CD4+ CAR-T cell exhaustion associated with early relapse of multiple myeloma after BCMA CAR-T cell therapy.

Multiple myeloma is characterized by frequent clinical relapses following conventional therapy. Recently, chimeric antigen receptor T (CAR-T) cells targeting B-cell maturation antigen (BCMA) has been established as a treatment option for patients with relapsed or refractory disease. However, while >70% of patients initially respond to this treatment, clinical relapse and disease progression occur in most cases. Recent studies showed persistent expression of BCMA at the time of relapse, indicating that immune intrinsic mechanisms may contribute to this resistance. While there were no pre-existing T cell features associated with clinical outcomes, we found that patients with a durable response to CAR-T cell treatment had greater persistence of their CAR-T cells compared to patients with transient clinical responses. They also possessed a significantly higher proportion of CD8+ T effector memory cells. In contrast, patients with short-lived responses to treatment have increased frequencies of cytotoxic CD4+ CAR-T cells. These cells expand in vivo early after infusion but express exhaustion markers (HAVCR2 and TIGIT) and remain polyclonal. Finally, we demonstrate that non-classical monocytes are enriched in the myeloma niche and may induce CAR-T cell dysfunction through mechanisms that include TGFß. These findings shed new light on the role of cytotoxic CD4+ T cells in disease progression after CAR-T cell therapy.

A time out for prayer.

Compassionate care of the surgical patient recognizes the wholeness of each individual. Patients and their caregivers come to healthcare providers with the hope of relief from pain and suffering and aspirations for the potential to feel well or be "normal" again. Many lean on their personal faith and prayer for spiritual comfort and petitions for healing. We discuss a case in which prayer is incorporated into the surgical Time Out, a scenario not uncommon in faith-based hospitals, and offer a framework to evaluate the practice that incorporates ethical principles of beneficence, non-maleficence, patient/parental autonomy, justice, and the fiduciary responsibility of the healthcare provider.

Effect of Antibiotic Spacer Dosing on Treatment Success in Two-Stage Exchange for Periprosthetic Joint Infection.

INTRODUCTION: In two-stage exchange for periprosthetic joint infection (PJI), adding antibiotics to cement spacers is the standard of care; however, little is known about optimal dosage. There is emphasis on using >3.6 g of total antibiotic, including ≥2.0 g of vancomycin, per 40 g of cement, but these recommendations lack clinical evidence. We examined whether recommended antibiotic spacer doses affect treatment success. METHODS: This was a retrospective review of 202 patients who underwent two-stage exchange for PJI from 2004 to 2020 with at least 1-year follow-up. Patients were separated into high (>3.6 g of total antibiotic per 40 g of cement) and low-dose spacer groups. Primary outcomes were overall and infectious failure. RESULTS: High-dose spacers were used in 80% (162/202) of patients. High-dose spacers had a reduced risk of overall (OR, 0.37; P = 0.024) and infectious (OR, 0.35; P = 0.020) failure for infected primary arthroplasties, but not revisions. In multivariate analysis, vancomycin dose ≥2.0 g decreased the risk of infectious failure (OR, 0.31; P = 0.016), although not overall failure (OR, 0.51; P = 0.147). CONCLUSION: During two-stage exchange for PJI, spacers with greater than 3.6 g of total antibiotic may reduce overall and infectious failure for infected primary arthroplasties. Furthermore, using at least 2.0 g of vancomycin could independently decrease the risk of infectious failure.

Racial Disparities in Treatment and Outcomes of Patients With Hepatitis C Undergoing Elective Total Joint Arthroplasty.

BACKGROUND: African Americans have the highest prevalence of chronic Hepatitis C virus (HCV) infection. Racial disparities in outcome are observed after elective total hip arthroplasty (THA) and total knee arthroplasty (TKA). This study sought to identify if disparities in treatments and outcomes exist between Black and White patients who have HCV prior to elective THA and TKA. METHODS: Patient demographics, comorbidities, HCV characteristics, perioperative variables, in-hospital outcomes, and postoperative complications at 1-year follow-up were collected and compared between the 2 races. Patients who have preoperative positive viral load (PVL) and undetectable viral load were identified. Chi-square and Fisher's exact tests were used to compare categorical variables, while 2-tailed Student's Kruskal-Wallis t-tests were used for continuous variables. A P value of less than .05 was statistically significant. RESULTS: The liver function parameters, including aspartate aminotransferase and model for end-stage liver disease scores, were all higher preoperatively in Black patients undergoing THA (P = .01; P < .001) and TKA (P = .03; P = .003), respectively. Black patients were more likely to undergo THA (65.8% versus 35.6%; P = .002) and TKA (72.1% versus 37.3%; 0.009) without receiving prior treatment for HCV. Consequently, Black patients had higher rates of preoperative PVL compared to White patients in both THA (66% versus 38%, P = .006) and TKA (72% versus 37%, P < .001) groups. Black patients had a longer length of stay for both THA (3.7 versus 3.3; P = .008) and TKA (4.1 versus 3.0; P = .02). CONCLUSIONS: The HCV treatment prior to THA and TKA with undetectable viral load has been shown to be a key factor in mitigating postoperative complications, including joint infection. We noted that Black patients were more likely to undergo joint arthroplasty who did not receive treatment and with a PVL. While PVL rates decreased over time for both races, a significant gap persists for Black patients.

Asthma and exercise-induced bronchoconstriction in athletes: Diagnosis, treatment, and anti-doping challenges.

Athletes often experience lower airway dysfunction, such as asthma and exercise-induced bronchoconstriction (EIB), which affects more than half the athletes in some sports, not least in endurance sports. Symptoms include coughing, wheezing, and breathlessness, alongside airway narrowing, hyperresponsiveness, and inflammation. Early diagnosis and management are essential. Not only because untreated or poorly managed asthma and EIB potentially affects competition performance and training, but also because untreated airway inflammation can result in airway epithelial damage, remodeling, and fibrosis. Asthma and EIB do not hinder performance, as advancements in treatment strategies have made it possible for affected athletes to compete at the highest level. However, practitioners and athletes must ensure that the treatment complies with general guidelines and anti-doping regulations to prevent the risk of a doping sanction because of inadvertently exceeding specified dosing limits. In this review, we describe considerations and challenges in diagnosing and managing athletes with asthma and EIB. We also discuss challenges facing athletes with asthma and EIB, while also being subject to anti-doping regulations.

Revision Dual Mobility Constructs With Unmatched Acetabular and Femoral Components Do Not Increase Failure Rate.

BACKGROUND: Dual mobility (DM) constructs for revision total hip arthroplasty (THA) have continued to grow in popularity to mitigate instability. This benefit comes at the cost of potential unique modes of failure, and there are theoretical concerns that combining femoral and acetabular components from different manufacturers could lead to increased failure rates. We aimed to investigate rates of reoperation between matched and unmatched DM implants used in revision THA. METHODS: We retrospectively reviewed 217 revision THAs performed with DM constructs between July 2012 and September 2021 at a single institution. Dual mobility (DM) constructs were classified as "matched" if the acetabular and femoral components were manufactured by the same company. They were classified as "unmatched" if the acetabular and femoral components were manufactured by different companies. The primary outcome was reoperation for any reason. RESULTS: There were 136 matched DM constructs and 81 unmatched constructs. Average follow-up was 4.6 years (range, 2.0 to 9.6 years). There was no difference in reoperation rate between matched and unmatched groups (11.0 versus 13.6%, P = .576). The most common reasons for reoperation in both groups were instability and periprosthetic joint infection. There was 1 revision for intraprosthetic dislocation in the matched group. CONCLUSIONS: The use of unmatched DM components in revision THA was common and did not increase the risk of reoperation at an average of 4.6-year follow-up. This information can be helpful in operative planning, but further research on long-term survival will be necessary.

Novel powered 5.0-mm endoscopic debridement catheter for endoscopic transmural necrosectomy of pancreatic walled-off necrosis: a case series of consecutive patients from a tertiary referral center (with video).

BACKGROUND AND AIMS: EUS-guided drainage and, if required, endoscopic necrosectomy (EN) has become the criterion standard for the treatment of pancreatic walled-off necrosis (WON). A dedicated powered endoscopic debridement system, the EndoRotor (Interscope Inc, Northbridge, Mass, USA), has been introduced as an alternative to snare necrosectomy. This study evaluates the novel EndoRotor catheter, NecroMax 6.0 (Interscope Inc, Whitinsville, Mass, USA), for EN in patients with WON. METHODS: This single-center retrospective case series included consecutive patients with WON treated with the NecroMax 6.0 catheter. Safety, ability to perform EN, and clinical resolution were evaluated. RESULTS: Twenty patients underwent 30 EN procedures with the NecroMax 6.0 catheter. One suspected device-related adverse event was observed (3.3%). In 1 procedure, EN could not be performed because of excessive bending of the endoscope. Eighteen patients (90.0%) achieved clinical resolution. CONCLUSIONS: EN with the NecroMax 6.0 catheter was technically feasible in 96.7% of patients with a low rate of adverse events.

EUS-guided transcolonic drainage and necrosectomy in walled-off necrosis: a retrospective, single-center case series.

Background and study aims Transgastric endoscopic ultrasound (EUS)-guided drainage and, if needed, necrosectomy is the preferred treatment in patients with pancreatic walled-off necrosis. EUS-guided transcolonic or transrectal drainage and necrosectomy may serve as a minimally invasive alternative in cases in which transgastric or percutaneous drainage is either impossible or fails to secure sufficient drainage. In this paper, we retrospectively evaluated the feasibility, safety, and efficacy of the treatment. We included nine patients and found a technical success rate of 100%, clinical success in 89%, and one adverse event (11%). Transrectal/transcolonic endoscopic necrosectomy was needed in seven patients (78%).

The effect of aerobic exercise training on asthma control in postmenopausal women (ATOM): a randomized controlled pilot study.

Objective: To evaluate if high-intensity interval training three times weekly for 12 weeks improves asthma control in overweight, postmenopausal women with uncontrolled, late-onset asthma. Methods: The reported study is a randomized clinical pilot study (www.clinicaltrials.gov; NCT03747211) that compared 12 weeks of high-intensity interval training (spinning) with usual care. The five-question Asthma Control Questionnaire (ACQ-5) was used as primary outcome. Secondary measures included systemic inflammation and inflammation of the airways, body composition, and cardiac function during exercise. Results: We included 12 women with asthma (mean age 65 years (SD 6); mean body mass index 30 kg/m2 (SD 2)) from whom eight were randomized to exercise and four to control. Baseline ACQ-5 was 1.95 (SD 0.53) in the control group and 2.03 (0.54) in the exercise group. Patients had a mean blood eosinophil level of 0.16 × 109cells/L (SD 0.07) and a mean fraction of exhaled nitric oxide of 23 ppb (SD 25). Mixed models showed that participants in the exercise group reduced their ACQ-5 by 0.55 points (95%CI -1.10 to -0.00; P = 0.08) compared with the control group. The exercise group significantly reduced their mean body fat percentage (-2.7%; 95%CI -4.5 to -0.8; P = 0.02), fat mass (-2.8 kg; 95%CI -5.1 to -0.4; P = 0.044) and android fat mass (-0.33 kg; 95%CI -0.60- -0.06; P = 0.038). In analyses of cardiac measures, we saw no significant effects on right ventricular function (fractional area change), diastolic function or left ventricular function. Conclusions: Although changes in ACQ-5 were slightly insignificant, these preliminary findings indicate that aerobic exercise training can be used as a means to improve asthma control in overweight, postmenopausal women with asthma.

Glucose variability in 6-12-month-old healthy infants.

Background: Metabolic programming of glucose homeostasis in the first 1,000 days of life may impact lifelong metabolic and cardiovascular health. Continuous glucose monitoring (CGM) devices may help measure the impact of dietary intake on glucose rhythms and metabolism in infants during the complementary feeding period. Objectives: Demonstrate the feasibility of CGM to measure and quantify glucose variability in response to infant feeding and to evaluate associations between macronutrient meal composition and glucose variability. Methods: The "FreeStyle Libre Pro®" device interstitial glucose meter was applied to the anterior thigh of 10 healthy 6-12-month-old infants. Parents recorded food intake, time of feeding, and used daily dairies to record sleep time and duration. Descriptive statistics were employed for food intake, sleep and key glycemic parameters over three full days. Mixed linear models were used to assess glycemic changes. Results: Mid-day, afternoon, and evening feeds contained >30 g carbohydrate and induced higher 2-h iAUC (3.42, 3.41, and 3.50 mmol/L*h respectively) compared to early and mid-morning feedings with ≤25 g carbohydrates (iAUC 2.72 and 2.81 mmol/L*h, p < 0.05). Early morning and evening milk feedings contained approximately 9 g of fat and induced a longer time to reach maximal glucose value (Tmax; 75 and 68 min, respectively) compared to lower fat feedings (2.9-5.9 g; Tmax range: 34-60 min; p < 0.05). Incremental glucose value at time of food intake (C0) increased significantly from 0.24 ± 0.39 mM in early morning to 1.07 ± 0.57 mM in the evening (p < 0.05). Over the day, 70% of glucose values remained within the normal range (3.5-5.5 mmol/L), 10% were between 5.5-10 mmol/L, and 20% were < 3.5 mmol/L. Conclusion: Our data support the feasibility of using CGM to measure glucose in 6-12-month-old infants. The observation of possible diurnal glucose variability and typical glucose values may have implications for future studies investigating metabolic adaptation to nutritional intake in early life.

A case of bilateral pneumothorax following computer-tomography guided transthoracic biopsy in a woman with suspected pulmonary cancer.

Computer-tomography-guided needle biopsies are useful for diagnosing, staging, and classification of peripheral pulmonary nodules. However, the procedure carries a risk of iatrogenic pneumothorax. This report describes a patient-case where a woman had undergone a computer-tomography guided biopsy. Approximately 4 hours following discharge the patient was admitted to the emergency ward with severe chest pain and dyspnea. Chest x-ray revealed bilateral pneumothorax and subcutaneous emphysema at the biopsy site. Pleural drainage was administered on the patient's right side. Another chest x-ray following drainage showed regression of pneumothorax on both sides thus indicating communicating pleural cavities. Medical history revealed that the patient had been thymectomized 2 years earlier and a computer tomography visualized that the patient lacked mediastinal separation of the two pleural cavities. It is possible that patients with a history of mediastinal or thoracic surgery should be observed longer following procedures carrying risk of iatrogenic pneumothorax.

Effect of High-Intensity Interval Training on Inhaled Corticosteroid Dose in Asthma Patients: A Randomized Controlled Trial.

BACKGROUND: Inhaled corticosteroids (ICS) are the cornerstone of asthma treatment. However, ICS has side effects, and dose reduction is recommended when possible. Physical exercise improves asthma control, but it is unknown whether it reduces the reliance on ICS. OBJECTIVE: To assess whether supervised high-intensity interval training reduces the need for ICS in untrained asthma patients. METHODS: An assessor-blinded single-center randomized controlled trial, Copenhagen, Denmark. One hundred fifty untrained ICS-treated adults with symptomatic asthma were randomly assigned (2:1) to 6 months of supervised exercise 3 times weekly or a lifestyle as usual control group. Every second month, a clinical algorithm based on symptom control was applied in both groups to adjust ICS dose. Primary outcome was the proportion who had their ICS dose reduced by 25% or more after 6 months. Secondary outcomes included actual ICS dosage in micrograms per day. RESULTS: Between October 2017 and December 2019, 102 patients were allocated to exercise intervention (86% completed) and 48 to the control (85% completed). At the 6-month visit, 63% versus 50% met the primary outcome in the exercise and control groups, respectively (adjusted risk difference 9.6% [95% CI -3.8 to 18.8]; P = .15). Daily ICS dose was reduced in favor of the exercise group, with a mean difference of -234 µg (95% CI -391 to -77; P = .0037), corresponding to a 24% reduction from baseline. This effect was sustained at 12 months. The intervention was safe and well tolerated. CONCLUSIONS: Six months of regular exercise results in reduction in daily ICS dose without compromising asthma control.

The Microbiome of Osteoarthritic Hip and Knee Joints: A Prospective Multicenter Investigation.

BACKGROUND: Recent advances in high-throughput DNA sequencing technologies have made it possible to characterize the microbial profile in anatomical sites previously assumed to be sterile. We used this approach to explore the microbial composition within joints of osteoarthritic patients. METHODS: This prospective multicenter study recruited 113 patients undergoing hip or knee arthroplasty between 2017 and 2019. Demographics and prior intra-articular injections were noted. Matched synovial fluid, tissue, and swab specimens were obtained and shipped to a centralized laboratory for testing. Following DNA extraction, microbial 16S-rRNA sequencing was performed. RESULTS: Comparisons of paired specimens indicated that each was a comparable measure for microbiological sampling of the joint. Swab specimens were modestly different in bacterial composition from synovial fluid and tissue. The 5 most abundant genera were Escherichia, Cutibacterium, Staphylococcus, Acinetobacter, and Pseudomonas. Although sample size varied, the hospital of origin explained a significant portion (18.5%) of the variance in the microbial composition of the joint, and corticosteroid injection within 6 months before arthroplasty was associated with elevated abundance of several lineages. CONCLUSIONS: The findings revealed that prior intra-articular injection and the operative hospital environment may influence the microbial composition of the joint. Furthermore, the most common species observed in this study were not among the most common in previous skin microbiome studies, suggesting that the microbial profiles detected are not likely explained solely by skin contamination. Further research is needed to determine the relationship between the hospital and a "closed" microbiome environment. These findings contribute to establishing the baseline microbial signal and identifying contributing variables in the osteoarthritic joint, which will be valuable as a comparator in the contexts of infection and long-term arthroplasty success. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Hormonal Contraceptives Are Associated With an Increase in Incidence of Asthma in Women.

BACKGROUND: Use of exogenous female sex hormones is associated with the development of asthma, but the question of whether the effect is protective or harmful remains unresolved. OBJECTIVE: To investigate whether initiation of hormonal contraceptive (HC) treatment was associated with development of asthma. METHODS: We performed a register-based, exposure-matched cohort study including women who initiated HC treatment of any kind between 10 and 40 years of age and compared the incidence of asthma with women who did not initiate HCs. Asthma was defined as 2 redeemed prescriptions of inhaled corticosteroids within 2 years. Data were analyzed using Cox regression models adjusted for income and urbanization. RESULTS: We included 184,046 women with a mean age of 15.5 years (SD 1.5 y), in which 30,669 initiated HC treatment and 153,377 did not. We found that initiation of HCs was associated with an increased hazard ratio (HR) of developing new asthma by 1.78 (95% CI 1.58-2.00; P < .001). The cumulative risk of new asthma was 2.7% after 3 years among users of HCs compared with 1.5% in nonusers. In the different subtypes of HCs, second- and third-generation contraceptives carried significant associations (second-generation HR 1.76; 95% CI 1.52-2.03; P < .001; third-generation HR 1.62 95% CI 1.23-2.12; P < .001). The association with increased incidence was seen only in women younger than 18 years. CONCLUSIONS: In this study, first-time users of HCs had an increased incidence of asthma compared with nonusers. Clinicians prescribing HCs should be aware that airway symptoms may develop.

Child-Pugh Class B or C Liver Disease Increases the Risk of Early Mortality in Patients With Hepatitis C Undergoing Elective Total Joint Arthroplasty Regardless of Treatment Status.

BACKGROUND: Patients with hepatitis C virus (HCV) undergoing primary elective total joint arthroplasty (TJA) are at increased risk of postoperative complications. Patients with chronic liver disease and cirrhosis, specifically Child-Pugh Class B and C, who are undergoing general surgery have high 2-year mortality risks, approaching 60% to 80%. However, the role of Child-Pugh and Model for End-Stage Liver Disease classifications of liver status in predicting survivorship among patients with HCV undergoing elective arthroplasty has not been elucidated. QUESTION/PURPOSE: What factors are independently associated with early mortality (< 2 years) in patients with HCV undergoing arthroplasty? METHODS: We performed a retrospective study at three tertiary academic medical centers and identified patients with HCV undergoing primary elective TJA between January 2005 and December 2019. Patients who underwent revision TJA and simultaneous primary TJA were excluded. A total of 226 patients were eligible for inclusion in the study. A further 25% (57) were excluded because they were lost to follow-up before the minimum study requirement of 2 years of follow-up or had incomplete datasets. After the inclusion and exclusion criteria were applied, the final cohort consisted of 75% (169 of 226) of the initial patient population eligible for analysis. The mean follow-up duration was 53 ± 29 months. We compared confounding variables for mortality between patients with early mortality (16 patients) and surviving patients (153 patients), including comorbidities, HCV and liver characteristics, HCV treatment, and postoperative medical and surgical complications. Patients with early postoperative mortality were more likely to have an associated advanced Child-Pugh classification and comorbidities including peripheral vascular disease, end-stage renal disease, heart failure, and chronic obstructive pulmonary disease. However, both groups had similar 90-day and 1-year medical complication risks including myocardial infarction, stroke, pulmonary embolism, and reoperations for periprosthetic joint infection and mechanical failure. A multivariable regression analysis was performed to identify independent factors associated with early mortality, incorporating all significant variables with p < 0.05 present in the univariate analysis. RESULTS: After accounting for significant variables in the univariate analysis such as peripheral vascular disease, end-stage renal disease, heart failure, chronic obstructive pulmonary disease, and liver fibrosis staging, Child-Pugh Class B or C classification was found to be the sole factor independently associated with increased odds of early (within 2 years) mortality in patients with HCV undergoing elective TJA (adjusted odds ratio 29 [95% confidence interval 5 to 174]; p < 0.001). The risk of early mortality in patients with Child-Pugh Class B or C was 64% (seven of 11) compared with 6% (nine of 158) in patients with Child-Pugh Class A (p < 0.001). CONCLUSION: Patients with HCV and a Child-Pugh Class B or C at the time of elective TJA had substantially increased odds of death, regardless of liver function, cirrhosis, age, Model for End-Stage Liver Disease level, HCV treatment, and viral load status. This is similar to the risk of early mortality observed in patients with chronic liver disease undergoing abdominal and cardiac surgery. Surgeons should avoid these major elective procedures in patients with Child-Pugh Class B or C whenever possible. For patients who feel their arthritic symptoms and pain are unbearable, surgeons need to be clear that the risk of death is considerably elevated. LEVEL OF EVIDENCE: Level III, therapeutic study.

Comparison of Static and Articulating Spacers After Periprosthetic Joint Infection.

INTRODUCTION: There is no consensus on whether articulating or static spacers are superior during two-stage exchange arthroplasty for periprosthetic joint infection. We aimed to compare surgical time, need for extensile exposure, surgical costs, and treatment success for articulating and static spacers. METHODS: This was a retrospective review of 229 periprosthetic joint infections treated with two-stage exchange with a minimum of one-year follow-up. For articulating and static spacers, we compared the need for extensile exposure during reimplantation and treatment failure based on an updated definition. Surgical time and costs at both stages were also compared. Subgroup analysis was performed for total knee and hip arthroplasties. RESULTS: There was no difference in the surgical time for spacer insertion; however, articulating spacers demonstrated reduced surgical time during reimplantation (181 vs. 234 minutes, P < 0.001). In multivariate analysis, there was no difference in extensile exposures (odds ratio 2.20, P = 0.081), but treatment failure was more likely for static spacers (odds ratio 2.17, P = 0.009). Overall surgical costs for two-stage exchange were similar between groups (23,782 vs. 23,766, P = 0.495). CONCLUSION: Articulating spacers demonstrated shorter surgical times and a trend toward decreased extensile exposures during reimplantation. They also had higher treatment success rates and similar surgical costs for overall two-stage exchange.

Urine concentrations of vilanterol and its metabolites, GSK932009 and GW630200, after inhalation of therapeutic and supratherapeutic doses.

The 2023 Prohibited List issued by the World Anti-Doping Agency (WADA) permits athletes to inhale the beta2 -agonist vilanterol at a standard dose of 25 µg daily. However, given limited data on urine pharmacokinetics, vilanterol has no urinary threshold or decision limit to discriminate therapeutic from supratherapeutic use. We investigated urine concentrations of vilanterol and its main metabolites GSK932009 and GW630200 over 0-72 h following inhalation of therapeutic (25 µg) or supratherapeutic (100 µg) doses and repeat-dose administration for 7 days of 25 or 100 µg·day-1 in 25 trained men and women. Vilanterol administration was followed by 1 h of exercise. GW630200 urine concentrations were low and insufficient for threshold purposes, and while GSK932009 had higher urine concentrations, it could not discriminate between therapeutic and supratherapeutic use. Mean (range) maximum urine concentrations of parent vilanterol were 1.2 (0.2-4.1) and 6.2 (1.4-14.3) ng·ml-1 for single-dose 25 and 100 µg vilanterol, respectively, and 2.0 (0.3-4.8) and 22.4 (6.4-42.1) ng·ml-1 for repeat-dose 25 and 100 µg·day-1 vilanterol. In 333 samples collected 6 h post-administration and considering WADA TD2022DL, a 3.1 ng·ml-1 vilanterol cut-off showed 30% sensitivity in detecting supratherapeutic use at 100 µg versus therapeutic use at 25 µg. Considering inter- and intra-individual variability and guard bands in doping analysis, a 6 ng·ml-1 decision limit, which could be shifted upwards in samples with specific gravity >1.018, appears sufficiently high to minimize risk of samples exceeding the decision limit after therapeutic use of vilanterol, while demonstrating the ability to detect supratherapeutic use at 100 µg.

EUS-guided drainage of large walled-off pancreatic necroses using plastic versus lumen-apposing metal stents: a single-centre randomised controlled trial.

OBJECTIVE: In treating pancreatic walled-off necrosis (WON), lumen-apposing metal stents (LAMS) have not proven superior to the traditional double pigtail technique (DPT). Among patients with large WON (>15 cm) and their associated substantial risk of treatment failure, the increased drainage capacity of a novel 20-mm LAMS might improve clinical outcomes. Hence, we conducted a study comparing the DPT and 20-mm LAMS in patients with large WON. DESIGN: A single-centre, open-label, randomised, controlled superiority trial using an endoscopic step-up approach in patients with WON exceeding 15 cm in size. The primary endpoint was the number of necrosectomies needed to achieve clinical success (clinical and CT resolution), while the secondary endpoints included technical success, adverse events, length of stay and mortality. RESULTS: Twenty-two patients were included in the DPT group and 20 in the LAMS group, with no significant differences in patient characteristics. The median size of WON was 24.1 cm (P25-P75: 19.6-31.1). The technical success rates were 100% for DPT and 95% for LAMS (p=0.48), while clinical success rates were 95.5% and 94.7%, respectively (p=1.0). The mean number of necrosectomies was 2.2 for DPT and 3.2 for LAMS (p=0.42). Five patients (12%) developed procedure-related serious adverse events (DPT=4, LAMS=1, p=0.35). The median length of stay was 43 (P25-P75: 40-67) and 58 days (P25-P75: 40-86) in the DPT and LAMS groups (p=0.71), respectively, with an overall mortality of 4.8%. CONCLUSIONS: For treating large WON, LAMS are not superior to DPT. The techniques are associated with comparable needs for necrosectomy and hospital stay, and no gross difference in adverse events. TRIAL REGISTRATION NUMBER: NCT04057846.