Retrospective Cohort Analysis Research Articles

Epidemiological trends and socioeconomic factors in malignant peripheral nerve sheath tumors with rhabdomyoblastic differentiation: A National Cancer Database study.

e23562 Background: Malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation, also called a malignant triton tumor (MTT) is both a rare and aggressive form of cancer with both the features of peripheral nerve sheath tumors as well as rhabdomyoblasts with high recurrence rates. There is a higher risk of patients with neurofibromatosis type 1 (NF1) developing MTT. Radiation can be used to excise higher grade large MTT, however, chemotherapy still has no consensus on efficacy. Despite the rarity of MTT with rhabdomyoblastic differentiation, increased efforts to understand epidemiological trends could increase overall understanding of the malignancy. Methods: We extracted data from 50 patients diagnosed with MTT(ICD-9561-3) using the 2004-2020 National Cancer Database (NCDB) to perform a retrospective cohort analysis. We focused on various demographic factors including age, sex, race, Hispanic status, income status, educational status, insurance status, facility type and location, distance from facility, and Charleson-Deyo score using descriptive statistics. Regression analysis was used to identify incidence trends. Results: In our study of 50 patients diagnosed with MTT, a majority of the patients were male (62%), identified as White, and were of non-Spanish/non-Hispanic (90%) ethnicity. The average age at diagnosis was 49 years (SD = 20, range = 3-90) most and patients were treated in academic/research facilities (32%) or integrated network cancer programs (18%). Most patients (48%) had private insurance, with a significant number relying on government-funded programs (44%). The majority of patients (88%) underwent surgery as their primary treatment, with 30% having no residual tumor post-surgery. Additional treatments included radiation therapy (38%), chemotherapy (34%) and the most frequent primary site was the retroperitoneum (30%).The average survival time post-treatment was 35 months, with a survival rate of 43% at 2 years, 23% at 5 years, and a 15% at 10 years. Patients qualified for the top quartile of median housing income( $74,063 ≈). Conclusions: This study is the first analysis of patients with MTT, using the NCDB. It fills a gap in our understanding of this rare and aggressive disease. The majority of MTT patients were male, Caucasian, with an average age at diagnosis of 49 years, which supports previous case report descriptions. In addition, this study reveals the socio-economic factors associated with these patients who mostly earned a median income of $74,063 or more, were insured primarily by private insurance or managed programs (48%), and were treated predominantly in academic or research institutions (32%). It is necessary to continue research to further understand the influence of demographic and socio-economic factors on the diagnosis, treatments, and overall survival of patients with MTT.

Cardiotoxicity from bruton tyrosine kinase inhibitors (BTKi)—an analysis of an administrative health claims database

BackgroundFirst generation Bruton tyrosine kinase inhibitors (BTKi) such as ibrutinib have been associated with cardiovascular toxicities. Newer generation BTKi (e.g.,acalabrutinib and zanabrutinib) have been associated with lower incidence of cardiotoxicity in clinical trials.ObjectiveGiven paucity in real-world data on the overall cardiac risk factor profile, especially with the newer BTKi, our study evaluated the incidence of cardiotoxicity with various BTKi among a large, commercially insured population of patients.MethodsWe performed a retrospective cohort analysis of all adults with a diagnosis of B-cell malignancy undergoing treatment with BTKi acalabrutinib and ibrutinib between January 2018 and June 2020 using Optum’s de-identified Clinformatics® Data Mart Database. We then identified patients who had pre-existing cardiac disease one year prior to starting BTKi. New incidence of atrial fibrillation/flutter, hypertension, bleeding, ventricular tachycardia/fibrillation and sudden cardiac death from the time of index presciption were compared with standard Chi Square or Student t-test where appropriate. Multivariate logistic regression models were also estimated to evaluate for confounding.ResultsA total of 1691 patients were included in the final analysis. 1595 (94%, median age 75 (19–90) years, 61% male gender) patients received ibrutinib, and 96 (6%, median age 73.5 (32–90) years, 62.5% male gender) patients received acalabrutinib. The median duration of drug exposure of ibrutinib was 238 (2-1084) days vs. 150 (30–870) days for acalabrutinib. There was lower new incidence of atrial fibrillation/flutter (4.6%-vs-17%, p = 0.013), hypertension (6.3%-vs-25%, p = NS), sudden cardiac arrest/death (0% vs. 1.5%, p = NS) in the acalabrutinib group compared to ibrutinib, of which only the lower incidence of atrial fibrillation/flutter was statistically significant. This was despite the finding of a higher prevalence of atrial fibrillation/flutter at baseline in patients receiving acalabrutinib.ConclusionsThere was lower incidence of new atrial fibrillation/flutter with acalabrutinib when compared to ibrutinib in a real-world cohort of patients.

In the fight against HIV/AIDS: the arduous implementation of government-funded pre-exposure prophylaxis programme in Taiwan

IntroductionThe government-funded pre-exposure prophylaxis (PrEP) programme was targeted to those aged under 30 years or serodiscordant couples and implemented in September 2018–October 2020 in Taiwan. The study aimed to examine...

Oncology Drug Approvals Under Health Canada’s Notice of Compliance With Conditions Policy: A Retrospective Cohort Analysis

Health Canada’s Notice of Compliance with conditions (NOC/c) policy provides expedited access to promising new therapies for serious conditions. This retrospective cohort analysis sought to examine the use of the NOC/c policy for oncology drugs, to determine whether confirmatory studies are aligned with the approved indication, and to assess the impact of the NOC/c policy by quantifying the number of oncology drugs approved under this policy that become the standard of care treatment for their respective indications. The findings suggest that Health Canada’s NOC/c policy has been successful in providing expedited access to promising new therapies. However, ensuring that confirmatory trials are under way at the time of NOC/c issuance may provide assurance that studies addressing the uncertainty associated with NOC/c will not be unnecessarily prolonged. The inclusion of real-world evidence (RWE) as part of confirmatory evidence may help fill gaps.

Real-world assessment of longitudinal opioid use and healthcare resource utilization in patients undergoing colorectal resection

Liposomal bupivacaine (LB) has been used in multimodal pain management regimens to improve postsurgical analgesia. This retrospective cohort analysis assessed clinical and economic outcomes of LB vs non-LB analgesia in minimally invasive colorectal resection surgery using real-world patient data from the IQVIA linkage claims databases. Patients who received LB were 1:1 matched to patients who did not receive LB (non-LB) via propensity scores. Outcomes included opioid use during the perioperative (2 weeks before surgery to 2 weeks after discharge), continued (>2 weeks to 3 months after discharge), and persistent (>3 months to 6 months after discharge) periods and healthcare resource utilization (HRU) during the first 3 months after discharge. Mean opioid consumption was lower in the LB (n = 4397) versus non-LB (n = 4397) cohort perioperatively (483 vs 538 morphine milligram equivalents [MMEs]; P = 0.001) and after discharge within ∼3 months (222 vs 328 MMEs; P < 0.0001) and 3–6 months (245 vs 384 MMEs; P < 0.0001). The LB cohort had shorter mean length of stay (5.2 vs 5.7 days; P < 0.0001) and fewer inpatient readmissions (odds ratio [OR], 0.71; P < 0.0001), emergency department visits (OR, 0.78; P < 0.0001), and outpatient/office visits (OR, 0.91; P = 0.028) than the non-LB cohort 3 months after discharge. These data suggest use of LB in minimally invasive colorectal resection surgery may reduce perioperative and postdischarge opioid use as well as HRU. Although additional studies are needed to confirm these findings, this analysis provides valuable real-world data from large claims databases to evaluate clinical and economic outcomes that complement other types of retrospective and prospective studies.

Granuloma annulare and the risk of autoimmune conditions: a multi-center retrospective cohort analysis.

Granuloma annulare and the risk of autoimmune conditions: a multi-center retrospective cohort analysis.

Vasoreactivity and inhaled treprostinil response in interstitial lung disease pulmonary hypertension

IntroductionDespite shared features with pulmonary arterial hypertension, acute vasoreactivity in pulmonary hypertension with interstitial lung disease (PH-ILD) is not well characterized, including its potential ability to predict therapeutic outcomes. We sought to determine if acute vasoreactivity in PH-ILD to oxygen (O2) and inhaled nitric oxide (iNO) predicts inhaled treprostinil (iTre) outcomes.Materials and MethodsIn this retrospective cohort analysis, we identified treatment-naïve PH-ILD patients with vasoreactivity testing using O2 and O2+iNO. Six-month iTre outcome was assessed. “iTre improvement” required fulfillment of criteria on objective assessment without clinical worsening. “iTre failure” was defined by lack of objective improvement or a clinical worsening event.ResultsAmong 75 PH-ILD patients, mPAP decreased by −3 mmHg (−12.6%) and PVR by −1.3WU (−23.7%) with O2+iNO. With O2+iNO, mPAP decreased ≥10 mmHg to &lt;40 mmHg in 4 patients (5.3%), and 23 (30.7%) had ≥20% reduction in mPAP and PVR. Among 33 iTre-treated patients, there were 13 improvements and 20 failures. The microvascular response, measured by distensibility, to O2 aloneversusO2+iNO correlated with 6-month iTre outcome. Patients with 6-month iTre improvement had large relative distensibility increases with O2+ iNO (versusfailure, 76.0%versus15.3%, p=0.004). Conversely, iTre failure was associated with increased distensibility with O2 alone (versusimprovement, 26.8%versus−3.9%, p=0.045).ConclusionsIn PH-ILD, the microvascular response to O2versusO2+iNO testing was associated with six-month iTre outcome, likely reflecting the differential contributions of hypoxic vasoconstriction and remodeling. Acute vasoreactivity may inform therapeutic decision-making in PH-ILD.

Body Mass Index Greater Than 46 Associated With Increased Risk of 30 Day Complications Following Adult Tonsillectomy: A Retrospective Cohort Study.

Background: The study aimed to identify data-driven body mass index (BMI) thresholds that are associated with varying risk of 30 day complications following adult tonsillectomy. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was utilized to conduct a retrospective cohort analysis of patients undergoing adult tonsillectomy from 2005 to 2019. Stratum-specific likelihood ratio (SSLR) analysis was conducted to determine data-driven BMI strata that maximized the likelihood of 30 day complications following adult tonsillectomy. Patient demographics and clinical comorbidities were compared using chi-squared analysis and student t tests, where appropriate, for each stratum. Multivariable regression analysis was conducted to confirm association between identified data-driven strata with 30 day complication rates. Results: In total, 44,161 patients undergoing adult tonsillectomy were included in this study. SSLR analysis identified 2 BMI categories: 18 to 45 and 46+. Relative to the 18 to 45 BMI cohort, the 46+ BMI cohort was more likely to have 30 day all-cause complications after surgery [odds ratio (OR): 1.62, P = .007]. Specifically, the 46+ BMI cohort had significantly higher odds for 30 day major medical complications (OR: 2.86, P = .001), pulmonary domain complications (OR: 1.86, P = .041), unplanned reintubation (OR: 2.65, P = .033), and deep vein thrombosis (OR: 6.54, P = .026). Conclusions: We identified a BMI threshold of 46+ that was associated with a significantly increased risk of 30 day all-cause complications following adult tonsillectomy. These BMI strata can guide preoperative planning and risk-stratifying models for predicting 30 day complications in tonsillectomy surgery.

Postoperative Delirium Screening Characteristics in Pediatric Intestinal, Liver, and Renal Transplant Recipients: Single-Center Retrospective Cohort Study.

To describe and compare the results of delirium screening in the immediate post-transplant PICU admission for pediatric intestinal, liver, and renal transplant recipients. We also examined associations with known and suspected risk factors for pediatric delirium (PD). Retrospective analysis of a single-center cohort, 2016-2022. Twenty-four-bed PICU in a high-volume transplant center. All intestinal, liver, and renal transplant recipients under 23 years old admitted between July 2016 and August 2022. We identified 211 pediatric transplant recipients: intestinal (n = 36), liver (n = 78), and renal (n = 97). Results of the Cornell Assessment for PD during the immediate post-transplant PICU admission were reviewed and patients were categorized into screen positive, screen negative, and unscreened. Corresponding data on known and suspected risk factors for PD were also collected. Data on delirium subtypes were not collected. Screens were available for 156 of 211 patients (74%) who were included in the final analysis. The prevalence of a positive screen by transplant category was: intestine 80% (24/30), liver 75% (47/63), and renal 14% (9/63). A positive screen was associated with younger age, greater duration of mechanical ventilation, and greater PICU length of stay (LOS) in bivariate analysis. In multivariable analysis, age and PICU LOS remained strongly correlated with a positive screen (p < 0.05). Deep sedation and agitation as categorized by the State Behavioral Scale was associated with a positive screen, as was significant iatrogenic withdrawal symptoms (p < 0.05). Most patients screened positive by post-transplant days 2 and 3 (58/80 [72%] and 64/80 [80%], respectively). In our 2016 to 2022 experience, we found a high prevalence of positive PD screens in pediatric intestinal and liver transplant recipients in the immediate post-transplant PICU admission. A positive screen was associated with younger age and greater PICU LOS.

African American patients have a higher probability of cognitive impairment after incident stroke: An analysis of national electronic health record data

BackgroundCognitive impairment (CI) and stroke are diseases with significant disparities in race and geography. Post stroke cognitive impairment (PSCI) can be as high as 15–70 % but few studies have utilized large administrative or electronic health records (EHR) to evaluate trends in PSCI. We utilized an EHR database to evaluate for disparities in PSCI in a large sample of patients after first recorded stroke to evaluate for disparities in race. MethodsThis is a retrospective cohort analysis of Cerner Health Facts® EHR database, which is comprised of EHR data from hundreds of hospitals/clinics in the US from 2009–2018. We evaluated patients ≥40 years of age with a first time ischemic stroke (IS) diagnosis for PSCI using ICD9/10 codes for both conditions. Patients with first stroke in the Cerner database and no pre-existing cognitive impairment were included, we compared hazard ratios for developing PSCI for patient characteristics ResultsA total of 150,142 IS patients with follow-up data and no pre-existing evidence of CI were evaluated. Traditional risk factors of age, female sex, kidney injury, hypertension, and hyperlipidemia were associated with PSCI. Only African American stroke survivors had a higher probability of developing PSCI compared to White survivors (HR 1.347, 95 % CI (1.270, 1.428)) and this difference was most prominent in the South. Among those to develop PSCI, median time to documentation was 1.8 years in African American survivors. ConclusionIn a large national database, African American stroke survivors had a higher probability of PSCI five years after stroke than White survivors.

Factors associated with early postoperative mortality after total anomalous pulmonary venous connection repair: A retrospective cohort study.

Total anomalous pulmonary venous connection (TAPVC) is a rare congenital defect where pulmonary venous plexus fails to connect with the left atrium (LA). Surgical repair is the primary treatment for TAPVC, but factors influencing outcomes are not fully understood. This study investigates the early outcomes of surgical repair for TAPVC and associated factors. A retrospective cohort analysis was conducted on TAPVC patients who underwent surgical repair between 2012 and 2022. Data were collected from medical records and supplemented with phone call validation. Demographic characteristics, surgical data, diagnostic tests, and outcomes were analyzed. Statistical analysis included chi-square, t-tests, and multivariate logistic regression using SPSS. A total of 88 patients underwent surgical repair for TAPVC, resulting in a mortality rate of 21.6%. Weight and bypass time were significantly associated with patient survival. Female patients had a higher likelihood of death. The anatomic type did not significantly influence mortality. Patients with pulmonary venous obstruction (PVO) experienced a higher mortality rate. Notably, ligation of the vertical vein in supracardiac and infracardiac types was associated with lower mortality. In conclusion, our study identifies several key factors contributing to higher mortality rates following TAPVC surgery, including low weight, female gender, prolonged bypass time, and preoperative vein obstruction. Highlighting the significance of surgical technique, particularly the sutureless approach, we advocate for its meticulous consideration to achieve improved outcomes. Furthermore, our findings indicate a potential decrease in mortality associated with vertical vein ligation, which may mitigate the risk of post-repair heart failure. We suggest further rigorous studies to gain comprehensive insights into TAPVC surgical interventions.

Intraoperative Methadone and Postoperative Anesthesia Care Unit Outcomes: A Retrospective Cohort Analysis.

Intraoperative Methadone and Postoperative Anesthesia Care Unit Outcomes: A Retrospective Cohort Analysis.

Value of 24h ambulatory ECG for prediction of sufficient number of premature ventricular complexes during catheter ablation

Abstract Introduction Successful catheter ablation (CA) of premature ventricular complexes (PVCs) depends on identification of the site of origin (SOO), but no parameter suggested for prediction of success from CA have been sufficiently validated in previous studies. Activation mapping and pace-mapping are invasive methods for the identification of SOO, and the burden of PVCs is critical for activation mapping to identify SOO. The number of PVCs in 24h ambulatory ECGs is claimed to predict occurrence of PVCs during the procedure, and hence procedural success, but the predictive value remains unknown. Purpose The primary objective of this study was to quantify the predictive value of pre-procedural of 24h ambulatory ECG with regard to sufficient number of PVCs during the CA procedure. Methods Patients admitted for CA of PVCs at our hospital from 2011-2020 were included. Data were retrospectivity collected from electronic health records. Clinical characteristics, results from clinical pre-procedural examinations, including 24h ambulatory ECG, exercise testing and echocardiogram, as well as acute outcomes were recorded. Results A total of 332 patients were included, CA was performed in 285 (86 %) patients, while 47 (14 %) patients had insufficient number of PVCs to allow adequate identification of SOO. Neither clinical characteristics nor results of cardiac imaging separated patients with sufficient and insufficient number of PVCs for CA, respectively. Patients with sufficient number of PVCs had nominally more PVCs in the preceding 24h ambulatory ECG, although the difference was not statistically significant (16007 (6509-26205) vs. 8332 (3066-20974), p = 0.055). A receiver operating characteristics (ROC) curve analysis of sufficient number of PVCs during CA and number of PVCs in the preceding 24h ambulatory ECG had an area under curve (AUC) of 0.610 (0.95% CI 0.498-0.722, p = 0.055). The commonly clinically used cut-off of &amp;gt;10 000 PVCs/24h had a positive predictive value of 67 % and a negative predictive value of 57 % for sufficient number of PVCs during CA. The median period from the 24h ambulatory ECGs to CA was 183 days (6 months). The positive and negative predicative values for &amp;gt;10 000 PVCs in 24h ambulatory ECG performed &amp;gt;6 months prior to the procedure were 67 % and 71 %, respectively, compared to 53 % and 61 % for 24h ECGs performed &amp;lt;6 months prior to the procedure. The ROC curve for sufficient number of PVCs during the procedure and number of PVCs in a 24h ambulatory ECG performed &amp;gt;6 months and &amp;lt;6 months prior to the procedure did not differ, with had AUC values of 0.665 and 0.584, respectively (p = 0.4). Conclusion In this retrospective analysis of a large cohort of patients admitted for CA of PVCs, number of PVCs in 24h ambulatory ECGs recorded prior to the procedure had a low predictive value for presence of PVCs during CA. Others parameters need to be evaluated to improve prediction.

Clinical findings and outcomes of Brugada syndrome in women

Abstract Introduction Brugada syndrome (BrS) is a genetic disorder characterized by typical ECG changes and association with spontaneous ventricular tachyarrhythmia (VTA) and sudden death in young patients. BrS has been widely established to be particularly prevalent in men, however less information exists regarding female patients and their long-term risk. Objectives The purpose of this study was to investigate the clinical characteristics and long-term prognosis of women with BrS. Methods This study includes a retrospective analysis of a single-center cohort of patients followed and observed for relevant clinical outcomes. The data collected included demographic data, severity of symptoms (e.g. syncope, VTA), cardioverter-defibrillator logs and occurrence of sudden cardiac death. Results 317 patients were diagnosed with BrS between 1998 and 2023. Among those, 112 (36%) were female. At presentation, 5 patients (4%) were symptomatic with history of survived cardiac arrest and/or documented VTA. 29 (26%) had history of unexplained syncope and 78 (70%) were asymptomatic. The average age at diagnosis was 42.1±15.1 yrs. as opposed to 40.1±14.2 yrs. in men. Females presented less frequently with a type 1 ECG pattern (5% vs 21%; p&amp;lt;0.01), had a trend to a higher rate of family history of sudden cardiac death (31% vs 25%; p=n.s.), and had less sustained VTA during programmed ventricular stimulation (4% vs 19%; p&amp;lt;0.01). Genetic testing was performed in 89 females (79% of the sample) and pathogenic variants were present in 36 (40%) women. An implantable cardioverter defibrillator was inserted in 24 (31%) females for primary prevention. During mean follow-up of 138±72 months, 11 women had cardiovascular events (syncope, VT/VF or death). Syncope was most common and occurred in 8 cases. No VTA were documented in any female patient. In the group of ICD patients, 8 shocks have occurred. None of these were deemed appropriate by medical controls. There were 3 deaths. Two were considered non-arrhythmic due to pulmonary embolism and breast carcinoma. One ICD patient died suddenly during sleep. Unfortunately, no device interrogation data was available. Conclusion Women typically present less symptomatic and demonstrate a reduced incidence of life-threatening arrhythmias during follow-up , often experiencing a frequent occurrence of inappropriate implantable defibrillator therapy. The less frequent prevalence of the BrS ECG pattern in women adds complexity to the diagnostic process. Further studies are still needed to elucidate gender differences for risk stratification of BrS.

Selective nonoperative versus operative management of liver gunshot injuries: a retrospective cohort study.

Experience accumulated over the last decades suggests nonoperative management (NOM) of civilian gunshot liver injuries can be safely applied in selected cases. This study aims to compare the outcomes of selective NOM versus operative management (OM) of patients sustaining gunshot wounds (GSW) to the liver. A registry-based retrospective cohort analysis was performed for the period of 2008 to 2016 in a Brazilian trauma referral. Patients aged 16-80 years sustaining civilian GSW to right-sided abdominal quadrants and liver injury were included. Baseline data, vital signs, grade of liver injury, associated injuries, injury severity scores, blood transfusion requirements, liver- and non-liver-related complications, length-of-stay (LOS), and mortality were retrieved from individual registries. A total of 54 patients were eligible for analysis, of which 37 underwent NOM and 17 underwent OM. The median age was 25 years and all were male. No statistically significant differences were observed between groups regarding patients' demographics, injury scores, grade of liver injury and associated lesions. NOM patients tended to sustain higher-grade injuries (86.5% vs 64.7%; p = 0.08), and failure of conservative management was recorded in two (5.4%) cases. The rate of complications was 48% with no between-group statistically significant difference. Blood transfusion requirements were significantly higher in the OM group (58.8% vs 21.6%; p = 0.012). The median LOS was seven days. No deaths were recorded. Patients with liver GSW who are haemodynamically stable and without peritonitis are candidates for NOM. In this study, NOM was safe and effective even in high-grade injuries.

Sodium-glucose cotransporter-2 inhibitors and incidence of atrial fibrillation in older adults with type 2 diabetes: a retrospective cohort analysis

ObjectivesTo investigate the risk of atrial fibrillation (AF) with sodium-glucose cotransporter-2 inhibitors (SGLT2is) compared to dipeptidyl peptidase-4 inhibitor (DPP4i) use in older US adults and across diverse subgroups.MethodsWe conducted a retrospective cohort analysis using claims data from 15% random samples of Medicare fee-for-service beneficiaries. Patients were adults with type 2 diabetes (T2D), no preexisting AF, and were newly initiated on SGLT2i or DPP4i. The outcome was the first incident AF. Inverse probability treatment weighting (IPTW) was used to balance the baseline covariates between the treatment groups including sociodemographics, comorbidities, and co-medications. Cox regression models were used to assess the effect of SGLT2i compared to DPP4i on incident AF.ResultsOf the 97,436 eligible individuals (mean age 71.2 ± 9.8 years, 54.6% women), 1.01% (n = 983) had incident AF over a median follow-up of 361 days. The adjusted incidence rate was 8.39 (95% CI: 6.67–9.99) and 11.70 (95% CI: 10.9–12.55) per 1,000 person-years in the SGLT2i and DPP4i groups, respectively. SGLT2is were associated with a significantly lower risk of incident AF (HR 0.73; 95% CI, 0.57 to 0.91; p = 0.01) than DPP4is. The risk reduction of incident AF was significant in non-Hispanic White individuals and subgroups with existing atherosclerotic cardiovascular diseases and chronic kidney disease.ConclusionCompared to the use of DPP4i, that of SGLT2i was associated with a lower risk of AF in patients with T2D. Our findings contribute to the real-world evidence regarding the effectiveness of SGLT2i in preventing AF and support a tailored therapeutic approach to optimize treatment selection based on individual characteristics.

#1039 Characteristics and outcome of IgA nephropathy in Switzerland – a single center perspective

Abstract Background and Aims IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide leading to end-stage kidney disease (ESKD) in roughly 40% of affected patients by ten years. Geographic differences in clinical course and response to treatment may partly result from different disease entities. The purpose of this retrospective cohort analysis was to study all cases of IgAN from a single tertiary center with respect to clinical and histological characteristics, treatment practices and outcome. Method This retrospective cohort analysis identified 158 cases of adult biopsy-proven IgAN by chart review diagnosed between 1980 and 2017. Detailed phenotypisation including clinical, paraclinical, histological, treatment and outcome parameters was performed. Remission status was defined as described previously (Reich 2007). Statistical analysis was performed using Excel and SPSS software and included standard descriptive methods and included standard descriptive methods and student's t-test on a significance level of 0.05. Results Subjects were majorly male and of Caucasian descent. Mean estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration formula at diagnosis was 55.3 ml/min/1.73 m2, mean proteinuria was 3.2 g/d. 70.3% of patients were hypertensive at presentation. Clinical presentation varied according to age. Thus, younger patients (18-39 years) presented more frequently with macrohematuria, asymptomatic urine abnormalities and by trend acute kidney injury whereas nephrotic syndrome and extrarenal symptoms were recorded in similar proportions of patients (Fig. 1). 28.5% of initial biopsies showed moderate to severe tubular atrophy and interstitial fibrosis (IFTA), 38% included crescents, 1.9% &amp;gt; 50% crescents. 86.1% of the patients were treated by renin-angiotensin-aldosterone-system inhibitors, 46.8% received immunosuppressive therapy including steroids in 46.2% and other immunosuppressive medications in 19.6% the most common being azathioprine (Fig. 2). There were 33.5% complete and 13.3% partial remissions. Progression to ESKD was noted in 42.1%. 51.4% of patients treated with immunosuppressive therapy experienced remission. Recurrence rate after transplantation was 18.4%. Patients treated by immunosuppressants had higher levels of baseline proteinuria (3.2 ± 2.3 vs. 1.6 ± 1.6 g/d, p &amp;lt; 0.00001), lower baseline eGFR (50 ± 31 vs. 61 ± 30 ml/min/1.73 m2, p = 0.04), higher number of crescents (9.4 ± 15.0 vs 2.3 ± 8.5%, p = 0.001), higher IFTA scores (1.7 ± 0.8 vs. 1.3 ± 0.6, p = 0.007) and higher fluorescence intensity scores for C3 (2.0 ± 0.9 vs. 1.6 ± 0.9, p = 0.02) on initial biopsy as compared to patients treated conservatively. Patients progressing to ESKD presented with higher blood pressure (146 ± 26 vs. 135 ± 18 mmHg systolic, p = 0.005; 89 ± 14 vs. 82 ± 14 mmHg diastolic, p = 0.006), lower eGFR (41 ± 29 vs. 64 ± 28 ml/min/1.73 m2, p = 0.00001), higher levels of proteinuria (3.4 ± 2.0 vs. 1.8 ± 1.9 g/d, p = 0.0001), higher number of crescents (9 ± 17 vs. 4 ± 9%, p = 0.03) and higher IFTA scores (1.8 ± 0.8 vs. 1.3 ± 0.6, p = 0.00001) as compared to patients without ESKD at last follow up. Baseline blood pressure (134 ± 18 vs. 147 ± 26 mmHg systolic, p = 0.004; 82 ± 14 vs. 89 ± 15 mmHg diastolic, p = 0.01), eGFR (60 ± 29 vs. 41 ± 27 mmHg, p = 0.0007), proteinuria (2.3 ± 1.9 vs. 3.2 ± 2.3 g/d, p = 0.03) and severity of IFTA (1.4 ± 0.6 vs. 1.8 ± 0.9, p = 0.003) differed significantly between patients who experienced any remission vs. those who did not achieve remission respectively. Conclusion This analysis gives insight into the characteristics and treatment practices of a Swiss single center cohort of IgAN patients from 1980-2017.

#2507 Enhancing critical care nephrology: analyzing continuous renal replacement therapy with a citrate-based anticoagulation focus

Abstract Background and Aims Continuous renal replacement therapy (CRRT) is pivotal for managing acute kidney injury (AKI) unstable patients. However, questions persist regarding prescription and the role of anticoagulation. This study aims to examine CRRT practices, focus on citrate-based anticoagulation and clarify contraindications. Method This study comprises a retrospective analysis of a patient cohort requiring CRRT and admitted to the Postoperative Intensive Care Unit and Burn Unit. Inclusion criteria involved the need for CRRT and adult age, with exclusion criteria based on treatment duration (&amp;lt;48 hours), reducing the initial cohort from 256 to 176 patients. Clinical variables, including gender, age, underlying pathology, CRRT modality, and anticoagulation type, were characterized. Subsequently, the association between anticoagulation type and clot formation within 48 hours and in-hospital mortality was investigated. Furthermore, an analysis of citrate-based CRRT was conducted, evaluating laboratory values (Table 1) at the beginning and 48 hours using the Wilcoxon test, and their correlation with clot development and mortality. Additionally, we used a logistic regression model to explore the relationship between AST, ALT, and lactate values with citrate accumulation. Finally, a survival analysis was conducted. Results The sample consisted of 66.5% males and 33.5% females, with an average age of 59.48 years. Reasons for admission are depicted in Fig. 1. CRRT modalities were 20.5% HDVVC, 76.1% HDFVVC, and 3.4% HFVVC. Anticoagulation included 35.2% none, 28.4% heparin, 33.5% citrate, and 2.8% alprostadil. Filter clotting occurred in 29.1% withing 48 hours. Heparin was associated with a 5.4-fold increased risk of clotting compared to citrate. Mortality was 63.3%, with no anticoagulation type showing a significant association. Parameters at CRRT initiation and 48 hours for citrate-based CRRT patients and Wilcoxon test results are presented in Table 1. Only 5.1% had filter clotting &amp;lt;48 hours, and no baseline parameters were significantly associated with an increased clotting risk. There was one case of citrate intoxication due to a programming error, which was not included. 76.81% had CaT/CaI &amp;lt;2.1, and 7.25% had CaT/CaI &amp;gt;2.1, requiring technique adjustments. Aminotransferases and lactate values, often considered as contraindications for citrate, were analyzed: The average AST and ALT values were 188.53 IU/l and 108.08 IU/l, respectively. When AST levels exceeded 5 times the normal range and ALT levels exceeded 3 times the normal range, a statistically significant association with CaT/CaI &amp;gt;2.1 at the 48-hour mark of CRRT utilization was observed (p &amp;lt; 0.001 for both).The average lactic acid value was 1.74 mg/dl. Having a lactic acid level &amp;gt;4 was associated (p &amp;lt; 0.05) with a higher risk of developing CaT/CaI &amp;gt;2.1. 54.2% of the sample died. No baseline parameters were significantly associated with it. At 48 hours, higher bicarbonate levels and metabolic alkalosis were associated with increased mortality (p &amp;lt; 0.05). The median survival time was 11 days (±4.38). Conclusion This study supports the use of citrate-based anticoagulation in CRRT, as no cases of citrate intoxication (CaT/CaI &amp;gt;2.5) were found. Nonetheless, a significantly elevated AST (&amp;gt;5 times normal), ALT (&amp;gt;3 times normal), and lactate (&amp;gt;4 mg/dl), were associated with a higher risk of citrate accumulation (CaT/CaI &amp;gt;2.1). Customized approaches and preventive measures to mitigate the development of metabolic alkalosis are essential for optimizing patient outcomes.

Cytogenomic characterization of pediatric T-cell acute lymphoblastic leukemia reveals TCR rearrangements as predictive factors for exceptional prognosis

BackgroundT-cell acute lymphoblastic leukemia (T-ALL) represents a rare and clinically and genetically heterogeneous disease that constitutes 10–15% of newly diagnosed pediatric ALL cases. Despite improved outcomes of these children, the survival rate after relapse is extremely poor. Moreover, the survivors must also endure the acute and long-term effects of intensive therapy. Although recent studies have identified a number of recurrent genomic aberrations in pediatric T-ALL, none of the changes is known to have prognostic significance. The aim of our study was to analyze the cytogenomic changes and their various combinations in bone marrow cells of children with T-ALL and to correlate our findings with the clinical features of the subjects and their treatment responses.ResultsWe performed a retrospective and prospective comprehensive cytogenomic analysis of consecutive cohort of 66 children (46 boys and 20 girls) with T-ALL treated according to BFM-based protocols and centrally investigated cytogenetics and immunophenotypes. Using combinations of cytogenomic methods (conventional cytogenetics, FISH, mFISH/mBAND, arrayCGH/SNP and MLPA), we identified chromosomal aberrations in vast majority of patients (91%). The most frequent findings involved the deletion of CDKN2A/CDKN2B genes (71%), T-cell receptor (TCR) loci translocations (27%), and TLX3 gene rearrangements (23%). All chromosomal changes occurred in various combinations and were rarely found as a single abnormality. Children with aberrations of TCR loci had a significantly better event free (p = 0.0034) and overall survival (p = 0.0074), all these patients are living in the first complete remission. None of the abnormalities was an independent predictor of an increased risk of relapse.ConclusionsWe identified a subgroup of patients with TCR aberrations (both TRA/TRD and TRB), who had an excellent prognosis in our cohort with 5-year EFS and OS of 100%, regardless of the presence of other abnormality or the translocation partner. Our data suggest that escalation of treatment intensity, which may be considered in subsets of T-ALL is not needed for nonHR (non-high risk) patients with TCR aberrations.

Genetic etiology of agenesis of the corpus callosum: a retrospective single-center cohort analysis of 114 fetuses.

The identification and prognosis of the agenesis of the corpus callosum (ACC) for prenatal consultation are complex and currently unclear. This study aims to explore the correlated genetic mutations of prenatal ACC. We retrospectively analyzed 114 prenatal cases of ACC. All cases (n = 114) were subjected to chromosomal microarray analysis (CMA), and 66 CMA-negative cases underwent prenatal exome sequencing (pES) for further analysis. CMA was diagnosed positively in 15/114 (13.2%) cases and pES was diagnosed positively in 24/66 (36.4%) CMA-negative cases. The detection rate of genetic causes between complete and partial ACCs was not significantly different (P > 0.05). Between isolated and non-isolated (other anomalies present) ACCs, the diagnostic rate of pES in non-isolated cases was significantly higher (P < 0.001), while CMA results did not differ (P > 0.05). The diagnostic rate of CMA was significantly increased in cases combined with intracranial and extracranial malformations (P = 0.014), while no CMA positivity was detected in cases combined with only intracranial malformations. For fetuses with prenatal ACC, further pES analysis should be recommended after negative CMA results. Chromosome abnormalities are less likely to occur when ACC with only intracranial malformations combined.