Translocation (11;14) on interphase fluorescent in situ hybridization in plasma cells is regarded as a standard risk prognostic marker in multiple myeloma based on studies conducted before ...introduction of current therapies. We identified 365 patients with t(11;14), and 730 matched controls:132 patients with non-(11;14) translocations and 598 patients with no chromosomal translocation. The median progression-free survival for the three groups were 23.0 (95% confidence interval (CI), 20.8-27.6), 19.0 (95% CI, 15.8-22.7) and 28.3 (95% CI, 25.7-30.6) months, respectively (P<0.01). The median overall survival (OS) for t(11;14), non-(11;14) translocation and no-translocation groups were 74.4 (95% CI, 64.8-89.3), 49.8 (95% CI, 40.0-60.6) and 103.6 (95% CI, 85.2-112.3) months, respectively (P<0.01). Excluding those with 17p abnormality, the median OS in the three groups were 81.7 (95% CI, 67.0-90.7), 58.2 (95% CI, 47.0-76.4) and 108.3 (95% CI, 92.4-140.1) months, respectively (P<0.01). The above relationship held true in patients with age <65 years, international staging system (ISS) I/II stage or those who received novel agent-based induction. Advanced age (hazard ratio (HR): 1.98), 17p abnormality (HR: 2.2) and ISS III stage (HR: 1.59) at diagnosis predicted reduced OS in patients with t(11;14). These results suggest that outcomes of t(11;14) MM are inferior to other standard risk patients.
Micro-Abstract The follow-up examination of patients with monoclonal gammopathy of undetermined significance (MGUS) to screen for malignant transformation is a common practice; however, evidence is ...lacking. Our population-based study has shown that patients with multiple myeloma, Waldenström macroglobulinemia, and lymphoplasmacytic lymphoma who had MGUS follow-up examinations 1 year before a cancer diagnosis might have fewer major complications and longer survival compared with those without such follow-up.
The National Heart, Lung, and Blood Institute convened an expert panel April 28 to 29, 2008, to identify gaps and recommend research strategies to prevent atrial fibrillation (AF). The panel reviewed ...the existing basic scientific, epidemiological, and clinical literature about AF and identified opportunities to advance AF prevention research. After discussion, the panel proposed the following recommendations: (1) enhance understanding of the epidemiology of AF in the population by systematically and longitudinally investigating symptomatic and asymptomatic AF in cohort studies; (2) improve detection of AF by evaluating the ability of existing and emerging methods and technologies to detect AF; (3) improve noninvasive modalities for identifying key components of cardiovascular remodeling that promote AF, including genetic, fibrotic, autonomic, structural, and electrical remodeling markers; (4) develop additional animal models reflective of the pathophysiology of human AF; (5) conduct secondary analyses of already-completed clinical trials to enhance knowledge of potentially effective methods to prevent AF and routinely include AF as an outcome in ongoing and future cardiovascular studies; and (6) conduct clinical studies focused on secondary prevention of AF recurrence, which would inform future primary prevention investigations.
This study aimed to assess the effect of exposure to organic pollutants in adults with chronic kidney disease (CKD).
This was a cross-sectional and longitudinal analysis.
Forty adults enrolled in the ...Chronic Renal Insufficiency Cohort (CRIC).
Exposure at baseline and longitudinally to various organic chemical pollutants.
The outcomes were as follows: death; composite of congestive heart failure, myocardial infarction, and stroke; event-free survival from kidney failure or ≥50% decline in estimated glomerular filtration rate (eGFR); and longitudinal trajectory of eGFR.
We used high-performance liquid chromatography with tandem mass spectrometry to measure urinary concentrations of bisphenols, phthalates, organophosphate pesticides, polycyclic aromatic hydrocarbons, melamine, and cyanuric acid at years 1, 3, and 5 after enrollment in the CRIC. Univariate and multivariable logistic regression were used to examine the association of individual compounds and classes of pollutants with the outcomes. The Cox proportional hazards model and Kaplan-Meier method were used to calculate hazard ratios and 95% CIs for each class of pollutants.
Median baseline eGFR and urinary protein-to-creatinine ratio were 33 mL/min/1.73 m2 and 0.58 mg/g, respectively. Of 52 compounds assayed, 30 were detectable in ≥50% of participants. Urinary chemical concentrations were comparable in patients with CKD and healthy individuals from contemporaneous National Health and Nutrition Examination Survey cohorts. Phthalates were the only class with a trend toward higher exposure in patients with CKD. There was an inverse relationship between exposure and the eGFR slopes for bisphenol F, mono-(3-carboxypropyl) phthalate, mono-benzyl phthalate, mono-2-(carboxymethyl)hexyl phthalate, and melamine. There were no associations between organic pollutant exposure and cardiovascular outcomes.
Small sample size, evaluation of single rather than combined exposures.
Simultaneous measurement of multiple organic pollutants in adults with CKD is feasible. Exposure levels are comparable with healthy individuals. Select contaminants, especially in the phthalate class, may be associated with more rapid deterioration in kidney function.
The effect of exposure to organic pollutants has not been studied in adults with chronic kidney disease. (CKD). To fill this gap, we measured the exposure to a wide range of chemicals that are found in plastics, personal care products, and food preparation. Overall, the exposure was similar to that noted in the healthy population living in the United States. Only select compounds, mainly phthalates, demonstrated a trend with a more rapid decline in kidney function. These findings provide a useful reference for future studies that aim to evaluate organic pollutant exposure in patients with CKD. This is significant because these exposures represent a modifiable risk factor for disease progression through alterations in diet or lifestyle.
Malignant histiocytosis (MH) is an extremely rare neoplasm of the macrophage–dendritic cell lineage. We report the clinical characteristics, molecular aberrations, treatments, and outcomes of ...patients with MH seen at two referral centers from January 2000 to May 2023. We identified 43 patients with MH, of which 26 had histiocytic sarcoma (MH‐H), 9 interdigitating dendritic cell sarcoma (MH‐IDC), and 8 Langerhans cell sarcoma (MH‐LC). The median age at diagnosis was 61 years (range, 3–83). Thirty‐three patients (77%) had multifocal disease, while 10 had unifocal involvement. Tumor specimens from 22 patients (51%) underwent targeted next generation sequencing, and 19 of 22 (86%) had at least one pathogenic mutation, including mutations in MAPK pathway genes (73%). The median overall survival (OS) among the entire cohort was 16 months (95% CI: 8–50). The outcomes of those with multifocal disease were significantly shorter than their unifocal counterpart: median OS of 10 months versus 50 months (p = .07). Patients with risk organ involvement (bone marrow, spleen, or liver) had significantly inferior outcomes. Chemotherapy and surgery were the most common first‐line treatments for multifocal and unifocal disease, respectively. While the outcome for patients with multifocal disease was poor, there was a subset of patients who had durable responses to treatment. Our study highlights that MH has heterogeneous clinical presentation, frequent oncogenic mutations, and prognosis, which is strongly tied to disease extent and type of organ involvement.
Molecular features and outcomes in malignant histiocytosis.
IMPORTANCE Randomized trials of implantable cardioverter-defibrillators (ICDs) for primary prevention predominantly used single-chamber devices. In clinical practice, patients often receive ...dual-chamber ICDs, even without clear indications for pacing. The outcomes of dual- vs single-chamber devices are uncertain. OBJECTIVE To compare outcomes of single- and dual-chamber ICDs for primary prevention of sudden cardiac death. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of admissions in the National Cardiovascular Data Registry's (NCDR) ICD registry from 2006-2009 that could be linked to Centers for Medicare & Medicaid Services fee-for-service Medicare claims data. Patients were included if they received an ICD for primary prevention and did not have a documented indication for pacing. MAIN OUTCOMES AND MEASURES Adjusted risks of 1-year mortality, all-cause readmission, heart failure readmission, and device-related complications within 90 days were estimated with propensity-score matching based on patient, clinician, and hospital factors. RESULTS Among 32 034 patients, 12 246 (38%) received a single-chamber device and 19 788 (62%) received a dual-chamber device. In a propensity-matched cohort, rates of complications were lower for single-chamber devices (3.51% vs 4.72%; P < .001; risk difference, −1.20 95% CI, −1.72 to −0.69), but device type was not significantly associated with 1-year mortality (unadjusted rate, 9.85% vs 9.77%; hazard ratio HR, 0.99 95% CI, 0.91 to 1.07; P = .79), 1-year all-cause hospitalization (unadjusted rate, 43.86% vs 44.83%; HR, 1.00 95% CI, 0.97-1.04; P = .82), or hospitalization for heart failure (unadjusted rate, 14.73% vs 15.38%; HR, 1.05 95% CI, 0.99-1.12; P = .19). CONCLUSIONS AND RELEVANCE Among patients receiving an ICD for primary prevention without indications for pacing, the use of a dual-chamber device compared with a single-chamber device was associated with a higher risk of device-related complications and similar 1-year mortality and hospitalization outcomes. Reasons for preferentially using dual-chamber ICDs in this setting remains unclear.
We explored the association between bone marrow plasma cells (BMPCs) and disease presentation and outcome among 1574 AL patients. Three BMPC groups were formulated: <5% (n = 231, 15% of study ...population), 5-19% (n = 1045, 66%), and ≥20% (n = 298, 19%). Heart and renal involvement were more and less prevalent, respectively, with increasing BMPCs. Patients with ≥20% BMPCs had higher likelihood for classic myeloma phenotype with less skewed lambda restriction, a higher rate of intact immunoglobulin secretion, a lower hemoglobin and higher rates of hypercalcemia and bone lytic lesions. High-risk cytogenetic abnormalities were more common in ≥20% BMPCs. Complete hematological response was less frequent with rising BMPCs. The median survival was inversely associated with the BMPC groups (81, 33, 12 months for <5%, 5-19%, and ≥20% BMPCs, respectively; P < 0.001). Survival discrimination was maintained at 1-year landmark and in those who achieved a complete response. Multivariate analysis accounting for known prognostic markers yielded an independent prognostic role for ≥20% BMPCs, but not for the other BMPC groups. AL patients with 20% or greater BMPCs have poorer outcome independent of their cardiac risk category and stem cell transplant eligibility. Distinct interventions in these patients should be explored to improve outcome.
OBJECTIVE—To investigate the effect of LPA gene variants and renal function on lipoprotein(a) Lp(a) levels in people with chronic kidney disease and determine the association between elevated Lp(a) ...and myocardial infarction and death in this setting.
APPROACH AND RESULTS—The CRIC Study (Chronic Renal Insufficiency Cohort) is an ongoing prospective study of 3939 participants with chronic kidney disease. In 3635 CRIC participants with genotype data, carriers of the rs10455872 or rs6930542 variants had a higher median Lp(a) level (mg/dL) compared with noncarriers (73 versus 23; P<0.001 and 56 versus 22; P<0.001, respectively). The 3744 participants (55% male and 41% non-Hispanic White) with available baseline Lp(a) levels were stratified into quartiles of baseline Lp(a) (mg/dL)<9.8, 9.8 to 26.0, 26.1 to 61.3, and >61.3. There were 315 myocardial infarctions and 822 deaths during a median follow-up of 7.5 years. The second quartile had the lowest event rate. After adjusting for potential confounders and using a Cox proportional hazards model, the highest quartile of Lp(a) was associated with increased risk of myocardial infarction (hazard ratio, 1.49; 95% confidence interval, 1.05–2.11), death (hazard ratio, 1.28; 95% confidence interval, 1.05–1.57), and the composite outcome (hazard ratio, 1.29; 95% confidence interval, 1.07–1.56) compared with the second quartile of Lp(a).
CONCLUSIONS—Among adults with chronic kidney disease, elevated Lp(a) is independently associated with myocardial infarction and death. Future studies exploring pharmacological Lp(a) reduction in this population are warranted.
An elevated fibroblast growth factor 23 (FGF-23) level is independently associated with adverse outcomes in populations with chronic kidney disease, but it is unknown whether FGF-23 testing can ...improve clinical risk prediction in individuals.
Prospective cohort study.
Participants in the Chronic Renal Insufficiency Cohort (CRIC) Study (n = 3,789).
Baseline carboxy-terminal FGF-23 (cFGF-23) level.
All-cause and cardiovascular (CV) mortality, incident end-stage renal disease (ESRD), heart failure (HF) admission, and atherosclerotic events at 3, 5, and 8 years.
We assessed changes in model performance by change in area under the receiver operating characteristic curve (ΔAUC), integrated discrimination improvement (IDI), relative IDI, and net reclassification index (NRI) above standard clinical factors. We performed sensitivity analyses, including an additional model comparing the addition of phosphate rather than cFGF-23 level and repeating our analyses using an internal cross-validation cohort.
Addition of a single baseline value of cFGF-23 to a base prediction model improved prediction of all-cause mortality (ΔAUC, 0.017 95% CI, 0.001-0.033; IDI, 0.021 95% CI, 0.006-0.036; relative IDI, 32.7% 95% CI, 8.5%-56.9%), and HF admission (ΔAUC, 0.008 95% CI, 0.0004-0.016; IDI, 0.019 95% CI, 0.004-0.034; relative IDI, 10.0% 95% CI, 1.8%-18.3%), but not CV mortality, ESRD, or atherosclerotic events at 3 years of follow-up. The NRI did not reach statistical significance for any of the 3-year outcomes. The incremental predictive utility of cFGF-23 level diminished in analyses of the 5- and 8-year outcomes. The cFGF-23 models outperformed the phosphate model for each outcome.
Power to detect increased CV mortality likely limited by low event rate. The NRI is not generalizable without accepted prespecified risk thresholds.
Among individuals with CKD, single measurements of cFGF-23 improve prediction of risks for all-cause mortality and HF admission but not CV mortality, ESRD, or atherosclerotic events. Future studies should evaluate the predictive utility of repeated cFGF-23 testing.
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