Multicenter Retrospective Observational Study Research Articles

Multicenter evaluation of ceftazidime-avibactam use in carbapenem-resistant Klebsiella pneumoniae bloodstream infections in OXA-48 endemic regions

Data in the literature on the use of ceftazidime-avibactam (CAZ-AVI) in carbapenem-resistant Klebsiella pneumoniae bloodstream infections (CRKP-BSIs) are limited especially in OXA-48 (Oxacillinase-48) predominant regions. Our study aimed to evaluate the effect of CAZ-AVI use on outcomes in CRKP-BSIs in Turkey, where OXA-48 is endemic. A multicenter retrospective observational study was conducted between January 2017 and September 2021. The effects of clinical and treatment characteristics on 30-day mortality and relapse in CRKP-BSIs were analyzed. Predictors of outcomes were detected using a Cox regression model. The study enrolled 106 adults with CAZ-AVI-sensitive CRKP-BSIs who received CAZ-AVI for at least 72 h. Patients who received CAZ-AVI as initial therapy had lower mortality rates when compared to those who switched from last resort regimens [14.3% (n = 3/21) vs. 37.7% (n = 32/85), p = 0.04]. In multivariate analysis, older age and severe neutropenia were detected to be associated with higher mortality, significantly. Initiation of CAZ-AVI on the day of blood culture was obtained, was found to be significantly associated with lower mortality (HR: 0.25, CI: 0.07–0.84, p = 0.025). CAZ-AVI monotherapy is an important treatment option for CRKP-BSIs in OXA-48 endemic areas. Early initiation of CAZ-AVI should be preferred rather than switching from a last-resort regimen as it profoundly improves the survival rates.

Radiolucent lines and revision risk in total knee arthroplasty using the conventional versus the Attune S+ tibial baseplate.

This multicentre retrospective observational study's aims were to investigate whether there are differences in the occurrence of radiolucent lines (RLLs) following total knee arthroplasty (TKA) between the conventional Attune baseplate and its successor, the novel Attune S+, independent from other potentially influencing factors; and whether tibial baseplate design and presence of RLLs are associated with differing risk of revision. A total of 780 patients (39% male; median age 70.7 years (IQR 62.0 to 77.2)) underwent cemented TKA using the Attune Knee System) at five centres, and with the latest radiograph available for the evaluation of RLL at between six and 36 months from surgery. Univariate and multivariate logistic regression models were performed to assess associations between patient and implant-associated factors on the presence of tibial and femoral RLLs. Differences in revision risk depending on RLLs and tibial baseplate design were investigated with the log-rank test. The conventional and novel Attune baseplates were used in 349 (45%) and 431 (55%) patients, respectively. At a median follow-up of 14 months (IQR 11 to 25), RLLs were present in 29% (n = 228/777) and 15% (n = 116/776) of the tibial and femoral components, respectively, and were more common in the conventional compared to the novel baseplate. The novel baseplate was independently associated with a lower incidence of tibial and femoral RLLs (both regardless of age, sex, BMI, and time to radiograph). One- and three-year revision risk was 1% (95% CI 0.4% to 1.9%)and 6% (95% CI 2.6% to 13.2%), respectively. There was no difference between baseplate design and the presence of RLLs on the the risk of revision at short-term follow-up. The overall incidence of RLLs, as well as the incidence of tibial and femoral RLLs, was lower with the novel compared to the conventional tibial Attune baseplate design, but higher than in the predecessor design and other commonly used TKA systems.

Epidemiology of paediatric winter sports-related injuries in France: The WINTRAUMA-1 retrospective cohort study.

To describe the epidemiology of injuries related to winter sports in patients younger than 15 years in France. We conducted a retrospective observational multicentre cohort study of patients younger than 15 years who were seen by mountain-community general practitioners for winter-sports injuries in 1999-2022. Of the 108 619 patients (mean age, 11.4 ± 2.8 years), 76 724 (70.6%), 26 186 (24.1%) and 2132 (2.0%) were injured while skiing, snowboarding and sledding, respectively. Helmet use was noted in 50 164 (46.2%) patients and increased over time but remained low among sledders. A collision was the mechanism in 12.3% of patients overall and 32.1% of sledders. The most common injuries overall were wrist fractures (48.5%), head and trunk injuries (42.3%), and anterior cruciate ligament (ACL) tears (23.7%), with wrist fractures being more common in beginners (24.7%) and head/trunk injuries and ACL tears in advanced participants (18.3% and 2.6%, respectively). Only 3699 (3.4%) patients were admitted after the general-practitioner visit, notably for leg or ankle fractures (9.5%). Winter sports-related injuries vary according to age, sex, skill level and sport. Admission rates are low but might be further decreased by better prevention. Protective measures should be tailored to each sport and individual.

Reduction Rate of Uric Acid in Blood During Continuous Renal Replacement Therapy for Acute Kidney Injury: A Multicenter Retrospective Observational Study

Introduction: Continuous renal replacement therapy (CRRT) eliminates these small solutes with equal efficacy under the same conditions. However, variations in the reduction rates of these solutes observed in patients with CRRT are likely influenced by factors other than removal through CRRT. This study evaluated the reduction rates of these small solutes during CRRT and their possible association with mortality. Methods: This study used the data of limited patients registered in the CHANGE study, which is a large retrospective observational study on CRRT management across 18 Japanese ICUs. Reduction rates of three solutes in blood, calculated on the 1st and 2nd days, were compared in patients with acute kidney injury (AKI) treated by CRRT. The potential association between solute reduction rates and mortality during CRRT or within 7 days after the termination of CRRT was evaluated. Results: In total, 163 patients with AKI were included in the analysis. The reductuin rates of uric acid (UA) were significantly higher than those of urea and creatinine for the 1st and 2nd tests in the entire cohort. Receiver operating curve (ROC) analysis revealed that lower UA reduction rates were significantly associated with mortality during CRRT or within 7 days after CRRT termination (area under the ROC curve: 0.62 [95% confidence interval {CI} 0.52–0.71] for the 1st test and 0.63 [95%CI 0.54–0.72] for the 2nd test). After adjusting for age and SOFA score, a significant association was observed between lower UA reduction rates and hospital mortality for both tests. Conclusion: Among the small solutes, UA reduction rates in patients with AKI treated with CRRT were notably higher than those of creatinine and urea. Furthermore, the significant association between lower UA reduction rates and mortality suggests that UA reduction rate may serve as a valuable indicator of insufficient removal of uremic solutes by CRRT, although the decline in UA production must be taken into account.

Long-term clinical outcomes informed by artificial intelligence-enabled single-lead ECG detection of reduced ejection fraction

Abstract Background * Reduced left ventricular ejection fraction (LVEF) is linked to poor clinical outcomes (1, 2). * Despite its increasing prevalence, reduced LVEF is often undetected due to resource-limited echocardiography and lack of suitable point-of-care diagnostic tools. * Previous studies have shown that an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm can accurately identify patients with reduced LVEF, but may also offer novel insights on long-term prognosis (3, 4). Purpose We aimed to determine if an AI-ECG algorithm designed for detecting reduced LVEF can also independently predict 2-year major adverse cardiovascular events (MACE) and all-cause mortality. Method * A retrospective multicentre observational study investigating the ability of AI-ECG to predict long-term clinical outcomes (i.e. over two years' follow up). * Analysis included a total of 1,007 consecutive unselected patients attending for routine echocardiography, with a single-lead ECG recording performed at the same time. * An AI-ECG algorithm, designed to identify impaired LVEF, was applied to each single-lead ECG. * Occurrence of MACE and all-cause mortality associated with AI-ECG results (Figure 1) was investigated using Cox regression; evaluating performance of AI-ECG results as a classifier (0 or 1) and as a probability score (0 to 1). * The study was approved by the UK Health Research Authority (reference 21/LO/0051). Results * The mean age was 62.3 years. 52.4% of patients were male and 57.5% of patients were White. * Appropriately, patients with a positive AI-ECG had a higher MACE rate compared to those with a negative AI-ECG (34.2% vs. 11.9%; adjusted hazard ratio (aHR) 2.02; 95% CI, 1.46 – 2.81; p < 0.005), primarily driven by increased mortality (23% vs. 9.6%; p < 0.0001; aHR 1.65; 95% CI, 1.12 – 2.43) and heart failure hospitalization (14.5% vs. 1%; p < 0.0001) – Figure 2. * AI-ECG probability score (per 10% increase) was significantly associated with MACE (aHR 1.17; 95% CI, 1.09 – 1.25; p < 0.005) and all-cause mortality (aHR 1.11; 95% CI, 1.02 – 1.20; p = 0.01). * Importantly, sub-analysis of AI-ECG for those who have a normal LVEF (i.e. ≥50%) continued to show association between positive AI-ECG and MACE (27.2% vs. 11.9%; p < 0.0001; aHR 1.70, 95% CI 1.17 – 2.48) and all-cause mortality (20.4% vs. 9.6%; p < 0.0001; aHR 1.53, 95% CI 1.00 – 2.36). Conclusion An AI-ECG algorithm designed to identify impaired LVEF can identify patients at risk of MACE and all-cause mortality from single-lead ECG screening – regardless of their LVEF. Such results may enable further risk stratification for cardiovascular investigations through the simple addition of single-lead ECG recording.

Effectiveness and safety of levodopa-entacapone-carbidopa infusion in Parkinson disease: A real-world data study.

Levodopa-entacapone-carbidopa intestinal gel (LECIG) infusion is a recently developed device-aided therapy for advanced Parkinson disease (PD) patients. The aim of this study was to report real-world evidence about the effectiveness, tolerability, and safety of LECIG in PD patients. A multicenter observational retrospective study of the first patients who initiated LECIG in Spain was performed. All neurologists with an experience of at least two patients treated until 30 March 2024 were invited to participate. Data about effectiveness and safety from the medical records (V0, pre-LECIG; V1, initiation of LECIG; V2, post-LECIG follow-up) with a total of 246 variables were collected. Seventy-three PD patients (61.6% males, 70.1 ± 9.1 years old) from 21 Spanish centers with a mean disease duration of 14.4 ± 6.3 years (range = 5-31) were included. Twenty-six patients (35.6%) were switched directly from levodopa-carbidopa intestinal gel. The mean exposure to LECIG was 177.3 ± 110.5 days (range = 7-476). The mean daily OFF time decreased from 5.2 ± 3 (pre-LECIG) to 1.9 ± 1.8 (post-LECIG; n = 66, p < 0.0001). Global improvement was observed in >85% of the patients. No significant change was detected in the levodopa equivalent daily dose from V0 to V2. Only 7% received 24-h infusion, and 24.7% required more than one cartridge per day at V2. Thirty-four patients (46.6%) had at least one adverse event related to LECIG and/or the device system. Five patients (6.8%) discontinued LECIG. LECIG was safe and effective in advanced PD patients.

Flexible bronchoscopy-assisted removal of aspirated scarf pins from the tracheobronchial tree: the experience of 146 subjects.

Aspiration of scarf pins is a common problem in specific geographical locations where the Muslim population is high, especially in countries like Egypt, Bangladesh, Middle Eastern countries, and certain regions in India. This condition is also referred to as hijab-pin syndrome. We discuss the largest experience of flexible bronchoscopic extraction of aspirated scarf pins from the tracheobronchial tree. A multicenter retrospective observational study was conducted on 146 patients from 4 different centers in Egypt, Bangladesh, India, and Germany. Flexible bronchoscopy was successful in the extraction of aspirated scarf pins in all 146/146 patients with a 100% success rate. 136/146 (93.15%) patients were females, with the most common age group between 12 and 18 years (34.24%). 132/146 (90.4%) remembered the aspiration event before coming to the hospital. Cough was the predominant presenting symptom. (71.22%). In all 146 cases, the foreign body was identified on a standard chest X-ray. The left main bronchus was the most common site of aspiration, 67/146 (45.89%), followed by the right main bronchus, 56/146 (38.35%). 14 patients (9.58%) had a history of unsuccessful attempts to remove by rigid bronchoscopy, and flexible bronchoscopy was successful in these 14 (100%) patients who had a prior unsuccessful attempt to remove. The current series is the largest in literature and demonstrated an excellent success rate in the removal of the aspirated scarf pin.

Identification of novel sub-phenotypes of severe ARDS requiring ECMO using latent class analysis

BackgroundSub-phenotyping of acute respiratory distress syndrome (ARDS) could be useful for evaluating the severity of ARDS or predicting its responsiveness to given therapeutic strategies, but no studies have yet investigated the heterogeneity of patients with severe ARDS requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO).MethodsWe conducted this retrospective multicenter observational study in adult patients with severe ARDS treated by V-V ECMO. We performed latent class analysis (LCA) for identifying sub-phenotypes of severe ARDS based on the radiological and clinical findings at the start of ECMO support. Multivariate Cox regression analysis was conducted to investigate the differences in mortality and association between the PEEP setting of ≥ 10 cmH2O and mortality by the sub-phenotypes.ResultsWe identified three sub-phenotypes from analysis of the data of a total of 544 patients with severe ARDS treated by V-V ECMO, as follows: Dry type (n = 185; 34%); Wet type (n = 169; 31%); and Fibrotic type (n = 190; 35%). The 90-days in-hospital mortality risk was higher in the patients with the Fibrotic type than in those with the Dry type (adjusted hazard ratio [95% confidence interval] 1.75 [1.10–2.79], p = 0.019) or the Wet type (1.50 [1.02–2.23], p = 0.042). The PEEP setting of ≥ 10 cmH2O during the first 3 days of ECMO decreased the 90-days in-hospital mortality risk only in patients with the Wet type, and not in those with the Dry or Fibrotic type. A significant interaction effect was observed between the Wet type and the PEEP setting of ≥ 10 cmH2O in relation to the 90-day in-hospital mortality (pinteraction = 0.036).ConclusionsThe three sub-phenotypes showed different mortality rates and different relationships between higher PEEP settings in the early phase of V-V ECMO and patient outcomes. Our data suggest that we may need to change our management approach to patients with severe ARDS during V-V ECMO according to their clinical sub-phenotype.

Simultaneous versus staged approach in transcatheter aortic valve implantation for severe stenosis and endovascular aortic repair for thoracic and abdominal aortic aneurysm.

Thoracic/abdominal aortic aneurysms(T/AAAs) and aortic stenosis(AS) may be concomitant diseases requiring both transcatheter aortic valve implantation(TAVI) and endovascular aneurysm repair(T/EVAR) in high risk patients for surgical approaches, but temporal management is not clearly defined, yet. Aim of the study was to analyze outcomes of simultaneous vs staged TAVI and T/EVAR. Retrospective observational multicentre study on patients requiring TAVI and T/EVAR from 2016 to 2022. Patients were divided into 2 groups: "Simultaneous group" if T/EVAR+TAVI were performed in the same procedure and "Staged group" if T/EVAR and TAVI were performed in two steps, but within 3 months. Primary outcomes were: technical success, 30-day mortality/major adverse events and follow-up survival. Secondary outcomes were procedural metrics and length of stay (LOS). Forty-four cases were collected; 8(18%) had TEVAR and 36(82%) EVAR, respectively. Upon temporal determination 25(57%) and 19(43%) were clustered in simultaneous and staged groups, respectively. In staged group, median time between procedures was 72(interquartile-range-IQR : 57-87) days. Preoperative and intraoperative figures were similar. There was no difference in 30-day mortality(Simultanoeus : 0/25 vs Staged : 1/19; p = 0.43). Pulmonary events(Simultaneous : 0/25 vs Staged : 5/19; p = 0.01) and need of postoperative cardiac pacemaker(Simultaneous : 2/25 vs Staged : 7/19; p = 0.02) were more frequent in Staged patients. The overall LOS was lower in Simultaneous group[Simultaneous : 7(IQR : 6-8) vs Staged : 19(IQR : 15-23)days; p = 0.001]. The median follow-up was 25(IQR : 8-42) months and estimated 3-year survival was 73% with no difference between groups(Simultanoeus : 82% vs Staged : 74%; p = 0.90). Both simultaneous or staged T/EVAR and TAVI procedures are effective with satisfactory outcomes. Despite the small numbers, simultaneous repair seems to reduce length-of-stay and pulmonary complications, maintaining similar follow-up survival.

Clinical Significance of Prior Ramucirumab Use on the Effectiveness of Nivolumab as the Third-Line Regimen in Gastric Cancer: A Multicenter Retrospective Study.

Because vascular endothelial growth factor inhibition has been suggested to improve immune cell function in the cancer microenvironment, we examined whether using ramucirumab (RAM) before nivolumab usage is more effective in advanced gastric cancer. This was a multicenter retrospective observational study. We analyzed patients who received nivolumab monotherapy as the third-line regimen for unresectable advanced or recurrent gastric cancer between October 2017 and December 2022. They were divided into the RAM (RAM-treated) group and the non-RAM (non-treated) group according to the RAM usage in the second-line regimen. The primary outcome was to compare the overall survival after nivolumab administration in the third-line regimen between the RAM and non-RAM groups. Fifty-two patients were included in the present study: 42 patients in the RAM group and ten patients in the non-RAM group. The median overall survival was significantly longer in the RAM group than in the non-RAM group (8.5months vs 6.9months, p<0.05). In the RAM group, patients without peritoneal metastasis had significantly better median overall survival than those with peritoneal metastasis (23.8months vs 7.7months, p=0.0033). Multivariate Cox-proportional hazards analyses showed that the presence of peritoneal metastasis (hazard ratio, 2.4; 95% confidence interval 1.0-5.7) alone was significantly associated with overall survival in the RAM group. The use of RAM prior to nivolumab monotherapy may contribute to prolonged survival in patients with gastric cancer, especially those without peritoneal metastasis.

Impact of a novel-covered colonic stent in obstructive colon cancer.

Although the short-term outcomes of bridge-to-surgery (BTS) procedures using self-expandable metal stents are favorable, concerns remain regarding worsened prognosis due to tissue injury in the tumor area. Herein, we describe a newly developed covered stent, the Kawasumi Jabara colonic stent™, designed to reduce tissue damage/injury associated with stent-related complications in BTS procedures. This study aimed to evaluate the efficacy and safety of the Kawasumi Jabara colonic stent as a BTS for obstructive colorectal cancer (OCC). This multicenter retrospective observational study included 44 OCC patients who underwent BTS with stents at four facilities between September 2020 and November 2022. The groups of patients receiving the Kawasumi Jabara and non-covered colonic stents were designated Groups C and NC, respectively. Treatment outcomes related to stent placement and surgery were compared using propensity score matching (PSM) analysis. Groups NC and C (n = 34 and 10, respectively) showed no significant differences in sex, age, tumor location, histological type, Colorectal Obstruction Scoring System (CROSS) score, or cStage; however, the stent placement duration was shorter in Group C. No significant differences were found in terms of the technical and clinical success rates for stent placement. Stent dislocation was observed in 0 and 2 cases in Groups C and NC, respectively. PSM analysis between eight cases, each from Groups C and NC, revealed no significant differences in stent-related or surgical outcomes between the groups. However, regarding the gross injury score in the resected specimens, Group C had a lower score than Group NC (1.8 vs. 5.5), and the proportion of pathological tissue injury involving deeper layers was also lower in Group C (37.5% vs. 100%). Compared to conventional non-covered stents, the Kawasumi Jabara colonic stent™ demonstrated favorable safety during stent insertion, retention, and surgery, with only mild tissue injury.

Safety of the use of dinoprostone gel and vaginal insert for induction of labor: A multicenter retrospective cohort study.

To assess adverse obstetric and neonatal outcomes associated with the use of dinoprostone for induction of labor, with particular attention on categories for which caution is recommended by the Italian Medicines Agency and the European Medicine Agency. A retrospective multicenter observational study was conducted on a population of 1687 patients undergoing induction of labor with vaginal dinoprostone (gel or insert) between August 2019 and June 2022. Patients were subdivided based on maternal age, gestational age, and obstetric disorders. Data regarding the mode of delivery, the incidence of tachysystole, and the obstetric and perinatal outcomes were collected. The main adverse event associated with the use of dinoprostone was tachysystole. However, tachysystole was not associated with an increased risk of cesarean section (CS), neonatal intensive care (NICU) admission, low 1-min Apgar, or umbilical cord acidosis. Maternal age greater than 35 years, gestational age greater than 40 weeks, and obstetric disorders were not associated with an increased rate of tachysystole, NICU admission, low 1- and 5-min Apgar scores, and cord acidosis. The only associated adverse outcomes in those categories were postpartum hemorrhage with age greater than 35 years and tachysystole with gestational diabetes mellitus and hypertensive disorders. Not a single case of severe outcome (disseminated intravascular coagulation, uterine rupture, maternal and fetal death) was reported in the cohort. Providing there is adequate maternal and fetal surveillance, in an inpatient setting, dinoprostone could be safely administered for the induction of labor and considered appropriate in high-risk pregnancies. Tachysystole can be self-identified by the patient and effectively managed.

The efficacy and safety of a novel PD-1/CTLA-4 bispecific antibody cadonilimab (AK104) in advanced non-smallcell lung cancer: A multicenter retrospective observational study.

For patients with advanced non-small cell lung cancer (NSCLC) who have received frontline immunochemotherapy, subsequent treatment options are limited. As the first dual programmed cell death-1 (PD-1)/cytotoxic T lymphocyte-associated antigen-4 bispecific antibody approved globally, cadonilimab demonstrated potential antitumor activity in advanced NSCLC patients resistant to anti-PD-1/PD-L1 antibodies. We retrospectively collected efficacy and safety data from advanced NSCLC patients treated with cadonilimab-based regimens in later therapy lines. A total of 41 advanced NSCLC patients refractory to anti-PD-1/PD-L1 therapy were enrolled. More than half of the patients received cadonilimab-based regimen as a fourth or later line of treatment. At the data cutoff date, treatment efficacy could be evaluated in 23 patients. One patient (4.3%) achieved partial response, eight patients (34.8%) experienced stable disease, and 14 patients (60.9%) progressed. The objective response rate and disease control rate were 4.3% and 39.1%, respectively. The median progression-free survival for all evaluated patients was 108.0 days. Due to the short follow-up period, the median overall survival has not yet been reached. Treatment-related adverse events (TRAEs) and immune-related AEs occurred in 63.4% and 22% patients, respectively. The most common TRAEs included gamma-glutamyl transferase elevation (17.1%), coughing (14.6%), and fatigue (12.2%). Five patients (12.2%) experienced grade ≥3 TRAEs. In this heavily pretreated cohort of advanced NSCLC patients, cadonilimab-based regimens showed moderate antitumor efficacy with a generally tolerable and manageable safety profile. However, more evidence is needed to support the administration of cadonilimab in NSCLC patients refractory to previous anti-PD-1/PD-L1 therapy.

The effect of male factors on embryo morphokinetics: a retrospective analysis of 2726 blastocysts.

Male infertility may influence fertilization rates, embryo morphology, and implantation rates in in vitro fertilization (IVF) cycles. Oocyte competence plays a major role in embryo development, but there is a limited understanding of the connection between sperm quality, embryo development, and morphokinetic parameters using donor oocytes. The study evaluated if sperm quality may influence the morphokinetic parameters in IVF cycles. A retrospective multicentric observational cohort study included 747 ICSI cycles using donor oocytes with fresh or frozen sperm. Embryos were cultured in time-lapse incubators until the blastocyst stage. The population was divided into three groups according to sperm concentration, as control group (> 16 mill/mL), severe oligospermia (0-5 mill/mL), and moderate oligospermia group (5-16 mill/mL). Morphokinetic analysis showed no difference in the time from the 2-cell to 6-cell stage of embryo development. A significant difference was observed on day 3 of embryo development, specifically at the 7-cell stage (t7), severe oligospermia 53.37 ± 9.81, moderate oligospermia 56.95 ± 9.78, and control 55.1 ± 8.85h post-insemination (hpi) (p = 0.024), and 8-cell stage (t8), severe oligospermia 55.41 ± 10.83, moderate oligospermia 61.86 ± 12.38 hpi (p < 0.001), and control 58.61 ± 11.33. Accordingly, the synchrony of the four cleavages going from 4 to 8 cells (s3) was found statistically different among the groups in the severe oligospermia 8.05 ± 9.99, moderate oligospermia 11.66 ± 11.04 hpi, and control 8.55 ± 8.58 (p = 0.009). Morphokinetic time ranges were obtained for t6, t7, t8, and s3 in order to identify the good-quality blastocysts. Poor sperm quality is associated with alterations in morphokinetic parameters on day 3 in IVF cycles with donor oocytes, underlining the important role of spermatozoa during embryo development.

Clinical Efficacy of Isatuximab Plus Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients.

Isatuximab, a novel anti-CD38 monoclonal antibody, is approved in combination with carfilzomib and dexamethasone (Isa-Kd) in relapsed/refractory multiple myeloma (RRMM) patients. Because of its recent introduction, real-world efficacy and safety are poorly reported. In this Italian multicenter real-life observational retrospective study, efficacy and safety of the Isa-Kd regimen were evaluated in a cohort of 103 RRMM patients. Overall response rate (ORR) was 85%, with stringent (sCR) or complete response (CR) in 18% of cases and very good partial response (VGPR) in 39%. Median PFS and OS were not reached within the study period, while 1-year PFS and OS were 72% and 77%, respectively. Hematological toxicities were observed in 42% of subjects, and cardiac toxicities occurred in 24% of cases. Moreover, we conducted a subanalysis on patients (N = 69) treated with Isa-Kd after one prior line of therapy, showing an ORR of 88%, with sCR + CR in 20% of subjects, VGPR in 46%, and PR in 22% of patients. In this group, median PFS and OS were not reached, while 1-year PFS and OS were 92% and 95%, respectively. In conclusions, our study confirmed Isa-Kd as an effective treatment option for RRMM with a manageable safety profile even in real-life settings.

Tranexamic Acid in Pediatric Traumatic Brain Injury: A Multicenter Retrospective Observational Study

ObjectiveTranexamic acid (TXA) can be used after trauma to prevent bleeding. Our goal was to examine the impact of TXA on morbidity and mortality for children with severe traumatic brain injury (TBI). MethodsWe identified children aged <18 years with a severe TBI [Glasgow Coma Scale score <8) presenting to one of the 291 hospitals contributing to the Japanese Trauma Data Bank between 2019 and 2023. The primary outcomes was in-hospital death and the secondary outcome was poor neurologic outcome defined with Glasgow Outcome Scale score of 1–3 at hospital discharge. Our primary exposure was any TXA administered in the hospital. Using propensity score-based inverse probability weighting, we used logistic regression to measure the association between TXA administration and death as well as poor neurologic outcome. ResultsOf the 342 included patients, 30 (14%) died and 102 (45%) had a GCS score <8 at discharge. After inverse propensity weighting, TXA administration was not associated with either mortality [adjusted odds ratio (aOR) 1.25, 95% confidence interval (CI) 0.61–2.54) or poor neurologic outcome (aOR 0.86, 95% CI 0.47–1.56). ConclusionsTXA administration was not associated with either death or poor neurologic outcome. Prospective clinical trials of TXA usage in children with severe TBI are needed.

Chromosomal abnormalities in oocyte donor candidates: a French survey of over 8200 karyotypes.

To study karyotypes of more than 8,200 oocyte donor candidates in nulliparous or multiparous women compared to a reference population. A retrospective observational multicentric study. The study included two cohorts of oocyte donor candidates recruited between January 2005 and October 2021: multiparous women with at least one child at the time of recruitment, and nulliparous women. Both were compared to a reference population composed of female newborns from literature. Not applicable. Blood lymphocyte karyotype. A total of 8229 oocyte donor candidates from 22 fertility centers were included in this study. Nulliparous women (n=1890) and multiparous ones (n=6339) were compared to 8102 female newborns. Overall, 65 candidates were carriers of chromosomal abnormalities and were therefore excluded from the donation process (0.79%, 95% CI: 0.60-0.98). The occurrence of balanced structural chromosomal rearrangements was globally increased in the study population (0.49%, 95% CI: 0.34-0.64) compared to female newborns (0.24%, 95% CI: 0.34-0.64, p=0.0086). The number of reciprocal translocations was increased 5-fold in nulliparous oocyte donor candidates (0.37%, 95% CI: 0.10-0.64, p=0.013). The incidence of sex chromosome mosaicism was notably increased in multiparous oocyte donor candidates, with 17 cases (0.27%, 95% CI: 0.14-0.40, p=0.0052). Among chromosomal aberration carriers only two nulliparous women (one reciprocal translocation and one sex chromosome mosaicism) had fertility issues with a diagnosis of premature ovarian failure. In this comprehensive 16-years French experience of karyotyping in oocyte donor candidates, we confirmed an increased incidence of balanced structural chromosomal rearrangements, especially among those without children at the time of recruitment. Karyotyping could be considered to identify any chromosomal abnormalities that may not be easily detectable through medical questioning. These abnormalities pose an inherent genetic risk for gamete recipients if left undetected.

Diagnostic accuracy of percutaneous transthoracic needle biopsy among peripheral pulmonary lesions: a multicenter observational study

Introduction: The diagnosis of peripheral pulmonary lesions (PPL) poses a significant challenge, prompting the widespread utilization of various modalities to ensure the precision in diagnosis. This study aims to assess the diagnostic accuracy of computed tomography-guided percutaneous transthoracic needle biopsy (CT-PTNB) in the context of pulmonary malignancy. Methods and materials: This multicenter retrospective observational study, included 1317 cases of CT-PTNB performed on adult patients with PPLs from January 2018 to December 2022 in Mashhad, Iran. The pathology results of CT-PTNB from 94 cases were compared to the definitive pathology results obtained through methods such as surgery to assess the sensitivity, specificity, and overall accuracy of CT-PTNB in diagnosing of pulmonary malignancy. Results: CT-PTNB exhibits an accuracy of 82.98%, with sensitivity and specificity rates of 75.41 and 91.43%, respectively. This study underscores the issue of false-negative results in CT-PTNB and underscores the importance of integrating clinical, radiological, and additional diagnostic modality to guide diagnostic decisions. Conclusion: In this large-scale multicenter study, the accuracy of CT-PTNB for diagnosis of pulmonary malignancy is acceptable but fairly low compared to previous studies.

Causes, Diagnostic Testing, and Treatments Related to Clinical Deterioration Events Among High-Risk Ward Patients.

Timely intervention for clinically deteriorating ward patients requires that care teams accurately diagnose and treat their underlying medical conditions. However, the most common diagnoses leading to deterioration and the relevant therapies provided are poorly characterized. We aimed to determine the diagnoses responsible for clinical deterioration, the relevant diagnostic tests ordered, and the treatments administered among high-risk ward patients using manual chart review. This was a multicenter retrospective observational study in inpatient medical-surgical wards at four health systems from 2006 to 2020. Randomly selected patients (1000 from each health system) with clinical deterioration, defined by reaching the 95th percentile of a validated early warning score, electronic Cardiac Arrest Risk Triage, were included. Clinical deterioration was confirmed by a trained reviewer or marked as a false alarm if no deterioration occurred for each patient. For true deterioration events, the condition causing deterioration, relevant diagnostic tests ordered, and treatments provided were collected. Of the 4000 included patients, 2484 (62%) had clinical deterioration confirmed by chart review. Sepsis was the most common cause of deterioration (41%; n = 1021), followed by arrhythmia (19%; n = 473), while liver failure had the highest in-hospital mortality (41%). The most common diagnostic tests ordered were complete blood counts (47% of events), followed by chest radiographs (42%) and cultures (40%), while the most common medication orders were antimicrobials (46%), followed by fluid boluses (34%) and antiarrhythmics (19%). We found that sepsis was the most common cause of deterioration, while liver failure had the highest mortality. Complete blood counts and chest radiographs were the most common diagnostic tests ordered, and antimicrobials and fluid boluses were the most common medication interventions. These results provide important insights for clinical decision-making at the bedside, training of rapid response teams, and the development of institutional treatment pathways for clinical deterioration.

Utility of pan-immune-inflammation value as a predictor of the prognosis of childhood lupus.

Systemic lupus erythematosus (SLE) is a chronic inflammatory multisystemic disease. Monitoring disease activity thoughtout the disease course is important for effective management and assessment of disease outcome. To assess whether the pan-immune inflammation value (PIIV) at diagnosis could predict organ involvement and disease activity in childhood SLE (cSLE) patients after 12months of disease onst. This is an observational retrospective multicenter study that comprised cSLE patients seen and followed at the participating centers between January 2010 and December 2022. All patients met the EULAR/ACR-19 criteria, were immunosuppressive drug-naïve at the time of SLE diagnosis and had a minimal follow-up period of 12months. The data included clinical and laboratory findings and disease activity using the SLEDAI-2K. Receiver operating characteristic (ROC) curves were employed to determine the optimal cut-off value of PIIV and assess its predictive potential for disease activity, and organ involvement. A total of 125 patients (104 female) with a median age of 16.0 (IQR 5.6) years, a median age at disease onset of 10.9 (IQR 3.0) years, and a median disease duration of 4.8 (IQR 5.3) years were included. The most frequent involved organs at diagnosis were hematological (89.6%), musculoskeletal (68.8%), mucocutaneous (63.2%), and renal (58.4%). However, at a 12-month follow-up visit, the most frequent involved organs were renal (40.0%), hematological (39.2%), musculoskeletal (15.2%), and mucocutaneous (10.4%). The median PIIV at diagnosis was 139 (IQR 229.6), while the median SLEDAI was 12 (IQR 6.5) and 3.5 (IQR 7.0) at diagnosis and 12months, respectively. An optimal PIIV cut-off of 250 was found to be a predicative for disease activity, with a sensitivity of 45% and a specificity of 86%. The study revealed that the PIIV successfully predicted four systems in our cohort of patients. Our work suggests the PIIV might be a reasonable predictor for organ involvement and disease activity in newly diagnosed cSLE, though further research, particularly larger studies, is required to validate these findings, especially regarding organ involvement.