International Multicenter Study Research Articles

Feasibility and inter-reporter variability of submaximal outcomes derived from cardiopulmonary exercise testing in people with advanced cystic fibrosis lung disease

BackgroundCardiopulmonary exercise testing (CPET) provides prognostic information in people with advanced cystic fibrosis lung disease (pwACFLD). This project aimed to ascertain feasibility and inter-reporter variability in the identification of submaximal CPET outcomes for pwACFLD as potential predictors of prognosis where no peak exercise data are available.MethodsWe utilised data from an international retrospective multicentre study involving pwACFLD, for whom raw CPET data were available. Two experienced operators independently reviewed and analysed CPET tests with a focus on three pre-defined measures: oxygen uptake (V̇O2) at the anaerobic threshold (AT), the breathing reserve index at the AT (BRIAT), and the slope of the minute ventilation to carbon dioxide production ratio (V̇E/V̇CO2-slope). We calculated intra-class correlation coefficients (ICC) with their 95% confidence intervals (CI), and limits of agreement using the Bland-Altman method.ResultsThe original cohort included 174 pwACFLD. Among those, raw CPET data were available for 101 individuals, of which 89 tests were of sufficient technical quality for submaximal analysis. In 72 out of 89 technically-acceptable tests (81%), the AT could be confidently identified by both operators. Furthermore, ICCs indicated good-to-excellent inter-reporter agreement for V̇O2at the AT [ICC (95% CI) 0.79 (0.62 to 0.88)], the V̇E/V̇CO2-slope [0.95, 0.93 to 0.97)], and BRIAT [0.76, 0.63 to 0.85].ConclusionsSubmaximal CPET data can be reliably obtained in most pwACFLD by trained CPET operators. Future studies may ascertain the prognostic value of submaximal CPET outcomes in pwACFLD.

Safe Implementation of Treatments in Stroke: a study on intravenous thrombolysis in patients over 80 years of age with acute ischaemic stroke

ObjectivesTo investigate the safety and efficacy outcomes of intravenous thrombolysis (IVT) in patients aged >80 years with acute ischaemic stroke (AIS) after IVT was approved in this patient population in...

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study

Comparison of two aspirin doses for the prophylaxis of pre-eclampsia in twin pregnancy: a multicentre retrospective study with propensity score matching.

Aspirin has proved its efficacy in reducing the rate of preeclampsia in singleton pregnancy, however, there is discrepancy about the efficient dosage that should be used. While some societies recommend daily 75-81mg, others recommend higher dosage (160mg). This discrepancy is due to the lack of randomized controlled studies that compare these two dosages. Moreover, there remains a considerable gap in our knowledge concerning the appropriate prophylactic aspirin dosage for twin pregnancies. This study aimed to assess the efficacy of various aspirin prophylaxis dosages in the prevention of preeclampsia and hypertensive disorders of pregnancy (HDP) in twin pregnancies. This was an international multicentre retrospective cohort study that was conducted in three European centers. We included all twin pregnancies with 2 live fetuses at 13 weeks of gestation (WG). We excluded fetal malformations, twin-twin transfusion syndrome, twin anemia polycythemia sequence, twin reversed arterial perfusion sequence, twin pregnancies at onset but continued as singletons (vanishing twin/arrest before 13 WG), and loss of follow-up. Patients were categorized into three groups: no aspirin, daily 80-100mg aspirin, and daily 160mg aspirin. Primary outcomes were the incidence of preeclampsia and HDP, whereas secondary outcomes were small-for-gestational age, postpartum hemorrhage>1000 mL, antenatal bleeding of obstetrical origin, thrombocytopenia, miscarriage, intrauterine fetal demise (IUFD), neonatal death, and gastritis. Propensity score matching and multivariate analyses were conducted to assess outcomes including pre-eclampsia, gestational hypertension, maternal complications, and gastritis. Propensity score matching was used to balance the three groups of study. Cox regression models were done for each outcome after matching to compare the three groups. A p-value<0.05 was considered statistically significant. A total of 1907 twin pregnancies were included: 1423 (74,62%) received no aspirin, 212 (11.12%) received 80-100 mg, and 272 (14.26%) received 160 mg. After using propensity score matching for maternal age, body mass index, race, parity, history of preeclampsia, chronic hypertension, diabetes mellitus, thrombophilia, spontaneous conception, and type of twin pregnancy, the three groups were adequately balanced (absolute standardized difference [ASD] <15%), except for age and thrombophilia (ASD 22.1% and 16.4% respectively). The administration of aspirin 160mg decreased the hazard ratio (HR) for preeclampsia to 0.63 and for HDP to 0.56, whereas the administration of aspirin 80-100mg failed to decrease both HR below 1. In addition, aspirin 160mg decreased the risk for preeclampsia <34 WG. No significant increase for aspirin-related complications, such as bleeding or thrombocytopenia, or other obstetrical outcomes was observed with the higher dose of aspirin. The use of 160 mg aspirin for the prevention of hypertensive disorders of pregnancy may offer superior outcomes in twin pregnancies, with no discernible rise in complications when compared to aspirin doses ranging from 80-100 mg. Further research should explore long-term impacts and refine dosage strategies for optimal outcomes in twin pregnancies.

Genome-wide meta-analysis associates donor-recipient non-HLA genetic mismatch with acute cellular rejection post-liver transplantation.

Acute cellular rejection (ACR) remains a common complication causing significant morbidity post-liver transplantation. Non-human leukocyte antigen (non-HLA) mismatches were associated with an increased risk of ACR in kidney transplantation. Therefore, we hypothesized that donor-recipient non-HLA genetic mismatch is associated with increased ACR incidence post-liver transplantation. We conducted an international multicenter case-control genome-wide association study of donor-recipient liver transplant pairs in 3 independent cohorts, totaling 1846 pairs. To assess genetic mismatch burden, we calculated sum scores for single-nucleotide polymorphism (SNP) mismatch based on all non-HLA functional SNPs, specifically SNPs coding for transmembrane or secreted proteins as they more likely affect the immune system. We analyzed the association between the non-HLA mismatch scores and ACR in a multivariable Cox regression model per cohort, followed by a weighted meta-analysis. During the first year post-transplantation, 90 of 689 (13%), 161 of 720 (22%), and 48 of 437 (11%) recipients experienced ACR in cohorts 1-3, respectively. Weighted meta-analyses showed that higher mismatch in functional non-HLA SNPs was associated with an increased incidence of ACR (HR 5.99; 95% CI: 1.39-20.08; p=0.011). Moreover, we found a larger effect of mismatch in SNPs coding for transmembrane or secreted proteins on ACR (HR 7.54; 95% CI 1.95-28.79; p=0.003). Sensitivity analyses showed that imputed HLA mismatch did not affect the associations between both non-HLA mismatch scores and ACR. Donor-recipient mismatch of functional non-HLA SNPs overall and, especially, of SNPs encoding transmembrane or secreted proteins correlated with 1-year ACR post-liver transplantation. Identifying high-risk immunological burdens between pairs may prevent early graft rejection and aid in personalizing immunosuppressive therapy. Future studies are, however, needed to validate our findings using a genotyped HLA cohort.

Incorporation of the Central Vein Sign into the McDonald Criteria

BackgroundDiagnosis of multiple sclerosis (MS) frequently relies on MRI dissemination in time (DIT) and space (DIS), as codified in 2017 McDonald criteria (McD 2017). The central vein sign (CVS) is a proposed MS diagnostic biomarker, but its optimal incorporation into McD 2017 has not been extensively studied. ObjectiveEvaluate the diagnostic performance of several methods incorporating CVS into McD 2017 radiological DIS criteria. MethodsData were obtained from the CAVS-MS Pilot, a cross-sectional, international multi-center study conducted by the North American Imaging in MS Cooperative (NAIMS) that recruited adults referred for suspicion/diagnosis of demyelinating disease. Diagnostic performance of methods incorporating CVS into McD 2017 radiological DIS were evaluated by comparing sensitivity, specificity, and accuracy. Results78 participants (37 MS, 41 others) were included. For MS diagnosis, sensitivity, specificity, and accuracy of DIS based on brain imaging (DIS-B) alone was 92%, 69%, and 78%. Requiring at least one lesion with CVS in any brain location in addition to DIS-B increased specificity (sensitivity 92%, specificity 81%, accuracy 86%). Presence of 2 deep white matter lesions with CVS as an additional topography for DIS-B had higher sensitivity (sensitivity 97%, specificity 59%, accuracy 77%). ConclusionsIncorporation of CVS in McD 2017 DIS criteria can be used to improve diagnostic accuracy. Validation in additional prospective studies is needed.

Risk of cancer and reoperation after ileorectal anastomosis and ileal pouch-anal anastomosis in familial adenomatous polyposis.

To prevent colorectal cancer (CRC), most patients with familial adenomatous polyposis (FAP) undergo (procto)colectomy with ileorectal anastomosis (IRA) or ileal pouch-anal anastomosis (IPAA). After surgery, these patients remain at risk of developing cancer in the remnant rectum or rectal cuff/pouch. We aimed to compare the long-term risk of cancer following IRA or IPAA in FAP. We performed an international multicenter historical cohort study of FAP patients undergoing IRA or IPAA from 1990 to 2023. The proportion of patients developing cancer following surgery was estimated using the Kaplan-Meier method. (Procto)colectomy was performed in 685 patients (53.6% female); 366 (53.4%) had IRA and 319 (46.6%) IPAA. Median age at IRA and IPAA was 23 and 27 years, and median follow-up was 12 and 15 years, respectively. Overall, 8 patients (2.2%) developed rectal and/or rectal cuff/pouch cancer after IRA and 0.9% after IPAA. The estimated 10- and 20-year cancer incidence after IRA vs IPAA were 1.6% vs 0.4% and 2.5% vs 0.9%, respectively (log-rank p=0.15. Reoperations, mainly for extensive polyposis, were performed in 39 (10.7%) patients with an IRA and 24 (7.5%) patients following IPAA. The number of post-operative endoscopic surveillance endoscopies was higher in patients with an IRA compared to those with an IPAA (p<0.001). Over the last three decades, few patients were diagnosed with cancer in the rectum or rectal cuff/pouch after (procto)colectomy in FAP. This might be due to an improved selection of the type of (procto)colectomy and close endoscopic surveillance including prophylactic polypectomies.

Standardizing and Classifying Anterior Cruciate Ligament Injuries: An International Multicenter Study Using a Mobile Application.

Background/Objectives: This international multicenter study aimed to assess the effectiveness of the Pivot-Shift Meter (PSM) mobile application in diagnosing and classifying anterior cruciate ligament (ACL) injuries, emphasizing the need for standardization to improve diagnostic precision and treatment outcomes. Methods: ACL evaluations were conducted by eight experienced orthopedic surgeons across five Latin American countries (Bolivia, Chile, Colombia, Ecuador, and Mexico). The PSM app utilized smartphone gyroscopes and accelerometers to standardize the pivot-shift test. Data analysis from 224 control tests and 399 standardized tests included non-parametric statistical methods, such as the Mann-Whitney U test for group comparisons and chi-square tests for categorical associations, alongside neural network modeling for injury grade classification. Results: Statistical analysis demonstrated significant differences between standardized and control tests, confirming the effectiveness of the standardization. The neural network model achieved high classification accuracy (94.7%), with precision, recall, and F1 scores exceeding 90%. Receiver Operating Characteristic (ROC) analysis yielded an area under the curve of 0.80, indicating reliable diagnostic accuracy. Conclusions: The PSM mobile application, combined with standardized pivot-shift techniques, is a reliable tool for diagnosing and classifying ACL injuries. Its high performance in predicting injury grades makes it a valuable addition to clinical practice for enhancing diagnostic precision and informing treatment planning.

Metastasis-directed stereotactic radiotherapy in patients with breast cancer: results of an international multicenter cohort study

Metastasis-directed therapy (MDT) for oligometastatic breast cancer (≤ 5 metastases) has shown little effect in specific scenarios of randomized trials. Therefore, we aimed to assess outcomes after metastasis-directed stereotactic radiotherapy (SRT) in various clinical scenarios. We conducted an international retrospective cohort study in thirteen centers including breast cancer patients receiving SRT to any metastatic site. Outcomes included local recurrence (LR), progression-free survival (PFS), and overall survival (OS). Cumulative incidence analysis was used for LR, Kaplan–Meier estimates for PFS and OS. Covariables included patient, disease, and SRT characteristics. We performed univariable and multivariable analyses (MVA). Among 444 patients, 751 metastases were treated with SRT. Of these, 73% were intracranial and 27% extracranial lesions. Oligometastatic disease (OMD) was present in 66% of the patients. LR after two years occurred significantly more often in intracranial (25%) versus extracranial lesions (7%). In MVA of patients with OMD treated for intracranial sites, higher performance status was significantly associated with longer PFS. Further, higher performance status, biologic subtype (HR-pos./HER2-pos.), and MDT to all sites were significantly associated with longer OS. In MVA of oligometastatic patients treated for extracranial sites, biologic subtype (HR-neg./HER2-pos.) and synchronous metastasis were associated with significantly longer PFS, whereas higher grading was associated with significantly shorter PFS. Moreover, biologic subtype (HR-neg./HER2-neg.) was associated with significantly shorter OS. In conclusion, the role of MDT for breast cancer may vary per clinical scenario. Patients with OMD treated for intracranial lesions who had MDT to all sites showed superior OS. Our results should be validated prospectively.

Are ultrasound salivary parenchymal lesions more severe in primary Sjögren patients with a longer disease duration? A cross-sectional study.

Salivary gland ultrasound (SGUS) has an interest in primary Sjögren's disease (pSD) for diagnosis, but the evolution of parenchymal lesions over time is unknown. The objective of this study was to assess the severity of ultrasound abnormalities in relation to pSD duration from the time of buccal dryness onset. In this cross-sectional international multicentre study, patients with pSD according to the 2002 or 2016 ACR/EULAR classification criteria were included. Parenchymal abnormalities were classified according to the semiquantitative score as defined by OMERACT. Patients were separated into 4 groups (Group A: < 5 years, Group B: 5-9 years, Group C: 10-20 years, and Group D: > 20 years from the onset of buccal dryness). The association between disease duration groups and SGUS lesions was quantified in terms of odds ratios and 95% confidence intervals. A total of 247 patients were consecutively included between May 2019 and February 2022. Eighty-nine percent of patients had a focus score ≥1/4 mm2, and 85% had positive anti-Ro/SSA. pSD duration was associated with a pathological OMERACT score (score 2 or 3): OR for 5-year duration: 1.23 [95% CI 1.04; 1.47], p= 0.0383). Considering each US item, the only statistical association with pSD duration was found regarding the presence of hyperechoic bands (25% or more): OR for five-year duration 1.18 [95% CI 1.03; 1.36], p= 0.038), independent of an older age. pSD duration was associated with the presence of hyperechoic bands, but not with hypoechoic areas, suggesting a progressive fibro-adipose evolution.

Machine Learning-Based Prediction Model for ICU Mortality After Continuous Renal Replacement Therapy Initiation in Children.

Continuous renal replacement therapy (CRRT) is the favored renal replacement therapy in critically ill patients. Predicting clinical outcomes for CRRT patients is difficult due to population heterogeneity, varying clinical practices, and limited sample sizes. We aimed to predict survival to ICUs and hospital discharge in children and young adults receiving CRRT using machine learning (ML) techniques. Patients less than 25 years of age receiving CRRT for acute kidney injury and/or volume overload from 2015 to 2021 (80%). Internal validation occurred in a testing group of patients from the dataset (20%). Retrospective international multicenter study utilizing an 80/20 training and testing cohort split, and logistic regression with L2 regularization (LR), decision tree, random forest (RF), gradient boosting machine, and support vector machine with linear kernel to predict ICU and hospital survival. Model performance was determined by the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC) due to the imbalance in the dataset. Of the 933 patients included in this study, 538 (54%) were male with a median age of 8.97 years and interquartile range (1.81-15.0 yr). The ICU mortality was 35% and hospital mortality was 37%. The RF had the best performance for predicting ICU mortality (AUROC, 0.791 and AUPRC, 0.878) and LR for hospital mortality (AUROC, 0.777 and AUPRC, 0.859). The top two predictors of ICU survival were Pediatric Logistic Organ Dysfunction-2 score at CRRT initiation and admission diagnosis of respiratory failure. These are the first ML models to predict survival at ICU and hospital discharge in children and young adults receiving CRRT. RF outperformed other models for predicting ICU mortality. Future studies should expand the input variables, conduct a more sophisticated feature selection, and use deep learning algorithms to generate more precise models.

Efficacy of CycloMesh™ + Ropivacaine in the treatment of uncomplicated inguinal hernia after the Lichtenstein procedure: Results of a prospective multicentric double-blind study

Twenty to 30% of patients undergoing inguinal hernia surgery (20 million patients per year worldwide) present early postoperative pain. The aim of this study was to assess the interest of a mesh (CycloMesh™, Cousin Biotech) soaked with ropivacaine for managing early postoperative pain. This was a randomized, phase III, comparative superiority, double-blind, international multicenter study. From October 2019 to February 2022, 290 patients underwent surgery for uncomplicated inguinal hernia, under general anesthesia, using the Liechtenstein technique. Each patient was randomly assigned to either the experimental group (mesh soaked in ropivacaine hydrochloride 10mg/mL) or the control group (mesh soaked in physiological saline solution). The primary endpoint was the pain at cough assessment with the visual analogue scale (VAS) at H6 after the surgery. The secondary endpoints were the global pain assessment at H2, H4, H6, day 1, day 2, day 3, day 7, 1month, 1year, and 2years after the surgery, assessment of antalgic consumption, description of the surgical procedure and postoperative complications rate, hospitalization and post-hospital discharge data (number of conversions from outpatient to inpatient care), and recurrence. Of the 290 patients included in the study, 150 and 140 patients were in the experimental or control group respectively. The per-protocol (PP) population (240 patients) comprised 125 patients in the ropivacaine group and 115 in the control group. The mesh soaking solution had no significant effect on the pain at cough at H6, either in the intention-to-treat population (3.3 vs 3.2, P=0.12) or in the PP population (3.3 vs 3.7, P=0.15). The ropivacaine-soaked prosthesis resulted in a reduction in overall pain at H2 (2.3 vs 3.2, P<0.0001), H4 (2.3 vs 3.1, P<0.0001) and H6 (2.3 vs 2.7, P=0.0039). There was no difference between the two groups in terms of antalgic consumption, postoperative complications, or the number of ambulatory conversions. The placement of CycloMesh™ soaked with ropivacaine did not reduce the pain at cough at H6 but did reduce overall pain in the first 6hours after surgery and could simplify patient management.

Defining and Predicting Early Recurrence for Optimal Treatment Strategies for Intraductal Papillary Mucinous Neoplasm-Derived Pancreatic Cancer: An International Multicenter Study.

Early recurrence in intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) is poorly defined. Predictors are lacking and needed for patient counseling, risk stratification, and postoperative management. This study aimed to define and predict early recurrence for patients in resected IPMN-derived PDAC and guide management. A lowest p value for survival after recurrence (SAR) was used to define early recurrence in resected IPMN-derived PDAC from five international centers. Overall survival (OS) and SAR were compared using log-rank tests. A multivariable logistic regression identified odds ratios (ORs) with 95 % confidence intervals (CIs) for early recurrence. Rounded ORs were used to stratify patients into low-, intermediate-, and high-risk groups using upper and lower quartile score distributions. Adjuvant chemotherapy was assessed by Cox regression and log-rank tests for OS in risk groups. Recurrence developed in 160 (42 %) of 381 patients. Early recurrence was defined at 10.5 months and observed in 61 patients (38 % of recurrences). The median SAR for the patients with early recurrence was 8.3 months (95 % CI, 3.1-16.1 months) compared with 12.9 months (95 % CI, 5.2-27.5 months) for the patients with late recurrence. The independent predictors of early recurrence were CA19-9 (OR, 3.80; 95 % CI, 1.54-9.41) and N2 disease (OR, 7.29; 95 % CI, 3.22-16.49). The early recurrence rates in the low-, intermediate-, and high-risk groups were respectively 1 %, 14 %, and 32 %. Adjuvant chemotherapy was associated with improved OS only for the high-risk patients (hazard ratio, 0.50; 95 % CI, 0.32-0.79). In IPMN-derived PDAC, the optimal cutoff for early recurrence is 10.5 months. Both CA19-9 and N stage predict early recurrence. Adjuvant chemotherapy is associated with survival benefit only for high-risk patients.

Predictors of poor outcome in acute stroke patients with posterior cerebral artery occlusion and medical management.

The clinical evolution of acute ischemic stroke patients with isolated proximal posterior cerebral artery (PCA) occlusion treated with medical management alone has been poorly described. We aimed to determine the clinical and radiological factors associated with poor functional outcome in this population. We conducted a multicenter international retrospective study of consecutive stroke patients with isolated occlusion of the first (P1) or second (P2) segment of PCA admitted within 6hrs from symptoms onset in 26 stroke centers in France, Switzerland and the USA, treated with best medical management alone. Poor functional outcome was defined as a modified Rankin scale (mRS) ≥2 at 3-month or no return to pre-stroke mRS. The associations between pretreatment variables and poor outcome were studied in univariable then multivariable analyses, as well as the association between poor outcome and key follow-up radiological variables. Overall, 585 patients were included. Median age was 74 years (IQR, 63-83), median NIHSS was 6 (3-10), 80% received intravenous thrombolysis (IVT), 22% and 78% had P1 and P2 occlusion, respectively. Poor outcome occurred in 56% of patients. In multivariable analysis focusing on pretreatment variables, age (adjusted OR=1.12 per 5-year increase [95%CI 1.05-1.20]; P=0.001), NIHSS score (aOR=1.12 per each point increase [1.08-1.18]; P<0.001), infarct volume (aOR=1.16 per 5mL increase [1.07-1.25]; P<0.001), and the lack of IVT use (aOR=1.79 [1.10-2.94], P=0.020) were independently associated with poor outcome. Regarding 24-hr follow-up radiological variables, complete recanalization (defined as no clot in the vascular tree at or beyond the primary occlusive lesion, aOR=0.37 95%CI 0.21-0.65, P<0.001) and parenchymal hematoma occurence (aOR=2.37 95%CI 1.01-5.56, P=0.048) were independently associated with poor 3-month outcome. Poor outcome occurred in more than half of medically treated PCA-related acute stroke patients. Facilitating IVT use may improve functional outcome. Therapeutic approaches aimed at enhancing recanalization and reducing hemorrhagic transformation need to be studied in clinical trials.

Widening the infantile hypotonia with psychomotor retardation and characteristic Facies-1 Syndrome's clinical and molecular spectrum through NALCN in-silico structural analysis.

Infantile hypotonia with psychomotor retardation and characteristic facies-1 (IHPRF1, MIM#615419) is a rare, birth onset, autosomal recessive disorder caused by homozygous or compound heterozygous truncating variants in NALCN gene (MIM#611549) resulting in a loss-of-function effect. We enrolled a new IHPRF1 patients' cohort in the framework of an international multicentric collaboration study. Using specialized in silico pathogenicity predictors and ad hoc structural analyses, we assessed the mechanistic consequences of the deleterious variants retrieved on NALCN structure and function. To date 38 different NALCN variants have been retrieved from 33 different families, 26 from unrelated and 22 from related patients. We report on five new IHPRF1 patients from four different families, harboring four newly identified and one previously retrieved variant that exhibited a markedly significant functional impact, thereby compromising the functionality of the protein complex. By widening the functional spectrum of biallelic variants affecting the NALCN gene, this article broadens the IHPRF1 syndrome's genotype-phenotype correlation and gives new insight into its pathogenic mechanism, diagnosis, and clinical management.

Preventing Severe COVID-19 with Tixagevimab-Cilgavimab in Hematological Patients Treated with Anti-CD20 Monoclonal Antibodies: An International Multicenter Study.

Despite the declining public health emergency status, COVID-19 still poses significant risks, especially for immunocompromised individuals. We aimed to evaluate the effectiveness of tixagevimab-cilgavimab (T-C) prophylaxis in preventing severe COVID-19 in patients with hematologic malignancies (HM) treated with anti-CD20 therapy during the early Omicron variant phase of the pandemic. The European Society of Clinical Microbiology and Infectious Diseases Study Group for Respiratory Viruses (ESGREV) conducted a multicenter retrospective cohort study involving 15 centers from 5 countries. The study included 749 patients with HM treated with anti-CD20 between February 15 and June 30, 2022, comparing 215 who received T-C prophylaxis to 534 who did not. The study revealed a significant reduction in the risk of COVID-19 among patients who received T-C prophylaxis compared to those who did not (11.2% vs 23.4%, p < 0.001), with hazard ratio (HR) of 0.40 (95% CI 0.26-0.63), adjusted for age, sex, vaccination status, baseline HM malignancy and type of anti-CD-20. We also demonstrated a reduction for severe-critical diseases within all study populations, 1.4% vs 5.2%, p = 0.017, HR 0.26 (95% CI 0.08-0.84). T-C prophylaxis effectively prevented COVID-19 and severe-critical COVID-19 in patients with HM treated with anti-CD20 monoclonal antibodies during the early Omicron variant phase of the pandemic. Even though T-C is ineffective against current variants, these findings highlight the importance of additional protective measures and the continued development of monoclonal antibodies to protect immunocompromised individuals to mitigate the impact of COVID-19 and other respiratory viral diseases.

Evaluation of risk factors for postpartum cerebral venous sinus thrombosis, a multicenter retrospective observational study.

The postpartum period is a well-defined risk factor for cerebral venous sinus thrombosis (CVST). However, it is unclear which patients are at risk for CVST in the postpartum period. Thus, determining some CVST risk factors in postpartum patients may be useful for preventing the disorder in this population. Previous studies have shown that preeclampsia (PE) is a risk factor for pulmonary thromboembolism and deep vein thrombosis, but whether it is related to postpartum CVST has not yet been evaluated. This study aimed to determine if this relationship exists. This study was a case-control study of retrospectively screened patients diagnosed with CVST between 2018 and 2023 at the Uludağ University Faculty of Medicine Department of Neurology, the Eskişehir Osmangazi University Faculty of Medicine and the Bursa City Hospital Health Sciences University Department of Neurology. All of the women who delivered between 2018 and 2023 at the Uludağ University Faculty of Medicine Department of Obstetrics and Gynaecology were included in the control group. In total, 57 out of 322 cases and 4299 out of 4452 controls were included in this study. A nonsignificant relationship was found between CVST and spinal anesthesia, but a significant relationship was found between PE and stillbirth. Women with PE who had recently delivered were found to be at increased risk of developing CVST. The primary limitation of this study is that it was retrospective, and the control group was hospital-based. We recommend that these findings be confirmed by multicenter prospective international studies.

International survey on diagnostic reference levels based on clinical indications in plain radiography.

To collect and analyze radiation dose-related data as part of international cooperation; to define diagnostic reference levels (DRL) for 24 X-ray projections in plain radiography (DX) considering anatomical region, clinical task, and procedural technique; and to harmonize the exposure practice across country borders. A multicenter study was performed in Austria, Germany, Italy, and Switzerland in 2022-23 to provide dose-related data. Healthcare facilities were asked to provide processed data from their dose management systems. A 5%-level was used for assessing the statistical significance of dose differences between various groups. Dose-related data from 85 radiographic systems in academic and non-academic, public, and private healthcare facilities were analyzed. Dose-related parameters differed significantly for many projections with different clinical tasks and techniques. Dose-related data of the procedures varied by a maximum factor of 16 for the same system, and median dose values also differed between hospitals by a maximum factor of 31. A fifth of the surveyed systems exhibit doses above more than half of the new DRLs defined in this study. Apart from the three reference procedures, no significant dose differences were observed between X-ray systems of different ages, from different manufacturers, or from different countries. This is the first survey in which exposure practices were investigated in institutions in different central European countries by establishing clinical DRLs for radiography. The observed dose variations could be explained by different reasons, such as non-optimized dose protocols. The new DRLs help to harmonize the exposure practice across country borders. Question What is the exposure practice for plain radiography procedures for which no clinical diagnostic reference levels (DRLs) have been defined? Are there differences between countries? Findings The dose for the same clinical task and technique can vary considerably among institutions but, on average, do not significantly differ between neighboring countries in Europe. Clinical relevance In this international multicenter study, clinical DRLs were defined for 24 plain radiography projections to promote the optimization of the exposure practice, to reduce dose variations among institutions even across national borders, and to strengthen international cooperation among users.

Resistant and refractory migraine – two different entities with different comorbidities? Results from the REFINE study

BackgroundResistant and refractory migraine are commonly encountered in specialized headache centers. Several comorbidities, mostly psychiatric conditions, have been linked to migraine worsening; however, there is little knowledge of the comorbidity profile of individuals with resistant and refractory migraine.MethodsREFINE is a prospective observational multicenter international study involving individuals with migraine from 15 headache centers. Participants were categorized into three groups based on the European Headache Federation criteria: non-resistant and non-refractory (NRNRM), resistant (ResM), and refractory (RefM). We explored the prevalence of 20 comorbidities at baseline in the three groups.ResultsOf the 689 included patients (82.8% women), 262 (38.0%) had ResM, 73 (10.4%) had RefM and 354 (51.4%) NRNRM. A higher prevalence of psychiatric comorbidities, trigger points, temporomandibular joint disorders, thyroiditis, and cerebrovascular diseases was observed in the RefM group, followed by ResM and NRNRM. Multiple comorbidities were more common in the RefM group, followed by the ResM group and by the NRNRM group (41.6% vs. 24.5% vs. 14.1% respectively; p < 0.001). At the sensitivity analysis, exploring participants with chronic migraine, significant differences among the NRNRM, ResM, and RefM groups were found in the prevalence of anxiety (p < 0.001), asthma and rhinitis (p = 0.013), bipolar and other psychiatric disorders (p = 0.049), cerebrovascular diseases (p < 0.001), depression (p < 0.001), obesity (p = 0.002), thyroiditis (p < 0.001), and trigger points (p = 0.008).ConclusionREFINE data indicate that individuals with ResM and RefM have a higher burden of comorbidities than those with NRNRM. It can be postulated that those comorbidities may have an impact on the progression of migraine from a form that is easy to treat to a form that is resistant or refractory to treatments. Longitudinal studies are needed to understand the direction of the association between ResM or RefM and those comorbidities and if proper treatment of comorbidities might help overcome treatment resistance or refractoriness.

Patterns, timing and predictors of recurrence following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: An international multicentre retrospective cohort study

Patterns, timing and predictors of recurrence following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: An international multicentre retrospective cohort study