Prospective Multicenter Study Research Articles

Ablation strategy for idiopathic outflow tract premature ventricular complexes: rationale and design of the ABOUT-PVC study, a prospective multicenter study

Abstract Background An idiopathic outflow tract premature ventricular complex (OT-PVC) is a common arrhythmia, and the accuracy of site of origin prediction using the 12-lead electrocardiogram (ECG) algorithm is not high. There are no studies about a systematic strategy that can provide practical help to electrophysiologists in OT-PVC mapping and ablation. This study aims to evaluate the efficacy and safety of the proposed ablation protocol and establish an optimal catheter ablation strategy by simultaneously investigating and synthesizing various indicators observed during the mapping procedure. Methods and design This study (ABOUT-PVC) was designed as a prospective multicenter study to enroll 210 patients from 11 tertiary university hospitals over an estimated 27 months. Patients with idiopathic OT-PVC requiring catheter ablation will receive the procedure through a proposed ablation strategy and will be followed up for at least 12 months. The primary outcome is the acute procedural success rate. The secondary outcomes are clinical success rate, procedure time, complication rate, symptom relief, and changes in echocardiographic parameters. Conclusions The ABOUT-PVC study was designed to investigate the efficacy and safety of the proposed ablation strategy and establish an optimal catheter ablation strategy. We expect this study to overcome the limitations of the ECG prediction algorithms and provide a practical guide to electrophysiologists, increasing the procedure’s success rate and reducing complications and procedure time.

Comparison of disease and risk classifications of AML before and after incorporation of NGS analysis of bone marrow samples.

Mutation profiling by next-generation sequencing (NGS) has facilitated understanding of the molecular pathogenesis of acute myeloid leukemia (AML), and has been incorporated into the new disease classification (International Consensus Classification; ICC) and risk classification (European LeukemiaNet [ELN] 2022; ELN2022). We compared disease subtypes between the previous disease classification (4th edition of the WHO classification; WHO-4) and the ICC in 91 patients with AML diagnosed at our institution. We also compared disease risk classifications using the previous risk classification (ELN2017) and the ELN2022. Targeted sequencing of bone marrow samples was conducted at Kyoto University. We found that entities under AML with recurrent genetic abnormalities were well-established, with almost no change from the WHO-4 to the ICC. In contrast, 16.7% of cases of AML, not otherwise specified in the WHO-4 were reclassified into AML with mutated TP53, and 36.7% were reclassified into AML with myelodysplasia-related gene mutations or cytogenetic abnormalities per the ICC. Meanwhile, the ELN2017 and ELN2022 showed no difference in concordance indexes in multivariate Cox regression analysis for progression-free and overall survival. The superiority of the ELN2022 over the ELN2017 could not be confirmed in our single-center retrospective study, and further investigation including multicenter prospective studies is needed.

Risk factors for gastrointestinal bleeding in patients with intracerebral hemorrhage: A propensity score matching analysis

BackgroundGastrointestinal bleeding (GIB) is a common complication of intracerebral hemorrhage (ICH). Rate pressure product (RPP) is an objective hemodynamic index that is closely related to the prognosis of cardia-cerebrovascular disease. The purpose of this study was to investigate the relationship between RPP and GIB in ICH patients. MethodsWe retrospectively analyzed data from ICH patients admitted to the neurosurgery department of Nanchang University affiliated with Ganzhou Hospital from January 2019 to December 2021. The patients were divided into a GIB group and a non-GIB group according to whether they had GIB. Propensity score matching was used to match between the two groups. Univariate analysis was used to select factors affecting GIB, and multivariate conditional logistic regression was used to analyze the independent factors associated with GIB. ResultsThere were 1232 patients included in the study, including 182 in the GIB group and 1050 in the non-GIB group, and 182 pairs of patients were successfully matched through propensity score matching. The univariate analysis showed that high RPP, low Glasgow coma score (GCS), fibrinogen, D-dimer and PPIs were factors associated with GIB. Multivariate conditional logistic regression showed that high RPP, low GCS and urokinase were independent risk factors for GIB, and PPIs was a protective factor for GIB. ConclusionsHigh RPP, low GCS and urokinase were independent risk factors for GIB, and PPIs was a protective factor for GIB. Patients with a high risk of developing GIB should be monitored closely. Nevertheless, multicenter prospective studies with more patients are needed to further validate the results.

Loss of copy numbers of retrotransposons (HERVK) on chromosome 7p11.2 impacts EGFR (Epidermal Growth Factor Receptor)-induced phenotypes for platinum sensitivity and long-term survival in ovarian cancer-A study from the OVCAD consortium.

We analyzed variations in the epidermal growth factor receptor (EGFR) gene and 5'-upstream region to identify potential molecular predictors of treatment response in primary epithelial ovarian cancer. Tumor tissues collected during debulking surgery from the prospective multicenter OVCAD study were investigated. Copy number variations in the human endogenous retrovirus sequence human endogenous retrovirus K9 (HERVK9) and EGFR Exons 7 and 9, as well as repeat length and loss of heterozygosity of polymorphic CA-SSR I and relative EGFR mRNA expression were determined quantitatively. At least one EGFR variation was observed in 94% of the patients. Among the 30 combinations of variations discovered, enhanced platinum sensitivity (n = 151) was found dominantly with HERVK9 haploidy and Exon 7 tetraploidy, overrepresented among patients with survival ≥120 months (24/29, p = .0212). EGFR overexpression (≥80 percentile) was significantly less likely in the responders (17% vs. 32%, p = .044). Multivariate Cox regression analysis, including age, FIGO stage, and grade, indicated that the patients' subgroup was prognostically significant for CA-SSR I repeat length <18 CA for both alleles (HR 0.276, 95% confidence interval 0.109-0.655, p = .001). Although EGFR variations occur in ovarian cancer, the mRNA levels remain low compared to other EGFR-mutated cancers. Notably, the inherited length of the CA-SSR I repeat, HERVK9 haploidy, and Exon 7 tetraploidy conferred three times higher odds ratio to survive for more than 10 years under therapy. This may add value in guiding therapies if determined during follow-up in circulating tumor cells or circulating tumor DNA and offers HERVK9 as a potential therapeutic target.

Energy Intake and Dietary Glycemic Load in Late Morning and Risk of Type 2 Diabetes: The Hispanic Community Health Study/Study of Latinos-A Multicenter Prospective Cohort Study.

To evaluate the association between meal timing and type 2 diabetes risk in U.S. Hispanic/Latino adults. The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a multicenter, community-based, prospective cohort study. This study included 8,868 HCHS/SOL adults without diabetes at baseline (2008-2011) and attending the visit 2 examination (2014-2017). Energy intake and glycemic load (GL) in each meal timing were assessed at baseline using two 24-h dietary recalls. Incident diabetes was identified through annual follow-up calls or at visit 2. Hazard ratios (HRs) for incident diabetes were estimated using Cox models, accounting for the complex survey design. The study population (50.9% female) had a baseline mean age of 39.0 (95% CI, 38.4-39.5) years. Over a median (range) follow-up of 5.8 (0.8-9.6) years, 1,262 incident diabetes cases were documented. Greater energy intake and GL in late morning (9:00-11:59 a.m.) were associated with a lower diabetes risk, whereas greater energy intake and GL in other meal timings were not. After accounting for diet quantity and quality, sociodemographic characteristics, lifestyle factors, and chronic conditions, the HRs were 0.94 (95% CI, 0.91-0.97) per 100-kcal energy intake increment and 0.93 (0.89-0.97) per 10-unit GL increment in late morning. Replacing energy intake or GL from early morning (6:00-8:59 a.m.), afternoon (12:00-5:59 p.m.), or evening (6:00-11:59 p.m.) with late-morning equivalents was associated with a comparably lower diabetes risk. This study identified late morning as a favorable meal timing in Hispanic/Latino adults, providing a novel perspective on type 2 diabetes prevention that warrants confirmation.

The prognostic utility of Lactate/Albumin*Age score in septic patient with normal lactate level

BackgroundA previous study has shown that the lactate/albumin*age (LAA) score is useful for predicting mortality in patients with sepsis admitted to the ICU. We aimed to evaluate the clinical significance of the LAA score in patients with sepsis who presented to the emergency department (ED) MethodsThis retrospective observational study used data from the Korean Shock Society Registry collected between January 2017 and December 2021. The prognostic performance of the LAA score for predicting the 28-day mortality was evaluated. Lactate and albumin levels were measured immediately after arrival to the ED. ResultsOf the 5346 patients with sepsis, data from 3240 were analyzed. The area under the receiver operating characteristic curve (AUROC) of the LAA score (0.737, 95% confidence interval (CI) 0.716-0.757), was higher than that of lactate (0.699, 95% CI 0.677-0.720, p<0.001), lactate/albumin (LA) ratio (0.730, 95% CI 0.709-0.751, p=0.016), and Sequential Organ Failure Assessment (SOFA) score (0.698, 95% confidence interval 0.676-0.720, p=0. 004), and Acute Physiology and Chronic Health Evaluation (APACHE) II scores (0.672; 95% confidence interval 0.649-0.694, p<0.001). The optimal cut-off value for the LAA score was 119.9. In the Kaplan-Meier analysis according to the optimal cutoff value, the 28-day mortality rates were higher in the high LAA score group (log-rank test, p<0.001). The LAA score was independently associated with 28-day mortality in the multivariate Cox proportional hazards model (adjusted hazard ratio 2.07, 95% CI 1.76-2.43, p<0.001). In the normal (<2 mmol/L) lactate group, the AUROC value for LAA score was higher than LA ratio (normal group 0.674 vs 0.634, p<0.004). In patients over 65 years old, LAA score (0.731) showed a higher AUROC value than LA ratio (0.725). (p<0.001) ConclusionThe LAA score may be used as an independent predictor of mortality in patients with sepsis in the emergency department. Our results show that it performs better than serum lactate alone, LA ratio, and SOFA and APACHE II scores. While this suggests that the LAA could provide clinicians with a useful tool for timely early intervention and care planning in patients with a poor prognosis, further validation in large multicenter prospective studies are necessary to confirm its reliability and practicality as a readily available and objective biomarker.

Development and External Validation of Motor-intention Integrated Prediction Model for Upper Extremity Motor Recovery After Intention-driven Robotic-hand Training for Chronic Stroke.

To derive and validate a prediction model for minimal clinically important differences (MCID) in upper extremity (UE) motor function after intention-driven robotic-hand training using residual voluntary EMG signals from affected UE. A prospective longitudinal multicenter cohort study. We collected pre-intervention candidate predictors: demographics, clinical characteristics, Fugl-Meyer assessment of UE (FMAUE), Action Research Arm Test scores, and motor-intention of flexor digitorum and extensor digitorum (ED) measured by EMG during maximal voluntary contraction (MVC). For EMG measures, recognizing challenges for stroke survivors to move paralyzed hand, peak signals were extracted from eight time-windows during MVC-EMG (0.1s-5s) to identify subjects' motor-intention. Classification And Regression Tree algorithm was employed to predict survivors with MCID of FMAUE. Relationship between predictors and motor-improvements was further investigated. Nine rehabilitation centers. Chronic stroke survivors (N=131), including 87 for Derivation-sample, and 44 for Validation-sample. All participants underwent 20-session robotic-hand training (40min/session, 3-5sessions/week). Prediction efficacies of models were assessed by area under the receiver operating characteristic curve (AUC). The best effective model was final model and validated using AUC and overall accuracy. The best model comprised FMAUE (cut-off score: 46) and peak activity of ED from one-second MVC-EMG (MVC-EMG 4.604 times higher than resting-EMG), which demonstrated significantly higher prediction accuracy (AUC: 0.807) than other time-windows or solely using clinical-scores (AUC: 0.595). In external validation, this model displayed robust prediction (AUC: 0.916). Significant quadratic relationship was observed between ED-EMG and FMAUE increases. This study presents a prediction model for intention-driven robotic-hand training in chronic stroke survivors. It highlights significance of capturing motor-intention through 1-second EMG-window as a predictor for MCID improvement in UE motor-function after 20-session robotic-training. Survivors in two conditions showed high percentage of clinical motor-improvement: moderate-to-high motor-intention and low-to-moderate function; as well as high-intention and high-function.

Sleep-disordered breathing increases mortality in patients with diabetes.

Sleep-disordered breathing (SDB) and diabetes mellitus (DM) are often concomitant; however, data on the impact of SDB on mortality in the population with diabetes remain scarce. The population from the Sleep Heart Health Study, a multicenter prospective observational study representing 5780 patients with polysomnography and mortality data, including 453 patients with DM, was analyzed to assess the impact of SDB variables and the presence of DM on all-cause, cardiovascular disease (CVD), and non-CVD associated mortality. Survival analysis and proportional hazard regression models were used to calculate the adjusted hazard ratios (aHR) for mortality. Patients with DM and the average SpO2 >91.4% had significantly lower all-cause (aHR 0.52, CI 0.34-0.80) and CVD mortality risk (aHR 0.44, CI 0.22-0.87) as compared with patients with SpO2 below this value. Apnea-hypopnea index >31 (aHR 1.58, CI 1.10-2.28) and oxygen desaturation index >13.3 (aHR 1.58, CI 1.10-2.25) were associated with increased all-cause mortality in participants with DM on treatment. Sleep efficiency and proportion of rapid-eye movement (REM) sleep did not have any impact on mortality in patients with DM and thus differed significantly from individuals without DM, where increased all-cause mortality was observed in those with sleep efficiency <81.4% (aHR 0.77, CI 0.68-0.87) or REM sleep <14.9% (aHR 0.78, CI 0.68-0.89). Patients with diabetes on treatment and moderate to severe sleep-disordered breathing experience increased all-cause mortality. Reduced average oxygen saturation predicted both all-cause and cardiovascular death in the population with diabetes.

Urologist communication is a primary factor leading to erectile dysfunction treatment postprostatectomy.

Studies have shown insufficient utilization of care for patients with erectile dysfunction (ED) after radical prostatectomy (RP). The aim of this study was to evaluate variables associated with barriers to seeking and receiving ED treatment. In this multicenter prospective cross-sectional study, the functional outcomes of 936 patients were assessed 10 to 15years after RP. A total of 525 patients with ED or incontinence were asked about their treatment experiences or lack thereof. The data were analyzed using the chi-square test, t test, and multivariate logistic analyses. Patients answered validated questionnaires regarding information sources, communication with their partner and urologist, and barriers to ED treatment. Of the 525 patients, 80 were not available to survey. A total of 304 patients answered the survey (response: 68.0%). A total of 246 patients had ED and were included in this study. The mean age at surgery was 64.4 ± 6.1years, and the mean age at the time of this survey was 77.1 ± 6.2years. The mean follow-up duration was 12.7 ± 1.5years. Forty-six percent (n = 114 of 246) of the patients had never received ED treatment. The most important conversation partners regarding the ED were the partner (69% [n = 169 of 246]) and the urologist (48% [n = 118 of 246]). Patients who never received ED treatment were less likely to have conversations with their urologist (34% vs 60%; P < .001), had less support (51% vs 68%; P = .01), and had less interest in sex from their partner (20% vs 40%; P = .001). Communication with other groups (general practitioners, other physicians, family, friends, and the Internet) had no influence on ED treatment utilization. The most relevant barrier to receiving ED treatment was the belief that treatment would not help (65%). No interest in sex from their partner (odds ratio, 3.9) and no conversation with their urologist about ED (odds ratio, 2.9) were found to be independent predictors of not receiving ED treatment. Urologists should have enhanced awareness of how to approach patients directly about their ED and actively offer them treatment options. These results should be further validated in a multicenter, prospective study. Response bias may have affected the results. Furthermore, the current cohort was relatively old. This study revealed that no interest in sex from one's partner and insufficient communication with a urologist were relevant barriers to insufficient utilization of ED treatment after RP.

Disease characteristics and medications use in idiopathic inflammatory myopathy: a multi-center prospective observational study of decentralized remote vs. traditional clinic enrollment.

Idiopathic Inflammatory Myopathies (IIM) are rare and characterized by heterogeneous manifestations and clinical trajectories. Utilizing tele-research methods has the potential to improve participant recruitment and advance the understanding of the disease. We aimed to evaluate disease characteristics in IIM patients throughout the U.S. and compare these parameters between patients recruited remotely through mobile application or website vs those recruited locally in myositis clinics. "Myositis Patient Centered Tele-Research" (My PACER) is a multicentre prospective observational study of U.S. IIM subjects, competitively recruited through traditional in-person clinic visits (Center-Based Cohort [CBC]), and remotely using mobile application or website and social media (Tele-Research Cohort [TRC]). Data collection comprised baseline demographic and clinical variables, encompassing symptoms, organ involvement, diagnostic tests results and medication use. The study included 120 IIM patients, 82 in the TRC and 38 in the CBC. The average age was 55 ± 13.4, 75% females and 81% Caucasians. Both cohorts exhibited similar demographic characteristics. Overall, 41% dermatomyositis, 27% polymyositis, 23% anti-synthetase syndrome, and 9% necrotizing myositis patients were enrolled, with comparable subtypes prevalence among cohorts (p= 0.85). The groups demonstrated similarities in multiple clinical factors, including muscle enzymes, diagnostic delay, employment status, various patient and physician-reported outcomes, functional tests, and the frequency of abnormal findings in chest CT, pulmonary function tests, and electromyography. TRC patients received biologics and csDMARDs more frequently (p< 0.001 and p= 0.013, respectively). Tele-research recruitment yielded a patient cohort resembling traditionally recruited patients demographically and clinically, indicating its effectiveness for robust and diverse patient recruitment in clinical studies.

Müller Muscle Conjunctival Resection: A Prospective Multicenter Comparison of Eyelid Height at the Immediate, 1-Week, and 3-Month Postoperative Time Points.

The primary objective was to document change in postoperative marginal reflex distance-1 (MRD1) after Müller muscle conjunctival resection surgery. The secondary objective was to identify predictors of change in postoperative MRD1. A multicenter prospective cohort study was performed on patients consecutively recruited for Müller muscle conjunctival resection. MRD1 was measured immediately after Müller muscle conjunctival resection, at the 1-week postoperative visit, and the ≥3-month postoperative visit. MRD1 at the immediate and 1-week time points were compared with MRD1 ≥3 months using descriptive statistics. Predictors of change in MRD1 were analyzed using multivariate regression analysis. A total of 150 patients (226 eyelids) were included. Regarding the immediate to ≥3-month interval, 53.8% of eyelids remained clinically similar (rise or fall ≤0.5 mm), 19.8% rose ≥1 mm, and 26.4% fell ≥1 mm. Regarding the 1-week to ≥3-month interval, 76.5% remained clinically similar, 17.3% rose ≥1 mm, and 6.2% fell ≥1 mm. No variable predicted change in MRD1 over either interval with both clinical and statistical significance. Immediate postoperative MRD1 is likely to reflect the late result in only 54% of cases. However, 1-week postoperative MRD1 is similar to the late result in 77% of cases and is highly unlikely (6%) to fall by the final visit. No variable significantly impacts change in postoperative MRD1.

Particle therapy for intrahepatic cholangiocarcinoma: A multicenter prospective registry study, systematic review and meta-analysis

Introduction: A prospective study was started in May 2016 to evaluate the efficacy and safety of particle therapy for intrahepatic cholangial carcinoma (ICC). To compare treatment modalities, we also conducted a meta-analysis of literature data and a systematic comparison using registry data. Methods: Patients who received particle therapy for ICC from May 2016 to June 2018 were registered. Nineteen manuscripts (4 particle therapy, 8 3D-CRT, 7 SBRT) were selected for the meta-analysis. Results: A total of 85 cases (proton beam therapy 59, carbon therapy 26) were registered. The median OS of the 85 patients was 22.1 months (95%CI 12.9-31.3); the 1-, 2-, 3- and 4-year OS rates were 70.9% (95% CI 61.1-80.7%), 47.6% (36.8-58.4%), 37.7% (26.7-48.7%), and 22.7% (10.2-35.2%), respectively; and the 1-, 2-, 3- and 4-year local recurrence rates were 8.2% (1.1-15.3%), 21.6% (9.3-33.9%), 33.4% (16.7-50.1%), and 33.4% (16.7-50.1%), respectively. In the meta-analysis and registry data, the 1-year OS for particle therapy, SBRT and 3D-CRT were 71.8% (95% CI 64.6-77.8%), 59.2% (53.0-64.9%, p=0.0573), and 47.2% (36.8-56.9%, p=0.0004), respectively. The incidence of grade 3 or higher late non-hematological toxicity in the meta-analysis and registry data were 7.4-12% for particle therapy, 6.7-16.7% for SBRT, and 8.1-14.3% for 3D-CRT. Conclusions: Particle therapy achieved a good therapeutic effect for ICC, and a meta-analysis indicated that particle therapy is a better treatment modality than SBRT and 3D-CRT.

A New Self-Expandable Metallic Stent with Low Axial Force and a High Axial Force Zero-Border Shows a Very Low Perforation Rate in Malignant Colorectal Obstruction: A Japanese Multicenter Prospective Study

Background: Recently, there has been a significant increase in the utilization of self-expandable metallic stents (SEMSs) for treating malignant colorectal obstructions through colorectal stenting. The mechanical properties of SEMSs are usually considered to affect clinical outcomes of patients with malignant colorectal obstructions. Methods: This single-arm, prospective, multicenter study of SEMS with a lower axial force and high axial force zero-border included 200 patients with malignant colorectal obstruction. Technical and clinical success, stent patency, and adverse events associated with SEMS placement were evaluated. Results: One patient was excluded, and 199 patients were evaluated. The treatment intent was bridge-to-surgery in 129 and palliation in 70 patients. Technical and clinical success rates were 99.5% and 97.0%, respectively. The percentage of the ColoRectal Obstruction Scoring System scores of 3 or higher improved significantly from 19.2% before placement to 93.9% after placement. Clinical success was not achieved in five patients due to insufficient stent expansion in four patients and stent occlusion in one patient. Only one patient underwent emergency surgery for perforation of the proximal colon, far from where the stent was placed; the rescue procedure was not performed, despite no improvement in proximal dilatation due to insufficient stent expansion. Among the palliation cohort, 15 patients received chemotherapy, including molecular-targeted agents such as bevacizumab. There were no fatal cases related to stent placement. Conclusions: For management of malignant colorectal obstruction, this newly developed SEMS with low axial force and a high axial force zero-border showed high technical and clinical success rates, and an extremely low perforation rate (0.5%).

Development and Validation of an Integrative Risk Score for Future Risk of Crohn’s Disease in Healthy First-Degree Relatives: A Multicentre Prospective Cohort Study

Development and Validation of an Integrative Risk Score for Future Risk of Crohn’s Disease in Healthy First-Degree Relatives: A Multicentre Prospective Cohort Study

Frailty index is an independent predictor of all-cause and cardiovascular mortality in Eastern Europe: a multicentre cohort study

BackgroundThis study investigates the association between frailty and mortality in Eastern European populations, which remains largely unexplored compared with Western Europe. The aim is to assess the risk of all-cause...

Impact of altitude on the development of low bone mineral density and osteoporosis in individuals aged 50 years and older: protocol for a multicentre prospective cohort study

IntroductionOsteoporotic fractures are a leading cause of disability and contribute significantly to medical care costs worldwide. Variations in bone mineral density and the risk of osteoporosis are notably influenced by...

Incidence, risk factors and long-term outcomes for extubation failure in intensive care unit in patients with obesity A retrospective analysis of a multicenter prospective observational study

BackgroundNo large observational study has compared the incidence and risk factors for extubation failure within 48 hours and during intensive care unit (ICU) stay in the same cohort of unselected critically ill patients with and without obesity. Research questionWhich are the incidence and risk factors of extubation failure in patients with and without obesity? Study design and methodsIn this prospective multicenter observational FREE-REA study in 26 intensive care units, the primary objective was to compare the incidence of extubation failure within 48 hours in patients with and without obesity. Secondary objectives were to describe and to identify the independent specific risk factors for extubation failure using first a logistic regression model and second a decision tree analysis. ResultsOf 1,370 extubation procedures analyzed, 288 (21%) were performed in patients with obesity and 1082 (79%) in patients without obesity. The incidence of extubation failure within 48 hours among patients with or without presence of obesity was 23/288 (8.0%) versus 118/1082 (11%) respectively; unadjusted odds ratio (OR) 0.71 95% confidence interval (CI, 0.45-1.13), P=0.15); alongside patients with obesity receiving significantly more noninvasive ventilation (87/288, 30% versus 233/1082, 22%, P=0.002) and physiotherapy (165/288, 57% versus 527/1082, 49%, P=0.02) than patients without obesity. Risk factors for extubation failure also differed according to obesity status: female gender [adjusted (a)OR 4.88 95%CI(1.61-13.9), P=0.002] and agitation before extubation [aOR 6.39 95%CI (1.91-19.8), P=0.001] in patients with obesity; absence of strong cough before extubation [aOR 2.38 95%CI (1.53-3.84), P=0.0002] and duration of invasive mechanical ventilation before extubation [aOR 1.03 per day 95%CI (1.01-1.06), P=0.01] in patients without obesity. The decision tree analysis found similar risk factors. InterpretationOur findings indicate that anticipation and application of preventive measures for patients with obesity before and after extubation led to similar rate of extubation failure among patients with and without obesity. Clinical trial registrationNCT XXX

Early versus late response to PD-1-based immunotherapy in metastatic melanoma

BackgroundImmune checkpoint inhibition (ICI) currently is the most effective treatment to induce durable responses in metastatic melanoma. The aims of this study are the characterization of patients with early, late and non-response to ICI and analysis of survival outcomes in a real-world patient cohort. MethodsPatients who received PD-1-based immunotherapy for non-resectable stage-IV melanoma in any therapy line were selected from the prospective multicenter real-world DeCOG study ADOREG-TRIM (NCT05750511). Patients showing complete (CR) or partial (PR) response already during the first 3 months of treatment (Early Responders, EarlyR) were compared to patients showing CR/PR at a later time (Late Responders, LateR), a stable disease (SD) and to patients showing progressive disease (Non-Responders, NonR). ResultsOf 522 patients, 8.2% were EarlyR (n=43), 19.0% were LateR (n=99), 37.0% had a SD (n=193) and 35.8% were NonR (n=187). EarlyR, LateR and SD patients had comparable baseline characteristics. Multivariate logbinomial regression analyses adjusted for age and sex revealed positive tumor PD-L1 (RR=1.99, 95%-CI=1.14-3.46, p=0.015), and normal serum CRP (RR=1.59, 95%-CI=0.93-2.70, p=0.036) as independently associated with the achievement of an early response compared to NonR. The median progression-free and overall survival was 46.0 months (95% CI 19.1; NR) and 47.8 months (95% CI 36.9; NR) for EarlyR, NR (95% CI NR; NR) for LateR, 8.1 months (7.0; 10.4) and 35.4 months (29.2; NR) for SD, and 2.0 months (95% CI 1.9; 2.1) and 6.1 months (95%CI 4.6; 8.8) for NonR patients. ConclusionLess than 10% of metastatic melanoma patients achieved an early response during the first 3 months of PD-1-based immunotherapy. Early responders were not superior to late responders in terms of response durability and survival.

Prognostic value of the 5-SENSE Score to predict focality of the seizure-onset zone as assessed by stereoelectroencephalography: a prospective international multicentre validation study

IntroductionEpilepsy surgery is the only curative treatment for patients with drug-resistant focal epilepsy. Stereoelectroencephalography (SEEG) is the gold standard to delineate the seizure-onset zone (SOZ). However, up to 40% of...

Measuring Pectus Excavatum Severity, External Caliper, or Cross-Sectional Imaging: Family Perceptions

IntroductionPatients with pectus excavatum (PE) often undergo cross-sectional imaging (CSI) to quantify severity for insurance authorization before surgical repair. The modified percent depth (MPD), an external caliper-based metric, was previously validated to be similar to the pectus index and correction index. This study explored family perceptions of CSI and MPD with respect to value and costs. MethodsThis is a cross-sectional survey study including families of patients enrolled in an ongoing prospective multicenter study evaluating the use of MPD as an alternative to CSI for quantifying PE severity. Families of PE patients who underwent both MPD and CSI completed a survey to determine their perceptions of MPD and costs of CSI. Responses were described and associations were evaluated using chi squared, Wilcoxon rank-sum test and logistic regression as appropriate. Statistical significance was set to 0.05. ResultsThere were 136 surveys completed for a response rate of 88%. Respondents were confident in MPD (86%) and confident in its similarity to CSI (76%). Families of females were less confident in the measurements than males (55% versus 80%, P = 0.02; odds ratio 0.30 (0.11, 0.83). Obtaining CSI required time off work/school in 90% and a copay in 60%. Nearly half (49%) of respondents reported CSI was a time/financial hardship. Increasing copay led to decreased reassurance in CSI (55%: copay > $100 versus 77%: lower copay/75%: no copay; P = 0.04). ConclusionsFrom the family perspective, MPD is valuable in assessing the severity of PE. Obtaining CSI was financially burdensome, particularly for those with higher copays. MPD measurements provide high value at low cost in assessing the severity of PE.