in multiple beneficial effects in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Efficacy may vary according to baseline diuretic use, and semaglutide treatment could modify diuretic dose. Methods In this pre-specified analysis of pooled data from the STEP-HFpEF and STEP-HFpEF-DM trials (n = 1145), which randomized participants with HFpEF and body mass index ≥ 30 kg/m2 to once weekly semaglutide 2.4 mg or placebo for 52 weeks, we examined whether efficacy and safety endpoints differed by baseline diuretic use, as well as the effect of semaglutide on loop diuretic use and dose changes over the 52-week treatment period. Results At baseline, across no diuretic (n = 220), non-loop diuretic only (n = 223), and loop diuretic [<40 (n = 219), 40 (n = 309), and >40 (n = 174) mg/day furosemide equivalents] groups, there was progressively higher prevalence of hypertension and atrial fibrillation; and greater severity of obesity and heart failure. Over 52 weeks of treatment, semaglutide had a consistent beneficial effect on change in body weight across diuretic use categories (adjusted mean difference vs. placebo ranged from −8.8% [95% confidence interval (CI) −10.3, −6.3] to −6.9% [95% CI −9.1, −4.7] from no diuretics to the highest loop diuretic dose category; interaction P = .39). Kansas City Cardiomyopathy Questionnaire clinical summary score improvement was greater in patients on loop diuretics compared to those not on loop diuretics (adjusted mean difference vs. placebo: +9.3 [6.5; 12.1] vs. +4.7 points [1.3, 8.2]; P = .042). Semaglutide had consistent beneficial effects on all secondary efficacy endpoints (including 6 min walk distance) across diuretic subgroups (interaction P = .24–.92). Safety also favoured semaglutide vs. placebo across the diuretic subgroups. From baseline to 52 weeks, loop diuretic dose decreased by 17% in the semaglutide group vs. a 2.4% increase in the placebo group (P < .0001). Semaglutide (vs. placebo) was more likely to result in loop diuretic dose reduction (odds ratio [OR] 2.67 [95% CI 1.70, 4.18]) and less likely dose increase (OR 0.35 [95% CI 0.23, 0.53]; P < .001 for both) from baseline to 52 weeks. Conclusions In patients with obesity-related HFpEF, semaglutide improved heart failure-related symptoms and physical limitations across diuretic use subgroups, with more pronounced benefits among patients receiving loop diuretics at baseline. Reductions in weight and improvements in exercise function with semaglutide vs. placebo were consistent in all diuretic use categories. Semaglutide also led to a reduction in loop diuretic use and dose between baseline and 52 weeks. Clinical Trial Registration NCT04788511 and NCT04916470.