Utilization of Point-of-Care Ultrasound as an Imaging Modality in the Emergency Department: A Systematic Review and Meta-Analysis.

Point-of-care ultrasound (POCUS) is an imaging modality that has become a fundamental part of clinical care provided in the emergency department (ED). The applications of this tool in the ED have ranged from resuscitation, diagnosis, and therapeutic to procedure guidance. This review aims to summarize the evidence on the use of POCUS for diagnosis and procedure guidance. To achieve this, CrossRef, PubMed, Cochrane Library, Web of Science, and Google Scholar databases were extensively searched for studies published between January 2000 and November 2023. Additionally, the risk of bias assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies 2 (for studies on the diagnostic role of POCUS) and Cochrane Risk of Bias tool (for studies on the use of POCUS for procedure guidance). Furthermore, diagnostic accuracy outcomes were pooled using STATA 16 software (StatCorp., College Station, TX, USA), while outcomes related to procedure guidance were pooled using the Review Manager software. The study included 81 articles (74 evaluating the diagnostic application of POCUS and seven evaluating the use of POCUS in guiding clinical procedures). In our findings sensitivities and specificities for various conditions were as follows: appendicitis, 65% and 89%; hydronephrosis, 82% and 74%; small bowel obstruction, 93% and 82%; cholecystitis, 75% and 96%; retinal detachment, 94% and 91%; abscess, 95% and 85%; foreign bodies, 67% and 97%; clavicle fractures, 93% and 94%; distal forearm fractures, 97% and 94%; metacarpal fractures, 94% and 92%; skull fractures, 91% and 97%; and pleural effusion, 91% and 97%. A subgroup analysis of data from 11 studies also showed that the two-point POCUS has a sensitivity and specificity of 89% and 96%, while the three-point POCUS is 87% sensitive and 92% specific in the diagnosis of deep vein thrombosis. In addition, the analyses showed that ultrasound guidance significantly increases the overall success rate of peripheral venous access (p = 0.02) and significantly reduces the number of skin punctures (p = 0.01) compared to conventional methods. In conclusion, POCUS can be used in the ED to diagnose a wide range of clinical conditions accurately. Furthermore, it can be used to guide peripheral venous access and central venous catheter insertion.

CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma.

Therapeutic approaches for clear cell renal cell carcinoma (ccRCC) remain limited; however, chimeric antigen receptor (CAR) T-cell therapies may offer novel treatment options. CTX130, an allogeneic CD70-targeting CAR T-cell product, was developed for the treatment of advanced or refractory ccRCC. We report that CTX130 showed favorable preclinical proliferation and cytotoxicity profiles and completely regressed RCC xenograft tumors. We also report results from 16 patients with relapsed/refractory ccRCC who received CTX130 in a phase I, multicenter, first-in-human clinical trial. No patients encountered dose-limiting toxicity, and disease control was achieved in 81.3% of patients. One patient remains in a durable complete response at 3 years. Finally, we report on a next-generation CAR T construct, CTX131, in which synergistic potency edits to CTX130 confer improved expansion and efficacy in preclinical studies. These data represent a proof of concept for the treatment of ccRCC and other CD70+ malignancies with CD70-targeted allogeneic CAR T cells. SIGNIFICANCE: Although the role of CAR T cells is well established in hematologic malignancies, the clinical experience in solid tumors has been disappointing. This clinical trial demonstrates the first complete response in a patient with RCC, reinforcing the potential benefit of CAR T cells in the treatment of solid tumors.

Metabolic collaboration between cells in the tumor microenvironment has a negligible effect on tumor growth.

The tumor microenvironment is composed of a complex mixture of different cell types interacting under conditions of nutrient deprivation, but the metabolism therein is not fully understood due to difficulties in measuring metabolic fluxes and exchange of metabolites between different cell types in vivo. Genome-scale metabolic modeling enables estimation of such exchange fluxes as well as an opportunity to gain insight into the metabolic behavior of individual cell types. Here, we estimated the availability of nutrients and oxygen within the tumor microenvironment using concentration measurements from blood together with a metabolite diffusion model. In addition, we developed an approach to efficiently apply enzyme usage constraints in a comprehensive metabolic model of human cells. The combined modeling reproduced severe hypoxic conditions and the Warburg effect, and we found that limitations in enzymatic capacity contribute to cancer cells' preferential use of glutamine as a substrate to the citric acid cycle. Furthermore, we investigated the common hypothesis that some stromal cells are exploited by cancer cells to produce metabolites useful for the cancer cells. We identified over 200 potential metabolites that could support collaboration between cancer cells and cancer-associated fibroblasts, but when limiting to metabolites previously identified to participate in such collaboration, no growth advantage was observed. Our work highlights the importance of enzymatic capacity limitations for cell behaviors and exemplifies the utility of enzyme-constrained models for accurate prediction of metabolism in cells and tumor microenvironments.

Efficacy and Safety of Different Dosing Regimens of Rivaroxaban in Patients With Atrial Fibrillation for Stroke Prevention: A Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) poses a substantial risk of stroke, necessitating effective anticoagulation therapy. This systematic review and meta-analysis (SRMA) evaluates the efficacy and safety of different dosing regimens of rivaroxaban in patients with AF. A comprehensive search of relevant databases, focusing on studies published from 2017 onward, was conducted. Inclusion criteria comprised randomized controlled trials (RCTs) and observational studies comparing standard and reduced dosing of rivaroxaban in AF. Data extraction and risk of bias (ROB) assessment were performed, and a meta-analysis was conducted for relevant outcomes. A total of 21 studies fulfilled the inclusion criteria. Standard dosing demonstrates a slightly lower risk of composite effectiveness outcomes and safety outcomes (HR: 0.79, 95% CI: 0.66-0.94, P=0.01) compared to reduced dosing (HR: 0.83, 95% CI: 0.71-0.97, P=0.02). Notable differences in major bleeding, gastrointestinal bleeding (GIB), and intracranial bleeding favored standard dosing. Hemorrhagic stroke and all-cause stroke rates differed significantly, with standard dosing showing a more favorable profile for ischemic stroke prevention. This study highlights the pivotal role of personalized anticoagulation therapy in AF. Standard dosing of rivaroxaban emerges as a preferred strategy for stroke prevention, balancing efficacy and safety. Clinical decision-making should consider individual patient characteristics and future research should delve into specific subpopulations and long-term outcomes to further refine treatment guidelines. The study bridges evidence from clinical trials to real-world practice, offering insights into the evolving landscape of AF management.

Pathomolecular epidemiology, antimicrobial resistance, and virulence genes of Streptococcus dysgalactiae subsp. equisimilis isolates from slaughtered pigs in India.

AIMS: We aimed to investigate the prevalence, pathology, and characterization of Streptococcus dysgalactiae subsp. equisimilis (SDSE) in slaughtered pigs of India. METHODS AND RESULTS: We collected 1254 morbid tissues (lungs-627 and spleen-627) and 627 heart-blood from 627 slaughtered pigs. The bacterial isolation, antibiogram, virulence gene profiling, and mouse pathogenicity testing were performed for the detection and characterization of SDSE. A total of 177 isolates (heart-blood-160 and tissues-17) were recovered from 627 slaughtered pigs with higher isolation rate in heart-blood (25.51%). The prevalence of SDSE was 11% in morbid tissues by polymerase chain reaction. Majority of isolates showed higher detection of streptolysin O, followed by streptokinase and extracellular phospholipase A virulence genes with higher degree of resistance to azithromycin, clindamycin, erythromycin, and penicillin antibiotics. Mouse pathogenicity testing confirmed virulence based on histopathological lesions and re-isolation of SDSE. CONCLUSIONS: Our findings highlight the high prevalence of SDSE in slaughtered pigs. The presence of virulence genes and mouse pathogenicity testing confirm their pathogenic potential.

Alleviating Hypertension by Selectively Targeting Angiotensin Receptor-Expressing Vagal Sensory Neurons.

Cardiovascular homeostasis is maintained, in part, by neural signals arising from arterial baroreceptors that apprise the brain of blood volume and pressure. Here, we test whether neurons within the nodose ganglia that express angiotensin type-1a receptors (referred to as NGAT1aR) serve as baroreceptors that differentially influence blood pressure (BP) in male and female mice. Using Agtr1a-Cre mice and Cre-dependent AAVs to direct tdTomato to NGAT1aR, neuroanatomical studies revealed that NGAT1aR receive input from the aortic arch, project to the caudal nucleus of the solitary tract (NTS), and synthesize mechanosensitive ion channels, Piezo1/2 To evaluate the functionality of NGAT1aR, we directed the fluorescent calcium indicator (GCaMP6s) or the light-sensitive channelrhodopsin-2 (ChR2) to Agtr1a-containing neurons. Two-photon intravital imaging in Agtr1a-GCaMP6s mice revealed that NGAT1aR couple their firing to elevated BP, induced by phenylephrine (i.v.). Furthermore, optical excitation of NGAT1aR at their soma or axon terminals within the caudal NTS of Agtr1a-ChR2 mice elicited robust frequency-dependent decreases in BP and heart rate, indicating that NGAT1aR are sufficient to elicit appropriate compensatory responses to vascular mechanosensation. Optical excitation also elicited hypotensive and bradycardic responses in ChR2-expressing mice that were subjected to deoxycorticosterone acetate (DOCA)-salt hypertension; however, the duration of these effects was altered, suggestive of hypertension-induced impairment of the baroreflex. Similarly, increased GCaMP6s fluorescence observed after administration of phenylephrine was delayed in mice subjected to DOCA-salt or chronic delivery of angiotensin II. Collectively, these results reveal the structure and function of NGAT1aR and suggest that such neurons may be exploited to discern and relieve hypertension.

Treatment of geographic atrophy: an update on data related to pegcetacoplan.

PURPOSE OF REVIEW: Geographic atrophy is an advanced and currently untreatable form of age-related macular degeneration (AMD), which leads to significant compromise of visual function and quality of life. Dysregulation of the complement cascade has been directly implicated in AMD pathogenesis. Pegcetacoplan is a pegylated highly selective bicyclic peptide that inhibits the cleavage of complement component 3 (C3), which represents a key step in propagation of the complement cascade. The phase 2 FILLY trial as well as the phase 3 OAKS and DERBY trials have evaluated the safety and efficacy of pegcetacoplan for the treatment of GA. RECENT FINDINGS: The FILLY, OAKS and DERBY trials have demonstrated that local inhibition of C3 cleavage with pegcetacoplan can reduce geographic atrophy lesion growth compared with sham with an effect size of approximately 11-35% depending on the specific trial and specific geographic atrophy phenotype considered. Overall pegcetacoplan has appeared to be well tolerated with the notable side effect of a dose-dependent increase in the rate of exudative AMD development in treated eyes. SUMMARY: The FILLY, OAKS and DERBY trials have demonstrated that pegcetacoplan is a potentially viable treatment for geographic atrophy. Additional data from the 2-year outcomes of DERBY and OAKS as well as data from the ongoing 3-year GALE extension study will provide additional insights into the potential therapeutic benefit of pegcetacoplan. Future studies assessing complement inhibition at earlier stages of AMD, with the goal of preventing geographic atrophy formation, are warranted.

Glucose regulation by newly synthesized boronic acid functionalized molecules as dipeptidyl peptidase IV inhibitor: a potential compound for therapeutic intervention in hyperglycaemia.

Management of type 2 diabetes mellitus (T2DM) using dipeptidyl peptidase IV (DPP IV) inhibitors is gaining precedence as this enzyme plays an indispensable role in cleaving and inactivating peptides, such as glucagon-like peptide-1 (GLP-1), incretin hormones, and glucose-dependent insulinotropic polypeptide (GIP). There are several DPP IV inhibitors used to treat T2DM, but limited by side effects such as disturbed GIT, flu-like symptoms, etc. Thus, there is an urgent need for the development of novel and better DPP IV inhibitors for the management of the same. In the present study, we investigated the effect of new boronic acid-based thiazole compounds as DPP IV inhibitors. We used substituted anilines that were progressively modified through a multi-step synthesis and then chemically characterised. These molecules have good binding affinity and molecular interactions at the active site of the DPP IV enzyme. Two boronic acid-based molecules, i.e. PC06R58 and PC06R108, were used for the assessment of their in-vitro enzymatic activities. Both molecules (PC06108 and PC06R58) exhibited potent uncompetitive DPP IV enzyme inhibition at two different concentrations of 90.9 and 15.6 nM, respectively, compared to sitagliptin having an IC50 of 17.3 nM. Furthermore, the oral glucose tolerance test suggested significantly reduced blood glucose levels at 20 mg/kg of the body weight upon administration of PC06R58 and PC06R108 molecules in rats after glucose ingestion (2 g/kg of the body weight). The compounds showed satisfactory DPP IV inhibition. Furthermore, DPP IV inhibitory activity and acceptable pre-ADME/Tox profile indicate it is a lead compound in this novel class of DPP IV inhibitors.Communicated by Ramaswamy H. Sarma.

Physician Assessment of ChatGPT and Bing Answers to American Cancer Society's Questions to Ask About Your Cancer.

OBJECTIVES: Artificial intelligence (AI) chatbots are a new, publicly available tool for patients to access health care-related information with unknown reliability related to cancer-related questions. This study assesses the quality of responses to common questions for patients with cancer. METHODS: From February to March 2023, we queried chat generative pretrained transformer (ChatGPT) from OpenAI and Bing AI from Microsoft questions from the American Cancer Society's recommended "Questions to Ask About Your Cancer" customized for all stages of breast, colon, lung, and prostate cancer. Questions were, in addition, grouped by type (prognosis, treatment, or miscellaneous). The quality of AI chatbot responses was assessed by an expert panel using the validated DISCERN criteria. RESULTS: Of the 117 questions presented to ChatGPT and Bing, the average score for all questions were 3.9 and 3.2, respectively ( P < 0.001) and the overall DISCERN scores were 4.1 and 4.4, respectively. By disease site, the average score for ChatGPT and Bing, respectively, were 3.9 and 3.6 for prostate cancer ( P = 0.02), 3.7 and 3.3 for lung cancer ( P < 0.001), 4.1 and 2.9 for breast cancer ( P < 0.001), and 3.8 and 3.0 for colorectal cancer ( P < 0.001). By type of question, the average score for ChatGPT and Bing, respectively, were 3.6 and 3.4 for prognostic questions ( P = 0.12), 3.9 and 3.1 for treatment questions ( P < 0.001), and 4.2 and 3.3 for miscellaneous questions ( P = 0.001). For 3 responses (3%) by ChatGPT and 18 responses (15%) by Bing, at least one panelist rated them as having serious or extensive shortcomings. CONCLUSIONS: AI chatbots provide multiple opportunities for innovating health care. This analysis suggests a critical need, particularly around cancer prognostication, for continual refinement to limit misleading counseling, confusion, and emotional distress to patients and families.

Intensive care risk and long-term outcomes in pediatric allogeneic hematopoietic cell transplant recipients.

ABSTRACT: Allogeneic hematopoietic cell transplantation (HCT) can be complicated by life-threatening organ toxicity and infection necessitating intensive care. Epidemiologic data have been limited by single-center studies, poor database granularity, and a lack of long-term survivors. To identify contemporary trends in intensive care unit (ICU) use and long-term outcomes, we merged data from the Center for International Blood and Marrow Transplant Research and the Virtual Pediatric Systems databases. We identified 6995 pediatric patients with HCT aged ≤21 years who underwent first allogeneic HCT between 2008 and 2014 across 69 centers in the United States or Canada and followed patients until the year 2020. ICU admission was required for 1067 patients (8.3% by day +100, 12.8% by 1 year, and 15.3% by 5 years after HCT), and was linked to demographic background, pretransplant organ toxicity, allograft type and HLA-match, and the development of graft-versus-host disease or malignancy relapse. Survival to ICU discharge was 85.7%, but more than half of ICU survivors required ICU readmission, leading to 52.5% and 42.6% survival at 1- and 5-years post-ICU transfer, respectively. ICU survival was worse among patients with malignant disease, poor pretransplant organ function, and alloreactivity risk factors. Among 1-year HCT survivors, those who required ICU in the first year had 10% lower survival at 5 years and developed new dialysis-dependent renal failure at a greater rate (P<.001). Thus, although ICU management is common and survival to ICU discharge is high, ongoing complications necessitate recurrent ICU admission and lead to a poor 1-year outcome in select patients who are at high risk.

Allogeneic hematopoietic cell transplantation for blastic plasmacytoid dendritic cell neoplasm: a CIBMTR analysis.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes.

Oral Therapeutics Post Menopausal Osteoporosis.

Osteoporosis affects a significant number of postmenopausal women in the United States. Screening is performed using clinical assessments and bone mineral density scans via dual x-ray absorptiometry. Oral therapy is indicated to prevent pathologic fractures in those deemed at increased risk following screening. Bisphosphonates including alendronate, ibandronate, and risedronate are currently first-line oral therapeutics in fracture prevention following the diagnosis of osteoporosis. Hormonal therapies include estrogen-containing therapies, selective estrogen receptor modulators, and other compounds that mimic the effects of estrogen such as tibolone. Lifestyle modifications such as supplementation and physical activity may also contribute to the prevention of osteoporosis and are used as adjuncts to therapy following diagnosis. These therapeutics are limited primarily by their adverse effects. Treatment regimens should be tailored based on significant risk factors demonstrated by patients, adverse effects, and clinical response to treatment. The most severe risk factors relevant to pharmacological selection involve hormone replacement therapies, where concern for venous thrombosis, coronary artery disease, breast, and uterine cancer exist. Bisphosphonates are most commonly associated with gastrointestinal discomfort which may be mitigated with proper administration. Although adverse effects exist, these medications have proven to be efficacious in the prevention of vertebral and non-vertebral fractures in post-menopausal women. Fracture risk should be weighed against the risk of adverse events associated with each of the regimens, with clinical judgment dictating the treatment approach centered around patient goals and experiences.

Private Equity: The Bad and the Ugly.

Private equity's (PE) presence has grown within dermatology over the last decade, creating a new landscape for dermatologists to navigate. Although dermatology PE-backed groups (DPEGs) claim to partner with physicians and improve health care delivery, their actions show that investment returns and profits are prioritized. The history of PE in medicine, the corporate practice of medicine, maturation of the dermatology market, monopolistic practices, overleveraging of nonphysician practitioners, dependence on debt, training under PE, and professional and lifestyle considerations are discussed. Dermatologists should be wary of DPEGs in order to protect the profession and patients.

Diabetic Ketoacidosis-Induced "Terrible Triad" Associated With Seizures and Acute Renal Failure: A Report of a Rare Case.

We report a case of a 17-year-old male patient who came to the emergency department with abdominal pain, headaches for two days, lethargy, and Kussmaul breathing. Diabetic ketoacidosis (DKA) was diagnosed. The patient's clinical course was complicated with a severely elevated triglyceride (TG) level (25,585 mg/dL), acute pancreatitis, renal involvement, and generalized seizures. The proposed mechanism is triglyceride excess due to increased lipolysis, resulting in the formation of excess free fatty acids. The objective of this case report is to present and describe the clinical features, laboratory investigations, case management, and natural course of hypertriglyceridemia in DKA.

Impact of Prefilled Syringes and Masking on Postintravitreal Injection Endophthalmitis.

Purpose: To compare rates of endophthalmitis (1) following intravitreal injection of antivascular endothelial growth factor therapies with glass-vial preparation (GVP) vs prefilled syringes (PFS) and (2) before and after masking protocols were implemented. Methods: Medical records within a multicenter retina practice in Houston, Texas, from January 2015 to August 2021 were retrospectively reviewed. The primary outcome was rate of endophthalmitis after intravitreal injection. Results: A total of 307 349 injections were performed during the study period and 101 cases of endophthalmitis were identified (0.033%). PFS use was associated with a decreased risk of endophthalmitis (relative risk [RR], 0.320; 95% CI, 0.198-0.518, P < .001); 54 cases of endophthalmitis occurred in the GVP group of aflibercept and ranibizumab (0.052%) compared with 24 in the PFS group (0.017%). There was no difference in the endophthalmitis rates with or without universal masking (RR, 0.953; 95% CI 0.616-1.473, P = .91). Discussion: PFS use was associated with a significant reduction in the rate of endophthalmitis while the use of surgical face masks did not appear to significantly impact the rate of endophthalmitis.

Allogeneic stem cell transplant for multiple myeloma & myelofibrosis with split-dose busulfan, fludarabine & cyclophosphamide.

Allogeneic stem cell transplant can have high morbidity and mortality in patients with myelofibrosis (MF) and multiple myeloma (MM). This phase 2 study used a novel myeloablative regimen of split-dose busulfan, fludarabine, and then post-transplant cyclophosphamide. Four patients with MF and 2 with MM were enrolled. At 1 year, non-relapse mortality was 33.3%, and overall survival was 50%. Incidence of acute and chronic GVHD was 33.3% and 16.7%, respectively. Those surviving beyond 1 year (MF = 1, MM = 2) had durable remissions with a median follow-up of 42 months. This small study demonstrates relative safety & favorable key outcomes using this novel approach.

Does Chemo-Radiotherapy Improve Survival Outcomes vs. Radiotherapy Alone for High-Grade cT1 Urothelial Carcinoma of the Bladder?

BACKGROUND: Non-muscle invasive bladder cancer (non-MIBC) that is high-grade and confined to the lamina propria (HGT1) often has an aggressive clinical course. Currently, there is limited data on the comparative effectiveness of RT vs. CRT for HGT1 non-MIBC. We hypothesized that CRT would be associated with improved overall survival (OS) vs. RT in HGT1 bladder cancer. METHODS: Patients diagnosed with HGT1 non-MIBC, and treated with transurethral resection of bladder tumor followed by either treatment with RT alone or CRT, were identified in the National Cancer Database. Inverse probability of treatment weighting (IPTW) was employed and weight-adjusted multivariable analysis (MVA) using Cox regression modeling was used to compare overall survival (OS) hazard ratios. OS was the primary endpoint, and was estimated using the Kaplan-Meier method and log-rank tests. RESULTS: A total of 259 patients with HGT1 UC were treated with: (i) RT alone (n = 123) or (ii) CRT (n = 136). Propensity-weighted MVA showed that combined modality treatment with CRT was associated with improved OS relative to radiation alone (Hazard Ratio [HR]: 0.62, 95% Confidence Interval (95% CI): 0.44-0.88, P = .007). Four-year OS for the CRT vs. RT alone was 36% and 19%, respectively (log-rank P <.008). CONCLUSION: For patients with HGT1 bladder cancer, concurrent CRT was associated with improved OS compared with radiation alone in a retrospective cohort. These results are hypothesis-generating. The NRG is currently developing a phase II randomized clinical trial comparing CRT to other novel, bladder preservation strategies.

Critical Illness Risk and Long-Term Outcomes Following Intensive Care in Pediatric Hematopoietic Cell Transplant Recipients.

Background: Allogeneic hematopoietic cell transplantation (HCT) can be complicated by the development of organ toxicity and infection necessitating intensive care. Risk factors for intensive care admission are unclear due to heterogeneity across centers, and long-term outcome data after intensive care are sparse due to a historical paucity of survivors. Methods: The Center for International Blood and Marrow Transplant Research (CIBMTR) was queried to identify patients age ≤21 years who underwent a 1st allogeneic HCT between 2008-2014 in the United States or Canada. Records were cross-referenced with the Virtual Pediatric Systems pediatric ICU database to identify intensive care admissions. CIBMTR follow-up data were collected through the year 2020. Result: We identified 6,995 pediatric HCT patients from 69 HCT centers, of whom 1,067 required post-HCT intensive care. The cumulative incidence of PICU admission was 8.3% at day +100, 12.8% at 1 year, and 15.3% at 5 years post HCT. PICU admission was linked to younger age, lower median zip code income, Black or multiracial background, pre-transplant organ toxicity, pre-transplant CMV seropositivity, use of umbilical cord blood and/or HLA-mismatched allografts, and the development of post-HCT graft-versus-host disease or malignancy relapse. Among PICU patients, survival to ICU discharge was 85.7% but more than half of ICU survivors were readmitted to a PICU during the study interval. Overall survival from the time of 1st PICU admission was 52.5% at 1 year and 42.6% at 5 years. Long-term post-ICU survival was worse among patients with malignant disease (particularly if relapsed), as well as those with poor pre-transplant organ function and alloreactivity risk-factors. In a landmark analysis of all 1-year HCT survivors, those who required intensive care in the first year had 10% lower survival at 5 years (77.1% vs. 87.0%, p<0.001) and developed new dialysis-dependent renal failure at a greater rate (p<0.001). Conclusions: Intensive care management is common in pediatric HCT patients. Survival to ICU discharge is high, but ongoing complications necessitate recurrent ICU admission and lead to a poor 1-year outcome in many patients. Together, these data suggest an ongoing burden of toxicity in pediatric HCT patients that continues to limit long-term survival.

Improvement in International Prostate Symptom Score after prostatic urethral lifts is dependent on prostatic volume.

INTRODUCTION: Prostatic urethral lifts (PUL) provide improvement in urinary symptoms for men with benign prostatic hyperplasia (BPH). The aim of this study is to determine operative factors associated with improvement in urinary symptoms after PUL in men with bothersome BPH. MATERIALS AND METHODS: Men with BPH undergoing PUL at a single, tertiary center were identified from 2019 to 2022. Inclusion criteria included documented prostate volume as well as preoperative and postoperative cystoscopic images of the prostatic urethra. Multivariate regression modeling was performed to determine the predictive factors-including prostate volume, number of implants, and degree of unobstructed prostatic urethral channel-for improvement in International Prostate Symptom Score (IPSS) after PUL. RESULTS: Of the 47 men, the distribution of prostate volume was 1 patient with < 30 grams, 33 patients with 30-79 grams, five patients with 80-100 grams, and six patients with > 100 grams. The mean number of implants used was six implants. The mean preoperative and postoperative IPSS were 23 and 14, respectively. The mean (standard error (SE)) change and percent change in IPSS score following PUL was 14 and 60%, respectively. The mean percent improvement in prostatic urethral channel after anterior clip placements was 67%. On multivariate analysis, larger prostate volume was associated with greater change in IPPS follow surgery (p = 0.0091) while number of implants and percent of prostatic urethral opening were not associated with change in IPSS (p = 0.3094 and p = 0.2249, respectively). CONCLUSION: Men with larger prostates are associated with greater improvement in urinary symptom after PUL regardless of number of implants utilized and degree of prostatic urethral channel opening after prostatic implants.