Multicenter Study Research Articles

MRI and Blood-based Biomarkers Are Associated With Surgery in Children and Adults With Ileal Crohn's Disease.

Despite advances in medical therapy, many children and adults with ileal Crohn's disease (CD) progress to fibrostenosis requiring surgery. We aimed to identify MRI and circulating biomarkers associated with the need for surgical management. This prospective, multicenter study included pediatric and adult CD cases undergoing ileal resection and CD controls receiving medical therapy. Noncontrast research MRI examinations measured bowel wall 3-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA). Circulating biomarkers were measured on the same day as the research MRI and included CD64, extracellular matrix protein 1 (ECM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (Ab). Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. Our study sample included 50 patients with CD undergoing ileal resection and 83 patients with CD receiving medical therapy; mean participant age was 23.9 ± 13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR], 2.87; P = .0009), normalized 3D MTR (OR, 1.05; P = .002), log MOLLI T1 (OR, 0.01; P = .02), log IVIM perfusion fraction (f; OR, 0.38; P = .04), and IVIM apparent diffusion coefficient (ADC; OR, 0.3; P = .001). The multivariable model for surgery based upon correctedAkaike information criterion included age (OR, 1.03; P = .29), BMI (OR, 0.91; P = .09), log GM-CSF Ab (OR, 3.37; P = .01), normalized 3D MTR (OR, 1.07; P = .007), sMaRIA (OR, 1.14; P = .61), luminal narrowing (OR, 10.19; P = .003), log C-reactive protein (normalized; OR, 2.75; P = .10), and hematocrit (OR, 0.90; P = .13). After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with the need for surgery in ileal CD.

Harmonizing tumor mutational burden analysis: Insights from a multicenter study using in silico reference data sets in clinical whole-exome sequencing (WES).

Tumor mutational burden (TMB) is a significant biomarker for predicting immune checkpoint inhibitor response, but the clinical performance of whole-exome sequencing (WES)-based TMB estimation has received less attention compared to panel-based methods. This study aimed to assess the reliability and comparability of WES-based TMB analysis among laboratories under routine testing conditions. A multicenter study was conducted involving 24 laboratories in China using in silico reference data sets. The accuracy and comparability of TMB estimation were evaluated using matched tumor-normal data sets. Factors such as accuracy of variant calls, limit of detection (LOD) of WES test, size of regions of interest (ROIs) used for TMB calculation, and TMB cutoff points were analyzed. The laboratories consistently underestimated the expected TMB scores in matched tumor-normal samples, with only 50% falling within the ±30% TMB interval. Samples with low TMB score (<2.5) received the consensus interpretation. Accuracy of variant calls, LOD of the WES test, ROI, and TMB cutoff points were important factors causing interlaboratory deviations. This study highlights real-world challenges in WES-based TMB analysis that need to be improved and optimized. This research will aid in the selection of more reasonable analytical procedures to minimize potential methodologic biases in estimating TMB in clinical exome sequencing tests. Harmonizing TMB estimation in clinical testing conditions is crucial for accurately evaluating patients' response to immunotherapy.

Predicting early mortality and severe intraventricular hemorrhage in very-low birth weight preterm infants: a nationwide, multicenter study using machine learning

Our aim was to develop a machine learning-based predictor for early mortality and severe intraventricular hemorrhage (IVH) in very-low birth weight (VLBW) preterm infants in Taiwan. We collected retrospective data from VLBW infants, dividing them into two cohorts: one for model development and internal validation (Cohort 1, 2016–2021), and another for external validation (Cohort 2, 2022). Primary outcomes included early mortality, severe IVH, and early poor outcomes (a combination of both). Data preprocessing involved 23 variables, with the top four predictors identified as gestational age, birth body weight, 5-min Apgar score, and endotracheal tube ventilation. Six machine learning algorithms were employed. Among 7471 infants analyzed, the selected predictors consistently performed well across all outcomes. Logistic regression and neural network models showed the highest predictive performance (AUC 0.81–0.90 in both internal and external validation) and were well-calibrated, confirmed by calibration plots and the lowest two mean Brier scores (0.0685 and 0.0691). We developed a robust machine learning-based outcome predictor using only four accessible variables, offering valuable prognostic information for parents and aiding healthcare providers in decision-making.

The impact of inhalation injury on fluid resuscitation in major burn patients: a 10-year multicenter retrospective study

BackgroundIt remains unclear whether additional fluid supplementation is necessary during the acute resuscitation period for patients with combined inhalational injury (INHI) under the guidance of the Third Military Medical University (TMMU) protocol.MethodsA 10-year multicenter, retrospective cohort study, involved patients with burns ≥ 50% total burn surface area (TBSA) was conducted. The effect of INHI, INHI severity, and tracheotomy on the fluid management in burn patients was assessed. Cumulative fluid administration, cumulative urine output, and cumulative fluid retention within 72 h were collected and systematically analyzed.ResultsA total of 108 patients were included in the analysis, 85 with concomitant INHI and 23 with thermal burn alone. There was no significant difference in total fluid administration during the 72-h post-burn between the INHI and non-INHI groups. Although no difference in the urine output and fluid retention was shown in the first 24 h, the INHI group had a significantly lower cumulative urine output and a higher cumulative fluid retention in the 48-h and 72-h post-burn (all p < 0.05). In addition, patients with severe INHI exhibited a significantly elevated incidence of complications (Pneumonia, 47.0% vs. 11.8%, p = 0.012), (AKI, 23.5% vs. 2.9%, p = 0.037). For patients with combined INHI, neither the severity of INHI nor the presence of a tracheotomy had any significant influence on fluid management during the acute resuscitation period.ConclusionsAdditional fluid administration may be unnecessary in major burn patients with INHI under the guidance of the TMMU protocol.

Results of the multicenter early feasibility study (EFS) of the Renata Minima stent as treatment for branch pulmonary artery stenosis and coarctation of aorta in infants.

Stent implantation has become standard of care in older children and adults for treatment of branch pulmonary artery stenosis (BPAS) and coarctation aorta (CoAo). There are no stents approved or available for infants that have the potential to be dilated to adult diameters. The Minima stent was designed to fulfill this unmet need. Multicenter, prospective, nonrandomized early feasibility studyevaluating safety and effectiveness of the Minima stent for treatment of BPAS and CoAo. Primary endpoints included: (1) successful deployment across lesion, (2) stenosis relief defined by an increase in angiographic diameter of >50% and (3) freedom from stent explant, embolization or migration at 30 days and 6 months. Between 2/2022 and 5/2022, 10 pts underwent Minima stent implantation with a median age and weight of 9 months (4-43 months) and 7.6 kg (5.1-16.9 kg). Procedural success and predefined stenosis relief was achieved in all cases (CoAo [n = 4], BPAS [n = 6]). Adverse events occurred in 3 pts: transient diminished lower extremity pulse (n = 2), distal stent on-balloon displacement successfully managed in the catheterization suite (n = 1). There were no deaths or major adverse events. All patients were free from stent explant and migration at 30 days and 6 months with no evidence for significant restenosis at latest follow-up. Implantation of the Renata Minima stent was safe and effective for the treatment of BPAS and CoAo in this small cohort of infants and young children during early follow-up. Based on these early results, an expanded study with longer follow-up is warranted.

[Analysis of compliance with lung protective mechanical ventilation strategy in patients with acute respiratory distress syndrome].

Objective: To assess the compliance with a lung protective ventilation strategy and to evaluate the relationship with prognosis in patients with acute respiratory distress syndrome (ARDS). Methods: In the prospective multicenter cohort study (CHARDS), patients with ARDS undergoing invasive mechanical ventilation were enrolled to collect essential information, mechanical ventilation data, and prognostic data. Compliance was operationally defined as tidal volume ≤7 ml/kg predicted body weight (PBW) or plateau pressure ≤30 cmH2O or driving pressure≤15 cmH2O. Tidal volume data collected 7 days prior to ventilation after ARDS diagnosis were categorized into four groups: standard group (Group A, 100% compliance), non-standard group (Group B, 50%-99% compliance, Group C,1%-49% compliance,and Group D,totally non-compliant). Plateau pressure and drive pressure measurements were recorded on the first day. Stepwise regression, specifically Logistics regression, was used to identify the factors influencing ICU survival. Results: A total of 449 ARDS patients with invasive mechanical ventilation were included; the proportion of mild, moderate, and severe patients was 71 (15.8%), 198 (44.1%) and 180 (40.1%), respectively. During the first 7 days, a total of 2880 tidal volume measurements were recorded with an average tidal volume of (6.89±1.93) ml/kg PBW. Of these measurements, 53.2% were found to be≤7 ml/kg PBW. The rates of compliance with lung protective mechanical ventilation were 29.8% (134/449), 24.5% (110/449), 23.6% (106/449), and 22% (99/449) in groups A, B, C, and D, respectively. In the standard group, the tidal volume for mild ARDS patients was 18.3%(13/71), while it was 81.7%(58/71)in the non-standard group. Similarly, in patients with moderate ARDS, the tidal volume was 25.8% (51/198) in the standard group, while it was 74.2% (147/198) in the non-standard group. Finally, in patients with severe ARDS, the tidal volume was 38.9% (70/180) in the standard group, while it was 61.1% (110/180) in the non-standard group. Notably, the compliance rate was higher in patients with moderate and severe ARDS in group A compared to patients with mild and moderate ARDS (18.3% vs. 25.8% vs. 38.9%, χ2=13.124, P=0.001). Plateau pressure was recorded in 221 patients, 95.9% (212/221) patients with plateau pressure≤30 cmH2O, and driving pressure was recorded in 207 patients, 77.8% (161/207) patients with a driving pressure ≤15 cmH2O.During the first 7 days, the mortality rate in the intensive care unit (ICU) was lower in the tidal volume standard group compared to the non-standard group (34.6% vs. 51.3%, χ2=10.464, P=0.001). In addition, the in-hospital mortality rate was lower in the standard group compared to the non-standard group (39.8% vs. 57%, χ2=11.016, P=0.001).The results of the subgroup analysis showed that the mortality rates of moderate and severe ARDS patients in the standard group were significantly lower than those in the non-standard group, both in the ICU and in the hospital (all P<0.05). However, there was no statistically significant difference in mortality among mild ARDS patients (all P>0.05). Conclusions: There was high compliance with recommended lung protective mechanical ventilation strategies in ARDS patients, with slightly lower compliance in patients with mild ARDS, and high compliance rates for plateau and drive pressures. The tidal volume full compliance group had a lower mortality than the non-compliance group, and showed a similar trend in the moderate-to-severe ARDS subgroup, but there was no significant correlation between compliance and prognosis in patients with mild ARDS subgroup.

Use of anticoagulant drugs for hospitalised patients: A multicentre study

Background: Anticoagulants are indicated for several types of diseases with progression related to coagulation. Patients administered this drug need to be evaluated by the pharmacist regarding its effectiveness and possible side effects. Objective: This research aimed to analyse the profile use of anticoagulants among patients at Yogyakarta Hospital. Method: This research was a multicentre study conducted retrospectively using the medical records of inpatients who received anticoagulants. Result: Among a total of 486 respondents, the majority were male (63.58%), and the adult age category (18-59 years) was 55.76%. Most anticoagulants were used in cases of cardiovascular disease, diagnosed with NSTEMI as much as 20.21%. The most used anticoagulant drug was heparin (48.9%), followed by fondaparinux (34.3%) and enoxaparin (16.8%). The most duration of anticoagulant use was one to four days (73.02%) with the dose range being 200-1000 units/day. Conclusion: Heparin was the anticoagulant widely used in patients with NSTEMI. Although the elderly were the group most at risk of ADR due to anticoagulants, most of these drugs were precisely taken by adults, who also required serious attention. Further research is needed to provide a more comprehensive approach to anticoagulant therapy.

NSAID PRESCRIPTION SURVEY IN INTEGRATED TRADITIONAL AND WESTERN MEDICINE TREATMENT: ASSESSING GASTROINTESTINAL AND CARDIOVASCULAR RISKS

Introduction: Non-steroidal anti-inflammatory drug (NSAID) usage should be carefully considered based on gastrointestinal (GI) and cardiovascular (CV) risks. In light of restricted evidence, this study aims to assess the prescription of NSAIDs concerning the GI and CV risks in the integrated treatment of Traditional medicine (TM) and Western medicine (WM). Materials and method: A retrospective cross-sectional study was conducted on 393 medical records of inpatients using NSAIDs in 2022 at the Traditional Medicine Hospital of Ho Chi Minh City. GI and CV risks, as well as information regarding NSAID prescriptions, were recorded. A multivariable regression model was employed to identify factors associated with the prescription of NSAID groups. Results: NSAIDs were primarily prescribed for musculoskeletal and connective tissue disorders (87.28%). Approximately half of the cases exhibited moderate to high GI risk (47.59%), while for CV risk, there were 68.95% with moderate to very high risk. COX-2 inhibitors were the most commonly prescribed (94.66%), even when considering GI and CV risks separately. In the majority, NSAID prescriptions aligned with both risks according to American College of Gastroenterology (ACG) guidelines (73.79%). The prescription of NSAID groups was significantly influenced by patient gender, ailment type, and physician education (p&lt;0.05), but not by GI and CV risks (p&gt;0.05). Conclusion: Patients receiving NSAIDs in integrated TM and WM treatment often faced an increased GI and CV risk, with the majority adhering to ACG guidelines. However, GI and CV risks were not significantly considered for NSAID group selections. Multi-center studies should be conducted.

An analysis of the association between breast density and body mass index with breast cancer molecular subtypes in early breast cancer: data from a Spanish population.

Breast cancer is an important health problem, like obesity and dyslipidemia, with a strong association between body mass index (BMI) and breast cancer incidence and mortality. The risk of breast cancer is also high in women with high mammographic breast density (MBD). The purpose of this study was to analyze the association between BMI and MBD according to breast cancer molecular subtypes. This transversal, descriptive, multicenter study was conducted at three Spanish breast cancer units from November 2019 to October 2020 in women with a recent diagnosis of early breast cancer. Data were collected at the time of diagnosis. The study included 162 women with a recent diagnosis of early breast cancer. The median age was 52years and 49.1% were postmenopausal; 52% had normal weight, 32% overweight, and 16% obesity. There was no association between BMI and molecular subtype but, according to menopausal status, BMI was significantly higher in postmenopausal patients with luminal A (p = 0.011) and HER2-positive (p = 0.027) subtypes. There was no association between MBD and molecular subtype, but there were significant differences between BMI and MBD (p < 0.001), with lower BMI in patients with higher MBD. Patients with higher BMI had lower HDL-cholesterol (p < 0.001) and higher insulin (p < 0.001) levels, but there were no significant differences in total cholesterol or vitamin D. This study showed higher BMI in luminal A and HER2-positive postmenopausal patients, and higher BMI in patients with low MBD regardless of menopausal status.

Prognostic significance of HER2 loss after HER2-targeted neoadjuvant treatment in patients with HER2-positive locally advanced breast cancer

Loss of human epidermal growth factor receptor 2 (HER2) expression can be seen in almost 25–30 % patients after HER2 receptor directed neoadjuvant treatment. These patients have unclear clinical outcomes in previous studies. We aimed to investigate the importance of HER2 loss, additionally with predictive factors for the loss of HER2. This was a retrospective and multicenter study that included 272 HER2-positive BC patients with no pathological complete response who received neoadjuvant chemotherapy plus HER2-targeted treatments. The factors that may affect the loss of HER2 detected by immunohistochemistry(IHC) and the association with survival were analyzed.The rate of HER2 loss after neoadjuvant treatments(NAT) was 27.9 % (n = 76). Disease recurrence was observed in 18(23.7 %) patients with HER2 loss, while it was detected in 62 (31.7 %) patients without HER2 loss(p = 0.23). Pre and post-NAT ER status, and post-NAT ki-67 status had a significant impact on disease-free survival(DFS) (p = 0.0012, p = 0.004, and p = 0.04, respectively).There were no significant association between DFS and loss of HER2 (p = 0.64) and dual anti-HER2 blockade (p = 0.21). Pre-NAT clinical stage (HR:1.65 p = 0.013), post-NAT LN status (HR:3.18, p = 0.02) and pre-NAT ER status (HR:0.24, p = 0.041) were significant independent prognostic factors for DFS while post-NAT residual disease in axillar tissue was an independent prognostic factor for OS (HR:1.54 p = 0.019). Moreover, age (<40 years vs ≥40 years) (p = 0.031) and tumor grade (p = 0.004) were predictive factors for HER2 loss. Our results showed that HER2 loss did not affect survivals. However, young age and being high grade tumor may predict HER2 loss.

Parameters affecting the success rate of microscopic testicular sperm extraction in male patients with a solitary testis and non-obstructive azoospermia.

We aimed to compare the success rate of spermatozoa retrieval through microscopic testicular sperm extraction (mTESE) in non-obstructive azoospermic (NOA) men with a solitary testis with that of mTESE in NOA men with bilateral testes and the parameters affecting these rates. A retrospective cross-sectional study of factors contributing to infertility in NOA patients with a solitary testis and men with bilateral testes was carried out. In this multicenter study, 74 patients with NOA with a solitary testis were matched with 74 patients with bilateral testes in terms of age, duration of infertility, and volume of the solitary testis from 2770 patients with NOA with bilateral testes. Hormonal parameters, presence of varicocele, history of varicocelectomy, history of undescended testis and karyotype analysis results were compared. Spermatozoa were obtained from 40 (54.1%) patients with a solitary testis and 42 (56.76%) patients with bilateral testes. No differences were found regarding age, duration of infertility, or mean testicular volume between patients with a solitary testis and patients with bilateral testes. When serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were compared regardless of sperm retrieval status, it was observed that both levels were greater in the group of patients with a solitary testis (p < 0.01). Patients with solitary and bilateral testes from whom spermatozoa were obtained had larger testes than those from whom spermatozoa could not be obtained (p < 0.05). Similarly, the serum levels of FSH and LH were significantly greater in patients with a solitary testis than in those with bilateral testes (p < 0.05). To the best of our knowledge, this is the first study in the literature to evaluate the parameters that influence mTESE outcome in NOA patients with a solitary testis and NOA patients with bilateral testes. Greater testicular volume was found to positively affect spermatozoa retrieval for patients with a solitary testis. The higher levels of FSH and LH in patients with a solitary testis than in patients with bilateral testes of similar testicular volume may be due to a compensatory mechanism developed by the hypothalamic-pituitary-gonadal axis. The fact that these hormones are higher in patients with a solitary testis does not mean that the number of spermatozoa obtained through mTESE will be decreased.

Interpretable multiphasic CT-based radiomic analysis for preoperatively differentiating benign and malignant solid renal tumors: a multicenter study.

To develop and compare machine learning models based on triphasic contrast-enhanced CT (CECT) for distinguishing between benign and malignant renal tumors. In total, 427 patients were enrolled from two medical centers: Center 1 (serving as the training set) and Center 2 (serving as the external validation set). First, 1781 radiomic features were individually extracted from corticomedullary phase (CP), nephrographic phase (NP), and excretory phase (EP) CECT images, after which 10 features were selected by the minimum redundancymaximum relevance method. Second, random forest (RF) models were constructed from single-phase features (CP, NP, and EP) as well as from the combination of features from all three phases (TP). Third, the RF models were assessed in the training and external validation sets. Finally, the internal prediction mechanisms of the models were explained by the SHapley Additive exPlanations (SHAP) approach. A total of 266 patients with renal tumors from Center 1 and 161 patients from Center 2 were included. In the training set, the AUCs of the RF models constructed from the CP, NP, EP, and TP features were 0.886, 0.912, 0.930, and 0.944, respectively. In the external validation set, the models achieved AUCs of 0.860, 0.821, 0.921, and 0.908, respectively. The "original_shape_Flatness" feature played the most important role in the prediction outcome for the RF model based on EP features according to the SHAP method. The four RF models efficiently differentiated benign from malignant solid renal tumors, with the EP feature-based RF model displaying the best performance.

Vibro-tactile stimulation of the neck reduces pain in people with cervical dystonia: a proof-of-concept study.

Pain is a common non-motor symptom in patients with cervical dystonia (CD), severely impacting their quality of life. The pathophysiology of CD is incompletely understood but it involves altered processing of proprioceptive and pain signals. The purpose of this proof-of-concept study was to determine if vibro-tactile stimulation (VTS)-a non-invasive form of neuromodulation targeting the somatosensory system-can modulate neck pain in people with CD. In a multi-center study, 44 CD patients received VTS to sternocleidomastoid and/or trapezius muscles for up to 45min under 9 different stimulation conditions that either targeted a single or a pair of muscles. The primary outcome measure was a perceived pain score (PPS) rated by participants on a 100-point analogue scale. During VTS, 29/44 (66%) of participants experienced a reduction in PPS of at least 10% with 17/44 (39%) reporting a reduction in pain of 50% or higher. After VTS cessation, 57% of participants still reported a 10% or higher reduction in PPS. Effects were significant at the group level and persisted for up to 20min post-treatment. No distinct optimal stimulation profiles were identified for specific CD phenotypes. Clinical markers of disease severity or duration did not predict the degree of VTS-induced pain reduction. This proof-of-concept study demonstrates the potential of VTS as a new non-invasive therapeutic option for treating neck pain associated with CD. Further research needs to delineate optimal dosage and long-term effects.

To close, not to close, or to act bigger? Managing the defect of large direct inguinal hernia to reduce the risk of recurrence during laparoscopic TAPP repair: a retrospective cohort study.

Hernia recurrence is a common complication after inguinal hernia repair. Recent studies suggest that laparoscopic mesh repair with closure of direct hernia defects can reduce recurrence rates. Our study examines the effectiveness of this approach. A retrospective, multi-center cohort study was conducted on cases performed from January 2013 to April 2021. Patients with direct inguinal hernias (M3 according to EHS classification) undergoing TAPP were included. Three groups were present: closed-defect group, non-closed placing a standard-sized mesh group or non-closed placing an XL-sized mesh group. A 2-year follow-up was recorded. A total of 158 direct M3 inguinal hernias in 110 patients who underwent surgery were present. After propensity score matching at a 1:1 ratio, 22 patients for each group were analyzed. The mean age of patients was 62years (41-84); with the majority being male (84.8%). 22 patients (40 hernias) underwent closure of the defect; 22 patients (39 hernias) did not undergo closure and used a standard-sized mesh; 22 patients (27 hernias) did not undergo closure and used an XL-sized mesh. There were 5 recurrences at 1year post-operatively: all in the non-closure group with standard-sized mesh. This difference was statistically significant (p = 0.044). There were 7 recurrences (6.6%) at 2years post-operatively: 6 in the non-closure group with standard-sized mesh and 1 in the non-closure group with XL-sized mesh (p = 0.007). Closing large direct inguinal hernia defects has shown promise in reducing early recurrence rates. However, conducting larger RCTs in the future could provide more conclusive evidence that might impact the way we approach laparoscopic inguinal hernia repair.

Real-World Patent Foramen Ovale (PFO) Closure in Japan - 30-Day Clinical Outcomes From the AmplatzerTM PFO Occluder Japan Post-Marketing Surveillance Study.

The AmplatzerTM PFO Occluder was approved for marketing in Japan in May 2019, and the Amplatzer PFO Occluder Japan Post-marketing Surveillance (PFO Japan PMS) study was initiated in December 2019. This analysis presents 30-day clinical outcomes for PFO Japan PMS study patients.Methods and Results: PFO Japan PMS is a prospective single-arm non-randomized multicenter clinical study. Eligible patients were indicated for patent foramen ovale (PFO) closure and underwent an implant attempt with the AmplatzerTM PFO Occluder. Technical success was defined as successful delivery and release of the occluder; procedural success was defined as technical success with no serious adverse events (SAEs) within 1 day of the procedure. The primary safety endpoint includes predefined device- and/or procedure-related SAEs through 30 days after the procedure. From December 2019 to July 2021, 500 patients were enrolled across 53 Japanese sites. The mean (±SD) patient age was 52.7±15.4 years, and 29.8% of patients were aged >60 years. Technical and procedural success rates were both high (99.8% and 98.8%, respectively). Further, there was only one primary safety endpoint event (0.2%): an episode of asymptomatic paroxysmal atrial fibrillation that occurred 26 days after the procedure. In this real-world Japanese study with almost one-third of patients aged >60 years, PFO closure with the AmplatzerTM PFO Occluder was performed successfully and safely, with a low incidence of procedure-related atrial arrhythmias.

Association of serum 25-hydroxyvitamin D with cardiovascular mortality and kidney outcome in patients with early stages of CKD.

While serum 25-hydroxyvitamin D (25[OH]D) deficiency is prevalent in chronic kidney disease (CKD), the effects of 25(OH)D deficiency on cardiovascular mortality and kidney outcomes in patients with early-stage CKD remain incompletely understood. This multicenter retrospective cohort study included adult patients with stages 1-3 CKD from 19 medical centers across China between January 2000 and May 2021. The primary outcome was cardiovascular mortality. The secondary study outcome included CKD progression (defined as a sustained > 40% eGFR decrease from baseline or progress to end-stage kidney disease), and annual percentage change of eGFR. Of 9229 adults with stages 1-3 CKD, 27.0% and 38.9% had severe (< 10ng/mL) and moderate (10 to < 20ng/mL) serum 25(OH)D deficiency, respectively. Compared with patients having 25(OH)D ≥ 20ng/mL, a significantly higher risk of cardiovascular mortality (hazard ratio [HR] 1.90, 95% CI 1.37-2.63), CKD progression (HR 2.20, 95% CI 1.68-2.88), and a steeper annual decline in eGFR (estimate - 7.87%; 95% CI - 10.24% to - 5.51% per year) was found in those with serum 25(OH)D < 10ng/mL. Similar results were obtained in subgroups and by sensitivity analyses. 25(OH)D deficiency is associated with increased risks of cardiovascular mortality and CKD progression in patients with early-stage CKD. Studies are needed to determine whether early intervention for 25(OH)D deficiency could improve the prognosis of patients with early-stage CKD.

Childhood Autism Spectrum Disorder: Knowledge, Attitudes, and Practice of Health Professionals in Togo

Background. Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in behavior, social communication, and interaction. Objectives. To describe health staff's knowledge, attitudes, and practices regarding ASD in Lomé. Methods. From January to March 2020, we conducted a multicenter, cross-sectional, descriptive, and analytical study on ASD in childhood. A survey was administered to a sample of healthcare professionals in 5 facilities in Lomé, Togo. A questionnaire assessed the knowledge, attitudes, and practices of ASD among 139 participants (pediatricians, neurologists, general practitioners, psychologists, speech therapists, and nurses). Results.The participation rate was 84.2 % (117 / 139). One hundred seven health workers (91.5 %) had heard of ASD. Inaccurate knowledge was observed: 65.4 % gave a good definition of autism, 73.2 % did not know the autistic triad, the early warning signs (64.6 %), or the age of onset (61.0 %). Only 22.0 % of staff were familiar with autism screening tools. The highest knowledge was significantly associated with being a speech therapist or pediatrician practicing in a tertiary health facility (p &lt; 0,0001). Higher-graded staff also observed better knowledge levels (p = 0, 0128). Concerning attitudes or practices regarding autistic children, 26 of those surveyed (22,2 %) had already screened for ASD, of whom 23 (88,5 %) worked with other specialties in case management. Conclusion. This study highlights inappropriate knowledge, attitudes, and practices among health staff. These findings warrant the need for good initial training on ASD, awareness campaigns, and the setting up a specialized center in Togo.

Multicentric experience of antegrade thoracic endovascular aortic repair for the treatment of thoracic aortic diseases.

Aim of this multicentre retrospective cohort study is to evaluate technical success, early and late outcomes of thoracic endovascular repair (TEVAR) with grafts deployed upside-down through antegrade access, to treat thoracic aortic diseases. Antegrade TEVAR performed between January 2010 and December 2021 have been collected and analyzed. Both elective and urgent procedures were included. Exclusion criteria were endografts deployed into previous or concomitant surgical or endovascular repairs. Fourteen patients were enrolled; 13 males (94%) with mean age of 71 years (IQR 62; 78). Five patients underwent urgent procedures (2 ruptured aortas and 3 symptomatic patients). Indication to treatment were 8 (57%) aneurysms/pseudoaneurysms, 3 (21%) dissections and 3 (21%) penetrating aortic ulcers. Technical success was achieved in all procedures. Early mortality occurred in 4 (28%) cases, all urgent procedures. Median follow-up was 13 months (IQR 1; 44). Late death occurred in 2 (20%) patients, both operated in elective setting. The first died at 19 months due to aortic-related reintervention, the second died at 34 months for a not aortic-related cause. Two patients (14%) underwent aortic-related reintervention for late type I endoleak. Survival rate in elective procedures was 100%, 84% and 67% at 12, 24 and 36 months respectively. Freedom from reintervention was 92%, 56% and 56% at 12, 24 and 36 months respectively. Antegrade TEVAR can seldomly be considered an alternative when traditional retrograde approach is not feasible. Despite good technical success and low access-site complications, this study demonstrates high rates of late type I endoleak and aortic-related reinterventions.

Association between the length of in vitro embryo culture, mode of ART, and the initial endogenous hCG rise in ongoing singleton pregnancies.

Is there an association between the length of in vitro culture, mode of ART and the initial endogenous hCG rise, in cycles with a foetal heartbeat after single embryo transfer (ET) and implantation? Both the length of in vitro culture and the mode of ART have an impact on the initial endogenous rise in hCG in singleton pregnancies. Different factors have been identified to alter the kinetics of hCG in pregnancies. Current studies show conflicting results regarding the kinetics of hCG after different types of ART (fresh vs frozen ET (FET)), the inclusion or not of preimplantation genetic testing (PGT), and the length of time in in vitro culture. This was a multicentre cohort study, using prospectively collected data derived from 4938 women (5524 treatment cycles) undergoing IUI (cycles, n = 608) or ART (cycles, n = 4916) treatments, resulting a in singleton ongoing pregnancy verified by first-trimester ultrasound scan. Data were collected from the Danish Medical Data Centre, used by the three participating Danish public fertility clinics at Copenhagen University hospitals: Herlev Hospital, Hvidovre Hospital, and Rigshospitalet, from January 2014 to December 2021. The fresh ET cycles included cleavage-stage (2 or 3 days in vitro) and blastocyst (5 days in vitro) transfers. FET cycles included cleavage-stage (3 days in vitro before cryopreservation) or blastocyst (5 or 6 days in vitro before cryopreservation) transfers. The IUI cycles represented no time in vitro. To attain a comparable interval for serum-hCG (s-hCG), the ovulation induction time was identical: 35-37 h before oocyte retrieval or IUI. The conception day was considered as: the insemination day for pregnancies conceived after IUI, the oocyte retrieval day for fresh ET, or the transfer day minus 3 or 5 as appropriate for FET of Day 3 or 5 embryos. Multiple linear regression analysis was used, including days post-conception for the hCG measurement as a covariate, and was adjusted for the women's age, the cause of infertility, and the centre. For FET, a sensitivity analysis was used to adjust for endometrial preparation. The study totally includes 5524 cycles: 2395 FET cycles, 2521 fresh ET cycles, and 608 IUI cycles. Regarding the length of in vitro culture, with IUI as reference (for no time in in vitro culture), we found a significantly lower s-hCG in pregnancies achieved after fresh ET (cleavage-stage ET or blastocyst transfer). S-hCG was 18% (95% CI: 13-23%, P < 0.001) lower after fresh cleavage-stage ET, and 23% (95% CI: 18-28%, P < 0.001) lower after fresh blastocyst transfer compared to IUI. In FET cycles, s-hCG was significantly higher after blastocyst transfers compared to cleavage-stage FET, respectively, 26% (95% CI: 13-40%, P < 0.001) higher when cryopreserved on in vitro Day 5, and 14% (95% CI: 2-26%, P = 0.02) higher when cryopreserved on in vitro Day 6 as compared to Day 3. Regarding the ART treatment type, s-hCG after FET blastocyst transfer (Day 5 blastocysts) cycles was significantly higher, 33% (95% CI: 27-45%, P < 0.001), compared to fresh ET (Day 5 blastocyst), while there was no difference between cleavage-stage FET (Days 2 + 3) and fresh ET (Days 2 + 3). S-hCG was 12% (95% CI: 4-19%, 0.005) lower in PGT FET (Day 5 blastocysts) cycles as compared to FET cycles without PGT (Day 5 blastocysts). The retrospective design is a limitation which introduces the risk of possible bias and confounders such as embryo score, parity, and ovarian stimulation. This study elucidates how practices in medically assisted reproduction treatment are associated with the hCG kinetics, underlining a potential impact of in vitro culture length and mode of ART on the very early embryo development and implantation. The study provides clinicians knowledge that the type of ART used may be relevant to take into account when evaluating s-hCG for the prognosis of the pregnancy. No funding was received for this study. AP has received consulting fees, research grants, or honoraria from the following companies: Preglem, Novo Nordisk, Ferring Pharmaceuticals, Gedeon Richter, Cryos, Merck A/S, and Organon. AZ has received grants and honoraria from Gedeon Richter. NLF has received grants from Gedeon Richter, Merck A/S, and Cryos. MLG has received honoraria fees or research grants from Gedeon Richter, Merck A/S, and Cooper Surgical. CB has received honoraria from Merck A/S. MB has received research grants and honoraria from IBSA. MPR, KM, and PVS all report no conflicts of interest. The study was registered and approved by the Danish Protection Agency, Capital Region, Denmark (Journal-nr.: 21019857). No approval was required from the regional ethics committee according to Danish law.

Invasive Fungal Infections Among Patients with Hematological Malignancies: A Two-Year Multicentric Study from Tehran, Iran

Background: Invasive fungal infection (IFI) is a life-threatening condition, particularly in individuals with compromised immune systems. Objectives: Our study aims to evaluate IFI in hospitalized patients with hematological malignancies. Methods: In this retrospective cross-sectional study, we evaluated patients with hematological malignancies admitted to two university hospitals in Tehran, Iran, from 2020 to 2021 for IFI. We selected only those patients who had been hospitalized for at least four days for antimicrobial treatment. Data analysis was conducted using SPSS-26 software, employing Mann-Whitney U, chi-square, and Fisher exact tests. Results: During the study period, 60 out of 213 patients with hematological malignancies were admitted for antimicrobial treatment. The average age of the patients was 57.1 years, with fever being the most common symptom, reported in 63.3% of cases. We identified 24 cases of IFI, including three proven cases (Candida spp.) and 21 probable cases. Statistical analysis showed a lower mean neutrophil count in the IFI group compared to the non-IFI group (3862 versus 12881, P = 0.001) and a higher mortality rate (58.3% versus 27.8%, P = 0.031). Conclusions: Our study revealed that severe neutropenia is a significant risk factor for IFI, and the mortality rate associated with IFI remains high despite advances in the treatment of hematological malignancies.