Faculty Bibliography
Searched for:
school:LISOM
Total Results:
13980
A case of renal cell carcinoma with tumor thrombus extension into the right atrium [Case Report]
INTRODUCTION/UNASSIGNED:Over the last half-century, mortality from renal cell carcinoma (RCC) has seen a dramatic reduction, while 5-year survival rates have reached an all-time high (34% to 75%). CASE PRESENTATION/UNASSIGNED:A 77-year-old female with Stage 4 RCC (cT3c, cN1, cM1) presented with acute onset chest and back pain. Imaging revealed interval enlargement of a left renal mass with propagation of tumor thrombus (TT) throughout the left renal vein, intrahepatic and suprahepatic inferior vena cava (IVC) with extension into the right atrium (RA). The patient successfully underwent a high-risk open left nephrectomy with caval thrombectomy, retroperitoneal lymph node dissection, and atrial thrombectomy. DISCUSSION/UNASSIGNED:Approximately, 1% of RCC cases involve the right atrium, and radical nephrectomy with vena caval thrombectomy remains the most effective treatment for cavoatrial TT, with 5-year survival rates between 30% and 72%. While patients with renal vein involvement have better survival rates than those with IVC involvement, advanced TT cases (Types III and IV) often require extracorporeal circulation. Though the patient understood the prognosis of her RCC, discussing the risks of a complex procedure versus not intervening was challenging. Despite a typical median survival of 12 months for level IV tumor thrombus (TT), she remains stable 28 months post-surgery. CONCLUSION/UNASSIGNED:Although the 5-year survival rate for renal cell carcinoma (RCC) has increased from 34% to 75%, the disease still adversely affects patients' quality of life. A multidisciplinary approach is essential when managing metastatic RCC, particularly involving the heart. Despite the associated risks, surgical intervention is more effective in prolonging life by preventing sudden cardiac death due to embolic events.
PMCID:12140791
PMID: 40486613
ISSN: 2049-0801
CID: 5868932
A Phase 1/2 multicenter trial of DKN-01 as monotherapy or in combination with docetaxel for the treatment of metastatic castration-resistant prostate cancer (mCRPC)
BACKGROUND:Dickkopf-related protein 1 (DKK1) is a Wingless-related integrate site (Wnt) signaling modulator that is upregulated in prostate cancers (PCa) with low androgen receptor expression. DKN-01, an IgG4 that neutralizes DKK1, delays PCa growth in pre-clinical DKK1-expressing models. These data provided the rationale for a clinical trial testing DKN-01 in patients with metastatic castration-resistant PCa (mCRPC). METHODS:(combination) for men with mCRPC who progressed on ≥1 AR signaling inhibitors. DKK1 status was determined by RNA in-situ expression. The primary endpoint of the phase 1 dose escalation cohorts was the determination of the recommended phase 2 dose (RP2D). The primary endpoint of the phase 2 expansion cohorts was objective response rate by iRECIST criteria in patients treated with the combination. RESULTS:18 pts were enrolled into the study-10 patients in the monotherapy cohorts and 8 patients in the combination cohorts. No DLTs were observed and DKN-01 600 mg was determined as the RP2D. A best overall response of stable disease occurred in two out of seven (29%) evaluable patients in the monotherapy cohort. In the combination cohort, five out of seven (71%) evaluable patients had a partial response (PR). A median rPFS of 5.7 months was observed in the combination cohort. In the combination cohort, the median tumoral DKK1 expression H-score was 0.75 and the rPFS observed was similar between patients with DKK1 H-score ≥1 versus H-score = 0. CONCLUSION/CONCLUSIONS:DKN-01 600 mg was well tolerated. DKK1 blockade has modest anti-tumor activity as a monotherapy for mCRPC. Anti-tumor activity was observed in the combination cohorts, but the response duration was limited. DKK1 expression in the majority of mCRPC is low and did not clearly correlate with anti-tumor activity of DKN-01 plus docetaxel.
PMID: 38341461
ISSN: 1476-5608
CID: 5635542
25 years of palivizumab: a global historic review of its impact on the burden of respiratory syncytial virus disease in children
INTRODUCTION/UNASSIGNED:Respiratory syncytial virus (RSV) causes significant morbidity and mortality in young children. For 25 years, palivizumab has been the only effective pharmaceutical RSV preventive. AREAS COVERED/UNASSIGNED:We summarize the development and a quarter-century of real-world evidence with palivizumab. We highlight its positive impact on the burden of RSV in high-risk children. Based on lessons learnt from its implementation, we suggest strategies for effective and equitable deployment of newer RSV preventives. EXPERT OPINION/UNASSIGNED:Following failure of the formalin-inactivated RSV vaccine in 1967, RSV intravenous immunoglobulin was approved in 1996 after three decades' research. Subsequently, palivizumab emerged as the most effective and safe RSV preventive, demonstrated by the IMpact trial, and was licensed in 1998 in the United States. Over the last 25 years, the benefits of palivizumab have been firmly established through a wealth of evidence, predominantly from high-income countries (HICs). To achieve a global impact with the newer RSV preventives, evidenced-based universal guidelines must be developed and endorsed by regulatory authorities and relevant scientific societies. Independent economic evaluations should incorporate all RSV-associated healthcare costs, reduction of long-term respiratory sequelae, and standardized outcomes. Most importantly, equity in product availability and implementation, particularly in low- and middle-income countries (LMICs) is essential.
PMID: 40111069
ISSN: 1744-8336
CID: 5813572
Journal of the Society for Cardiovascular Angiography & Interventions. 2025:4(6).DOI: 10.1016/j.jscai.2025.103657
Corrigendum to 'Intravascular Coronary Imaging' Journal of the Society for Cardiovascular Angiography & Interventions 3;12 (2024) 102399
[This corrects the article DOI: 10.1016/j.jscai.2024.102399.].
PMID: 40630245
ISSN: 2772-9303
CID: 5890802
Co-Occurrence of Hypophysitis and Thyroiditis Induced by PD-L1 Inhibitor Avelumab: Clinical Insights [Case Report]
Various endocrinopathies have been described in patients with malignancies who are receiving treatment with immune checkpoint inhibitors (ICIs). We present the case of a patient who was hospitalized with an acute alteration in mental status and was referred to the endocrinology service for evaluation of abnormal thyroid function tests. Subsequent investigation revealed the presence of acute adrenal insufficiency, which was successfully managed with steroid replacement therapy. This case highlights a unique simultaneous presentation of thyrotoxicosis due to thyroiditis and adrenal insufficiency due to hypophysitis in a patient treated with ICI avelumab for 5 months.
PMCID:12066409
PMID: 40356788
ISSN: 2755-1520
CID: 5944832
Trends and Outcomes Following Percutaneous Coronary Intervention in Patients With Myeloproliferative Neoplasms: Insights From National Database
BACKGROUND:Myeloproliferative neoplasms (MPN) are associated with an increased cardiovascular risk including acute coronary syndrome. However, there is a lack of comprehensive data regarding the rate of percutaneous coronary intervention (PCI), as well as the in-hospital characteristics and outcomes for MPN patients. AIMS/OBJECTIVE:We aimed to evaluate the temporal trends and outcomes of PCI among patients with MPN. METHODS AND RESULTS/RESULTS:The National Inpatient Sample database from 2016 to 2020 was queried to identify all PCI hospitalizations. Temporal trends and outcomes of patients with and without MPN following PCI were analyzed. Propensity score matching (PSM) was implemented to compare outcomes between MPN and non-MPN groups. 2,237,210 PCI hospitalizations with 7560 (0.27%) patients with MPN were included in this study. Throughout the study period, the prevalence of MPN among PCI admissions remained stable (p-value for trend = 0.12). Within the MPN subgroup, essential thrombocythemia (ET) was the predominant condition (53.2). Patients with MPN had higher prevalence of cardiovascular comorbidities than non-MPN patients. Following PSM, MPNs were significantly associated with a higher risk of blood transfusions (OR: 1.66, 95% CI: 1.22-2.24, p = 0.001) and AKI (OR: 1.39, 95% CI: 1.17-1.65, p < 0.001). In contrast, the risk of in-hospital mortality (OR: 1.18, 95% CI: 0.83-1.69, p = 0.354 and bleeding (OR: 1.43, 95% CI: 0.90-2.27, p = 0.127) did not significantly differ between the two groups. CONCLUSIONS:Our study demonstrated that while the prevalence of MPN among patients undergoing PCI remained stable, those with MPN faced higher risks of bleeding, blood transfusion and acute kidney injury. Further research is warranted to explore the underlying reasons for these increased risks and to improve outcomes in this high-risk group.
PMCID:12159367
PMID: 40079618
ISSN: 1522-726x
CID: 5926362
Complete/Near-Complete Itch Response Observed in Patients with Moderate-to-Severe Atopic Dermatitis Initiating Dupilumab: 3-Year, Real-World, Interim Data from the PROSE Registry
INTRODUCTION/BACKGROUND:Atopic dermatitis (AD) is a chronic, relapsing disease that can start at any age and has a significant negative impact on quality of life, including a significant itch burden. Here we report the proportion of patients in a real-world study achieving a complete/almost complete resolution of itch, as measured by the Peak Pruritus Numeric Rating Scale (PP-NRS) and improvement in overall disease severity score (ODS), in patients aged ≥ 12 years with moderate-to-severe AD up to 3 years after commencing dupilumab treatment. METHODS:PROSE is an ongoing, prospective, observational, multicenter registry in the USA and Canada, collecting real-world data from patients aged ≥ 12 years with moderate-to-severe AD who initiated dupilumab in accordance with country-specific prescribing information. Assessments include patient-reported PP-NRS (range 0-10) and clinician-measured ODS score (range 0-4). RESULTS:A total of 857 patients were enrolled, of whom 42% were male and 6.4% were adolescents aged ≥ 12 to < 18 years. The mean [standard deviation (SD)] age was 40.1 (17.9) years, and the duration of AD was 17.4 (16.2) years. The subsequent mean (SD) duration of dupilumab treatment was 23.1 (13.7) months. The proportion of patients achieving complete/almost complete itch resolution (PP-NRS score of 0 or 1) improved consistently over time, from 2.7% (17/622) of patients at baseline to 56.3% (58/103) at 3 years. Additionally, by year 3, 65.1% (54/83) of patients had an ODS score of no/minimal disease (score of 0 or 1), versus 2.2% (19/852) at baseline. CONCLUSIONS:In this real-world setting of the PROSE registry, adult and adolescent patients with moderate-to-severe AD followed up for up to 3 years after the initiation of dupilumab treatment experienced sustained and substantial improvement in pruritus and ODS, using the stringent endpoints of PP-NRS 0 or 1 and ODS 0 or 1. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov identifier: NCT03428646.
PMID: 40234297
ISSN: 2193-8210
CID: 5827852
Mitochondrial Ca2+ uniporter b (MCUb) regulates neuronal Ca2+ dynamics and resistance to ischemic stroke
Mitochondrial Ca2+ transport regulates many neuronal functions including synaptic transmission, ATP production, gene expression and neuronal survival. The mitochondrial Ca2+ uniporter (MCU) is the core molecular component of the mitochondrial Ca2+ uptake complex in the inner mitochondrial membrane. MCUb is a paralog of MCU that negatively regulates mitochondrial Ca2+ uptake in the heart and the cells of the immune system. However, the function of MCUb in the brain is largely unknown. Here, we report that MCUb knockout (KO) led to enhanced mitochondrial Ca2+ uptake in cortical neurons. By simultaneously monitoring changes in cytosolic and mitochondrial Ca2+ concentrations, [Ca2+]cyt and [Ca2+]mt, respectively, we also found that MCUb KO reduced the [Ca2+]cyt threshold required to induce mitochondrial uptake in cortical neurons during electrical stimulation. Exposure of cortical neurons to toxic concentrations of glutamate led to a collapse of mitochondrial membrane potential (ΔΨmt) and [Ca2+]cyt deregulation, and MCUb deletion accelerated the development of both events. Furthermore, using the middle cerebral artery occlusion (MCAO) as a model of transient ischemic stroke in mice, we found that MCUb KO significantly increased MCAO-induced brain damage in male, but not female mice. These results suggest that MCUb regulates neuronal Ca2+ dynamics and excitotoxicity and reveal a sex-dependent role of MCUb in controlling resistance to brain damage following ischemic stroke.
PMCID:12094165
PMID: 40058292
ISSN: 1532-1991
CID: 5997702
Hypertension Prevention and Healthy Life Expectancy in Black Adults: The Jackson Heart Study
BACKGROUND/UNASSIGNED:The impact of preventing hypertension and maintaining normal blood pressure (BP) on life expectancy and healthy life expectancy (HLE) among Black adults, who are disproportionately affected by hypertension, has not been quantified. METHODS/UNASSIGNED:We used a discrete event simulation to estimate life expectancy and HLE among a cohort of Black adults from the Jackson Heart Study (n=4933) from age 20 to 100 years or until death. We modeled preventing hypertension as having BP <130/80 mm Hg and maintaining normal BP as having BP <120/80 mm Hg across the lifespan. In the primary analysis, we assumed that lowering BP decreased the risk of cardiovascular disease events, resulting in life expectancy and HLE gains. In a secondary analysis, we assumed that preventing hypertension and maintaining normal BP directly reduced both cardiovascular disease and mortality risk. RESULTS/UNASSIGNED:At age 20 years, the projected average life expectancy was age 80.8 (95% uncertainty interval [UI], 80.6-81.1) years, and HLE was 70.5 (95% UI, 70.3-70.7) healthy life years. In the primary analysis, preventing hypertension and maintaining normal BP added 0.9 (95% UI, 0.8-1.1) and 1.1 (95% UI, 0.9-1.3) years to life expectancy, respectively, and 2.7 (95% UI, 2.6-2.9) and 2.9 (95% UI, 2.7-3.1) healthy life years to HLE, respectively. In the secondary analysis, preventing hypertension and maintaining normal BP added 4.5 (95% UI, 4.3-4.6) and 4.6 (95% UI, 4.4-4.8) years to life expectancy, respectively, and 5.7 (95% UI, 5.6-5.8) and 5.9 (95% UI, 5.7-6.0) healthy life years to HLE, respectively. CONCLUSIONS/UNASSIGNED:Preventing hypertension and maintaining normal BP were projected to increase life expectancy and HLE among Black adults.
PMID: 40008433
ISSN: 1524-4563
CID: 5800912
Factors Associated With Stroke Recurrence After Initial Diagnosis of Cervical Artery Dissection
BACKGROUND/UNASSIGNED:Patients presenting with cervical artery dissection (CAD) are at risk for subsequent ischemic events. We aimed to identify characteristics that are associated with increased risk of ischemic stroke after initial presentation of CAD and to evaluate the differential impact of anticoagulant versus antiplatelet therapy in these high-risk individuals. METHODS/UNASSIGNED:This was a preplanned secondary analysis of the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection), a multicenter international retrospective observational study (63 sites from 16 countries in North America, South America, Europe, Asia, and Africa) that included patients with CAD predominantly between January 2015 and June 2022. The primary outcome was subsequent ischemic stroke by day 180 after diagnosis. Clinical and imaging variables were compared between those with versus without subsequent ischemic stroke. Significant factors associated with subsequent stroke risk were identified using stepwise Cox regression. Associations between subsequent ischemic stroke risk and antithrombotic therapy type (anticoagulation versus antiplatelets) among patients with identified risk factors were explored using adjusted Cox regression. RESULTS/UNASSIGNED:=0.01). CONCLUSIONS/UNASSIGNED:In this post hoc analysis of the STOP-CAD study, several factors associated with subsequent ischemic stroke were identified among patients with CAD. Furthermore, we identified a potential benefit of anticoagulation in patients with CAD with occlusive dissection. These findings require validation by meta-analyses of prior studies to formulate optimal treatment strategies for specific high-risk CAD subgroups.
PMID: 40143807
ISSN: 1524-4628
CID: 5816392
