Incidence Of Failure Research Articles

Triglyceride-lowering therapies in hypertriglyceridemia-associated acute pancreatitis in China: a multicentre prospective cohort study.

No specific triglyceride-lowering therapy is recommended in patients with hypertriglyceridemia-associated acute pancreatitis (HTG-AP), primarily because of the lack of quality evidence. This study aimed to describe practice variations in triglyceride-lowering therapies for early HTG-AP patients and assess whether more rapid triglyceride decline is associated with improving organ failure. This is a multicentre, prospective cohort study recruiting HTG-AP patients with elevated plasma triglyceride (> 11.3mmol/L) admitted within 72h from the onset of symptoms. Patients were dichotomised on study day 3 into either target reaching (plasma triglyceride ≤ 5.65mmol/L) or not. The primary outcome was organ failure-free days (OFFD) to 14days of enrolment. The association between target-reaching and OFFD was modelled. Additionally, the slope in plasma triglyceride over the first three days in response to treatment was calculated, and its association with OFFD was assessed as a sensitivity analysis. Among the 300 enrolled patients, 211 underwent exclusive medical treatment, and 89 underwent various blood purification therapies. Triglyceride levels were available in 230 patients on study day 3, among whom 122 (53.0%) had triglyceride levels of ≤ 5.65mmol/l. The OFFD was not different between these patients and those in whom plasma triglyceride remained > 5.65mmol/L [median (IQR): 13 (10-14) vs. 14 (10-14), p = 0.46], even after adjustment for potential confounders. For the decline slopes, there was no significant change in OFFD with a steeper decline slope [risk difference, - 0.088, 95% CI, - 0.334 to 0.158, p = 0.48]. Triglyceride-lowering therapies vary greatly across centres. More rapid triglyceride decline was not associated with improving incidence and duration of organ failure.

HPB SO20 - Evaluating the Impact of Enhanced Recovery After Surgery Protocols Post Hepatectomy in Patients with Chronic Liver Disease: A Meta-Analysis

Abstract Background Defined criteria for the resectability of liver disease continue to be refined. In the era of enhanced recovery after surgery (ERAS), data regarding its safety and efficacy in specific patient populations is required. Patients with liver cirrhosis are particularly vulnerable, owing to both operative and peri-operative risk. However, the application of ERAS in cirrhotic patients undergoing hepatectomy is absent from the most recent ERAS Society Group recommendations from 2022. We present a meta-analysis assessing outcomes after liver resection in patients with cirrhosis following an ERAS protocol compared to standard post-operative care. Method A systematic literature search was performed using PubMed, Embase and Web of Science. Studies were included if comparing ERAS protocols versus standard post-operative care in patients undergoing liver resection in which more than 50% of the patient population had cirrhosis at time of surgery. The primary outcome analysed was overall complication rates with secondary outcomes of post-operative mortality, estimated blood loss, operation time, post-operative incidence of liver failure, readmission and reoperation rates. Statistical analysis was performed using Review Manager by the Cochrane Collaboration. Results 930 records were screened for eligibility. Five articles were eligible for inclusion(ERAS n = 425 vs control group n = 423 patients). Cirrhotic patients enrolled in an ERAS program post-hepatectomy had a significantly reduced risk of overall complications (OR 0.45, 95% CI 0.33, 0.61, p<0.00001) and a shorter hospital stay when compared to standard post-operative care by 1.8 days (mean difference -1.83, 95% CI -2.22, -1.45, p<0.00001). No significant differences were noted in post-operative mortality, estimated blood loss, operation time, post-operative incidence of liver failure, readmission or reoperation rates between the ERAS group and control. Conclusion Application of an ERAS protocol for patients undergoing liver resection is safe and feasible in cirrhotic patients. ERAS protocols were successful in significantly reducing overall complication rates and length of inpatient hospital stay, and did not negatively impact secondary post-operative outcomes or mortality. ERAS protocols should be reflected in future guidelines, specifically for cirrhotic patients undergoing hepatectomy, and additional research on the utility of ERAS in higher risk patients is encouraged.

Incidence and predictors of clinical failure after early treatment for mild-to-moderate COVID-19 in high-risk individuals: A multicentric cohort study.

To estimate the risk of COVID-19-related hospitalization and death (CovH/D), among high-risk individuals early treated for COVID-19 and to identify associated factors. A multicenter cohort of 12,475 high-risk outpatients (female 50.2%, median age 70 years [IQR 57-80], fully vaccinated 79.1%, immunocompromised 23.2%) treated with monoclonal antibodies or antivirals for mild-to-moderate COVID-19 (March 2021-May 2023) in the Lazio region, Italy. The unadjusted risk of CovH/D by Day 30 was 3.08% (95% CI 2.7%-3.4%). By means of logistic regression models, which included a specific set of potential confounders for each exposure of interest, we observed a higher risk for the elderly, unvaccinated and immunocompromised participants. Using the "Delta period" as a reference, a decreased risk was observed for Omicron waves. Despite the administration of COVID-19 early treatment and the decreasing risk of CovH/D across the calendar periods, the elderly, the unvaccinated and the immunocompromised people remain at high risk of clinical progression.

Preparation and performance study of heparinized multi‐walled carbon nanotube/cellulose acetate hemodialysis membrane

AbstractCurrently, the incidence of kidney failure is increasing worldwide. Hemodialysis is the main method for the treatment of kidney diseases, and the continuous development of new hemodialysis membranes is the key to improve the treatment effect and the quality of life of patients. In this study, heparinized multi‐walled carbon nanotube/cellulose acetate (Hep/MWCNTs@CA) membranes were prepared by non‐solvent induced phase separation (NIPS). The morphology and pore structure of Hep/MWCNTs@CA membranes were characterized by scanning electron microscopy (SEM). The elongation at break and tensile strength of the membranes were characterized by a mechanical property universal tester. The results showed that mechanical properties of 0.1 wt% MWCNTs enhanced the membrane is best. The water contact angle test confirmed that MWCNTs can improve the membrane hydrophilicity, and combined with the adsorption test results for proteins, it was found that the hydrophilicity can reduce the adsorption of proteins to the composite membrane and improve the blood compatibility of the material. The dialysis performance of urea and lysozyme was tested by a self‐made simulated hemodialysis device, and the clearance rates of urea and lysozyme were 84% and 47.2%, respectively, which showed that the interfacial gap between MWCNTs and CA matrix can make the composite membrane retain a high retention rate of macromolecular proteins (92.3%) and further improved the clearance rate of small and medium molecular toxins. In addition, the good blood compatibility and biocompatible properties of the materials were confirmed by hemolysis, recalcification and cytotoxicity tests on Hep/MWCNTs@CA membranes. In conclusion, the prepared Hep/MWCNTs@CA holds great potential for application in the field of hemodialysis.

Abstract 4145802: Association between Glucagon-like peptide-1 receptor agonists and risk of Arrhythmias or Heart Failure among patients with Type 2 Diabetes: A Meta-Analysis of 29 Randomized Controlled Trials.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a reduction in major adverse cardiovascular events (MACE) among patients with type 2 diabetes mellitus (T2DM). However, their effect on reducing the risk of incidence of arrhythmias and heart failure has not been established, and there is very limited literature to date. Objective: We evaluated the effect of GLP-1 RAs on the incidence of arrhythmias and heart failure among patients with T2DM. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that enrolled patients with type 2 diabetes and compared GLP-1 RAs and control groups. PubMed and ClinicalTrials.gov were systematically searched from inspection till May 2024 without any language restrictions. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effect model. Results: A total of 29 RCTs with 72,868 patients (35,631 in the GLP-1 RA group and 37,237 in the control group) were included in the analysis. Pooled analysis showed that there is no significant association between GLP-1 RAs and incidence of atrial fibrillation (OR, 0.94(95%CI: 0.75-1.18), P=0.60), atrial flutter (OR, 0.87(95%CI: 0.60-1.26), P=0.46), cardiac arrest (OR, 0.79(95%CI: 0.51-1.23), P=0.30), ventricular tachycardia (OR, 1.37(95%CI: 0.90-2.07), P=0.14), and ventricular fibrillation (OR, 0.91 (95%CI: 0.45-1.84), P=0.80) when compared with control group. However, GLP-RAs reduced the incidence of atrioventricular block complete (OR, 0.58 (95%CI: 0.35-0.97), P=0.04), and heart failure (OR, 0.795 (95%CI: 0.634-0.997), P=0.047). Conclusion: This study shows that GLP-1 RAs reduced the incidence of atrioventricular block complete and incidence of heart failure. However, no significant association has been observed for arrhythmias.

Abstract 4127345: National Cohort Study on Hypertensive Disorders of Pregnancy Among Women with Congenital Heart Disease: Insights from Multiple Centers

Background: Hypertensive disorders of pregnancy (HDP) are among the primary reasons for maternal and perinatal deaths globally. Encompassing chronic hypertension, pregnancy induced hypertension (PIH), and preeclampsia, HDP are among the most frequent complications encountered during pregnancy. Considering the emerging congenital heart disease (CHD) population globally, research on HDP in pregnancies with CHD is urgently needed. Methods: Outcomes for 2220 pregnant women with CHD were evaluated retrospectively from 1993 to 2016 and prospectively from 2017 to 2019 from 7 tertiary hospitals. Maternal death, cardiac complications, obstetric and offspring complications of completed pregnancies and their demographics, cardiac characteristics, and comorbidities were collected. To identify the risk factors for HDP, univariate and multivariate analysis were performed through logistic regression. Results: Of 2220 completed pregnancies with CHD from 7 tertiary institutions, 77 women had PIH, and 76 women had preeclampsia. The main CHD diagnosis of patients with PIH was shunt lesion (including ASD, VSD, and PDA), left heart abnormality (including AS/AI, BAV, and COA), and single ventricle (SV). The main CHD diagnosis of patients with preeclampsia was shunt lesion (including ASD, VSD, and PDA), left heart abnormality (including AS/AI and MS/MI), and right heart abnormality (including TOF, PS/PAS/PI, DORV and DCRV). In parturients with PIH, the mortality and incidence of heart failure were 2.60% and 15.58%, respectively. In parturients with preeclampsia, the mortality and incidence of heart failure were 6.58% and 23.68%, respectively. Pregnancies with HDP had a significantly higher incidence of adverse maternal and offspring events than pregnancies without HDP. Independent risk factors for HDP included multiple gestation, use of medically assisted reproduction, having elevated brain natriuretic peptide (BNP) level, delayed first ANC visit, and absence of strict antenatal supervision. Conclusion: In summary, the presence of HDP in women with CHD significantly increased the risk of mortality and morbidity for both the mother and the child, particularly in cases involving preeclampsia.

Abstract 4147617: Depression and the Development of Cardiovascular Disease: Insights from All of Us Research Program

Introduction/Background: Depression is recognized as a risk factor for worse outcomes in patients with cardiovascular disease, but there is limited research on whether individuals with depression have an increased incidence of future cardiovascular disease. Research questions/Hypothesis: Do individuals with depression have an increased incidence of cardiovascular disease? Goals/Aims: This study was conducted to evaluate the association between a diagnosis of depression and the risk of developing future cardiovascular events, to determine whether the treatment of depression should be considered as a primary form of cardiovascular disease prevention. Methods/Approach: We conducted a prospective analysis using the “All Of Us” Research Program dataset. Participants who responded to the historical depression status in the “Personal/Family History Survey” and with linked electronic health records data were considered eligible for this study. We used Cox regression models to calculate the incidence of myocardial infarction (MI), stroke, heart failure (HF), and atrial fibrillation (AF) and the hazard ratio (HR) of a diagnosis of depression. Models were adjusted for sex, race, age, and prevalent hypertension, diabetes mellitus, hyperlipidemia, and smoking. The survival analysis of the four outcomes was conducted in parallel. We conducted sensitivity analysis by excluding participants with documentation of prior MI, stroke, HF, and/or AF. Results/Data: 100,030 participants were included in this study, with a mean age of 53.2 (standard deviation of 16.5). 68.4% of participants were female, 10% were Hispanic, 9.6% were Black, and 37.1% had a diagnosis of depression. The median follow up time was 3 years. Compared to participants without depression, participants with depression were at risk of developing MI (aHR 1.22, 95% CI 1.05–1.41), stroke (aHR 1.68, 95% CI 1.06–2.68), HF (aHR 1.28, 95% CI 1.15–1.43), and AF (aHR 1.14, 95% CI 1.02–1.27). In the sensitivity analysis, participants with depression were at risk of developing MI (aHR 1.22, 95% CI 1.03–1.44), stroke (aHR 1.68, 95% CI 1.06–2.68), and HF (aHR 1.31, 95% CI 1.15–1.48) but not AF (aHR 1.12, 95% CI 0.99–1.27). Conclusions: This study indicates that patients with a diagnosis of depression were more likely to develop cardiovascular disease, even if they had no known history of cardiovascular disease. Providers should include the treatment of depression as a part of a holistic approach to cardiovascular disease prevention.

Abstract 4145876: Prognostic significance of somatic mutations in myeloid cells of men with chronic heart failure – interaction between loss of Y chromosome and clonal hematopoiesis

Introduction: Age-associated clonal hematopoiesis of indeterminate potential (CHIP) has been associated with increased incidence and worse prognosis of chronic heart failure. CHIP is driven by somatic mutations in hematopoietic stem and progenitor cells (HSPC). Mosaic loss of the Y chromosome (LOY), the most common somatic mutation in blood cells of men, also correlates with clonal expansion of myeloid cells, increases with age and was experimentally shown to lead to diffuse cardiac fibrosis and subsequent heart failure in mice. However, the prognostic significance of LOY as well as its potential interaction with CHIP in patients with chronic heart failure is unknown. Aims/Methods: We investigated the prevalence and prognostic significance of the extent of LOY and the two most common CHIP-driver mutations DNMT3A and TET2 in 705 male patients with established chronic heart failure across the entire spectrum of left ventricular ejection fraction. Results: Both, LOY and DNMT3A/TET2 mutations, increased with age, and LOY co-occurred with DNMT3A/TET2 mutations in 27.1% of men at age > 70 years. LOY was an independent predictor of death during 3-years of follow-up across the entire spectrum of left ventricular ejection fraction. The co-occurrence of harboring LOY and DNMT3A/TET2 mutations significantly contributed to the observed increased mortality observed in carriers of DNMT3A/TET2 mutations. The detrimental effect of LOY on prognosis was confirmed in a validation cohort of patients with ischemic heart disease.scRNA sequencing of peripheral blood cells in patients with chronic ischemic heart failure showed increased profibrotic signaling in LOY monocytes with elevated markers of monocyte mediated inflammation and profibrotic cardiac remodeling (S100A8, TLR2, CLEC4D) and reduced expression of TGF-b inhibiting genes (SMAD7, TGIF2). The proinflammatory phenotype of LOY monocytes was further amplified in LOY monocytes of patients simultaneously harboring DNMT3A mutations, who displayed heightened expression of alarmins (S100A8, HMGB2) and interferon signaling related genes (IFNGR1, TRIM56, CD84) compared to patients without CHIP mutations. Conclusion: The age-associated acquisition of somatic mutations in blood cells of men with chronic heart failure is associated with increased mortality, with loss of Y chromosome emerging as an independent predictor of all-cause death across the entire spectrum of left ventricular function.

Clinical outcomes after extra-articular resection of hip joint tumour using a custom-made osteotomy guide and 3D-printed endoprosthesis with posterior column preserved.

For rare cases when a tumour infiltrates into the hip joint, extra-articular resection is required to obtain a safe margin. Endoprosthetic reconstruction following tumour resection can effectively ensure local control and improve postoperative function. However, maximizing bone preservation without compromising surgical margin remains a challenge for surgeons due to the complexity of the procedure. The purpose of the current study was to report clinical outcomes of patients who underwent extra-articular resection of the hip joint using a custom-made osteotomy guide and 3D-printed endoprosthesis. We reviewed 15 patients over a five-year period (January 2017 to December 2022) who had undergone extra-articular resection of the hip joint due to malignant tumour using a custom-made osteotomy guide and 3D-printed endoprosthesis. Each of the 15 patients had a single lesion, with six originating from the acetabulum side and nine from the proximal femur. All patients had their posterior column preserved according to the surgical plan. Postoperative pathological assessment revealed a negative surgical margin was achieved in all patients. At final follow-up, 13.3% (2/15) died and no recurrence occurred. The overall survival was 81.7% at five years. None of the patients showed any signs of aseptic loosening, and no wound healing issues were observed. In total, 20% (3/15) developed complications, with two cases of early hip dislocation and one case of deep infection. The cumulative incidence of mechanical and non-mechanical failure in this series was 13.7% and 9.3%, respectively, at five years. In this cohort, the mean time to full weightbearing was 5.89 (SD 0.92) weeks and the mean Musculoskeletal Tumor Society score was 24.1 (SD 4.4). For patients with a hip joint tumour who met the inclusion criteria and were deemed suitable for posterior column preservation, a custom-made osteotomy guide combined with 3D-printed endoprosthesis is worth performing when treating patients who require extra-articular resection of the hip joint, as it can achieve adequate margin for local control, maximize bone preservation to maintain pelvic ring integrity, reduce the risk of complications by simplifying the surgical procedure, and allow for more precise reconstruction for better function.

Abstract 4137942: Comparing Outcomes in Low versus High Activated Partial Thromboplastin Time-guided Anticoagulation Monitoring during Extracorporeal Membrane Oxygenation

Introduction: Systemic anticoagulation in Extracorporeal Membrane Oxygenation (ECMO) aims to reduce the risk of patient and circuit thrombosis, but requires monitoring due to risk of bleeding. Activated partial thromboplastin time (aPTT) is one of many tests utilized for this purpose. However, it lacks validation in ECMO patients and its clinical utility necessitates further analysis. Aim: We aim to elucidate associations between low versus high aPTT-guided anticoagulation monitoring and total time, survival, bleeding, and thrombotic events during ECMO. Methods: A retrospective review was conducted on 93 patients requiring ECMO at our institution between January 2020 and March 2021. Study inclusion required more than 2 days on ECMO and maintenance on anticoagulation with aPTT targets predominantly greater (>) or less than (<) 60 seconds (s). Final cohort was 74 subjects; 30 subjects with majority aPTT targets <60s composed the control “low” aPTT group and 44 subjects with aPTT targets >60s composed the “high” aPTT group. Primary outcomes were survival to decannulation, survival to discharge, average time on ECMO, and incidence of bleeding and thrombotic events during ECMO. Bleeding and thrombotic events were classified into subtypes and incidence of each was recorded. Statistical analyses were performed with Fisher’s exact, Pearson’s chi-square, and Student’s t-tests with an alpha level of .05 on IBM SPSS software. Results: The high group required a longer average time on ECMO (29.5 days versus 14.3 days; p = .002; 95% CI [5.5; 24.7]). Chi-square tests did not show an association between the low versus high groups and survival to decannulation (22/30 and 35/44; p = .533), survival to hospital discharge (17/30 and 30/44; p = .312), or overall incidence of bleeding (18/30 and 20/44; p = .219) and thrombotic events (7/30 and 14/44; p = .427). Regarding subtypes of events, Fisher’s exact test showed an association between aPTT target >60s and severe epistaxis (1/30 in the low and 9/44 in the high group; two-tailed p = .042). Though not significant, a greater incidence of oxygenator failure and circuit thrombosis was recorded in the high group. Conclusions: Our findings did not establish a relationship between aPTT target <60s or >60s and survival, bleeding, or thrombotic events. However, aPTT target >60s was associated with longer average ECMO time and severe epistaxis. Further investigation of aPTT-guided anticoagulation monitoring in ECMO patients is needed.

Abstract 4146315: Complications Associated With the 4798 Attain Stability Active Fixation Coronary Sinus Lead: Insights from the MAUDE Registry

Background: The Attain Stability Quad 4798 [Medtronic, Minneapolis, MN] lead was recently developed with a mechanism for active fixation into the venous wall, allowing for precise and secure placement in coronary venous branches. However, real-world data regarding complication rates are limited. Research Question: What are the real-world complications of the Medtronic 4798 lead? Goals: We reviewed the United States Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database for adverse events associated with the 4798 lead. Methods: We reviewed the MAUDE database on November 15, 2023, for all reported complications due to the 4798 lead from January 1, 2018 – a year before the lead was approved by the FDA – to the present. Results: A total of 2011 reports of adverse events occurred in mostly males (67.9%) patients with an average age of 70.86±12.1 years. Leads were used most frequently in 2023 (32.3%) for initial use (65.5%) but events commonly occurred intra-procedurally (73.7%). Device malfunction occurred in 43.4% of cases and included but was not limited to adverse events without an identified device problem (33.9%), device dislodgment (24.1%), infection (21.1%), and failure to capture (18.4%). In several cases, the guidewire was stuck (10.7%), or lead dislodgement (27.9%) occurred, resulting in direct helix damage (10.1%). Malfunctions resulted in injury and death in 55.8% and 1.1% of cases, respectively. Conclusions: The use of an active fixation CS lead has been associated with a significant incidence of intraprocedural helix mechanism malfunction. Further real-world surveillance and registry data can help clarify the true incidence of lead failure.

Home Dialysis for Latinx Individuals Living with Kidney Failure: A Qualitative Study of Interdisciplinary Dialysis Clinicians.

Latinx individuals experience 2 times the incidence of kidney failure compared to non-Latinx individuals and are less likely to utilize home dialysis therapies. In this qualitative study, interdisciplinary home dialysis clinicians were interviewed to understand the key factors and strategies used by clinicians to improve home dialysis uptake among the Latinx community. One-to-one, semi-structured interviews were conducted between November 2021 and March 2023 with 25 home dialysis interdisciplinary clinicians in Denver, Colorado and Houston, Texas. Interviews were audio-recorded, transcribed, and analyzed using thematic analysis. We identified three themes that focus on different levels of clinician advocacy in home dialysis uptake for the Latinx community: (1) Individual patient-level advocacy (helping patients overcome social challenges to home dialysis, cultivating personalized relationships, educating patients with in-person versus phone language interpretation, understanding cultural differences in communication), (2) Understanding patient influences on modality decision-making (acknowledging the importance of cultural concordance with clinician educator and patient peers, incorporating the patient lived experience, connecting with a patient's social support network, highlighting greater flexibility for employment, underscoring flexibility with culturally concordant foods) and (3) Changes to education at the dialysis facility level (standardizing routine and repeated modality education, promoting early and patient-centered education). Clinicians outlined efforts to improve access to home dialysis for Latinx groups on the patient and system level; in particular, individual and system level advocacy was grounded in trusting relationships and personalized education. A future intervention that improves the quality and personalization of dialysis modality education incorporating Latinx cultural values may improve access to home dialysis for Latinx people with kidney disease.

Eight-Year Outcomes of Cardiosphere-Derived Cells in Single Ventricle Congenital Heart Disease.

Cardiosphere-derived cell (CDC) infusion was associated with better clinical outcomes at 2 years in patients with single ventricle heart disease. The current study investigates time-to-event outcomes at 8 years. This cohort enrolled patients with single ventricles who underwent stage 2 or stage 3 palliation from January 2011 to January 2015 at 8 centers in Japan. The primary outcomes were time-dependent CDC treatment effects on death and late complications during 8 years of follow-up, assessed by restricted mean survival time. Among 93 patients enrolled (mean age, 2.3±1.3 years; 56% men), 40 received CDC infusion. Overall survival for CDC-treated versus control patients did not differ at 8 years (hazard ratio [HR], 0.60 [95% CI, 0.21-1.77]; P=0.35). Treatment effect had nonproportional hazards for death favoring CDCs at 4 years (restricted mean survival time difference +0.33 years [95% CI, 0.01-0.66]; P=0.043). In patients with heart failure with reduced ejection fraction, CDC treatment effect on survival was greater over 8 years (restricted mean survival time difference +1.58 years [95% CI, 0.05-3.12]; P=0.043). Compared with control participants, CDC-treated patients showed lower incidences of late failure (HR, 0.45 [95% CI, 0.21-0.93]; P=0.027) and adverse events (subdistribution HR, 0.50 [95% CI, 0.27-0.94]; P=0.036) at 8 years. By 8 years, CDC infusion was associated with lower hazards of late failure and adverse events in single ventricle heart disease. CDC treatment effect on survival was notable by 4 years and showed a durable clinical benefit in patients with heart failure with reduced ejection fraction over 8 years. URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01273857 and NCT01829750.

RADT-01. PRE-OPERATIVE SINGLE FRACTION VERSUS FRACTIONATED STEREOTACTIC RADIOTHERAPY: A SINGLE-INSTITUTION ANALYSIS OF 299 RESECTED METASTASES

Abstract The treatment standard for patients with large or symptomatic brain metastases and limited intracranial disease is surgical resection followed by post-operative (post-op) stereotactic radiosurgery (SRS). The multicenter PROPS-BM cohort showed how pre-operative (pre-op) SRS may lead to a reduced incidence of radiation necrosis (RN), local failure (LF), and meningeal disease (MD) compared to historical controls. Fractionated treatments can deliver a higher biological effective dose and may reduce the incidence of LF and MD. We hypothesize that pre-op fractionated stereotactic radiation therapy (FSRT) will reduce the incidence rate of RN, MD, and LF when compared to patients who receive pre-op SRS. Patients who had surgical resection and pre-operative radiation to at least one brain metastasis at a single institution were retrospectively analyzed. Outcomes were evaluated on a per-lesion basis. The primary outcome was a composite endpoint defined by 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN. 260 patients with 299 resected brain metastases were eligible for analysis. 64 metastases received SRS and 235 metastases received FSRT. 38 patients had multiple metastases resected pre-operatively. The median gross tumor volume was 4 ccs for SRS and 10 ccs for FSRT (p<0.001). Overall, 4 (6.3%) SRS and 6 (2.6%) FSRT patients experienced LF. 4 (6%) SRS and 21 (8.9%) FSRT patients experienced Grade 2 or higher RN. 3 (4.7%) SRS and 11 (4.7%) FSRT patients were diagnosed with MD. 14% of both SRS and FSRT patients experienced the composite endpoint. There were no statistically significant differences in outcome between these two treatment groups. In our study, pre-op SRS and FSRT both appear to be safe and effective options to treat resectable brain metastases. It is important to prospectively compare pre-op SRS and FSRT in matched cohorts to assess any differences in treatment efficacy and toxicity.

Populationwide Screening for Chronic Kidney Disease

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have changed clinical management of chronic kidney disease (CKD) and made populationwide screening for CKD a viable strategy. Optimal age of screening initiation has yet to be evaluated. To compare the clinical benefits, costs, and cost-effectiveness of population-wide CKD screening at different initiation ages and screening frequencies. This cost-effectiveness study used a previously published decision-analytic Markov cohort model that simulated progression of CKD among US adults from age 35 years and older and was calibrated to population-level data from the National Health and Nutrition Examination Survey (NHANES). Effectiveness of SGLT2 inhibitors was derived from the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial. Mortality, quality-of-life weights, and cost estimates were obtained from published cohort studies, randomized clinical trials, and US Centers for Medicare & Medicaid Services data. Analyses were performed from June 2023 through September 2024. One-time or periodic (every 10 or 5 years) screening for albuminuria, initiated at ages between 35 and 75 years, with and without addition of SGLT2 inhibitors to conventional CKD therapy (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers). Cumulative incidence of kidney failure requiring kidney replacement therapy (KRT); life years, quality-adjusted life years (QALYs), lifetime health care costs (2024 US currency), and incremental cost-effectiveness ratios discounted at 3% annually. For those aged 35 years, starting screening at age 55 years, and continuing every 5 years through age 75 years, combined with SGLT2 inhibitors, decreased the cumulative incidence of kidney failure requiring KRT from 2.4% to 1.9%, increased life expectancy by 0.13 years, and cost $128 400 per QALY gained. Although initiation of screening every 5 years at age 35 or 45 years yielded greater gains in population-wide health benefits, these strategies cost more than $200 000 per additional QALY gained. The comparative values of starting screening at different ages were sensitive to the cost and effectiveness of SGLT2 inhibitors; if SGLT2 inhibitor prices drop due to patent expirations, screening at age 55 years continued to be cost-effective even if SGLT2 inhibitor effectiveness were 30% lower than in the base case. This study found that, based on conventional benchmarks for cost-effectiveness in medicine, initiating population-wide CKD screening with SGLT2 inhibitors at age 55 years would be cost-effective.

Benefits and Harms of Coronary Revascularization in Non-Dialysis-Dependent Chronic Kidney Disease and Ischemic Heart Disease: A Systematic Review and Meta-Analysis.

Key Points In people with non–dialysis-dependent CKD, revascularization may lower all-cause mortality and risk of cardiovascular events.Adverse kidney events, which are often cited as a reason to avoid revascularization, were uncommon.Additional research on the effect of revascularization on patient-reported outcomes in people with non–dialysis-dependent CKD is needed. Background Cardiovascular disease is the leading cause of death in people with CKD. Coronary revascularization can improve cardiac function and prognosis in people with ischemic heart disease; however, in people with CKD, there is concern that potential harms could outweigh benefits of revascularization. Evidence on the balance of these risks and benefits, specifically in people with non–dialysis-dependent CKD, is lacking. Methods We conducted a systematic review of randomized controlled trials to assess the risks and benefits of revascularization, compared with medical management, among adults or children with ischemic heart disease and CKD not requiring KRT (dialysis or transplantation). We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials through December 12, 2023. Two people independently screened titles and abstracts followed by full-text review, serially extracted data using standardized forms, independently assessed risk of bias, and graded the certainty of evidence (COE). Results Evaluating data from nine randomized controlled trials, we found that people with CKD and ischemic heart disease treated with revascularization may experience lower all-cause mortality compared with people receiving medical management (risk ratio [RR], 0.80; 95% confidence interval [CI], 0.64 to 0.98; COE, low). Revascularization may reduce incidence of myocardial infarction (RR, 0.81; 95% CI, 0.64 to 1.04; COE, low) and heart failure (RR, 0.80; 95% CI, 0.52 to 1.23; COE, low). The effect on cardiovascular mortality is uncertain (hazard ratio, 0.67; 95% CI, 0.37 to 1.20; COE, very low). Evidence was insufficient for patient-reported outcomes and adverse kidney events. Data were limited by heterogeneity of patient populations and the limited number of trials. Conclusions In people with non–dialysis-dependent CKD, revascularization may be associated with lower all-cause mortality compared with medical management and may also lower the risk of cardiovascular events. Additional data surrounding kidney and patient-reported outcomes are needed to comprehensively engage in shared decision making and determine optimal treatment strategies for people with CKD and ischemic heart disease. Clinical Trial registry name and registration number: CRD42022349820 (PROSPERO).

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.

Risk factors for puncture-related complications after cerebrovascular angiography and neuroendovascular intervention with distal transradial approach

Background and purposeTo determine the risk factors for puncture-related complications after the distal transradial approach (dTRA) for cerebrovascular angiography and neuroendovascular intervention and to explore the incidence and potential mechanisms of procedural failure and puncture-related complications.Materials and methodsFrom February to November 2023, 62 patients underwent dTRA in our department. Demographic, clinical, and procedural data were collected retrospectively. Postoperative puncture-related complications were defined as a syndrome of major hematoma, minor hematoma, arterial spasm/occlusion, arteriovenous fistula, pseudoaneurysm, and neuropathy. Univariate and multivariate logistic regressions were performed to identify significant factors contributing to puncture-related complications.ResultsForty-five diagnostic cerebral angiograms and 17 neurointerventions were performed or attempted with dTRA in 62 patients. Procedural success was achieved via dTRA in 47 (75.8%) patients, whereas 15 (24.2%) required conversion to other approaches. Reasons for failure included puncture failure (n = 8), inability to cannulate due to arterial spasm (n = 6), and inadequate catheter support of the left vertebral artery (n = 1). 17.0% (8/47) of patients had postoperative puncture-related complications. Minor hematoma occurred in 8.5% (4/47) of patients, arterial spasm/occlusion in 6.3% (3/47), and neuropathy in 2.1% (1/47). No major complications were observed. On stepwise multivariable regression analysis, BMI (OR = 0.70, 95%CI 0.513 to 0.958; p = 0.026) was an independent risk factor for puncture-related complications, with a cut-off of 24.8 kg/m2 (sensitivity 66.7% and specificity 87.5%).ConclusionOur cohort is the first study of risk factors for puncture-related complications after neurointerventional interventions with dTRA. This study has shown that a low BMI (< 24.8 kg/m2) is independently associated with the development of puncture-related complications.

Composite Scaffold Materials of Nanocerium Oxide Doped with Allograft Bone: Dual Optimization Based on Anti-Inflammatory Properties and Promotion of Osteogenic Mineralization.

Spinal fusion technique is widely used in the treatment of lumbar degeneration, cervical instability, disc injury, and spinal deformity. However, it is usually accompanied by a high incidence of fusion failure and pseudoarthrosis, placing higher demands on bone implants. Therefore, materials with good biocompatibility, osteoconductivity, and even induce bone ingrowth, which can be used to improve spinal fusion rate and bone regeneration, have become a hot research topic. Here, ultra-small cerium oxide nanoparticles (CeO2 NPs) are prepared and loaded onto the surface of the homograft bone surface to prepare a composite scaffold AB@PLGA/CeO2. The composite scaffold shows the competitive ability to promote osteoblast differentiation in vitro. In vivo experiments show that AB@PLGA/CeO2 has a good bone enhancement effect. In particular, good biological effects of collagen fiber formation, osteogenic mineralization, and tissue repair are shown in intervertebral implant fusion. Further, transcriptome sequencing confirms that CeO2 NPs promote osteogenic differentiation and mineralization by regulating extracellular matrix (ECM) and collagen formation. Meanwhile, CeO2 NPs can regulate the function of the PI3K-Akt signaling pathway to exert its ability to promote osteogenic differentiation and mineralization and affect p53 and cell cycle signaling pathway to regulate osteogenic differentiation and mineralization. Hence, the proposed scaffold is a promising strategy for intervertebral fusion in the clinic.

Care of children with posterior urethral valves after initial endoscopic incision/ablation: what a nephrologist needs to know.

Posterior urethral valves (PUV) are the most common cause of congenital urethral obstruction and are unique in the challenges they pose in management. Endoscopic ablation/incision of the valves is usually offered as the primary treatment of choice. Following this, a range of different clinical patterns are observed, each with varying bladder dysfunction and continence issues and associated with different grades of chronic kidney disease. This review outlines a systematic approach that could help pediatric nephrologists, pediatricians, and pediatric urologists, as well as nursing and allied health specialists, assess these children and develop well-informed management plans. The need for surveillance for bladder dysfunction (incidence approximately 55%), identification of red flags for progression to kidney failure (incidence approximately 20%), and multidisciplinary approach to care are presented, with a focus on reducing long-term morbidity in patients and difficulties for the families. Where possible, an alternative in resource-constrained situations is suggested. We also briefly outline the role of pharmacotherapy, assisted bladder emptying/drainage, and other interventions that have a role in the medium- to long-term management of these patients.