National Multicenter Retrospective Study Research Articles

National Cohort of Compassionate Use of Meropenem–Vaborbactam: No Benefit over Meropenem for Pseudomonas aeruginosa

Background: Meropenem–vaborbactam (MEM-VAB) is a novel carbapenem-beta-lactamase-inhibitor combination that demonstrates activity against carbapenem-resistant (CR) Gram-negative bacteria, and more specifically KPC-producers, since vaborbactam is an effective inhibitor of KPC enzymes in vitro. This study aimed to describe the initial uses and efficacy of MEM-VAB for compassionate treatment during the first 21 months following its early access in France. Method: A national multicenter retrospective study was conducted, including all patients who received at least one dose of MEM-VAB between 20 July 2020, and 5 April 2022. Clinical characteristics and outcomes were collected using a standardized questionnaire. The minimum inhibitory concentration (MIC) of antimicrobials, and complete genome sequencing of bacteria were performed when bacterial isolates were available. Results: Ultimately, 21 patients from 15 French hospitals were included in the study. The main indication for MEM-VAB treatment was respiratory tract infections (n = 9). The targeted bacteria included Pseudomonas aeruginosa (n = 12), Klebsiella pneumoniae (n = 3), Enterobacter spp (n = 3), Citrobacter freundii (n = 1), Escherichia coli (n = 1), and Burkholderia multivorans (n = 1). Overall, no significant advantage of vaborbactam over meropenem alone was observed across all strains of P. aeruginosa in terms of in vitro susceptibility. However, MEM-VAB demonstrated a notable impact, compared to carbapenem alone, on the MIC for the two KPC-3-producing K. pneumoniae and B. multivorans. Conclusions: MEM-VAB seems effective as a salvage treatment in compassionate use, but vaborbactam was shown to lack benefits compared to meropenem in treating P. aeruginosa-related infections. Therefore, it is crucial to compare meropenem to MEM-VAB MICs, particularly for P. aeruginosa, before prescribing MEM-VAB.

Timing of coronary angiography in high-risk non-ST-elevation acute coronary syndrome: results from the Portuguese Registry for Acute Coronary Syndromes (ProACS).

Current guidelines recommend an early invasive coronary angiography (ICA) within 24 h of admission for high-risk patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). Nevertheless, meta-analyses failed to demonstrate a clear advantage of this strategy in reducing hard endpoints such as death or nonfatal myocardial infarction compared to a delayed approach. Thus, the optimal timing of ICA in high-risk NSTE-ACS remains undetermined. This study aimed to determine the optimal timing for ICA in high-risk NSTE-ACS, regarding 1-year all-cause mortality and cardiovascular rehospitalizations. We conducted a national multicenter retrospective study of high-risk NSTE-ACS patients included in the Portuguese Registry for Acute Coronary Syndromes. Patients were divided into three groups according to the time of ICA: within the first 24 h, between 24 and 48 h, and between 48 and 72 h. The incidence of in-hospital complications and mortality, 1-year mortality, and cardiovascular rehospitalizations were assessed. Of the 9949 patients included, 46.7% underwent early ICA. This was associated with a lower incidence of acute heart failure (8.5% vs. 11.1% vs. 11.5%, P < 0.001) and shorter length of stay (3 vs. 4 vs. 6 days, P = 0.012). It, however, did not reduce in-hospital complications or mortality (1.2 vs. 0.7 vs. 0.8%, P = 0.066). We also found no significant association with the composite endpoint of 1-year mortality or cardiovascular rehospitalization (15.1 vs. 15.9 vs. 15.7%, P = 0.887). Early ICA was associated with a lower incidence of acute heart failure and shorter length of stay, without a significant impact on 1-year mortality risk or cardiovascular rehospitalizations.

Midterm Outcome of Balloon-Expandable Covered Stenting of Femoral Access Site Complications.

Background: Vascular access site complications (VASCs) after endovascular interventions requiring a large-bore access are frequent and known to be associated with increased morbidity and mortality. Although balloon-expandable covered stents (BECSs) are increasingly used in such indications, their performance in this rather hostile territory is currently unknown. We aimed to evaluate the safety and efficacy of BECSs in common femoral artery (CFA) VASCs management. Methods: This is a national multicenter retrospective study of all patients who underwent BECS implantation of the CFA due to a VASCs after an endovascular procedure between January 2020 and May 2023 in major tertiary referral centers in Hungary. Operative data were collected and follow-up ultrasound examinations were performed. Our study is registered on ClinicalTrials.gov (NCT05220540) and followed the STROBE guidelines. Results: Of the 23 patients enrolled (13 females, mean age: 74.2 ± 8.6), technical success was achieved in 21 (91.3%) cases, with one perioperative death. After an average follow-up of 18.0 ± 11.4 months, another nine (39.1%) deaths occurred, and one was VASCs-associated. BECS occlusion was detected in one (4.3%) patient, being the only reintervention (4.3%) where revascularization was also achieved. Conclusions: Although BECS implantation for CFA VASCs is feasible with a relatively high technical success rate, the mortality rate is non-negligible. Until adequately evaluated, BECS implantation in such indications is to be used with caution, ideally only within the framework of a trial.

Prediction of hemorrhage rate after tonsil surgery in children based on random forest model

Objective:Hemorrhage after tonsil surgery in children is a serious and potentially life-threatening complication. The purpose of this study was to establish a risk warning model for hemorrhage after tonsil surgery in children through a national multi-center retrospective study, providing a basis for hierarchical management after tonsil surgery in children. Methods:Stratified sampling was performed on 8 854 children who underwent tonsillectomy under general anesthesia from 15 research centers in different provinces from January 15, 2022 to May 15, 2023. The sample size of this study was 2 724 cases, including 1 096 males and 1 628 females. Children were divided into bleeding and non-bleeding groups according to whether or not they had bleeding after surgery. The random forest algorithm was used to build a risk warning model. By continuously exploring the optimized model, the accuracy of predicting the postoperative bleeding rate of tonsils in children was improved, and the prediction effectiveness of the model was verified by ten-fold cross-validation. Results:Among 2 724 children, 117 had postoperative bleeding after tonsillectomy, with a bleeding rate of 4.30%. The model constructed by the random forest algorithm for the training set was verified in the test set, and the obtained prediction accuracy was 98.72%, the recall rate was 78.95%, and the area under the ROC curve AUC was 0.96. Conclusion:Although the recall rate of the random forest model needs to be improved, the overall accuracy is quite excellent. It can effectively avoid misjudging positive cases as negative cases. It is a useful tool that can be used to predict the postoperative bleeding rate of tonsils and clinical medical decision-making, laying a good foundation for subsequent optimization and improvement.

Childhood pancreatic neuroendocrine neoplasms: A national experience.

National multicenter retrospective study of all patients, aged from 0 to 17 years at diagnosis, treated from 2011 to 2020 for a pNEN and registered in the French National Registry of Childhood Cancers or FRACTURE database. Fifteen patients, 13 well-differentiated pancreatic neuroendocrine tumors (pNETs) and two neuroendocrine carcinomas (pNECs), were selected. Median age at diagnosis was 14 years (range, 7-17). Eight patients, all with localized disease, had a cancer predisposition syndrome (CPS), including five cases diagnosed during systematic screening. Five (31%) had metastatic disease at diagnosis: three grade 2 pNETs and two pNECs. First line therapy included exclusive pancreatectomy (seven cases, all M0), active surveillance (three cases, all M0), medical therapies (somatostatin analogues, chemotherapy; four cases, all M1), and surgery with medical therapy (one M1 case). Three-year progression-free survival was 57% (confidence interval [CI] 95%: 27-78) and was significantly better for patients with low-grade well differentiated (73vs. 0%; p<10-4) and localized (76vs. 20%; p=.02) tumors. The two patients with pNECs died. Three-year overall survival was 92% (CI95%: 59-99) and was significantly better in patients with low-grade tumor (100vs. 50%; p=10-4). Childhood pNENs occur more frequently in adolescents with CPS. Localized low-grade pNETs in children have a very good prognosis, whereas the treatment of high-grade and metastatic pNETs/pNECs should be better defined.

Prevalence of delivery mode in an Italian nationwide cohort with celiac disease: a SIGENP multicenter retrospective study (the CD-deliver-IT)

BackgroundStudies have indicated an association between cesarean section (CS), especially elective CS, and an increased risk of celiac disease (CD), but the conclusions of other studies are contradictory. The primary aim of this study (CD-deliver-IT) was to evaluate the rate of CS in a large population of CD patients throughout Italy. MethodsThis national multicenter retrospective study was conducted between December 2020 and November 2021. The coordinating center was the Pediatric Gastroenterology and Liver Unit of Policlinico Umberto I, Sapienza, University of Rome, Lazio, Italy. Eleven other referral centers for CD have participated to the study. Each center has collected data on mode of delivery and perinatal period of all CD patients referring to the center in the last 40 years.ResultsOut of 3,259 CD patients recruited in different Italian regions, data on the mode of delivery were obtained from 3,234. One thousand nine hundred forty-one (1,941) patients (60%) were born vaginally and 1,293 (40%) by CS (8.3% emergency CS, 30.1% planned CS, 1.5% undefined CS). A statistically significant difference was found comparing median age at time of CD diagnosis of patients who were born by emergency CS (4 years, CI 95% 3.40–4.59), planned CS (7 years, CI 95% 6.02–7.97) and vaginal delivery (6 years, CI 95% 5.62–6.37) (log rank p < 0.0001).ConclusionsThis is the first Italian multicenter study aiming at evaluating the rate of CS in a large population of CD patients through Italy. The CS rate found in our CD patients is higher than rates reported in the general population over the last 40 years and emergency CS seems to be associated with an earlier onset of CD compared to vaginal delivery or elective CS in our large nationwide retrospective cohort. This suggests a potential role of the mode of delivery on the risk of developing CD and on its age of onset, but it is more likely that it works in concert with other perinatal factors. Further prospective studies on other perinatal factors potentially influencing gut microbiota are awaited in order to address heavy conflicting evidence reaming in this research field.

Glucose metabolism outcomes after pituitary surgery in patients with acromegaly.

To investigate the impact of pituitary surgery on glucose metabolism and to identify predictors of remission of diabetes after pituitary surgery in patients with acromegaly. A national multicenter retrospective study of patients with acromegaly undergoing transsphenoidal surgery for the first time at 33 tertiary Spanish hospitals (ACRO-SPAIN study) was performed. Surgical remission of acromegaly was evaluated according to the 2000 and 2010 criteria. A total of 604 acromegaly patients were included in the study with a total median follow up of 91 months (interquartile range [IQR] 45-163). At the acromegaly diagnosis, 23.8% of the patients had diabetes mellitus (DM) with a median glycated hemoglobin (HbA1c) of 6.9% (IQR 6.4-7.9) [51.9 mmol/mol (IQR 46.4-62.8)]. In the multivariate analysis, older age (odds ratio [OR] 1.02, 95% CI 1.00-1.05), dyslipidemia (OR 5.25, 95% CI 2.81 to 9.79), arthropathy (OR 1.39, 95% CI 2.82 to 9.79), and higher IGF-I levels (OR 1.30, 95% CI 1.05 to 1.60) were associated with a greater prevalence of DM. At the last follow-up visit after surgery, 21.1% of the DM patients (56.7% of them with surgical remission of acromegaly) experienced diabetes remission. The cure rate of DM was more common in older patients (hazard ratio [HR] 1.77, 95% CI 1.31 to 2.43), when surgical cure was achieved (HR 2.10, 95% CI 1.01 to 4.37) and when anterior pituitary function was not affected after surgery (HR 3.38, 95% CI 1.17 to 9.75). Glucose metabolism improved in patients with acromegaly after surgery and 21% of the diabetic patients experienced diabetes remission; being more frequent in patients of older age, and those who experienced surgical cure and those with preserved anterior pituitary function after surgery.

Post-reduction observation and recurrence of pediatric intussusception in New Zealand: A national multicenter retrospective study

BackgroundIntussusception is the most common cause of preschool intestinal obstruction. International data suggest that following uncomplicated enema reduction, 4-hour observation with prompt return to oral diet is safe. We aimed to investigate the rate and timing of intussusception recurrence across Aotearoa New Zealand, compared to the cost of routine post-reduction observation. MethodsWe performed a national 15-year retrospective, multicenter cohort study of all children treated for intussusception between 01 Jan 2007 and 01 Jan 2022 across AoNZ. A robust clinical dataset was collected using a REDCap proforma. We also investigated the financial and time costs of current in-hospital observation practices. ResultsDuring this period, primary enema reduction without general anesthetic was successful in 339 cases, requiring a median of 2 attempts (1–8). The median age was 0.8 years; 70.8% were male, and 17.1% were Māori. The median length of hospital stay was 25.9 h, primarily comprised of post-reduction observation (21.6 h). Intussusception recurrence within 30 days occurred in 29 children (8.5%) at a median time of 24.7 h post-reduction. Of the 19 cases recurring before discharge, 12 (3.5%) recurred between 4 and 24 h. The median observation period for those with successful primary enema reduction was 21.6 h; if reduced to 4 h, savings of NZD 883,632 (USD 529,825) and 7342 ward hours were possible. ConclusionsNationally, the intussusception recurrence rate after uncomplicated enema reduction was 8.5%, but only 3.5% occurred between the 4–24 hour period post-reduction. Expediting discharge by avoiding routine overnight observation appears safe and economically viable.

Neoadjuvant immune checkpoint inhibitors for patients with resectable stage III/IV melanoma: A nationwide real-life study in France (NEOMEL).

9578 Background: Several studies have shown the efficacy of neoadjuvant treatment (NT) with immune checkpoint inhibitors (ICI) for resectable stage III/IV melanoma. However, real-life data are lacking. Methods: NEOMEL is a national multicenter retrospective study assessing the efficacy and tolerability of NT with ICI (NT-ICI) for resectable metastatic melanoma in a real-life setting. Data were obtained in patients (pts) with resectable stage III/IV melanoma who initiated NT-ICI (at least one infusion). Primary endpoint was pathologic complete response (pCR) (i.e no residual tumor) rate. Secondary endpoints were pathologic response (pR) according to INMC, radiologic response (RECIST), safety profile (CTCAE) and survival outcomes. Results: A total of 166 pts with resectable stage III/IV melanoma were included. Median age was 67 years (range, 24-96). Most pts had primary cutaneous melanoma (n=157, 89%), stage IIIB-D disease (n=156, 94%); a BRAF V600-mutant melanoma was observed in 47% (n=78); 8% (n=14) pts had received a previous systemic treatment. The median number of infusions of NT-ICI was 3 (range, 1-5). ICI regimens were anti-PD-1 monotherapy (n=122, 73%) or nivolumab + ipilimumab (NIVO + IPI) (n=44, 27%). Median follow-up was 6.5 months (range, 1-85). Overall, 143 pts (86%) underwent surgery. A pCR was observed in 44% of pts (n=63/143), including 52% (n=51/99) treated with anti-PD-1 monotherapy, and 27% (n=12/44) treated with NIVO + IPI. Of note, 78 pts (54%) were treated with 3 infusions of pembrolizumab (PBZ) (according to SWOG 1801 protocol) and had a pCR in 45% (n=35). A pR was assessed according to INMC criteria in 58% of pts (n=83/143): 51% of pCR (n=42), 8% of near-pCR (n=7) corresponding to a major pR of 59% (n=49/83), 16% of pathologic partial response (n=13) and 25% of pathologic non-response (n=21). Twenty-three pts (14%) did not undergo surgery because of progressive disease (n=10), clinical and radiologic responses (8 complete responses, 1 partial response, 1 stable disease), toxicity (n=2) or patient’s choice (n=1). Radiologic overall response rate according to RECIST (data available after NT in 49% of pts) was 54% (n = 44/82). All grade immune-related adverse events (irAEs) of NT-ICI occurred in 31% (n=51) of pts, including grade 3-4 irAEs in 10% (n=17) and one grade 5 irAE (pneumonitis with PBZ). Severe irAEs (grade 3 or more) were observed in 4% (n=4/99) of pts treated with anti-PD1 monotherapy and 32% (n=14/44) of pts treated with NIVO + IPI. Adjuvant treatment was started for 120 pts (84%). At last follow-up, 26 pts (18%) have had recurrence after surgery, including 3 pts with a pCR and 23 pts with a non-pCR to NT-ICI. Survival data are not yet available. Conclusions: NT-ICI for advanced melanoma demonstrated its efficacy with high rates of pCR in a real-life setting and an acceptable safety profile, particularly NT anti-PD1 monotherapy.

Use of Eculizumab in Pediatric Patients with High-Risk Transplantation-Associated Thrombotic Microangiopathy: Outcomes and Risk Factors Associated with Response and Survival. A Retrospective Study on Behalf of the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC)

Transplantation-associated thrombotic microangiopathy (TA-TMA) is associated with high morbidity and mortality. Although survival has improved significantly with the introduction of eculizumab, the need for improvement remains, especially in high-risk patients. This study aimed to describe the results obtained with eculizumab in a pediatric cohort with the attempt to define which risk factors could determine the response to treatment. We designed a national multicenter retrospective study of children treated with eculizumab for high-risk TA-TMA. The study cohort comprised 29 patients who had undergone a first (n = 28) or second (n = 1) allogeneic hematopoietic stem cell transplantation (HSCT) for malignant (n = 17) or nonmalignant (n = 12) disease. The median time from HSCT to TA-TMA diagnosis was 154 days (interquartile range [IQR], 103 to 263 days). Eleven patients (38%) who were initially diagnosed with low- to intermediate-risk TA-TMA progressed to high-risk TA-TMA (hrTA-TMA), within a median time of 4 days (IQR, 1 to 33 days). SC5b-9 was increased in 90% of 20 patients in whom it was measured. Renal (n = 12), pulmonary (n = 1), and intestinal (n = 1) biopsy confirmed the diagnosis in 12 of 14 patients (85%). Seventeen patients (58%) had extrarenal involvement with serositis (n = 13; 44,8%), pulmonary (n = 12; 41,4%), gastrointestinal (n = 8; 27.6%), cardiovascular (n = 7; 24.1%), or central nervous system (CNS) (n = 2; 6.9%) involvement. The median time from hrTA-TMA diagnosis to the initiation of eculizumab was 7 days (IQR, 1 to 8 days). Overall, 19 patients (65.5%) responded to eculizumab, of whom 17 (58.6%) achieved a complete response and 2 (6.9%) achieved a partial response. The remaining 10 patients (34.5%) did not show any of response. The overall response rate to eculizumab for TA-TMA was 27.59% (95% confidence interval [CI], 14.87% to 47.66%) at 1 month, 55.17% (95% CI, 38.43% to 73.48%) at 3 months, and 62.07% (95% CI, 45.10% to 79.13%) at 6 months after eculizumab initiation. In multivariate analysis, the pulmonary involvement decreased the probability of response (hazard ratio [HR], .18; P = .0298). The 1-year overall survival (OS) was 55.2% (95% CI, 35.6% to 71.0%) for the whole cohort and 83.3% (95% CI, 56.7% to 94.3%) for patients who responded to eculizumab. Pulmonary involvement (HR, 14.93; P = .0043) and CNS involvement (HR, 8.63; P = .0497) were associated with a statistically significant decrease in survival. We found that patients diagnosed with hrTA-TMA with pulmonary involvement had a poor response to eculizumab, and that patients with pulmonary and CNS involvement had significantly decreased survival. Given these results, we hypothesize that providing eculizumab therapy at an early stage of the disease before organ damage is established might significantly improve the response and, consequently, survival.

Central Precocious Puberty in Italian Boys: Data From a Large Nationwide Cohort.

There are only a few nationwide studies on boys with central precocious puberty (CPP) and the last Italian study is a case series of 45 boys that dates back to 2000. We aimed to evaluate the causes of CPP in boys diagnosed during the last 2 decades in Italy and the relative frequency of forms with associated central nervous system (CNS) abnormalities on magnetic resonance imaging (MRI) compared to idiopathic ones. We performed a national multicenter retrospective study collecting data from 193 otherwise normal healthy boys with a diagnosis of CPP. Based on MRI findings, the patients were divided into: Group 1, no CNS abnormalities; Group 2, mild abnormalities (incidental findings) unrelated to CPP; and Group 3, causal pathological CNS abnormalities. The MRI findings show normal findings in 86%, mild abnormalities (incidental findings) in 8.3%, and causal pathological CNS abnormalities in 5.7% of the cases. In Group 3, we found a higher proportion of patients with chronological age at diagnosis < 7 years (P = .00001) and body mass index greater than +2 SDS (P < .01). Gonadotropin-releasing hormone analogue therapy was started in 183/193 subjects. The final height appeared in the range of the target height in all groups and in 9 patients in whom the therapy was not started. In our study on a large nationwide cohort of boys referred for precocious puberty signs, the percentage of forms associated with CNS abnormalities was one of the lowest reported in the literature.

Congenital Duodenal Obstruction: National Trends in Management and Outcomes during the Last Quarter of a Century in Norway.

During the last quarter of a century, new surgical techniques in neonates have been introduced, and neonatal intensive care has developed. Few studies have explored the implementation of new techniques and if outcomes in neonates undergoing gastrointestinal surgery have improved in the last decades. Therefore, this study aimed to investigate possible changes in postoperative outcomes and surgical techniques in all neonates operated for congenital duodenal obstruction (CDO) 1995 to 2020 in Norway. This is a national multicenter retrospective study of all neonates undergoing surgery for CDO in Norway from 1995 to 2020. Results from three periods (1995-2003, 2004-2012, and 2013-2020) were compared. The study was approved by the local data protection officers (2020/13386) and (2020/15125). We included 186 patients: 41 in period 1 (1995-2003), 83 in period 2 (2004-2012), and 62 in period 3 (2013-2020). Seventy (38%) neonates had Down syndrome and 104 (62%) had additional malformations/disorders. Birth weight, gender, frequency of Down syndrome, and other malformations/disorders did not differ between the three periods. We observed an increased rate of prenatal diagnosis throughout the study period (p < 0.001). The only change in surgical technique was the increased use of transanastomotic feeding tubes (p < 0.001). Length of stay, postoperative complication rate, days with parenteral nutrition, and 30-day mortality rate were stable over time. Perioperative treatment and postoperative outcomes in neonates with CDO have been surprisingly unchanged during the last quarter of a century. Only an increased rate of prenatal diagnosis and more frequent use of transanastomotic feeding tubes were observed.

Infant Botulism, Israel, 2007–2021

Infant botulism (IB) is an intestinal toxemia that manifests as descending paralysis, constipation, and, in some cases, respiratory failure. Laboratory-confirmed IB cases are rare, and recent data in Israel are lacking. We conducted a national multicenter retrospective study of laboratory-confirmed IB cases reported in Israel during 2007-2021. A total of 8 cases were reported during the study period. During 2019-2021, incidence may have increased because of a cluster of 5 cases. Infant median age for diagnosis was 6.5 months, older than previously reported (3 months). Most cases occurred during March-July. Honey consumption was reported in 1 case, and possible environmental risk factors (living nearby rural or construction areas, dust exposure, and having a father who works as a farmer) were reported in 6 cases. Although IB is rare, its incidence in Israel may have increased over recent years, and its epidemiology and risk factors differ from cases reported previously in Israel.

Cardiac arrest in non-ST segment elevation myocardial infarction: what to expect

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Ischemic heart disease is the leading cause of cardiac arrest (CA). While in ST segment elevation myocardial infarction its approach is well defined, in non-ST segment elevation myocardial infarction (NSTEMI) it is still a matter of debate. This study aimed to characterize patients with NSTEMI and out-of-hospital CA and to evaluate its prognosis. Methods This was a national multicenter retrospective study of patients hospitalized for NSTEMI undergoing coronary angiography (ANG) between October 2010 and September 2019. Results Out of a total of 9544 patients, 96 were admitted after CA. The baseline characteristics of both groups were similar, with the exception of more past history of heart failure (10,5% vs 5,6%, p=0,038) and peripheral artery disease (11,5% vs 5,9%, p=0,023) in patients with CA. In the peri-arrest period, 64,6% of the patients reported chest pain. Patients with CA had worse left ventricular ejection fraction (49±13% vs 53±12%, p=0,006), ended up reaching higher Killip classes more often and needing more inotropic and mechanical support. The median time from admission to ANG was similar in both groups (0 (0;3) vs 1 (0;2) days, p=0,796). CA patients had more multivessel coronary disease (66% vs 55,5%, p=0,043) and left main artery involvement (25,3% vs 11,2%, p&amp;lt;0,001). The proportion of revascularization procedures was similar. During hospitalization, patients with CA were less treated with beta-blockers (77,9% vs 85,2%, p=0,046) and ACE inhibitors (77,7% vs 86,1%, p=0,018), a difference that disappeared at discharge. However, statin prescription at discharge was lower in CA patients (88,3% vs 94,4%, p=0,040). In a multivariate analysis for events occurred during hospitalization, CA was associated with a significant increase in myocardial reinfarction (adjusted OR 5,42 (95% CI 2,10-1,98)), stroke (adjusted OR 5,38 (95% CI 1,24-2,32)) and death (adjusted OR 13,86 (95% CI 5,98-32,17)). After excluding patients with indication for an immediate invasive strategy, we verified that mortality was higher in CA patients who underwent ANG in the first 24 hours. CA was not associated with a significant increase in the 1-year mortality rate (adjusted HR 0,67 (95% CI 0,10-4,90)). Conclusions In this study, NSTEMI patients surviving CA had more severe coronary events. CA was independently associated with a significant increase in in-hospital major adverse events. However, during the 1-year follow-up there was no significant increase in mortality.

Evaluation of the diagnosis and treatment of cesarean scar pregnancy induced in the second trimester: a national multicenter retrospective study

Objective: To study the risk factors of adverse pregnancy outcomes for induced abortion of cesarean scar pregnancy in midtrimester. Methods: A national multicenter retrospective study was conducted. A total of 154 singletons pregnant women with cesarean scar pregnancy during the second trimester induced abortion by various reasons in 12 tertiary A hospitals were selected, their pregnant outcomes were observed and the risk factors of serious adverse outcomes were analyzed with univariate and multivariate logstic regression; the role of ultrasound and MRI in predicting placenta accreta and severe adverse outcomes was evaluated, the effectiveness of uterine artery embolization (UAE) in preventing hemorrhage in pregnant women with and without placenta accreta was compared. Results: Among 154 subjects, the rate of placenta accreta was 42.2% (65/154), the rate of postpartum hemorrhage≥1 000 ml was 39.0% (60/154), the rate of hysterectomy was 14.9% (23/154), the rate of uterine rupture was 0.6% (1/154). The risk factor of postpartum hemorrhage≥1 000 ml and hysterectomy was placenta accreta (P<0.01). For each increase in the number of parity, the risk of placenta accreta increased 2.385 times (95%CI: 1.046-5.439; P=0.039); and the risk of placenta accreta decreased with increasing ultrasound measurement of scar myometrium thickness (OR=0.033, 95%CI: 0.001-0.762; P=0.033). The amount of postpartum hemorrhage and hysterectomy rate in the group with placenta accreta diagnosed by ultrasound combined with MRI were not significantly different from those in the group with placenta accreta diagnosed by ultrasound only or MRI only (all P>0.05). For pregnant women with placenta accreta, there were no significant difference in the amount of bleeding and hysterectomy rate between the UAE group [median: 1 300 ml; 34% (16/47)] and the non-embolization group (all P>0.05); in pregnant women without placenta accreta, the amount of bleeding in the UAE group was lower than that in the non-embolization group (median: 100 vs 600 ml; P<0.01), but there was no significant difference in hysterectomy rate [2% (1/56) vs 9% (3/33); P>0.05]. Conclusions: (1) Placenta accreta is the only risk factor of postpartum hemorrhage≥1 000 ml with hysterectomy for induced abortion of cesarean scar pregnancy in midtrimester; multi-parity and ultrasound measurement of scar myometrium thickness are risk factors for placenta accreta. (2) The technique of using ultrasound and MRI in predicting placenta accreta of cesarean scar pregnancy needs to be improved. (3) It is necessary to discuss of UAE in preventing postpartum hemorrhage for induced abortion of cesarean scar pregnancy in midtrimester.

Persistence and Severity of Cutaneous Manifestations in IgA Vasculitis Is Associated with Development of IgA Vasculitis Nephritis in Children

Background/Objective: The purpose of this study was to evaluate the prevalence and severity of skin involvement in children with IgA vasculitis (IgAV) and its relationship with clinical and biochemical parameters and the risk of developing IgA vasculitis nephritis (IgAVN), the only cause of long-term morbidity and the main prognostic factor in IgAV patients. Methods: This national multicenter retrospective study included 611 patients under the age of 18 years with IgAV referred to five Croatian tertiary hospitals between 2009 and 2019. Patient data were collected from a database with systematic analysis of IgAV patients in the Croatian population. Results: Among the 611 children, 205 (33.55%) had purpura on the lower extremities, in 207 (33.88%) the rash extended on the trunk, in 149 (24.39%) it extended to the upper extremities, in 32 (5.24%) the rash was generalized, while 15 (2.47%) had the most severe skin symptoms: bullae, ulcerations, and necroses. IgAVN developed in 130 (21.28%) and persistent IgAVN (present for >3 months) in 48 (7.86%) children. Multivariate logistic regression found that presence of ulcerations and necroses (OR 3.20 [95% CI 1.03–9.91]), persistent purpura (OR 2.89 [95% CI 1.71–4.88]), and higher age (OR 1.16 [95% CI 1.09–1.23]) were significant predictors of IgAVN, whereas persistent purpura (OR 20.11 [95% CI 1.09–372.52]), male sex (OR 3.32 [95% CI 1.13–9.80]), and higher age (OR 1.15 [95% CI 1.00–1.30]) were predictors of persistent IgAVN. Among the laboratory parameters, higher serum urea (OR 1.43 [95% CI 1.03–2.00]) and reduction in activated partial thromboplastin time (OR 0.83 [95% CI 0.74–0.93]) were shown to have a significant impact on increasing the risk of persistent IgAVN. Conclusion: With increasing severity and duration of cutaneous manifestations in IgAV, the risk of developing IgAVN increases, making the prognosis worse, with a greater likelihood to need more aggressive treatment.

Invasive Fungal Infections in Immunocompromised Children: Novel Insight Following a National Study

To obtain a national overview of the epidemiology and management of invasive fungal infections (IFIs) in France for severely immunocompromised children who were treated for acute leukemia or had undergone allogeneic hematopoietic stem cell transplantation (a-HSCT). We performed a national multicenter retrospective study to collect epidemiologic data for proven and probable IFIs in children with acute leukemia under first- line or relapse treatment or who had undergone a-HSCT. We also conducted a prospective practice survey to provide a national overview of IFI management in pediatrichematology units. From January 2014 to December 2017, 144 cases of IFI were diagnosed (5.3%) in 2721 patients, including 61 cases of candidiasis, 60 cases of aspergillosis, and 23 cases of infection with "emergent" fungi, including 10 cases of mucormycosis and 6 cases of fusariosis. The IFI rate was higher in patients with acute myelogenous leukemia (12.9%) (OR, 3.24; 95% CI, 2.15-4.81; P < .0001) compared with the rest of the cohort. Patients undergoing a-HSCT had an IFI rate of only 4.3%. In these patients, the use of primary antifungal prophylaxis (principally fluconazole) was associated with a lower IFI rate (OR, 0.28; 95% CI, 0.14-0.60; P=4.90 ×10-4) compared with a-HSCT recipients who did not receive antifungal prophylaxis. The main cause of IFI in children receiving prophylaxis was emergent pathogens (41%), such as mucormycosis and fusariosis, which were resistant to the prophylactic agents. The emerging fungi and new antifungal resistance profiles uncovered in this study should be considered in IFI management in immunocompromised children.

Improved transplant outcomes with myeloablative conditioning for hemophagocytic lymphohistiocytosis in HLA-matched and mismatched donors: a national multicenter retrospective study.

We report the results of national retrospective study of 45 children with hemophagocytic lymphohistiocytosis (HLH) who underwent allogeneic hematopoietic stem-cell transplantation (HSCT) in Israel between the years 2000-2018. Donors were either HLA-matched (n = 26), partially mismatched (n = 7), haploidentical (n = 8), or cord-blood (n = 4). Myeloablative conditioning (MAC) was used in 20 procedures, and reduced-intensity conditioning (RIC) in 25. Forty-two patients engrafted, two had primary graft failure (one successfully retransplanted), one died prior to engraftment, and two developed secondary graft failure. Of the eight patients who had mixed donor chimerism at day 30 (5-95%), five achieved stable mixed or full donor chimerism. The 5-year probabilities of overall survival and event-free survival (EFS) were 86% and 82%, respectively. Five-year EFS was lower for patients receiving RIC compared to MAC (72% vs. 100%, p = 0.018) and following alternative-donor transplant (68% vs. 92% for HLA-matched donors, p = 0.034), mostly due to increased transplant-related mortality (TRM). Thus, both HLA-matched and alternative donor transplant procedures may benefit form a myeloablative conditioning regimen.

Treatment Efficacy and Outcomes in HIV-Related Plasmablastic Lymphoma: The Results of Multicenter Retrospective Study in Russia

Background Plasmablastic lymphoma (PbL) is a rare and aggressive B-cell malignancy highly associated with HIV. Despite improved understanding of this disease, its prognosis remains poor with short overall survival. There is no standard of care for this entity. Recent advances in the treatment of HIV-associated and aggressive lymphomas have not yet significantly improved the outcomes of patients with PbL. Methods We investigate epidemiological characteristics and the results of the treatment of the HIV-related PbL in large cohort of HIV-related lymphoma patients for a 7-year period (2014-2020). During the observation period, 22 cases of HIV-related PbL were registered in three centers and selected for the analysis from the national multicenter retrospective study database. The median follow-up was 17,8 (4-57,4) months. Results The PbL accounted for 8,9% of lymphomas in HIV-infected patients (22/247). The median age was 42 years (32-61), males - 9 (41%). Most of the patients (n=19, 86%) had III-IV stages and B-symptoms were present in 8 patients (36%). CNS involvement was diagnosed in 8 patients (36%). The median of ECOG score was I (I-III). Half of patients had viral hepatitis as a co-infection including HCV (n=9), HCV and HBV (n=1), HCV, HBV and HDV (n=1). HIV and lymphoma were diagnosed simultaneously in 7 patients (32%). Median time from HIV infection to the lymphoma onset was 4 years (1,5 month - 17,5 years). The only one patient did not receive cART for an unknown reason. The median number of CD4+ cells at the moment of chemotherapy (CT) started was 151 cell/mcl (13 - 374). Frontline CT were following: CHOP±E - 9 (41%), EPOCH - 11 (50%), hyper-CVAD - 1 (4,5%), dexamethasone - 1 (4,5%). Bortezomib was added to frontline treatment in 3 (13,6%) patients, HDC with auto-HSCT had been done as a first line therapy in 2 (9%) patients. A total of 16 patients responded to the first line therapy with the overall response rate (ORR) of 72,7% including CR and PR in 4 (18,2%) and 12 (54,5%) patients respectively. Remaining patients had progression disease (n=5, 22,8%) and stable disease (n=1, 4,5%). The median course to achieve the ORR was 4 (2-6) cycles. Overall (OS) and progression-free survival (PFS) at 2 years after first line treatment was 59,1% and 40,9%, respectively. The median time to progression (TTP) was 7,95 (0,33-23,93) months. The addition of bortezomib and auto-HSCT in first line chemo improved OS (100% vs 47,1%, p=0,027), but non PFS (p=0,1) and TTP (p=0,4). Nine patients received second-line CT: DHAP - 4 (44,4%), ICE - 4 (44,4%), EPOCH - 1 (11,2%). Response was evaluated in 8 patients. CR, PR and progression disease was registered in 1 (12,5%), 2 (25%) and 5 (62,5%) patients respectively. PBSC harvesting was only successful in 1 of 3 cases (33%) and this patient received HDC with auto-HSCT. OS and PFS at 2 years after second line treatment was 44,4% and 22,2%, respectively. Two years after second line CT, 4 patients were still alive, including those after ICE, EPOCH (n=2), HDC with auto-HSCT (n=1) and nivolumab (27 cycles) as a third line therapy (n=1). Conclusions In a large cohort of patients PbL accounted for 8.9% of all HIV-related lymphomas. Bortezomib-containing chemotherapy and first line auto-HSCT show encouraging results, but data are obtained in a small group of patients. Prospective studies are needed for optimization of HIV-related plasmablastic lymphoma therapy. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: The is early clinical date on efficiency of Bortezomib in patients with plasmablastic lymphoma: https://doi.org/10.1111/bjh.15156

Pregnancy and Delivery in Women with Lower Urinary Tract Reconstruction: A National Multicenter Retrospective Study from the French-Speaking Neuro-Urology Study Group (GENULF) and the Neuro-Urology Committee of the French Association of Urology.

Management of pregnancy and delivery in women with lower urinary tract reconstruction is challenging and the currently available literature is insufficient to guide clinical practice. We report pregnancy and delivery outcomes in this specific population. We conducted a national multicenter retrospective study (16 centers) including 68 women with 96 deliveries between 1998 and 2019. These women had at least 1 successful pregnancy and delivery after augmentation enterocystoplasty, catheterizable channel creation and/or artificial urinary sphincter implantation. Maternal and fetal complications during pregnancy and delivery were reported, as well as postpartum functional outcomes, according to the delivery mode. The chi-square test and Student's t-test were used to compare categorical and continuous variables, respectively. Overall 32% of reported pregnancies were complicated by febrile urinary tract infections, 13.5% by renal colic and 14.6% required upper urinary tract diversion. In addition, 10% of patients reported transient self-catheterization difficulties and 13.5% reported de novo or increased urinary incontinence. The preterm delivery rate was 35.3%. Elective C-section was performed in 61% of pregnancies. Twenty complications occurred during delivery (20%), including 19 during elective C-section. Urinary continence at 1 year was unchanged for 93.5% of deliveries. Delivery mode (p=0.293) and multiparity (p=0.572) had no impact on urinary continence. In this population C-section appeared to be associated with a high risk of complications. In the absence of any obstetric or neurological contraindications, vaginal delivery should be proposed as the first line option to the majority of these women.