Faculty Bibliography
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school:LISOM
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14847
Diagnosis and Management of Philadelphia-Like Acute Lymphoblastic Leukemia in Adults
BACKGROUND:The entity of Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) accounts for approximately 20-30% of newly diagnosed adults with B-cell ALL cases in the USA. Compared to other B-cell subtypes, Ph-like ALL is associated with overall poor prognosis and inferior outcomes with high measurable residual disease rates following induction therapy, increased risk of treatment failure and relapse, as well as short event-free and overall survival. SUMMARY:Here we aim to highlight Ph-like ALL genetic subtypes and methods of genomic profiling for diagnosis and disease prognostication and to summarize current management approaches for frontline treatment including multiagent chemotherapy, immunotherapy, tyrosine kinase and small molecule inhibitors, and the role of allogeneic stem cell transplantation. KEY MESSAGES:Despite the improvement in the treatment outcomes of adult patients with newly diagnosed B-cell ALL, patients with Ph-like ALL continue to do poorly with standard therapy. Thus, tailored therapeutic studies are indeed warranted to refine frontline treatment approaches and to improve outcomes for patients with Ph-like ALL.
PMID: 41144606
ISSN: 1421-9662
CID: 6075182
Chorionic Villi Sampling among Early and Late Gestational Age: Does Timing Affect Yield and Outcomes?
BACKGROUND/UNASSIGNED:weeks to detect genetic abnormalities; however, a majority of providers opt to perform CVS after 11 weeks. This study evaluated the feasibility of CVS performed at varying gestational ages, comparing chorionic villi (CV) yield and procedural outcomes among early, typical, and late procedures. MATERIALS AND METHODS/UNASSIGNED:weeks). The primary outcome was median CV weight. Secondary outcomes included need for culture, time to microarray results, and a subanalysis of abnormal chromosomal microarray analysis (CMA) results, obstetric, and neonatal outcomes. RESULTS/UNASSIGNED:Of 719 patients, 8.1% underwent early, 83.2% typical, and 8.8% late CVS. The early cohort had a lower body mass index (BMI). Early CVS was most frequently performed transvaginally and for the indication of prior affected pregnancy, and less likely for abnormal genetic screening or ultrasound findings. Median villi weight did not differ significantly, and 89% of all procedures yielded adequate tissue, defined as ≥5 mg. The time to the microarray result was shortest in the typical group. There were no significant differences in other secondary outcomes of need for culture, number of passes, or procedure-related complication rates. There was no case of limb anomalies. CONCLUSION/UNASSIGNED:CVS performed before 11 weeks and after 14 weeks demonstrated comparable microarray outcomes and demonstrate the technical feasibility and diagnostic adequacy of CVS performed outside the typical gestational window. The results also support the availability of early CVS for cytogenetic testing in early pregnancy loss, where management may not allow for direct tissue testing. Prospective studies are warranted to validate these results and refine recommendations for optimal timing of CVS.
PMCID:13056434
PMID: 41953865
ISSN: 2157-6998
CID: 6075165
Impact of demographic factors on clinical outcomes of patients with acute myeloid leukemia
PMCID:12951143
PMID: 40931864
ISSN: 1592-8721
CID: 6075179
CAR HEMATOTOX independently predicts outcomes after CD19 CAR-T therapy for acute lymphoblastic leukemia
Chimeric antigen receptor (CAR) T-cell (CAR-T) treatment for B-cell acute lymphoblastic leukemia (ALL) induces high initial response rates, but most patients relapse. Low disease burden (often defined as <5% blasts in the bone marrow) is associated with better outcomes. CAR HEMATOTOX (HT) is a score using prelymphodepletion hematologic and inflammatory parameters to predict outcomes in lymphoma. Here, we assess its prognostic utility in a large multicenter adult B-cell ALL cohort. Patients who received brexucabtagene autoleucel across 33 centers in North America were included as part of the Real-World Outcomes Collaborative of CAR-T in Adult ALL (ROCCA) consortium. An independent cohort of 61 patients with ALL treated with an investigational CD19 CAR-T therapy at 1 center was also described. Among 199 ROCCA consortium patients, 43 (22%) patients with HTlow scores had lower rates of delayed neutrophil recovery than those with HThigh scores (26% vs 52%, P = .002) and fewer severe infections (2.5% vs 18.8%, P = .011). They also had higher response rates, overall survival (OS), and event-free survival (EFS), as well as lower nonrelapse mortality and cumulative incidence of relapse. The survival differences remained significant after multivariable adjustment for disease burden and other covariates. In the investigational cohort of 61 patients, patients with HTlow scores had improved OS and EFS, as well as higher peak CAR-T expansion. In summary, CAR HT score is a prognostic factor independent of disease burden in adult ALL. HTlow score is associated with superior outcomes after CD19 CAR-Ts and higher CAR-T expansion in a single-center cohort. These trials were registered at www.clinicaltrials.gov as #NCT01044069 and #NCT01860937.
PMID: 41052404
ISSN: 2473-9537
CID: 6075180
When Athletes Ask About Chronic Traumatic Encephalopathy
Athletes exposed to repetitive head impacts (RHI) may seek clinical evaluation because of concerns about chronic traumatic encephalopathy (CTE), a neuropathologically defined disease that cannot currently be diagnosed during life. As public awareness of CTE has expanded, clinicians face challenges communicating diagnostic uncertainty, interpreting non-specific symptoms, and addressing concerns about future neurological health. This Current Opinion examines the widening gap between public expectations and scientific capability and considers its implications for athlete-centered care. We discuss how clinicians can acknowledge uncertainty without dismissing patients' concerns, identify potentially treatable contributors to symptoms without prematurely attributing them to neurodegenerative disease, and use shared decision-making to guide individualized evaluation and management. We also consider how concerns about CTE may influence decisions about continued participation and return-to-sport among current athletes. Meeting these challenges requires coordinated interdisciplinary care, evidence-based communication, and clinical approaches that prioritize meaningful intervention even when diagnostic certainty remains unavailable.
PMCID:13722644
PMID: 42963510
ISSN: 2199-1170
CID: 6074819
Heart and Brain: Linking Obesity-Related Inflammation, Cardiovascular Disease and Cognitive Function
The heart and brain are interconnected, and risk factors that impact the heart can negatively affect the brain and cognition. Among the underlying features that foster both poor brain health and poor heart health are obesity, diabetes, physical inactivity and low sleep quality. Obesity and type 2 diabetes are associated with an increased likelihood of cognitive impairment and dementia. Further, obesity is a causal factor in obstructive sleep apnea, leading to intermittent hypoxemia, neuroinflammation and cognitive dysfunction. Cerebrovascular disease with reduced cerebral blood flow brings on stroke and elevates dementia risk. Like cardiovascular disease, cerebrovascular disease is also accelerated in the setting of obesity, likely through the same mechanisms involving endothelial dysfunction and damage to macrovasculature and microvasculature from hypertension, dyslipidemia and inflammation. Obesity is considered a risk factor for recurrent stroke. The protracted low-grade chronic elevation of inflammatory markers found with excess adiposity leads to oxidative stress and promotes both endothelial dysfunction and a pro-thrombotic state. Greater loss of brain volume has been documented in middle-aged and older adults with obesity compared with young adults with obesity. Obesity poses a threat to the cardiovascular and cerebrovascular health and well-being of individuals worldwide. Unfortunately, treatments directed at reducing caloric intake are of limited effectiveness. This review will focus on the latest research into the link between excess adipose tissue and cardiac and brain health, with attention to dietary and lifestyle interventions that may be protective of the integrity and function of the vasculature and brain.
PMCID:13705137
PMID: 42930873
ISSN: 2308-3425
CID: 6074718
Disseminated Histoplasmosis Presenting as an Obstructive Mass in Crohn's Disease: A Case Report [Case Report]
INTRODUCTION/UNASSIGNED:Patients with Crohn's disease are at increased risk for both colorectal carcinoma and opportunistic infections due to chronic inflammation and long-term immunosuppressive therapy. Fungal infections such as histoplasmosis may mimic malignancy or inflammatory exacerbation, leading to diagnostic delay. CASE PRESENTATION/UNASSIGNED:, confirmed by polymerase chain reaction. The urinary Histoplasma galactomannan antigen test was negative, while serum 1,3 β-D-glucan was positive. The patient was successfully treated with amphotericin B followed by itraconazole, with complete clinical recovery. Retrospective history revealed travel to Ecuador. CONCLUSION/UNASSIGNED:Gastrointestinal histoplasmosis can closely mimic Crohn's flare or malignancy, especially in immunosuppressed patients. Careful histopathologic evaluation and integration of clinical and laboratory findings are essential for timely diagnosis and effective antifungal therapy.
PMCID:13695535
PMID: 42927153
ISSN: 1662-0631
CID: 6074712
Balloon-occluded ethylene vinyl alcohol copolymer embolization of a hemorrhagic renal mass in an octogenarian initially unfit for nephrectomy [Case Report]
Palliative transarterial embolization is an established option for symptomatic renal tumors in patients who are poor surgical candidates, but conventional particle or coil techniques sacrifice uninvolved parenchyma and permit reflux-related non-target embolization. We report an 89-year-old man with atrial fibrillation, heart failure with preserved ejection fraction, and chronic obstructive pulmonary disease who presented with one month of gross hematuria, transfusion-requiring anemia, and acute kidney injury secondary to a 5.8 × 4.6 × 3.4 cm hypervascular right upper-pole renal mass extending into the collecting system. Deemed unfit for nephrectomy during the index admission, he underwent super-selective balloon-occluded embolization with ethylene vinyl alcohol copolymer delivered through a balloon-occlusion microcatheter. Hematuria resolved, hemoglobin stabilized without further transfusion, and creatinine returned to near baseline by post-procedure day 2. He remained free of hematuria for approximately 12 weeks despite resumption of apixaban. Recurrent intermittent bleeding from a persistent enhancing collecting-system component prompted readmission; surveillance imaging demonstrated a devascularized cortical tumor bed with an approximately 69% reduction in tumor volume and preserved parenchymal enhancement of the treated kidney. After interval stabilization, he underwent elective robotic nephrectomy with minimal blood loss. Pathology demonstrated clear cell renal cell carcinoma (grade 3, stage pT3a) with 50% tumor necrosis and post-embolization changes; urothelial carcinoma was excluded. Balloon-occluded ethylene vinyl alcohol copolymer embolization may provide effective temporizing hemostasis and histologically confirmed tumor devascularization in nonsurgical patients, serving in this case as a bridge to elective nephrectomy.
PMCID:13692164
PMID: 42921241
ISSN: 1930-0433
CID: 6074939
Global, Regional, and National Burden of Heart Failure, 1990-2023: A Systematic Analysis for the Global Burden of Disease Study 2023
IMPORTANCE/UNASSIGNED:Heart failure (HF) is a common condition with substantial geographical variation in its prevalence and underlying etiologies. Consistent and comparable data on the burden of HF within populations are needed to inform health system priorities. OBJECTIVE/UNASSIGNED:To estimate the global burden of HF. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cross-sectional study estimates disease burden using Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) methodologies to integrate multiple information sources. Data come from 204 countries and territories from 1990 to 2023 representing the global population with prevalent HF. EXPOSURE/UNASSIGNED:HF and underlying etiologies. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Estimates with 95% uncertainty intervals (UIs) for the prevalence and years lived with disability (YLDs) for HF by age, sex, location, year, and underlying etiology. RESULTS/UNASSIGNED:Globally, there were 56.0 million (95% UI, 49.9-62.2 million) estimated cases of HF in 2023. The estimated prevalence of HF generally increased with age for all locations. While ischemic heart disease and hypertensive heart disease were the 2 most common etiologies globally among older adults, there was substantial variation in etiological pattern by location and age. Congenital heart anomalies and rheumatic heart disease (RHD) were common etiologies in children and young adults, while the proportion of HF due to alcohol use peaked in middle adulthood. Location-specific estimates highlighted regions with higher burden of HF due to specific etiologies, including RHD (south Asia, east Asia, Oceania, southeast Asia, central sub-Saharan Africa, eastern sub-Saharan Africa, southern sub-Saharan Africa, and western sub-Saharan Africa), alcohol use (eastern Europe, Australasia, the Caribbean, and central Europe), and Chagas disease (southern, Andean, tropical, and central Latin America). CONCLUSIONS AND RELEVANCE/UNASSIGNED:Heart failure is a significant global public health burden, and the impact is likely to increase as populations age. However, most HF etiologies can be prevented by interventions that reduce exposure to modifiable risk factors, such as elevated blood pressure, excessive alcohol consumption, and tobacco use. Etiology- and location-specific estimates can provide necessary information for public health officials to determine how best to prioritize interventions to reduce HF disease burden.
PMID: 42814432
ISSN: 2380-6591
CID: 6074692
Corrigendum to "Precision nephrology identified tumor necrosis factor activation variability in minimal change disease and focal segmental glomerulosclerosis." Kidney International 2023;103,565-579
PMID: 42901693
ISSN: 1523-1755
CID: 6074875
