International Multicenter Study Research Articles

Aortic valve performance after remodelling versus reimplantation in a propensity-matched comparison.

Both aortic root remodelling and aortic valve (AV) reimplantation have been used for valve-sparing root replacement in patients with aortic root aneurysm with or without aortic regurgitation. There is no clear evidence to support one technique over the another. This study aimed to compare remodelling with basal ring annuloplasty versus reimplantation on a multicentre level with the use of propensity-score matching. This was a retrospective international multicentre study of patients undergoing remodelling or reimplantation between 2010 and 2021. Twenty-three preoperative covariates (including root dimensions and valve characteristics) were used for propensity-score matching. Perioperative outcomes were analysed along with longer-term freedom from AV reoperation/reintervention and other major valve-related events. Throughout the study period, 297 patients underwent remodelling and 281 had reimplantation. Using propensity-score matching, 112 pairs were selected and further compared. We did not find a statistically significant difference in perioperative outcomes between the matched groups. Patients after remodelling had significantly higher reintervention risk than after reimplantation over the median follow-up of 6 years (P = 0.016). The remodelling technique (P = 0.02), need for decalcification (P = 0.03) and degree of immediate postoperative AV regurgitation (P < 0.001) were defined as independent risk factors for later AV reintervention. After exclusion of patients with worse than mild AV regurgitation immediately after repair, both techniques functioned comparably (P = 0.089). AV reimplantation was associated with better valve function in longer-term postoperatively than remodelling. If optimal immediate repair outcome was achieved, both techniques provided comparable AV function.

Developing research priorities for palliative care in Colombia: a priority setting partnership approach

BackgroundA recent Lancet commission called for more research on palliative care in low- and middle-income (LMIC) countries such as Colombia. A research priority setting approach has been recommended by The Global Forum for Health Research to address the huge gap in research output between LMIC and high-income countries, with influential health service bodies recommending the active involvement of non-research expert stakeholders in establishing research priorities to address service user needs.MethodPriority setting partnership (PSP) following the four stages of the James Lind Alliance methodology; establishing the partnership, identifying evidence uncertainties, refining questions and uncertainties, and prioritization. Data from MS forms were analysed using descriptive statistics.ResultsA total of 33 stakeholders attended an online PSP workshop and completed the Mentimeter exercise in Microsoft Teams. A total of 48 attended the subsequent in person prioritisation exercise in urban Bogota (n = 22) and rural Popayan (n = 25). The stakeholders were a diverse group of health professionals (physicians, medical students, nurses, dentists, physiotherapists, nutritionist, occupational and speech therapists), financial and administrative staff and patients with life-limiting illness and caregivers. Top research priorities included patient and caregiver needs, service provider education and training, and better integration of palliative care with cancer and non-cancer services. The key challenges included a lack of interest in palliative care research, along with funding, time and resource constraints. Key solutions included collaboration across disciplines and settings, highlighting benefits of palliative research to help secure adequate resources, and multicentre, mixed method research, with patient involvement from the research development stage.ConclusionThe findings of this PSP should be disseminated among palliative care associations worldwide to inform international multicentre studies, and among governmental and nongovernmental organisations that promote research in Colombia. A focus on patient and family caregiver palliative care needs in Colombia should be prioritised.

A subset of image-defined risk factors predict completeness of resection in children with high-risk neuroblastoma: An international multicenter study.

Image-defined risk factors (IDRFs) were promulgated for predicting the feasibility and safety of complete primary tumor resection in children with neuroblastoma (NB). There is limited understanding of the impact of individual IDRFs on resectability of the primary tumor or patient outcomes. A multicenter database of patients with high-risk NB was interrogated to answer this question. Patients with high-risk NB (age <20years) were eligible if cross-sectional imaging was performed at least twice prior to resection. IDRFs and primary tumor measurements were recorded for each imaging study. Extent of resection was determined from operative reports. There were 211 of 229 patients with IDRFs at diagnosis, and 171 patients with IDRFs present pre-surgery. A ≥90% resection was significantly more likely in the absence of tumor invading or encasing the porta hepatis, hepatoduodenal ligament, superior mesenteric artery (SMA), renal pedicles, abdominal aorta/inferior vena cava (IVC), iliac vessels, and/or diaphragm at diagnosis or an overlapping subset of IDRFs (except diaphragm) at pre-surgery. There were no significant differences in event-free survival (EFS) and overall survival (OS) when patients were stratified by the presence versus absence of any IDRF either at diagnosis or pre-surgery. Two distinct but overlapping subsets of IDRFs present either at diagnosis or after induction chemotherapy significantly influence the probability of a complete resection in children with high-risk NB. The presence of IDRFs was not associated with significant differences in OS or EFS in this cohort.

The D-HCM score, a new diagnostic tool for distinguishing hypertrophic cardiomyopathy from hypertensive cardiopathy.

The diagnosis of hypertrophic cardiomyopathy (HCM) with moderate hypertrophy is challenging. Hypertensive heart disease (HHD) is the most common differential diagnosis that mimics the LVH of HCM. The aim of this study was to compare the QRS duration in HCM and HHD to create a novel diagnostic tool to identify primary HCM. We conducted an international retrospective multicentre study enrolling patients with true HCM and HHD. A total of 547 individuals with HCM and 139 with HHD were included. The median QRS duration was significantly shorter in HCM than in HHD (88ms [80-94] vs. 98ms [88-108]; P<0.01). Multivariable logistic regression identified for the novel diagnostic HCM (D-HCM) score: absence of antihypertensive drugs (+2); family history of unexplained sudden death (+2); QRS duration [<95ms]=+1; maximum wall thickness (mm) [≥17]=+1. A cumulative QRS-HCM score ≥2 supports the diagnostic certainty of true HCM with a sensitivity of 79%, specificity of 99%, negative predictive value (NPV) of 55%, and positive predictive value (PPV) of 99%. The QRS duration in patient with HCM is significantly shorter compared with patients with HHD-related LVH. QRS duration can be used as a diagnosis marker to distinguish between HCM and HHD. The D-HCM score is a novel, simple, and accurate diagnosis tool for HCM patients with mild to moderate phenotypes.

Development and validation of a novel predictive model for postpancreatectomy hemorrhage using lasso-logistic regression: an international multicenter observational study of 9,631 pancreatectomy patients.

Hemorrhage following pancreatectomy represents a grave complication, exerting a significant impact on patient prognosis. The formulation of a precise predictive model for postpancreatectomy hemorrhage risk holds substantial importance in enhancing surgical safety and improving patient outcomes. This study utilized the patient cohort from the American College of Surgeons National Surgical Quality Improvement Program database, who underwent pancreatectomy between 2014 and 2017 (n=5779), as the training set to establish the Lasso-logistic model. For external validation, a patient cohort (n=3852) from the Chinese National Multicenter Database of Pancreatectomy Patients, who underwent the procedure between 2014 and 2020, was employed. A predictive nomogram for postpancreatectomy hemorrhage was developed, and polynomial equations were extracted. The performance of the predictive model was assessed through the receiver operating characteristic curve, calibration curve, and decision curve analysis. In the training and validation cohorts, 9.0% (520/5779) and 8.5% (328/3852) of patients, respectively, experienced postpancreatectomy hemorrhage. Following selection via lasso and logistic regression, only nine predictive factors were identified as independent risk factors associated with postpancreatectomy hemorrhage. These included five preoperative indicators (BMI, ASA ≥3, preoperative obstructive jaundice, chemotherapy within 90 days before surgery, and radiotherapy within 90 days before surgery), two intraoperative indicators (total operation time, vascular resection), and two postoperative indicators (postoperative septic shock, pancreatic fistula). The new model demonstrated high predictive accuracy, with an area under the receiver operating characteristic curve of 0.87 in the external validation cohort. Its predictive performance significantly surpassed that of the previous five postpancreatectomy hemorrhage risk prediction models (P<0.001, likelihood ratio test). The Lasso-logistic predictive model we developed, constructed from nine rigorously selected variables, accurately predicts the risk of PPH. It has the potential to significantly enhance the safety of pancreatectomy surgeries and improve patient outcomes.

Exergaming in patients with heart failure. A pilot study of the HEART-EXERGAME (Heart-eXg) intervention

Abstract Background Physical activity in patients with heart failure (HF) can improve physical function, quality of life, reduce rehospitalization and mortality. A new approach increase physical activity for patients with heart failure (HF) is the use of exergames (games that requires physical activity to play). An international multi-centre RCT study, called the Heart-eXg study (clinicaltrials.gov ID: NCTxxx), is developed to determine the effectiveness of 3-months exergaming for patients with HF to decrease their sedentary time. The mobile exergame is co-designed for this study, entails a farming theme, and personalized on patients exercise capacity. The aim of this pilot study was to test the protocol of the intervention, in terms of recruitment, procedures of the intervention, assessment of outcomes and adherence to exergaming. Material and methods In the pilot study, the inclusion of patients was assessed. The randomization was tested but all patients were assigned to the exergame group. To further test the procedures the time was recorded of the installation/instructions to the exergame, the telephone follow-ups (to increase motivation) and outcome assessment. Outcomes were the 6-minute walk test (exercise capacity), Fried frailty test (frailty), VAS-Score EQ5D, 0-100 (quality of life), Canadian Occupational Performance Measure (occupational performance). Adherence (walking 10 minutes every day with the exergame) was assessed during the 3 months exergaming, as the time exergaming was recorded. Results Pilot study In total 13 patients were eligible and 5 included. Mean age was 71 (±10), 2 females, 1 patient in NYHA-class II and 4 patients in NYHA-class III. One patient dropped out directly after baseline (severe disease) and 1 never exergamed (time constraints). Result of exercise capacity, quality of life and occupational performance are presented in the Table. The procedures of the intervention were feasible, the visits to the hospital took between 1 hour and 1.5 hour and the telephone follow up approximately 5-10 minutes. Test of occupational performance took longer time than calculated (30 min instead of 15 min). Of the 3 patients who exergames, 1 patient played irregularly and stopped after 4 weeks. Two patients were adherent, see Figure. Conclusion The protocol of the intervention was feasible to use. In total, 38% of patients accepted to be included in the intervention and 20% of the patients dropped out (1 out of 5) and 50% were completely adherent to the intervention. Time for installation/introduction and telephone follow-ups were appropriate. As the occupational performance assessment took more time than then expected, we decided to test this in 100 out of the 600 patients planned to be included in the RCT study.TableFigure

Multinational Drug Survival Study of Omalizumab in Patients With Chronic Urticaria and Potential Predictors for Discontinuation

Treating patients with chronic urticaria using omalizumab has been shown to be safe and effective in randomized clinical trials. Multinational studies on long-term omalizumab performance in chronic urticaria in clinical practice settings are lacking, especially on drug survival. Drug survival, which refers to the length of time that patients are treated with a specific drug, is a comprehensive outcome covering effectiveness, safety, and patient and physician preferences. Furthermore, little is known about the reasons and potential predictors for omalizumab discontinuation. To investigate omalizumab drug survival as well as reasons and potential predictors for discontinuation in a large, diverse population. This international multicenter cohort study was conducted at 14 Urticaria Centers of Reference and Excellence in 10 countries, including all patients with chronic urticaria from these centers who were ever treated with omalizumab. Drug survival analysis was performed to assess time to discontinuation. Patient characteristics and treatment protocols were investigated by Cox regression analysis to identify potential predictors for omalizumab discontinuation. In 2325 patients with chronic urticaria who started omalizumab between June 2009 and July 2022, the mean (SD) age of the cohort was 42 (6) years, and 1650 participants (71%) were female. Overall omalizumab survival rates decreased from 76% to 39% after 1 to 7 years, respectively (median survival time, 3.3 [95 % CI, 2.9-4.0] years), primarily due to discontinuation from well-controlled disease in 576 patients (65%). Ineffectiveness and adverse effects were reasons for discontinuation in a far smaller proportion of patients, totaling 164 patients (18%) and 31 patients (4%), respectively. Fast treatment response was associated with higher rates of omalizumab discontinuation due to well-controlled disease (hazard ratio, 1.45 [95% CI, 1.20-1.75]), and disease duration of more than 2 years was associated with lower rates of discontinuation due to well-controlled disease (HR, 0.81 [95% CI, 0.67-0.98]). Immunosuppressive cotreatment at the start of omalizumab and autoimmune disease was associated with a higher risk for discontinuation due to ineffectiveness (HR, 1.65 [95% CI, 1.12-2.42]). The presence of spontaneous wheals (HR, 0.62 [95% CI, 0.41-0.93]) and access to higher dosages (HR, 0.40 [95% CI, 0.27-0.58) were both associated with a lower risk for discontinuation of omalizumab due to ineffectiveness. This multinational omalizumab drug survival cohort study demonstrated that treatment of chronic urticaria with omalizumab in a clinical setting is effective and safe, and well-controlled disease is the main reason for treatment discontinuation. These findings on omalizumab drug survival rates and reasons and potential predictors for discontinuation may guide patients and physicians in clinical decision-making and expectation management. These results may call for the identification of biomarkers for chronic urticaria remission in complete responders to omalizumab treatment.

Multicenter Study on Physician-Modified Endografts for Thoracoabdominal and Complex Abdominal Aortic Aneurysm Repair.

Physician modified endografts (PMEGs) have been widely used in the treatment of complex abdominal aortic aneurysm and thoracoabdominal aortic aneurysm, however, previous data are limited to small single center studies and robust data on safety and effectiveness of PMEGs are lacking. We aimed to perform an international multicenter study analyzing the outcomes of PMEGs in complex abdominal aortic aneurysms and thoracoabdominal aortic aneurysms. An international multicenter single-arm cohort study was performed analyzing the outcomes of PMEGs in the treatment of elective, symptomatic, and ruptured complex abdominal aortic aneurysms and thoracoabdominal aortic aneurysms. Variables and outcomes were defined according to the Society for Vascular Surgery reporting standards. Device modification and procedure details were collected and analyzed. Efficacy outcomes included technical success and safety outcomes included major adverse events and 30-day mortality. Follow-up outcomes included reinterventions, endoleaks, target vessel patency rates and overall and aortic-related mortality. Multivariable analysis was performed aiming at identifying predictors of technical success, 30-day mortality, and major adverse events. Overall, 1274 patients were included in the study from 19 centers. Median age was 74 (IQR, 68-79), and 75.7% were men; 45.7% were complex abdominal aortic aneurysms, and 54.3% were thoracoabdominal aortic aneurysms; 65.5% patients presented electively, 24.6% were symptomatic, and 9.9% were ruptured. Most patients (83.1%) were submitted to a fenestrated repair, 3.6% to branched repair, and 13.4% to a combined fenestrated and branched repair. Most patients (85.8%) had ≥3 target vessels included. The overall technical success was 94% (94% in elective, 93.4% in symptomatic, and 95.1% in ruptured cases). Thirty-day mortality was 5.8% (4.1% in elective, 7.6% in symptomatic, and 12.7% in ruptured aneurysms). Major adverse events occurred in 25.2% of cases (23.1% in elective, 27.8% in symptomatic, and 30.3% in ruptured aneurysms). Median follow-up was 21 months (5.6-50.6). Freedom from reintervention was 73.8%, 61.8%, and 51.4% at 1, 3, and 5 years; primary target vessel patency was 96.9%, 93.6%, and 90.3%. Overall survival and freedom from aortic-related mortality was 82.4%/92.9%, 69.9%/91.6%, and 55.0%/89.1% at 1, 3, and 5 years. PMEGs were a safe and effective treatment option for elective, symptomatic, and ruptured complex aortic aneurysms. Long-term data and future prospective studies are needed for more robust and detailed analysis.

An international multicentre study of SwiTching from Intravenous to subcutaneous inflixiMab and vEdolizumab in inflammatory bowel diseases: The TIME study.

Subcutaneous (SC) formulations of infliximab (IFX) and vedolizumab (VDZ) are approved for the treatment of inflammatory bowel diseases (IBDs). Our aim was to evaluate the effectiveness of switching from intravenous (IV) to SC formulations of IFX and VDZ in IBDs. This multicentre, retrospective study collected data of adult patients with Crohn's disease (CD) or ulcerative colitis (UC) switched to SC IFX or VDZ. The primary endpoint was clinical remission at 12 months stratified based on timing of switch. A composite endpoint consisting of therapy discontinuation, reverse-switch, need for steroids, and drug optimization was evaluated. A multivariate analysis investigated the association between patients' characteristics and outcomes. Two hundred and thirty-one patients (59% UC, 53% male, mean age 44 ± 15 years, 68% IFX) from 13 centres were included. The switch occurred at Week 6 in a third of cases (36%). Median time to switch was 13 months. Most patients switched to SC IFX and VDZ were in clinical remission at 3 (87% and 77%), 6 (86% and 83%) and 12 (63% and 60%) months. In the multivariate analysis, there was no difference in clinical remission rate at 12 months; however, patients switched at Week 6 had a higher rate of experiencing any therapeutic changes at 3 (false discovery rate (FDR) = .002), 6 (FDR <1 × 10-10) or 12 months (FDR = .08). Clinical disease activity at baseline (only in UC) (FDR = .07) and previous exposure to biologics (FDR = .001) were risk factors for composite endpoint at 6 and 12 months. SC IFX and VDZ are effective in daily clinical practice in IBD patients. Switching patients in remission reduces the risk of negative outcomes.

Factors related to accurate clinicians' prediction of survival: an international multicenter study in East Asia.

Recent guidelines for prognostic evaluation recommend clinicians' prediction of survival (CPS) for survival prediction in patients with advanced cancer. However, CPS is often inaccurate and optimistic. Studies on factors associated with overestimation or underestimation of CPS are limited. We aimed to investigate the factors associated with the overestimation and underestimation of CPS in patients with far-advanced cancer. The current study was a secondary analysis of an international multicenter prospective cohort study, which enrolled newly admitted patients with advanced cancer in palliative care units (PCUs) in Japan, Korea, and Taiwan from 2017 to 2018. We obtained the temporal CPS at enrollment and performed multivariate logistic regression analysis to identify the factors associated with "underestimation (less than 33% of actual survival)" and "overestimation (more than 33% of actual survival)." A total of 2571 patients were assessed and admitted in 37 PCUs between January 2017 and September 2018. Older age (adjusted odds ratio [aOR] 1.01; 95% confidence interval [CI] 1.01-1.02; P < 0.01) and reduced oral intake (aOR 0.68; 95% CI 0.51-0.89; P < 0.01) were identified as significant factors associated with underestimation. Dyspnea (aOR 1.28; 95% CI 1.06-1.54; P = 0.01) and hyperactive delirium (aOR 1.34; 95% CI 1.05-1.72; P = 0.02) were identified as significant factors associated with overestimation. Older age was related to underestimation, while dyspnea and hyperactive delirium were related to overestimation of CPS for patients with weeks of survival. However, reduced oral intake was less likely to lead to underestimation.

The impact of obesity on chronic oedema/lymphoedema of the leg - an international multicenter cross-sectional study (LIMPRINT).

Obesity and chronic oedema/lymphoedema are two distinct but related conditions, rarely investigated together. The aim was to study the impact of increased weight on chronic oedema and related factors. A cross-sectional study, 38 centers, nine countries. Patients with clinically confirmed chronic oedema/lymphoedema of the leg were included. Weight category was estimated as: normal weight (BMI 20-30), class I-II obesity (BMI 30-40), or class III obesity (BMI > 40). Factors were tested for an association with increased weight, using a multivariable model. A total of 7397 patients were included; 43% with normal weight, 36% class I-II obesity and 21% class III obesity. Increased weight was associated with more advanced stages of chronic oedema (ISL stage III; the most advanced form); affecting 14% in normal weight, 18% class I-II obesity and 39% class III obesity (p < 0.001). Ten factors were independently associated with increased weight: diabetes (OR 2.4), secondary lymphoedema (OR 2.7), cellulitis/erysipelas within 12 months (OR 1.2), bilateral lymphoedema (OR 3.6), compression therapy (OR 2.1), increased swelling duration (1-2 years OR 1.3, 2-5 years OR 2.5, 5-10 years OR 3.6, >10 years OR 3.5) decreased mobility (walking with aid OR 1.9, being chair bound OR 1.2) and age (reference<45 years; 45-64 years OR 1.5, 75-84 years OR 0.6, 85+ years OR 0.2). Increased weight was associated with a lower presentation of peripheral arterial disease (OR 0.7) and poorer chronic oedema control (OR 0.8). Patients with obesity had lower function, appearance and more severe symptoms (LYMQOL) and lower quality of life (EuroQol). Obesity negatively impacts chronic oedema, leading to more advanced stages. Achieving good control of swelling with compression is more difficult in these patients. Increased awareness of chronic oedema/lymphoedema as a complication of obesity is important for early detection and for developing effective strategies to prevent and manage them.

P-505 Clinical rescue rate of abnormally fertilized oocytes and the relationship with patient, embryo and laboratory features

Abstract Study question Which are the main patient, embryonic and laboratory variables associated with a diploid result in abnormally fertilized embryos? Summary answer Embryo diploid constitution is associated with maternal age, trophectoderm and inner cell mass quality as well as pronuclear (PN) number predicted by time-lapse incubator. What is known already In conventional in vitro fertilization cycles, morphological PN evaluation can identify proper fertilization and predict embryo ploidy constitution. Atypical PN patterns like 0PN, 1PN or more than 2PN are associated with ploidy abnormalities. However, we have previously shown that PN number is insufficient to predict embryo ploidy composition, and advanced single nucleotide polymorphism (SNP)-based methodologies for preimplantation genetic testing (PGT) detect a significant number of genetically diploid embryos from presumed abnormally fertilized oocytes. In this study, we characterized the diploid rescue rate associated with abnormal PN configurations, uncovering the link between ploidy results and relevant patient, embryonic and clinical/laboratory parameters. Study design, size, duration Retrospective observational study evaluating the association between diploid rescue rate of abnormally fertilized embryos and different patient, embryonic and laboratory features. Embryos were cultured in conventional or EmbryoScope™ time-lapse incubator (Vitrolife) until blastocyst stage and classified according to Gardner embryo grading system. Ploidy assessment was performed on 343 euploid trophectoderm (TE) biopsies collected between January 2021 and November 2023. Results were stratified according to patients age, embryo quality parameters and different laboratory procedures. Participants/materials, setting, methods Multi-center international study involving consenting patients using autologous gametes and undergoing PGT for aneuploidies (PGT-A) combined with ploidy analysis. Ploidy protocol was performed using a validated targeted NGS approach composed of a custom panel of 357 SNPs and a proprietary pipeline of analysis. Reliable ploidy classification was obtained using a combined algorithm strategy based on SNPs allele frequencies. Categorical variables were expressed in percentages. Nominal variables were analysed using the Cochran-Armitage test to detect trends. Main results and the role of chance Among 343 euploid embryos, diploidy rates obtained for 0PN, 1PN, 2.1PN and 3PN groups were 86.8% (n = 118/136;95%CI=79.89-91.96) 43.7% (n = 59/135;95%CI=35.19-52.50), 65.0% (n = 13/20;95%CI=40.78-84.61) and 26.9% (n = 14/52;95%CI=15.57-41.02) respectively. Regarding patient parameters, advanced maternal age, but not paternal age, was significantly associated with lower diploid rescue rates, with a decreasing trend from 72.5% (n = 79/109;95%CI=63.10-80.60) below age 35 to 42.9% (n = 30/70;95%CI=31.09-55.25) above age 40 (p &amp;lt; 0.01). When considering embryo morphological evaluations, Cochran Armitage test revealed a significant link between diploidy rates and TE quality with a decreasing trend going from 72.1% (n = 80/111;95%CI=62.76-80.17) to 52.7% (n = 79/150;95%CI=44.36-60.87) and 45.8% (n = 22/48;95%CI=31.37-60.83) for embryos classified with TE grade as A, B, and C, respectively (p-value&amp;lt;0.01). Similarly, a decreasing trend was reported in relation to inner cell mass (ICM) quality, when moving from grade A (67,1%, n = 94/140;95%CI=58.23-75.33) to grade C (54.8%, n = 17/31;95%CI=36.03-72.68) (p = 0.03). No clear association was reported for embryo expansion degree. Finally, among laboratory variables (oocyte freezing procedure, fertilization method, incubator type), only time-lapse significantly impacted expected diploid results. Overall, if abnormal PN number is confirmed by time-lapse (n = 42 samples), the accuracy in predicting ploidy abnormalities increased from 29.2% (n = 82/281;95%CI=23.93-34.87), in conventional incubators, to 83.3% (n = 35/42;95%CI=68.64-93.03) (p &amp;lt; 0.01). Consequently, expected diploid rescue rate decreased from 65.5% (n = 184/281;95%CI=59.60-71.03) to 16.7% (n = 7/42;95%CI=6.97-31.36) (p &amp;lt; 0.01). Limitations, reasons for caution Parental DNA analysis should be included to rule-out the residual risk of uniparental disomy in diploid embryos. The multi-center nature of the study didn’t support a uniform PN annotation, especially for centers lacking time-lapse observation. Future studies should focus on the clinical follow-up after the transfer of rescued euploid-diploid embryos. Wider implications of the findings We believe we reported the first evidence of maternal age effect on ploidy results in the largest dataset of abnormally fertilized embryos. We revealed a link between ploidy constitution and blastocyst morphological quality, providing important information for patient counselling. Time-lapse incubators offer a more accurate identification of abnormally fertilized oocytes. Trial registration number n/a

IRON: A retrospective international multicenter study on robotic versus laparoscopic versus open approach in gallbladder cancer

ObjectiveFor patients with T1b gallbladder cancer or greater, an adequate lymphadenectomy should include at least 6 nodes. Studies comparing short- and long-term outcomes of the open approach with those of laparoscopy and robotic approaches are limited, with small sample sizes, and there are none comparing laparoscopic and robotic approaches. This study compared patients who underwent robotic, laparoscopic, and open resection of gallbladder cancer, evaluating short- and long-term outcomes. MethodsWe conducted a multicenter retrospective study of patients with T1b gallbladder cancer or greater (excluding combined organ resection and T4) who underwent open, laparoscopic, and robotic liver resection and lymphadenectomy between January 2012 and December 2022. The 3 groups were matched in terms of patient baseline and disease characteristics based on propensity score matching, comparing robotic with open and robotic with laparoscopic groups. ResultsWe enrolled 575 patients from 37 institutions. After propensity score matching, the median number of harvested nodes was higher in the robotic group than in the open (7 vs 5; P = .0150) and laparoscopic groups (7 vs 4; P < .001). The Pringle maneuver time was shorter with robotic resection than with laparoscopy (38 vs 59 minutes; P = .0034), and the robotic group also had a lower conversion rate (3% vs 14%, respectively; P = .005) and less estimated blood loss than open and laparoscopic resections. The perioperative morbidity and mortality rates did not differ. The robotic and laparoscopic approaches were associated with faster functional recovery than the open group. In the multivariate analysis, the factors related to the retrieval of at least 6 nodes were the robotic approach over open (odds ratio, 5.1529) and over laparoscopy (odds ratio, 6.7289) and the center experience (≥20 minimally invasive liver resections/year) (odds ratio, 4.962). After a mean follow-up of 42.6 months, overall survival and disease-free survival were not different between groups. ConclusionCompared with open and laparoscopic surgeries, the robotic approach for gallbladder cancer performed in a center with appropriate experience in minimally invasive surgery can provide adequate node retrieval.

Clinical Validation of the Intermediate-risk Non–muscle-invasive Bladder Cancer Scoring System and Substratification Model Proposed by the International Bladder Cancer Group: A Multicenter Young Academic Urologists Urothelial Working Group Collaboration

Background and objectiveIntermediate-risk (IR) non–muscle-invasive bladder cancer (NMIBC) encompasses a broad spectrum of disease, with heterogeneous outcomes in terms of disease recurrence and progression. The International Bladder Cancer Group (IBCG) recently proposed an updated scoring model for IR substratification that is based on five key risk factors. Our aim was to provide a clinical validation of the IBCG scoring system and substratification model for IR NMIBC. MethodsThis was an international multicenter retrospective study. Patients diagnosed with IR NMIBC between 2012 and 2022 and treated with transurethral resection of the bladder and adjuvant intravesical chemotherapy were included. According to the presence or absence of risk factors, patients with IR NMIBC were further categorized in IR-low (no risk factors), IR-intermediate (1–2 risk factors), and IR-high (≥3 risk factors) groups. The 1-yr and 3-yr rates for recurrence-free survival (RFS) and progression-free survival (PFS) were evaluated for each subgroup. Cox regression analyses were used to compare oncological outcomes between the groups. Key findings and limitationsOf the 677 patients with IR NMIBC included in the study, 231 (34%), 364 (54%), and 82 (12%) were categorized in the IR-low, IR-intermediate, and IR-high groups, respectively. There were significant differences in RFS and PFS rates between these groups. Conclusions and clinical implicationsWe provide the first clinical validation of the IBCG scoring system and model for substratification of IR NMIBC. Patient summaryOur study demonstrates that patients with intermediate-risk non–muscle-invasive bladder cancer can be correctly classified into three distinct subgroups according to their risk of both disease recurrence and progression. Our results support use of this scoring system in clinical practice.

Clinical impact of CEUS on non-characterizable observations and observations with intermediate probability of malignancy on CT/MRI in patients at risk for HCC

BackgroundHepatocellular carcinoma (HCC) is a unique cancer allowing tumor diagnosis with identification of definitive patterns of enhancement on contrast-enhanced imaging, avoiding invasive biopsy. However, it is still unclear to what extent Contrast-Enhanced Ultrasound (CEUS) is a clinically useful additional step when Computed tomography (CT) or Magnetic resonance imaging (MRI) are inconclusive.MethodsA prospective international multicenter validation study for CEUS Liver Imaging Reporting and Data System (LI-RADS) was conducted between January 2018 and August 2021. 646 patients at risk for HCC with focal liver lesions were enrolled. CEUS was performed using an intravenous ultrasound contrast agent within 4 weeks of CT/MRI. Liver nodules were categorized based on LI-RADS (LR) criteria. Histology or one-year follow-up CT/MRI imaging results were used as the reference standard. The diagnostic performance of CEUS was evaluated for inconclusive CT/MRI scan in two scenarios for which the AASLD recommends repeat imaging or imaging follow-up: observations deemed non-characterizable (LR-NC) or with indeterminate probability of malignancy (LR-3).Results75 observations on CT or MRI were categorized as LR-3 (n = 54) or LR-NC (n = 21) CEUS recategorization of such observations into a different LR category (namely, into one among LR-1, LR-2, LR-5, LR-M, or LR-TIV) resulted in management recommendation changes in 33.3% (25/75) and in all but one (96.0%, 24/25) observation, the new management recommendations were correct.ConclusionCEUS LI-RADS resulted in management recommendations change in substantial number of liver observations with initial indeterminate CT/MRI characterization, identifying both non-malignant lesions and HCC, potentially accelerating the diagnostic process and alleviating the need for biopsy or follow-up imaging.ClinicalTrials.gov number, NCT03318380.

Rare causes of cryptogenic stroke

Stroke is one of the leading causes of mortality and disability in the world, which is why it is considered a key medical and social problem of modern medicine. According to international multicenter studies, ischemic stroke is the most frequent type of this condition. According to research, the pathogenetic subtype of ischemic stroke cannot be identified in a third of cases. Based on the TOAST classification, cryptogenic stroke requires exclusion of criteria for other pathogenetic subtypes. However, in clinical practice, the reasons for making this diagnosis are as follows: incomplete examination of the patient, negative test results, and identification of two or more causes. The high incidence and risk of recurrent ischemic events determines the need for a thorough diagnostic search in order to exclude rare causes and conduct reasonable secondary prophylaxis.

Irreversible Electroporation as a Valid Treatment Option for Hepatic Epithelioid Hemangioendothelioma: An International Multicenter Experience

PurposeHepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor with currently no established standard of care. This international multicenter retrospective study assesses the use of percutaneous irreversible electroporation (IRE) as an ablative tool to treat HEHE and provides a clinical overview of the current management and role of IRE in HEHE treatment.Material and MethodsBetween 2017 and 2023, 14 patients with 47 HEHE tumors were treated with percutaneous IRE using CT-scan guidance in 23 procedures. Baseline patient and tumor characteristics were evaluated. Primary outcome measures included safety and effectiveness, analyzed using Common Terminology Criteria for Adverse Events (CTCAE) and treatment response by mRECIST criteria. Secondary outcome measures included technical success, post-treatment tumor sizes and length of hospital stay. Technical success was defined as complete ablation with an adequate ablative margin (intentional tumor free ablation margin > 5 mm).ResultsIRE treatment resulted in technical success in all tumors. Following a median follow-up of 15 months, 30 tumors demonstrated a complete response according to mRECIST criteria. The average tumor size pre-treatment was 25.8 mm, accompanied by an average reduction in tumor size by 7.5 mm. In 38 out of 47 tumors, there was no evidence of local recurrence. In nine tumors, residual tumor was present. There were no cases of progressive disease. Median length of hospital stay was one day. Only one grade 3 CTCAE event occurred, a pneumothorax requiring chest tube placement.ConclusionThe current study provides evidence that IRE is a safe and efficacious minimally invasive treatment option for HEHE.Graphical

Incomplete partition type II in its various manifestations: isolated, in association with EVA, syndromic, and beyond; a multicentre international study.

Incomplete partition type II (IP-II) is characterized by specific histological features and radiological appearance. It may occur in isolation or in association with an enlarged vestibular aqueduct (EVA). Among those with IP-II and EVA, a subset has a diagnosis of Pendred syndrome. This study aimed to explore the prevalence of isolated IP-II, IP-II with EVA, and cases with a genetic or syndromic basis in our cohort. From a large, multicentre database of dysplastic cochleae (446 patients, 892 temporal bones), those with imaging features of IP-II were examined in detail, including whether there was a genetic or syndromic association. A total of 78 patients with IP-II were identified. Among these, 55 patients had bilateral IP-II and EVA (only 12 with typical Mondini triad), 8 with bilateral IP-II and normal VA, 2 with bilateral IP-II and unilateral EVA, and 13 with unilateral IP-II (9 with unilateral EVA). Among the group with bilateral IP-II and bilateral EVA in whom genetic analysis was available, 14 out of 29 (48%) had SLC26A4 mutations and a diagnosis of Pendred syndrome, 1 had a FOXI1 mutation, and a few other genetic abnormalities; none had KCNJ10 pathogenic variants. Bilateral IP-II-bilateral EVA may be seen in the context of Pendred syndrome (SLC26A4 or FOXI1 mutations) but, in the majority of our cohort, no genetic abnormalities were found, suggesting the possibility of unknown genetic associations. IP-II in isolation (without EVA) is favored to be genetic when bilateral, although the cause is often unknown.

A pilot case-control study on the fecal microbiota of pediatric functional abdominal pain-not otherwise specified and the role of early life stress

Background: Gut microbial features and the role of early life stress in pediatric functional abdominal pain-not otherwise specified (FAP-NOS) have never been investigated before. Here, we hypothesize that early life stress is more prevalent in FAP-NOS compared to healthy controls and that fecal microbial profiles and related metabolites differ between groups. Methods: In an international multicenter case-control study, FAP-NOS patients (n = 40) were compared to healthy controls (n = 55). Stool samples and demographic and clinical data including early life traumatic events and antibiotics treatments were collected from children aged four to twelve years. Fecal microbial profiles were assessed with 16S rRNA gene amplicon sequencing. Microbial metabolite concentrations in fecal supernatant, including short-chain fatty acids and amino acids, were detected via liquid chromatography. Results: Microbial richness was increased in FAP-NOS compared to healthy controls and microbial composition (unweighted UniFrac) differed between groups. Three distinct amplicon sequencing variants and two distinct species were enriched in FAP-NOS compared to controls, with no observed changes at higher taxonomic levels. No differences in microbial metabolites and early life stress were observed between groups. Conclusion: The presented hypothesis could not be proven, with no observed differences in occurrence of early life stress, and fecal microbial metabolic profiles between pediatric FAP-NOS and healthy controls. Pediatric FAP-NOS patients exhibited mild differences in the fecal microbial community compared with controls. Further large-scale studies with high-resolution techniques are warranted to address the biological relevance of present observations.

Long-Term Safety and Effectiveness of Rituximab Biosimilar RTXM83: A Retrospective Extension Study in Brazilian Patients with Diffuse Large B-Cell Lymphoma.

RTXM83, a biosimilar of rituximab, was approved after physicochemical, functional, non-clinical,and clinical studies demonstrated their similarity; these studies included RTXM83-AC-01-11, a multicentric double-blind international prospective pivotal study. Long-term data on biosimilars can potentially elucidate their clinical robustness and facilitate their broader adoption. In this retrospective observational study, we analyzed a dataset from a Brazilian cohort previously randomized in the RTXM83-AC-01-11 study followed by the assessment of long-term outcomes in an observational extension phase from randomization in the RTXM83-AC-01-11 study to the last recorded evaluation. Patients with diffuse large B cell lymphoma (DLBCL) received either reference rituximab (R) or RTXM83 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as adjuvant treatment. The median follow-up period was 77.0months. Patients with initial DLBCL stages III and IV comprised 50% of the R-CHOP group and 40% of the biosimilar group. Five (18.5%) patients, including two RTXM83-CHOP-treated and three R-CHOP-treated individuals, experienced late adverse events (AEs) of interest. No new safety signs were established. At the final assessment, the progression-free survival (PFS) rates were 93.3% and 50.0% in the RTXM83-CHOP and R-CHOP groups, respectively. Median PFS was not achieved in the RTXM83-CHOP group, which was 40.5months in the R-CHOP group. The overall survival (OS) rates were 100% and 66.7% in the RTXM83-CHOP and R-CHOP groups, respectively. The median OS was not reached in any group. This study demonstrated the long-term safety and effectiveness of RTXM83 in treating DLBCL; outcomes comparable to those of the reference product and potentially improved access to treatment have been indicated. However, further research with more diverse patient groups can validate these findings and advocate the broader adoption of biosimilars in cancer care. ClinicalTrials.gov Identifier:NCT04928573. June 16, 2021, "retrospectively registered".