Citations

PURPOSE Although most patients with follicular lymphoma (FL) can expect an indolent course, progressive lymphoma remains the primary cause of death during the first decade after diagnosis. Progression of disease within 24 months (POD24) of starting first-line (1L) immunochemotherapy defines a high-risk population with poor survival, but better risk stratification at diagnosis is needed. METHODS The FLIPI24 model was developed and internally validated to predict 24-month event rates using individual data from 4,485 patients treated with 1L immunochemotherapy from 10 observational cohorts of FL. Overall and cause-specific survival was further evaluated in FLIPI24 risk groups. External validation in the 1L immunochemotherapy setting was performed using the prospective observational Lymphoma Epidemiology of Outcomes (LEO) cohort (N = 565) and three randomized phase III trials (N = 3,192); extension to all patients with FL (any 1L therapy) was performed in the LEO cohort (N = 1,445) and its Molecular Epidemiology Resource subcohort (N = 1,074). RESULTS The FLIPI24 model uses age and four blood-based variables (hemoglobin, lactate dehydrogenase, beta-2 microglobulin, and WBC count). FLIPI24 showed consistent performance across validation and extension data sets, which was superior to existing prognostic tools. Across the four external immunochemotherapy validation data sets, patients with high-risk FLIPI24 (23%-32% of patients) had significantly higher 24-month event rates (22%-35%) and inferior 5-year overall survival (77%-83%) compared with patients with low-risk FLIPI24 (29%-31% of patients, 24-month event rates: 10%-12%; 5-year OS: 96%-97%). Results were consistent when evaluating lymphoma-related death and when extended to all patients with FL. CONCLUSION The FLIPI24 model robustly stratifies, at diagnosis, patients with FL at increased risk of lymphoma-related death versus patients with very low lymphoma-related mortality during the first decade after diagnosis. FLIPI24 can be used to enrich future clinical trial designs in newly diagnosed FL.

Abstract Objective To examine the influence of demographics on organ damage in a broad, multiethnic cohort of patients with Behçet’s syndrome (BS). Methods In this cross-sectional ancillary analysis of the PROBE project, the investigated demographic variables were sex, age, education level and geographic area of residence. Damage was measured by the BS Overall Damage Index (BODI). Multivariate linear (β) and logistic (adjusted odds ratio [adjOR]) regression analyses examined associations between demographics and the extent and prevalence of damage. Results A total of 970 patients were enrolled. The median (interquartile range) age was 40 (31–50) years; 56.5% were males; 21.4% had a low level of education. The median BODI score was 1 (0–3), with 65.6% of patients having a BODI ≥1. Males had higher damage (β 0.103) and a higher prevalence of total (adjOR 1.7, per 10 years), ocular (adjOR 1.6), and vascular (adjOR 2.1) damage. Age was associated with greater damage (β 0.104), and a higher prevalence of overall (adjOR 1.4), neuropsychiatric (adjOR 1.2) and miscellaneous (adjOR 2.0) damage. Low education was associated with a greater frequency of overall (adjOR 1.9) and ocular (adjOR 1.6) damage. North African patients experienced greater damage than South European (β 0.400) and Middle Eastern (β 0.314) patients, as well as a higher risk of overall damage (adjOR 13.9 and 10.7, respectively) across all organ domains, except for the reproductive and gastrointestinal systems. Conclusions This study demonstrates how the extent, prevalence and characteristics of damage in BS vary with demographic factors, underscoring their importance in research and personalized management.

Objective To assess the impact of renal replacement therapy in people with lupus nephritis (LN)–associated end‐stage kidney disease (ESKD) and support the development of the 2024 American College of Rheumatology LN treatment guidelines. Methods We conducted a systematic literature review and meta‐analysis to address three Population, Intervention, Comparison, and Outcome (PICO) questions related to renal replacement therapy for ESKD due to LN, including comparisons of kidney transplant versus dialysis, hemodialysis versus peritoneal dialysis, and preemptive kidney transplant versus no preemptive kidney transplant. Outcomes of interest included mortality, cardiovascular (CV) events, infections, lupus flares, disease‐related damage, graft failure, and quality of life. We conducted a meta‐analysis and analyzed hazard ratios for time‐to‐event analyses and risk ratios for dichotomous outcomes, as well as absolute risk estimates. Results Sixteen comparative observational studies addressed at least one of the three PICO questions. Kidney transplant was found to reduce the risks of all‐cause mortality, CV mortality, infection‐related mortality, and CV events compared with dialysis (high certainty). Dialysis modality (peritoneal vs hemodialysis) was not associated with mortality (high certainty) or with other outcomes of infection, CV complications, and systemic lupus erythematosus flares (low certainty). Preemptive kidney transplant was associated with lower risks of graft failure and mortality (low certainty). Conclusion This systematic review identified improved outcomes with kidney transplant versus dialysis for people with LN‐associated ESKD and potential benefits of preemptive kidney transplant. This evidence supports the use of kidney transplant as a preferred renal replacement therapy for people with LN‐ESKD.

Abstract Deep brain stimulation (DBS) of the subthalamic nucleus improves motor symptoms in patients with Parkinson’s disease. Using functional MRI, optimal DBS response networks have been characterized. However, neural activity associated with Parkinsonian symptoms is magnitudes faster than what can be resolved by this method. Although both spatial and temporal domains of these networks appear crucial, no single study has yet investigated both domains simultaneously. Here, we aimed at closing this gap by analysing electrophysiological data from a total of n = 127 hemispheres. Using subthalamic local field potentials that were recorded concurrently alongside whole-brain magnetoencephalography in a multi-centre cohort of patients who underwent subthalamic DBS for the treatment of Parkinson’s disease (n = 100 hemispheres), we analysed the DBS response network in both spatial and temporal domains. In every cortical vertex, cortico-subthalamic coupling was correlated with stimulation outcomes. This network spatially resembled functional MRI-based findings (R = 0.40, P = 0.039) and explained significant amounts of variance in clinical outcomes (βstd = 0.30, P = 0.002), whereas theta–alpha and low beta coupling did not show significant associations with DBS response (theta–alpha: βstd = −0.02, P = 0.805; low beta: βstd = −0.08, P = 0.426). The ‘optimal’ high beta coupling map was robust when subjected to various cross-validation designs (10-fold cross-validation: R = 0.29, P = 0.009; split-half design: R = 0.31, P = 0.026) and was able to predict outcomes across DBS centres [R = 0.74; P(1) = 8.9 × 10−5]. We identified a DBS response network that resembles the previously defined MRI network and operates in the high beta band. Maximal connectivity to this network was associated with optimal DBS outcomes and was able to cross-predict clinical improvements across DBS surgeons and centres.

Importance Assisted ventilation during delayed cord clamping (DCC) may improve the physiologic transition of extremely preterm infants immediately after birth. Objective To determine whether assisted ventilation during 120 seconds of DCC was associated with reduced higher-level resuscitative interventions (intubation, chest compressions, or epinephrine administration) compared with DCC for 30 to 60 seconds followed by resuscitation. Design, Setting, and Participants This was a secondary analysis of the VentFirst randomized clinical trial that was conducted from September 2, 2016, through February 21, 2023, at 12 centers in the US and Canada. Infants born at 23 weeks 0 days’ to 28 weeks 6 days’ gestational age (GA) were included. Intervention Infants randomized to the intervention received either positive-pressure ventilation or continuous positive airway pressure from 30 to 120 seconds after birth, followed by umbilical cord clamping. Those randomized to control received 30 to 60 seconds of DCC followed by assisted ventilation. Main Outcomes and Measures The main outcome was the odds of higher-level resuscitative interventions in the delivery room (DR). Intention-to-treat analyses within 2 a priori cohorts (infants breathing well and not breathing well 30 seconds after birth) used the Cochran-Mantel-Haenszel method to estimate the odds ratios (ORs) of intervention vs control. Results All 570 infants enrolled in the trial were included. Infants had a median (IQR) GA of 26.6 (25.2-27.9) weeks and 273 (47.9%) were female. A total of 271 infants (47.5%) were assessed as not breathing well 30 seconds after birth (150 intervention and 121 control), and 299 (52.5%) were assessed as breathing well 30 seconds after birth (128 intervention and 171 control). In the not-breathing-well cohort, 146 infants (53.9%) were intubated in the DR, 4 received chest compressions (2 intervention and 2 control), and 1 received epinephrine (control). Intubation was less frequent in the intervention group (71 infants [47.3%] vs 75 infants [62.0%]; OR, 0.52; 95% CI, 0.30-0.89). When adjusted by GA strata at randomization, infants in the 26 to 28 weeks’ GA stratum who were in the intervention group were less likely to be intubated in the DR (18 of 79 infants [22.8%] vs 29 of 60 infants [48.3%]; OR, 0.32; 95% CI, 0.15-0.65). However, there was no difference in intubation rates for infants in the 23 to 25 weeks’ GA stratum (53 of 71 infants [74.7%] vs 46 of 61 infants [75.4%]; OR, 0.96; 95% CI, 0.44-2.12). Among infants breathing well at 30 seconds, 74 (24.7%) were intubated in the DR, and none received compressions or epinephrine. Intubation rates were similar between intervention and control in the breathing-well cohort. Conclusions and Relevance While the VentFirst trial did not find a difference in death or intraventricular hemorrhage, this secondary analysis found that assisted ventilation during DCC was associated with less intubation in the DR, primarily among infants born at 26 to 28 weeks’ gestation who were not breathing well 30 seconds after birth. Additional studies are needed before implementing assisted ventilation during DCC in clinical practice. Trial Registration ClinicalTrials.gov Identifier: NCT02742454

Abstract Background and Objectives Lucid episodes (LEs) in advanced dementia are characterized by spontaneous, transient recovery of functional abilities. Despite recent increases in research on this previously understudied phenomenon, standard definitional criteria are lacking, presenting challenges for research. Researchers have proposed a preliminary framework to guide uniform labeling and operationalization of salient data elements for investigating LEs and developing definitional criteria. This study leverages this framework to characterize reports of LEs from caregivers and advance their definition and measurement. Research Design and Methods Family caregivers (N = 259) completed an electronic survey with quantitative and open-ended questions about LEs they witnessed (N = 479 episodes). Respondents were purposively sampled for qualitative interviews. Open-ended question responses (n = 208) and in-depth interviews (n = 24) were analyzed using content analysis. Results Caregiver descriptions suggest that the content and context of LEs are heterogeneous. Descriptions included observable changes from baseline, with behavior or communication that was distinguishable from routine cognitive fluctuations. LEs were sometimes, but not always specified by logically organized actions; recognition or awareness of people, emotions, and surroundings; and insight of their cognitive limitations. Many LEs required deep personal knowledge to attribute it as a meaningful shift. Discussion and Implications Findings suggest that definitional features may universally specify a significant return of ability with more flexible criteria for how this return manifests in observed actions and domains of recovery (i.e., insight, function, and communication). The impact of LEs on observers may be better measured separately, although further research should explore this.