Network Registry Research Articles

Kidney Biopsy-Proven Diabetic and Non-Diabetic Kidney Diseases and Outcomes in Patients With Type 2 Diabetes Receiving Dialysis: The REIN Registry.

Chronic kidney disease (CKD) in patients with diabetes does not always equate to diabetic kidney disease (DKD). This study aims to delineate and compare the clinical characteristics, survival rates, and access to kidney transplantation among patients with type 2 diabetes commencing dialysis, who were classified by kidney biopsy as having either DKD or non-diabetic kidney disease (non-DKD). We used the comprehensive French Renal Epidemiology and Information Network registry to analyze baseline clinical characteristics at dialysis inception and outcomes defined as death and access to kidney transplantation. We employed a multivariate Cox proportional hazards model and the Fine-Gray competing risk model to assess the probabilities of mortality and transplantation. Adults in the Renal Epidemiology and Information Network registry in France with a diagnosis of type 2 diabetes who initiated kidney replacement therapy from January 2009 to December 2015 and had a previous native kidney biopsy. We analyzed data from 2,869 patients with diabetes, 45% of whom had a biopsy-confirmed diagnosis of DKD. Among these patients, half presented additional histopathological findings indicative of nephroangiosclerosis and focal segmental glomerulosclerosis. The clinical profiles of patients with DKD and non-DKD were largely comparable. There were no significant differences in dialysis survival rates or kidney transplantation access between the groups, even after adjusting for confounding variables and considering competing risks. At the 6-year mark, the mortality rate was 60.3% (95% CI: 55.5-64.5) for the DKD group and 60.3% (95%CI: 55.9-64.3) for the non-DKD group. Multivariable Cox analysis revealed no significant difference in mortality risk between the DKD and non-DKD groups. The study limitations include potential residual confounders, lack of predialysis data, kidney biopsies possibly outdated, nonrandom biopsy indications, and survival bias because of analysis at dialysis inception. In patients with diabetes initiating dialysis, clinical characteristics and outcomes following dialysis initiation were similar in biopsy-proven DKD versus non-DKD. Our results suggest that the diabetic milieu has a more significant impact on outcomes in patients with diabetes treated with dialysis than the underlying pathological kidney diagnosis.

Prevalence and Prognostic Impact of Diabetes in Takotsubo Syndrome: Insights from the Tokyo Cardiovascular Care Unit Network Registry

Diabetes is a major risk factor for cardiovascular diseases. However, some reports have shown that diabetes has a low prevalence and is associated with favorable outcomes in Takotsubo syndrome. This phenomenon, known as the “diabetes paradox”, in which diabetes plays a protective role in the development of Takotsubo syndrome, remains controversial. Therefore, we investigated the prevalence of diabetes and the prognostic impact of diabetes and glycemic control in patients with Takotsubo syndrome. Using the Tokyo Cardiovascular Care Unit Network registry between 2015 and 2021, we identified 1,226 eligible patients with Takotsubo syndrome (median age, 77 years; male proportion, 21%). The prevalence of diabetes, its clinical characteristics, and its association with in-hospital mortality were assessed. The prevalence of diabetes was 17.0% in Takotsubo syndrome and 15.8% in the general population, with no significant difference (p=0.445). Diabetic patients were older and had higher body mass index, brain natriuretic peptide, and C-reactive protein levels than non-diabetic patients. Patients with diabetes tended to have a higher in-hospital mortality rate than those without (6.3% vs. 3.4%, p=0.057). The multivariable analysis revealed that neither diabetes (odds ratio, 1.83; 95% confidence interval, 0.88–3.80; p=0.106) nor hemoglobin A1c level was significantly associated with in-hospital mortality. In conclusion, diabetes is not uncommon and is not a good prognostic factor in this multicenter registry. Our observations do not support a protective effect of diabetes on the emergence and outcomes of Takotsubo syndrome.

Influence of HLA-B Leader (-21M/T) Dimorphism With Bw4/Bw6 Epitopes on Graft Versus Host Disease After Allogenic Haematopoietic Stem Cell Transplantation in North Indians.

High degree of variability in human leukocyte antigens (HLAs) system restricts availability of histocompatible HLA-matched-related donors, thus increasing reliance on worldwide bone marrow registries network. Nevertheless, due to limited coverage/accessibility/affordability of some ethnicities in these registries, haploidentical haematopoietic stem cell transplantation (HSCT) emerged as an alternative option, though with allorecognition-mediated graft versus host disease (GvHD) (>40% cases). A dimorphism [-21 methionine (M) or threonine (T)] in HLA-B leader peptide (exon 1) which differentially influences its HLA-E binding, plausibly regulates natural killer cell functionality, affecting GvHD vulnerability and clinically in practice for donor selection. Here, we analysed population-specific influence of this functionally relevant dimorphism on post HSCT GvHD occurrence and clinical utility (if any) towards defining donor permissibility. High resolution HLA-B genotyping data were analysed in 178 study participants, including 89 HSCT patient-donor pairs, for the frequency distribution of -21 leader dimorphism. Distribution of HLA-Bw4/Bw6 was deduced with killer cell immunoglobulin receptor ligand calculator tool in IPD-IMGT/HLA database. Though -21T (∼85%) was over represented in the study participants, no significant influence is observed for this variant between HLA-identical v/s haplo HSCT either with or without GvHD, at allelic and genotypic levels as well as in BLEAT (HLA-B Leader Assessment Tool)-based donor-recipient matching. Stratified analysis of -21M/T into Bw4/Bw6 groups revealed a higher frequency of -21T+Bw4 in GvHD (+) group compared to GvHD (-) (p<0.05), plausibly linking this haplotype with occurrence of GvHD post HSCT and importance of HLA class I-mediated NK cell functionality in GvHD.

Scoping review of registration of observational studies finds inadequate registration policies, increased registration, and a debate converging towards pro-registration.

We aimed to examine a) the policies of national and international clinical trial registries regarding observational studies; b) the time-trends of observational study registration; c) the published arguments for and against observational study registration. Scoping review of registry practices and published arguments. We searched the websites and databases of all 19 members of the World Health Organization's Registry Network to identify policies relating to observational studies and the number of observational studies registered annually from the beginning of the registries to 2022. Regarding documents with arguments, we searched Medline, Embase, Google Scholar, and top medical and epidemiological journals from 2009 to 2023. We classified arguments as "main" based on the number (n≥3) of documents they occurred in. Of 19 registries, 15 allowed observational study registration, of which seven (35%) had an explicit policy regarding what to register and two (11%) about when to register. The annual number of observational study registrations increased over time in all registries, e.g., ClinicalTrials.gov increased from 313 in 1999 to 9,775 in 2022. Fifty documents provided arguments concerning observational study registration: 31 argued for, 18 against, and one was neutral. Since 2012, 19 out of 25 documents argued for. We classified nine arguments as main: five for and four against. The two most prevalent arguments for were the prevention of selective reporting of outcomes (n=16) and publication bias (n=12), and against were that it will hinder exploration of new ideas (n=17) and it will waste resources (n=6). Few registries have policies regarding observational studies; an increasing number of observational studies were registered; there was a lively debate on the merits of registration of observational studies, which, since 2012, seems to converge towards pro-registration.

Anemia as a potent marker of in-hospital mortality in patients admitted to the cardiac intensive care unit: Data from the Critical Care Cardiology Trials Network (CCCTN) Registry

Anemia as a potent marker of in-hospital mortality in patients admitted to the cardiac intensive care unit: Data from the Critical Care Cardiology Trials Network (CCCTN) Registry

Over 100 Fontan Patients on Systemic Ventricular Assist Device Support: An ACTION Update.

As the Fontan population grows, understanding successful strategies for ventricular assist device (VAD) support of the failing Fontan circulation is needed. We performed a retrospective analysis of patients with Fontan circulation and systemic VAD support in the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry. Competing outcomes and Kaplan-Meier estimated survival methods were used. Between January 2012 and December 2022, 106 Fontan patients underwent VAD implant (median age 10 years, 20% age ≥18 years). At time of implant, 58% were on greater than or equal to 2 inotropes, 26% on extracorporeal membrane oxygenation (ECMO), and 41% intubated. Since 2018, there have been more patients implanted at INTERMACS profile 1 or 2 (88% vs. 71%, p = 0.02) and on inotropic support (95% vs. 76%, p = 0.01). Median duration of VAD support was 113 (interquartile range (IQR): 43-266) days. At 12 months post-VAD implant, 53% were transplanted, 27% were alive on device, 2% had successful recovery, and 18% had died. Overall, 75% experienced greater than or equal to 1 adverse event, with bleeding, infection, and neurologic dysfunction most common. Despite high acuity at the time of VAD implant and high rate of adverse events, the majority of Fontan patients were transplanted or still alive on device at 12 months post-VAD implant.

A multi-center, open-label, randomized clinical trial evaluating the preventive effect of perampanel on craniotomy-induced epileptogenesis in seizure-naive patients with supratentorial brain tumors: study protocol for a GRAMPAS trial.

Early seizures after craniotomy are significant perioperative complications that can adversely impact patient outcomes. Despite current guidelines advising against the routine use of antiseizure drugs for seizure after craniotomy prevention due to limited efficacy data, many clinicians continue prescribing them. This discrepancy highlights the need for robust evidence to guide clinical practice. This multi-center, randomized clinical trial was designed to investigate the efficacy of perampanel in preventing early seizures after craniotomy. This multi-center, open-label, randomized clinical trial will be conducted across five hospitals in Nagoya, Japan, from February 2024 to December 2026. A total of 142 seizure-naive patients with supratentorial brain tumors will be recruited and randomized (1:1) into the treatment and control groups. The treatment group will receive 2mg of perampanel starting 2days preoperatively and continuing for 28days postoperatively, while the control group will receive no antiseizure drugs. The primary outcome is the incidence of seizures within 28days after craniotomy. Secondary outcomes are length of hospital and intensive care unit stays and postoperative complications. This study addresses the critical need for evidence-based recommendations regarding antiseizure drug use for preventing early seizures after craniotomy. As the first multi-center, randomized trial evaluating perampanel's efficacy in this setting, the findings may significantly influence clinical guidelines and perioperative practices. This trial was registered with the Japan Registry of Clinical Trials (approval number: jRCTs041230117) on December 18, 2023, a member of the Primary Registry Network of the World Health Organization's International Clinical Trials Registry Platform.

Natural Language Processing to Identify Infants Aged 90 Days and Younger With Fevers Prior to Presentation.

Natural language processing (NLP) can enhance research studies for febrile infants by more comprehensive cohort identification. We aimed to refine and validate an NLP algorithm to identify and extract quantified temperature measurements from infants aged 90 days and younger with fevers at home or clinics prior to emergency department (ED) visits. We conducted a cross-sectional study using electronic health record (EHR) data from 17 EDs in 10 health systems that are part of the Pediatric Emergency Care Applied Research Network Registry. All visits between January 1, 2012, and May 31, 2023, for infants aged 90 days and younger were eligible, excluding those with trauma-related diagnoses. We iteratively refined a prespecified rules-based NLP algorithm in 7 successive samples of 200 visits and validated the algorithm on a held-out sample of 500 visits. The reference standard for pre-ED quantified temperature measurements was a temperature documented in clinical notes, excluding ED vital sign temperatures. In our final sample, 113 of 500 visits (23%) had quantified temperature measurements. The NLP algorithm had sensitivity 95% (95% CI: 88%-98%), specificity 96% (95% CI: 93%-97%), and positive predictive value 86% (95% CI: 78%-91%). When applying rules to exclude temperatures that may have been noted more than 24 hours previously, the NLP algorithm had lower sensitivity (88%; 95% CI: 81%-93%) but similar specificity (97%; 95% CI: 95%-98%). This highly accurate NLP algorithm can identify febrile infants without documented fevers in the ED to facilitate their inclusion in large studies using EHR data.

Does cultural and linguistic diversity impact timeliness of dementia diagnosis? Findings from the Australian Dementia Network Registry

Does cultural and linguistic diversity impact timeliness of dementia diagnosis? Findings from the Australian Dementia Network Registry

Suitability of low and middle-income country data-derived prognostics models for benchmarking mortality in a multinational Asia critical care registry network: a multicentre study

Background This study evaluates the predictive performance of prognostic models derived from low- and middle-income country (LMIC) data using a multinational Asian critical care dataset. The research also seeks to identify opportunities for improving these models' accuracy and utility in clinical research and for international benchmarking of critical care outcomes Methods This retrospective multicenter study evaluated the performance of four prognostic models: e-Tropical Intensive Care Score (e-TropICS), Tropical Intensive Care Score (TropICS), Simplified Mortality Score for the Intensive Care Unit (SMS-ICU), and Rwanda Mortality Probability Model (R-MPM) using a dataset of 64,327 ICU admissions from 109 ICUs across six Asian countries. The models' discriminative abilities were assessed using ROC curves, and calibration was evaluated with Hosmer-Lemeshow C-statistics and calibration curves. Recalibration was performed to improve model accuracy, and the impact of the COVID-19 pandemic on model performance was also analysed. Results The e-TropICS and R-MPM models showed relatively good discriminative power, with AUCs of 0.71 and 0.69, respectively. However, all models exhibited significant calibration issues, particularly at higher predicted probabilities, even after recalibration. The study also revealed variability in model performance across different countries, with India's data demonstrating the highest discriminative power. Conclusions The study highlights the challenges of applying existing prognostic models in diverse ICU settings, particularly in LMICs. While the e-TropICS and R-MPM models performed relatively well, significant calibration issues indicate a need for further refinement. Future efforts should focus on developing adaptable models that can effectively accommodate the diverse and dynamic nature of ICU populations worldwide, ensuring their utility in global healthcare benchmarking and decision-making.

Clinical Presentation, Care Pathways, and Delays in Access to Specialized Care in Patients With Systemic Lupus Erythematosus: A Study From Lupus Midwest Network (LUMEN).

We aimed to characterize presentation and care pathways of patients with systemic lupus erythematosus (SLE), and delays in access to SLE-specialized care. We included patients with incident SLE from the Lupus Midwest Network registry. Time from the first medical encounter for SLE clinical manifestation to access to SLE-specialized care, physician diagnosis, and treatment was estimated. Delays were defined as ≥6 months to access specialized care. We compared SLE manifestations, disease activity, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage indexes (SDI) between patients with and without delays. Logistic regression models assessed associations with delays. The study included 373 patients with SLE. The median time to access SLE-specialized care was 1.1 (95% confidence interval [CI] 0.9-1.5) months, time to diagnosis was 30.6 (95% CI 18.9-48.1) months, and time to treatment initiation was 4.7 (95% CI 3.9-8.4) months. Approximately 25% of patients (93 out of 373) experienced delays accessing specialized care, which were associated with fewer SLE manifestations at first SLE-related encounter (fewer than two SLE domains; 92% vs 72%, P < 0.001). Patients with mucocutaneous or musculoskeletal manifestations were less likely to experience delays, whereas hematologic (odds ratio [OR] 1.71, 95% CI 1.03-2.84) or antiphospholipid antibodies domains (OR 6.05, 95% CI 2.46-14.88) were associated with delays. Delays were associated with damage at first access to SLE-specialized care (SDI ≥1; 30% vs 7%, P < 0.001). Patients follow a heterogeneous pathway to receive care. One-fourth of patients experienced delays accessing SLE-specialized care, which was associated with disease-related damage. Fewer manifestations, hematologic manifestations, or antiphospholipidantibodies were associated with delays.

SOX17 - Associated Pulmonary Hypertension in Children: A Distinct Developmental and Clinical Syndrome

ObjectiveTo characterize clinical, hemodynamic, imaging, and pathologic findings in children with pulmonary arterial hypertension (PAH) and variants in SOX17, a novel risk gene linked to heritable and congenital heart disease-associated PAH. Study designWe assembled a multi-institutional cohort of children with PAH and SOX17 variants enrolled in the Pediatric Pulmonary Hypertension Network (PPHNet) and other registries. Subjects were identified through exome and PAH gene panel sequencing. Data were collected from registries and retrospective chart review. ResultsWe identified 13 children (8 female, 5 male) aged 1.6 to 16 years at diagnosis with SOX17 variants and PAH. Seven patients had atrial septal defects (ASD) and two had patent ductus arteriosus. At diagnostic cardiac catheterization, patients had severely elevated mean pulmonary artery pressure (mean 78, range 47-124 mmHg) and markedly elevated indexed pulmonary vascular resistance (mean 25.9, range 4.9-55 WU*m2). No patients responded to acute vasodilator testing. Catheter and CT angiography imaging demonstrated atypical pulmonary artery anatomy including severely dilated main pulmonary arteries, lack of tapering in third and fourth order pulmonary arteries, tortuous ‘corkscrewing’ pulmonary arteries, and abnormal capillary ‘blush.’ Several children had pulmonary artery stenoses and two had systemic arterial abnormalities. Histologic examination of explanted lungs from three patients disclosed plexiform arteriopathy and extensive aneurysmal dilation of alveolar septal capillaries. ConclusionsSOX17-associated PAH is a distinctive genetic syndrome characterized by early onset severe PAH, extensive pulmonary vascular abnormalities, and high prevalence of congenital heart disease with intracardiac and interarterial shunts, suggesting a role for SOX17 in pulmonary vascular development.

Influence of gender on Behçet's disease phenotype and irreversible organ damage: Data from the International AIDA Network Behçet's Disease Registry

ObjectivesGender impact on phenotypical expression of Behçet's disease (BD) has been specifically investigated only in a few large-scale studies. The main goal of the study was to examine gender differences in a large cohort of patients affected by BD. MethodsData were retrieved from the International AIDA Network Registry for BD. We assessed differences between males and females in terms of Behçet's syndrome Overall Damage Index (BODI), differences in the disease manifestations at onset and in the cumulative manifestations throughout disease course, as well as differences in the cardiovascular risk. Finally, predictive factors leading to major organ involvement were investigated. ResultsIn total, 1024 BD patients (567 males, 457 females) were enrolled in the study, with a male-to-female ratio of 1.24/1. Males displayed a significantly higher mean±SD BODI (1.92±2.09) at the last follow-up, compared to female patients (1.25±1.87) (P<0.0001). Uveitis (P<0.0001) and vascular involvement (P=0.0076) were significantly more frequent among males whereas female patients were significantly over-represented in arthralgia (P<0.0001), arthritis (P=0.00025), isolated headache (P<0.0001), central nervous system (CNS) involvement (P=0.040), and gastrointestinal involvement (P=0.00046). Regarding cardiovascular risk, no differences between the two groups emerged (P=0.617). Four variables were associated with the development of major organ involvement: male gender (OR=2.104, P=0.001), current treatment with biologic agents (OR=2.257, P=0.0003), origin from endemic countries (OR=2.661, P=0.0009), and disease duration (OR=1.002, P=0.024). ConclusionBD displays a more severe course among males. This subgroup develops more irreversible damage and presents more frequently ocular and vascular involvement during disease course. On the other hand, female patients are prone to experience articular involvement, headache, CNS and gastrointestinal involvement. These data suggest the existence of a gender-driven disease expression.

Young patients in the cardiac intensive care unit: insights from the critical care cardiology trials network registry

Abstract Background Elderly patients treated in the cardiac intensive care unit (CICU) have engendered much warranted investigation. However, little is known about young patients as another distinct population. Purpose: To describe the demographics, clinical profiles, and outcomes of young CICU patients in order to understand any distinct needs and challenges of this population. Methods: We analyzed consecutive admissions to adult CICUs from 2018 to 2023 in the Critical Care Cardiology Trials Network (CCCTN), a multicenter prospective registry of advanced CICUs in North America coordinated by the TIMI Study Group. Patients aged &amp;lt;40 years were classified as "young patients" and compared to patients ≥ 40 years of age. Results: Among 29,035 CICU admissions during the study period, the median age was 67 years (25th, 75th %iles: 56, 70). Admissions 18 to 40 years of age comprised 6.7% (n=1959) of total admissions. The young cohort was more likely to be female (40.0% vs 36.4%, p=0.0015) and non-Caucasian (55.3% vs. 43.0%, p&amp;lt;0.0001). Traditional cardiovascular risk factors were less common among the young, as were prior cardiovascular diagnoses other than congenital heart disease and pulmonary hypertension. Initial SOFA scores and serum lactate levels were similar in the 2 groups (Table). The most common CICU admission diagnoses in the young were heart failure (HF), arrhythmia, and acute coronary syndrome (ACS) (Panel A). Of these, HF was more common in the young (26.4% vs 19.5%, p&amp;lt;0.0001), while arrhythmia (16.8% vs 18.9%, p=0.03) and ACS (10.9% vs 29.4%, p&amp;lt;0.0001) were less common compared to the older group (Panel B). Tamponade, hypertensive emergency, and congenital disease were more common in the young (Panel B). Respiratory insufficiency was the most common indication for admission to CICU in the young (24.6%) followed by cardiogenic shock (22.4%), unstable arrythmia (15.7%), and cardiac arrest (12.7%, Panel C). Critical care resources, other than coronary angiography/PCI, were utilized significantly more often in the young group (Panel D). Overall utilization of mechanical circulatory support (MCS) was modestly higher among the young cohort (13.1% vs. 11.4%, p=0.03, Panel D); however, among those managed with MCS, the % of MCS that was ECMO was higher among the young (29.3% vs 9.9%, p&amp;lt;0.0001). Young admissions had longer CICU stays (2.7 [1.2-5.9] vs 2.3 [1.2-4.9], p&amp;lt;0.0001). CICU mortality (6.5% vs 10.5%, p&amp;lt;0.0001) and hospital mortality (9.5% vs 14.4%, p&amp;lt;0.0001) were significantly lower in the young. Conclusion: Patients under the age of 40 admitted to CICUs presented with similar disease severity to older patients but more often had shock or cardiac arrest, had longer ICU stays, and more use of advanced ICU therapies but with lower in-hospital mortality. This important patient cohort merits continued clinical and research focus.

Unraveling the paradox: the impact of one or more traditional risk factors on short-term mortality following acute coronary syndromes.

Abstract Background It has been recently suggested that individuals without exposure to any standardized modifiable risk factors may have an increased risk of all-cause mortality from acute coronary syndromes (ACS) compared with their counterparts with one or more risk factors, including diabetes. Purpose To estimate the individual contribution of the four traditional risk factors to the risk of adverse outcomes from first ACS. Methods We analyzed data from 70,953 Caucasian patients presenting with first ACS, but without prior coronary heart disease in the International Survey of Acute Coronary Syndromes (ISACS) Archives registry network from October 2005 to January 2021. The primary outcome was all-cause mortality within 30 days after hospital admission. We calculated sex-specific risk ratios (RRs) stratifying traditional risk factors, current smoking, diabetes, hypercholesterolemia and hypertension into mutually exclusive categories using a balancing strategy by inverse probability weighting. Results Compared with patients presenting without risk factors, those with diabetes had significantly higher 30-day mortality in both women (RR, 1.29; 95% CI, 1.06-1.57) and men (RR, 1.40; 95% CI, 1.16-1.69). By contrast, patients who were current smokers or presented with a history of hypercholesterolemia or hypertension had significantly lower 30-day mortality than patients with no risk factors with RRs ranging from 0.53; 95% CI 0.42–0.67 in women who were smokers to 0.46; 95% CI 0.37–0.59 in men with hypercholesterolemia. The impact of diabetes on mortality was obscured in patients who concomitantly presented with diabetes and one more traditional risk factor. The RRs in combination with current smoking were 1.39; 95% CI 0.92 -2.09 in women and 0.89; 95% CI 0.68 -1.17 in men; with hypercholesterolemia: 0.91; 95% CI 0.66 -1.25 in women and 0.75; 95% CI 0.53–1.06 in men; with hypertension: 1.14; 95% CI 0.99–1.32 in women and 1.12; 95% CI 0.96–1.31 in men. Conclusions Diabetes confers a significant independent excess mortality risk at 30 days following ACS. Dilution bias in this setting refers to the weakening of the observed effect of diabetes because of the inclusion of "one more" risk factor with lower risk profile. Potential misinterpretation of the relationship between diabetes and death from ACS may negatively affect healthcare organization

Access barriers to anti-CD19+ CAR T-cell therapy for NHL across a community transplant and cellular therapy network

AbstractWe analyzed access barriers to anti-CD19+ chimeric antigen receptor T cells (CARTs) for non-Hodgkin lymphoma (NHL) within a community-based transplant and cell therapy network registry. A total of 357 intended recipients of US Food and Drug Administration–approved anti-CD19+ CARTs were identified during the study period (2018-2022). Results showed that the median age at referral was 61 years; referral years were 2018 (4%), 2019 (14%), 2020 (18%), 2021 (26%), and 2022 (38%). Diagnoses included diffuse large B cell (69%), follicular (13%), follicular/large (7%), mantle cell (4%), or other (7%). CART products infused were axicabtagene ciloleucel (62%), Tisa-cel (16%), Brexu-cel (13%), and lisocabtagene maraleucel (9%). One hundred eighty-two patients received infusion with CARTs. The median durations between referral to consultation, consultation to apheresis, and collection to infusion were 11, 107, and 32 days, respectively. The median duration from consultation to CART infusion declined steadily from 207 days in 2019 to 108 days in 2022 (P < .0001). A total of 124 patients (41%) did not receive CART, mostly from disease progression (34%) or poor health (15%). Multivariable logistic regression showed no significant differences in demographic, financial, or social determinants compared with those receiving CART. Notably, the proportion of ineligible patients declined from 53% in 2018 to 2020 to 34% by 2021 to 2022 (P = .001). In conclusion, 41% of community patients were unable to access timely CART therapy for NHL, mostly related to attrition from disease-related causes, whereas the overall time to infusion exceeded 4 months. Time to infusion and the proportion receiving CARTs improved over time. Reducing time to apheresis, early referral, and careful attention to salvage/bridging strategies are necessary.

Early Effects of the ESRD Treatment Choices Model on Kidney Transplant Waitlist Additions.

Despite the mortality benefit of kidney transplantation over dialysis, only 13% of patients with end-stage kidney disease are on the transplant waitlist. Given the low rates of transplant waitlisting in the US, Medicare launched the End-Stage Renal Disease Treatment Choices (ETC) Model in 2021, the largest mandatory trial of payment incentives in kidney disease, which randomized 30% of healthcare markets to financial bonuses/penalties to improve kidney transplantation and home dialysis use. This study examines the effect of ETC payment adjustments on US kidney transplant waitlist additions. Using data from the Organ Procurement and Transplantation Network registry, we examined kidney transplant waitlisting trends between 01/01/2017 and 06/30/2022. Participants were divided into intervention and control arms of the ETC Model. Using an interrupted time series design, we compared slope changes in waitlist additions post-ETC Model implementation (implementation date: 01/01/2021) between the two arms, while accounting for differential changes during the COVID-19 pandemic. Results were stratified by race and ethnicity (White, Black, Hispanic, and other). To examine balance between the two ETC arms, we conducted supplementary analyses using United States Renal Data System and Medicare data. Following implementation of the ETC Model, there were 5,550 waitlist additions in the intervention and 11,332 additions in the control arm (versus 14,023 and 30,610 additions before the ETC Model). Post-ETC, there were no significant differences in kidney transplant waitlist additions between the two arms for the overall cohort (slope difference 6.9 new listings/month, 95% CI: -7.4 to 21.1) or among either White (slope difference 2.6/month, 95% CI -3.0 to 8.1), Black (slope difference 2.2/month, 95% CI: -4.3 to 8.7), or Hispanic (slope difference 0.2/month, 95% CI: -4.5 to 4.9) patients. In the 18 months following implementation, the ETC Model was not associated with significant changes in new kidney transplant waitlist additions.

Investigating the Impact of Additional Congenital Malformations on Speech Outcomes at age Five in Children with a Cleft Palate.

To determine whether children born with a cleft palate ± lip (CP ± L) and additional congenital differences (ACDs - including 'Congenital malformations and deformations' as coded in ICD-10), are less likely to meet the three national speech outcome standards at age five compared to children with CP ± L and no ACDs. An observational study, utilizing national data from the UK Cleft Registry and Audit NEtwork (CRANE) Database linked to national administrative data of hospital admissions. National Health Service, England. 2191 children (993 female, 1198 male) with CP ± L, born 2006-2012 in England, with complete speech data and consent to data linkage. Perceptual speech analysis utilised the Cleft Audit Protocol for Speech - Augmented (CAPS-A) rating and United Kingdom National Speech Outcome Standards (Speech Standard 1 (SS1), Speech Standard 2a (SS2a) and Speech Standard 3 (SS3)). Of 2191 children, 759 (35%) had at least one ACD. Presence of one ACD did not significantly impact speech outcomes but two or more ACDs reduced the odds of achieving all three speech standards: SS1 aOR 0.602 (CI 0.45-0.82, P = .002), SS2a aOR 0.563 (CI 0.41-0.77, P = .001), SS3 aOR 0.606 (0.43-0.84, P = .003). When exploring ACDs by ICD-10 groupings, congenital malformations of the 'Eye, ear, face and neck', 'Circulatory system', 'Digestive system', 'Musculoskeletal system' and 'Other congenital malformations' reduced a child's odds of achieving the speech standards. ACDs, in the absence of a known syndrome, have a significant impact on speech outcome at age five. Incorporating these factors into risk-adjustment models for service level outcome reporting is recommended.

Who gets better after surgery for degenerative cervical myelopathy? A responder analysis from the multicenter Canadian spine outcomes and research network

Degenerative cervical myelopathy (DCM) is the most common cause of acquired non-traumatic spinal cord injury worldwide. Surgery is a common treatment for DCM; however, outcomes often vary across patients. To inform preoperative education and counseling, we performed a responder analysis to identify factors associated with treatment response. An observational cohort study was conducted utilizing prospectively collected data from the Canadian Spine Outcomes Research Network (CSORN) registry collected between 2015-2022. We included all surgically treated DCM patients with complete 12-month follow-up and patient-reported outcomes (PROs) available at 1-year. Treatment response was measured using the minimal clinically important difference (MCID) in PROs including the Neck Disability Index (NDI) and EuroQol-5D (EQ-5D) at 12 months post-surgery. A Least Absolute Shrinkage and Selection Operator (LASSO) machine learning model was used to identify significant associations between 14 pre-operative patient factors and likelihood of treatment response measured by achievement of the MCID in NDI, and EQ-5D. Variable importance was measured using standardized coefficients. To test robustness of findings we trained a separate XGBOOST model, with variable importance measured using SHAP values. Among the 554 DCM patients included, 229 (41.3%) and 330 (59.6%) patients responded to treatment by meeting or surpassing MCID thresholds for NDI and EQ-5D at 1-year, respectively. LASSO regression for likelihood of treatment response measured through NDI found the variable importance rank order to be baseline NDI (OR 1.06 per 1 point increase; 95% CI 1.04 - 1.07), then symptom duration (OR 0.65; 95% CI 0.44-0.97). For EQ-5D, the variable importance rank order was baseline EQ-5D (OR 0.16 per 0.1-point increase; 95% CI 0.03 - 0.78), living independently (OR 2.17; 95% CI 1.22 - 3.85), symptom duration (OR 0.62; 95% CI 0.40 - 0.97), then number of levels affected (OR 0.80 per additional level; 95% CI 0.67 - 0.96). A separate XGBoost model of treatment response measured through NDI, corroborated findings that patients with higher baseline NDI, and shorter symptom duration were more likely to respond to treatment, and additionally found older patients, and those with kyphosis on baseline upright x-ray were less likely to respond. Similarly, an XGBoost model for treatment response measured through EQ-5D corroborated findings that patients with higher baseline EQ-5D, shorter symptom duration, living independently, with fewer affected levels were more likely to respond to treatment, and additionally found older patients were less likely to respond. Our findings suggest patients with shorter symptom duration, higher baseline patient NDI, lower EQ-5D, younger age, living independently, without kyphosis on pre-operative x-ray, and fewer affected levels are more likely to respond to treatment. Timing of surgery with respect to patient symptoms is underscored as a crucial and modifiable patient factor associated with improved surgical outcomes in DCM.

Comparison of Open and Endovascular Repair of Complex Abdominal Aortic Aneurysms

To compare perioperative and 5-year outcomes following endovascular (FEVAR) and open repair (OAR) of complex abdominal aortic aneurysms (cAAA) in males and females separately, given the known sex related differences in perioperative outcomes. We studied all elective cAAA repairs between 2014-2019 in the Vascular Implant Surveillance and Interventional Outcomes Network (VISION) registry. We stratified patients based on sex. We calculated propensity scores for assignment to either OAR or FEVAR. Covariates including age, race, diameter, baseline comorbidities, proximal extent of repair, annual center volumes, and annual surgeon volumes were introduced into the model for estimating propensity scores. Within matched cohorts, perioperative outcomes and 5-year outcomes (mortality, reinterventions, and ruptures) were evaluated using multivariable logistic and Cox regression models. We identified 2,825 patients of whom 29% were female. Within both the sexes, OAR was more commonly performed (OAR vs FEVAR: males: 53% vs 47%; females: 63% vs 37%). After matching, among males (n=1326), FEVAR was associated with lower perioperative mortality (FEVAR vs OAR: 2.3% vs 5.1%; p<.001). However, FEVAR was associated with comparable 5-year mortality (38% vs 28%; hazard ratio (HR) 1.2 [0.92-1.4]; p=.22) and a higher hazard of 5-year reintervention (19% vs 3.7%; aHR: 4.5 [2.6-7.6], p<.001). Among females (n=456), FEVAR and OAR showed similar perioperative mortality (8.3% vs 7.0%; p=.73). At 5 years, FEVAR was associated with higher hazards of mortality (43% vs 32%; aHR: 1.5 [1.03-2.2], p=.034) and reintervention (20% vs 3.0%; aHR: 4.8 [2.1-11], p<.001) compared with OAR. Among males, FEVAR was associated with favorable perioperative outcomes compared with OAR, though these advantages attenuate over time. However, among females, FEVAR was associated with similar perioperative outcomes, eventually leading to higher reinterventions and possibly higher mortality within 5 years. Future efforts should focus on determining the factors associated with these sex disparities to improve outcomes following FEVAR in females. Based on current evidence, females undergoing elective cAAA repair should be selected with due caution, especially for endovascular repair.