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BACKGROUND: Sarcomatoid urothelial cancer of the bladder (SBC) is a rare, but aggressive histological subtype for which novel treatments are needed. OBJECTIVE: We evaluated the clinical activity and safety of neoadjuvant cisplatin plus gemcitabine plus docetaxel (CGD) in muscle-invasive patients with SBC and assessed SBC tumor biology by whole transcriptome RNA sequencing. METHODS: A single-institution, retrospective analysis of muscle-invasive SBC patients treated with neoadjuvant CGD with molecular analysis. Patients received cisplatin 35âmg/m2â+âgemcitabine 800âmg/m2â+âdocetaxel 35âmg/m2 intravenously on days 1 and 8â+âpegfilgrastim 6âmg subcutaneously on day 9 every 3 weeks for 4 cycles followed by cystectomy. The primary endpoint was pathologic complete response (ypCR) rate. RESULTS: Sixteen patients with SBC received neoadjuvant CGD with a ypCR rate of 38% and aâ<âypT2 rate of 50%. Grade 3 and 4 toxicity occurred in 80% and 40% of patients, but was manageable with 81% of patients completingâ>â3 CGD cycles. Whole transcriptome RNA sequencing demonstrates co-clustering of SBC with conventional urothelial tumors. SBC tumors are characterized by basal-squamous and stroma rich gene signatures with frequent increased expression of immune checkpoint (CD274 (PD-L1)), chemokine (CXCL9), and T-cell (CD8A) genes. CONCLUSIONS: SBC is a chemosensitive subtype, with ypCR rate similar to urothelial bladder cancer following CGD neoadjuvant therapy. Whole transcriptome tissue analyses demonstrate increased expression of immune checkpoint and T-cell genes with therapeutic implications.
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BACKGROUND: Pivotal clinical trials supported survival benefits of liposomal irinotecan (nal-IRI) plus fluorouracil/leucovorin in patients with pancreatic ductal adenocarcinoma (PDAC) who previously received gemcitabine-based therapy. There are concerns about the benefits of nal-IRI in patients who received FOLFIRINOX (combined fluorouracil, leucovorin, IRI, and oxaliplatin) because of potential cross-resistance to IRI. The objective of this meta-analysis was to characterize the impact of the previous receipt of IRI on the outcomes of nal-IRI regimens in patients with advanced PDAC. METHODS: Real-world studies evaluating the outcomes of nal-IRI in patients who had prior IRI exposure published up to April 2023 were searched using electronic databases. The meta-analysis was conducted using a random effects model to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Eight studies (n = 1368 patients) were included. The pooled median progression-free survival (PFS) was 2.02 months (95% CI, 1.43-2.57 months), and the median overall survival (OS) was 4.26 months (95% CI, 3.03-5.39 months). Patients with prior IRI exposure had PFS (HR, 1.17; 95% CI, 0.94-1.47; p = .17) and OS (HR, 1.16; 95% CI, 0.95-1.42; p = .16) comparable to patients without prior IRI exposure. Likewise, patients who had progressive disease on conventional IRI had PFS (HR, 1.50; 95% CI, 0.73-3.08; p = .24) and OS (HR, 1.70; 95% CI, 0.68-4.27; p = .26) with nal-IRI comparable to patients who had no progressive disease. CONCLUSIONS: Prior IRI exposure does not affect the survival outcomes of nal-IRI regimens in patients who have advanced PDAC. The selection of later lines of chemotherapy regimens should be based on the differential safety profile, patient status, the cost of treatment, and health-related quality of life.
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BACKGROUND: Immune checkpoint inhibitors (ICI) have significantly improved survival outcomes of metastatic renal cell carcinoma (mRCC). However, ethnic and racial minorities are often underrepresented in ICI clinical trials, leading to limited knowledge about ICI-specific survival outcomes for mRCC across different racial and ethnic groups. We investigated the impact of race and ethnicity on the ICI-specific survival outcomes of mRCC. MATERIALS: We used The National Cancer Database (NCDB) to retrieve the data of 4858 mRCC patients diagnosed from 2014 to 2019 and receiving ICI-based regimens. We then compared survival outcomes using the Kaplan-Meier method and the Log-rank test. We analyzed the data using univariate and multivariable Cox regression analysis, adjusted for age, sex, comorbidity index, treatment centers, and grade. RESULTS: White and Asian patients had significantly longer median overall survival (mOS) than African American (AA) patients (23.2 [95% CI 21.6, 24.7; P = .001] and 22.2 [95% CI 16.4, 55.1; P = .047] vs. 14.8 [95% CI 11.9, 19.2] months, respectively). After adjustment, White patients had significantly longer median OS (adjusted hazard ratio [HR] 0.71 [95% CI 0.58, 0.84]; P = .001). There was no significant difference in the mOS between Hispanic and non-Hispanic patients (P = .39). CONCLUSION: Black race is an independent predictor of ICI-related survival in mRCC patients, independent of sociodemographics, clinicopathological, and treatment-related factors. Future research is required to understand the underlying reasons for these disparities, including potential genetic or biological differences and social and environmental factors.
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Carcinoma de Células Renales , Disparidades en Atención de Salud , Inhibidores de Puntos de Control Inmunológico , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/mortalidad , Masculino , Femenino , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Persona de Mediana Edad , Anciano , Disparidades en Atención de Salud/estadística & datos numéricos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia , Estados Unidos/epidemiología , Negro o Afroamericano/estadística & datos numéricos , Estudios Retrospectivos , Minorías Étnicas y Raciales/estadística & datos numéricos , Población Blanca/estadística & datos numéricos , Tasa de SupervivenciaRESUMEN
Health-related quality of life (HRQoL) is known to be an important prognostic indicator and clinical endpoint for patients with hepatocellular carcinoma (HCC). However, the correlation of the Barcelona Clinic Liver Cancer (BCLC) stage with HRQoL in HCC has not been previously studied. We examined the relationship between BCLC stage, Child-Pugh (CP) score, and Eastern Cooperative Oncology Group (ECOG) performance status on HRQoL for patients who presented at a multidisciplinary liver cancer clinic. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire. Fifty-one patients met our inclusion criteria. The FACT-Hep total and subscales showed no significant association with BCLC stages (p = 0.224). Patients with CP B had significantly more impairment in FACT-Hep than patients with CP A. These data indicate that in patients with HCC, impaired liver function is associated with reduced quality of life, whereas the BCLC stage poorly correlates with quality of life metrics. Impairment of quality of life is common in HCC patients and further studies are warranted to determine the impact of early supportive interventions on HRQoL and survival outcomes.
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Background: The efficacy of combination chemotherapy beyond the first-line setting remains modest in patients with advanced pancreatic adenocarcinoma (PAC). Evidence from recent clinical studies has shown that liposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU) and leucovorin (LV) resulted in survival benefits in patients with advanced pancreatic adenocarcinoma (APAC) after progression on gemcitabine-based treatment. However, the survival benefits of nal-IRI in the third and later lines, in which limited options are available, have yet to be extensively studied. Also, some studies have shown conflicting results regarding the impact of prior treatment with conventional IRI on patient outcomes following treatment with nal-IRI. Therefore, this real-world study aimed to evaluate the efficacy and safety of nal-IRI plus 5FU-LV in advanced PAC patients who progressed on conventional IRI-containing regimens. Methods: A retrospective chart review was conducted between November 2016 to December 2022 on 30 patients diagnosed with advanced PAC who completed at least one cycle of nal-IRI plus 5-FU- LV and were previously treated with conventional IRI. Data regarding survival outcomes were retrieved. Results: Thirty patients met the inclusion criteria. Overall, 76.7% of the patients received at least two lines of therapy prior to nal-IRI. The median overall duration of nal-IRI treatment was 2.0 months (IQR: 1.3 - 3.9 months). One patient (3.3%) had a partial response, and seven patients (23.3%) had stable disease as their best response. The median progression-free survival (PFS) was 1.9 months (95% CI 1.6 - 2.0) and the 6-month PFS rate was 20.0%. The median overall survival (OS) was 5.0 months (95% CI 3.4 - 7.0), and the 6-month OS rate was 36.7%. An interval between conventional IRI and nal-IRI ≥5.5 months was significantly associated with prolonged OS of 10.2 months (95% CI 3.3 - 12.1) versus 4.3 months (95% CI 2.1 - 5.9; p =0.003). Ten patients (33.3%) experienced grade 3 adverse events, most commonly nausea, fatigue, diarrhea, and non-neutropenic fever. Conclusion: Nal-IRI plus 5FU/LV had modest survival benefits and an acceptable safety profile in patients with prior conventional IRI. A longer interval between conventional IRI and nal-IRI was associated with increased survival outcomes.
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In the past two decades, molecular targeted therapy has revolutionized the treatment landscape of several malignancies. Lethal malignancies such as non-small cell lung cancer (NSCLC) have become a model for precision-matched immune- and gene-targeted therapies. Multiple small subgroups of NSCLC defined by their genomic aberrations are now recognized; remarkably, taken together, almost 70% of NSCLCs now have a druggable anomaly. Cholangiocarcinoma (CCA) is a rare tumor with a poor prognosis. Novel molecular alterations have been recently identified in patients with CCA, and the potential for targeted therapy is being realized. In 2019, a fibroblast growth factor receptor 2 (FGFR2) inhibitor, pemigatinib, was the first approved targeted therapy for patients with locally advanced or metastatic intrahepatic CCA who had FGFR2 gene fusions or rearrangement. More regulatory approvals for matched targeted therapies as second-line or subsequent treatments in advanced CCA followed, including additional drugs that target FGFR2 gene fusion/rearrangement. Recent tumor-agnostic approvals include (but are not limited to) drugs that target mutations/rearrangements in the following genes and are hence applicable to CCA: isocitrate dehydrogenase 1 (IDH1); neurotrophic tropomyosin-receptor kinase (NTRK); the V600E mutation of the BRAF gene (BRAFV600E); and high tumor mutational burden, high microsatellite instability, and gene mismatch repair-deficient (TMB-H/MSI-H/dMMR) tumors. Ongoing trials investigate HER2, RET, and non-BRAFV600E mutations in CCA and improvements in the efficacy and safety of new targeted treatments. This review aims to present the current status of molecularly matched targeted therapy for advanced CCA.
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Pulmonary arteriovenous malformation (PAVM) is an abnormal communication between the pulmonary artery and the pulmonary vein. PAVMs are usually congenital in origin; however, they may be acquired. Three-dimensional rotational angiography (3DRA) is a technique used increasingly for imaging in congenital heart disease but to our knowledge has never been used in imaging and planning device closure of PAVM. We describe the use of 3DRA technique for imaging and planning device closure of PAVMs and discuss the advantages of this modality. 3DRA is an excellent tool for imaging of various vascular anomalies. It provides high-quality accurate images through a quick and safe procedure, it is also very useful in planning interventional procedures in PAVM, as it clearly delineates all feeders to PAVM and gives an exact view for analysis and intervention.
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Advance care directives (ACDs) are instructions regarding what types of medical treatments a patient desires and/or who they would like to designate as a healthcare surrogate to make important healthcare decisions when the patient is mentally incapacitated. At end-of-life, when faced with poor prognosis for a meaningful health-related quality of life, most patients indicate their preference to abstain from aggressive, life-sustaining treatments. Patients whose wishes are left unsaid often receive burdensome life sustain therapy by default, prolonging patient suffering. The CoVID pandemic has strained our healthcare resources and raised the need for prioritization of life-sustaining therapy. This highlights the urgency of ACDs more than ever. Despite ACDs' potential to provide patients with care that aligns with their values and preferences and reduce resource competition, there has been relatively little conversation regarding the overlap of ACDs and CoVID-19. There is low uptake among patients, lack of training for healthcare professionals, and inequitable adoption in vulnerable populations. However, solutions are forthcoming and may include electronic medical record completion, patient outreach efforts, healthcare worker programs to increase awareness of at-risk minority patients, and restructuring of incentives and reimbursement policies. This review carefully describes the above challenges and unique opportunities to address them in the CoVID-19 era. If solutions are leveraged appropriately, ACDs have the potential to address the described challenges and ethically resolve resource conflicts during the current crisis and beyond.
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Planificación Anticipada de Atención/organización & administración , Directivas Anticipadas/psicología , COVID-19/psicología , Enfermedad Crítica/psicología , Toma de Decisiones , Humanos , Pandemias/estadística & datos numéricos , Relaciones Profesional-Paciente , Calidad de Vida/psicologíaRESUMEN
OBJECTIVES: Overuse of telemetry among hospitalized patients results in poor patient care and wasted health care dollars. Guidelines addressing telemetry use have been developed by the American Heart Association (AHA) and are effective when applied to specific clinical practices and high-value care. The purpose of our intervention was to facilitate more effective utilization of telemetry in our hospital. We aimed to reduce patient days on telemetry through use of AHA guideline criteria for telemetry. STUDY DESIGN: We used Plan-Do-Study-Act cycles with chart review for pre- and postintervention measurement collection. METHODS: We included patients hospitalized at The Brooklyn Hospital Center on inpatient general medical wards from January 1, 2017, through July 31, 2018. The intervention consisted of a standard process of reviewing patients on telemetry based on AHA guidelines, educating teams on the guidelines, and changes to telemetry order sets. The primary outcome measured was the total number of days that patients remained on telemetry. Secondary measures included the daily number of telemetry downgrades and total number of patients on telemetry. Diagnosis-related group and case mix index were also noted. RESULTS: Patient average days on telemetry changed from 7.20 days preintervention to 3.51 days post intervention (P < .0001). The number of patients on telemetry with a diagnosis meeting AHA guidelines for telemetry increased. CONCLUSIONS: The stated intervention resulted in more effective use of telemetry, evidenced by fewer patient days on telemetry and increased numbers of patients on telemetry meeting AHA guidelines for telemetry.
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Pacientes Internos , Telemetría , American Heart Association , Humanos , Estados UnidosRESUMEN
Purpose The purpose of this study was to identify best practices, strategies, and methods leading to the success of experienced and accomplished physicians to provide a reference for residents of graduate medical programs. Methods Ten practicing physicians and resident mentors each with at least 10 years of experience were interviewed with open-ended, narrative-based questions related to themes of paths to success, the proper role of a resident, lessons learned, helpful skills, and advice for a new resident/physician. Results Surprisingly, interviewees' answers reflected the Accreditation Council for Graduate Medical Education (ACGME) core competencies of patient care, medical knowledge, practice-based learning and improvement, interpersonal and communication skills, professionalism, and systems-based practice. The importance of mentorship was also emphasized. Conclusion ACGME core competencies serve as a roadmap to success based on the experience of many successful physicians. Given that mandated mentor programs in many graduate medical programs are ineffectively impersonal and mechanical, residents can follow interviewees' advice and proactively form mentor-mentee relationships with experienced physicians to learn the best paths of success.
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Double orifice mitral valve (DOMV) is a rare congenital anomaly of the mitral valve apparatus consisting of an accessory bridge of fibrous tissue, which partially or completely divides the mitral valve into two orifices. It usually occurs as an associated lesion. Encountering a DOMV as an isolated finding meriting intervention is indeed rare. We, here, report a case of "complete bridging type DOMV" occurring as an isolated entity and presenting as severe congenital MR requiring surgery.
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Patients with peripheral arterial disease (PAD) and critical limb ischemia are at risk for limb amputation and require urgent management to restore blood flow. Patients with PAD often have several comorbidities, including chronic kidney disease, diabetes mellitus, and hypertension. Diagnostic and interventional angiography using iodinated contrast agents provides excellent image resolution but can be associated with contrast-induced nephropathy (CIN). The use of carbon dioxide (CO2) as a contrast agent reduces the volume of iodine contrast required for angiography and reduces the incidence of CIN. However, CO2 angiography has been underutilized due to concerns regarding safety and image quality. Modern CO2 delivery systems with advanced digital subtraction angiography techniques and hybrid angiography have improved imaging accuracy and reduced the incidence of CIN. Awareness of the need for optimal imaging conditions, contraindications, and potential complications have improved the safety of CO2 angiography. This review aims to highlight current technological advances in the delivery of CO2 in vascular angiography for patients with PAD and critical limb ischemia, which result in limb preservation while preventing kidney damage.
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Congenital heart disease in adults, including congenital anomalies of the coronary arteries, can be asymptomatic and diagnosed incidentally, but they can also be a cause of sudden cardiac death. The recent guidelines on the management of adults with congenital heart disease from the American Heart Association (AHA) and the American College of Cardiologists (ACC) identify that an anomalous coronary artery origin can lead to myocardial ischemia, arrhythmias, or sudden cardiac death. When the course of the coronary artery runs between the aorta and pulmonary trunk, it is described as having a "malignant course." Emergency surgical correction is required to restore the normal anatomy of the aberrant coronary artery. This report is of a 57-year-old man with a history of hypertension who had a normal electrocardiogram (ECG). A nuclear exercise stress test showed a resting and exercise ejection fraction (EF) of 56% with transient ischemic dilatation (TID) of the left ventricle. Coronary artery computed tomography angiography (CTA) identified an anomalous right coronary artery (AORCA) originating from the left sinus of Valsalva and coursing between the aorta and pulmonary trunk. TID on nuclear imaging is usually associated with left ventricular hypertrophy, microvascular disease, or multivessel macrovascular disease and has not been previously described in AORCA.
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Endovascular intervention and bypass surgery are the main options of treatments for infrapopliteal artery disease. Although post-intervention treatment with antiplatelet (AP) and/or anticoagulant (AC) drugs has reduced morbidity and mortality rates from cardiovascular complications; the ideal antithrombotic treatment regimen is unknown. The aim of this review was to compare the efficacy and safety of various anticoagulation and/or AP therapy regimens in patients undergoing below-knee endovascular treatment for infrapopliteal artery disease. We reviewed published literature in PubMed and Google Scholar, and Cochrane, evaluating efficacy and safety outcomes after antithrombotic treatment following endovascular intervention or bypass surgery in patients with infrapopliteal artery disease. We extracted relevant efficacy and safety data with related statistics from each study. We found that AP treatment should be administered to patients receiving endovascular therapy or bypass. We did not find superior effects for dual AP treatment (DAPT) over mono-AP therapy (MAPT) for endovascular intervention or bypass surgery with venous graft, suggesting that MAPT suffices for these groups. Also, aspirin + clopidogrel was effective over aspirin alone for prosthetic, but not venous graft, albeit higher non-severe bleeding incidences, suggesting a potential benefit of this regime for below-knee prosthetic graft. AP + AC yielded superior results compared to AP following endovascular procedure and bypass surgery, suggesting the potential benefit of this regime in the absence of contraindications. More prospective studies with large number of patients are warranted to identify the best treatment for infrapopliteal artery diseases.
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Endovascular intervention is often used to treat critical limb ischemia (CLI). Post-intervention treatment with antiplatelet and/or anticoagulant therapy has reduced morbidity and mortality due to cardiovascular complications. The purpose of this review is to shed light on the various pharmacologic treatment protocols for treating CLI following endovascular procedures. We reviewed the literature comparing outcomes after antithrombotic treatment for patients with CLI. We characterized antithrombotic therapies into three categories: (1) mono-antiplatelet therapy (MAPT) vs. dual antiplatelet therapy (DAPT), (2) MAPT vs. antiplatelet (AP) + anticoagulant (AC) therapy, and (3) AC vs. AP + AC therapy. Relevant results and statistics were extracted to determine differences in the rates of the following outcomes: (1) re-stenosis, (2) occlusion, (3) target limb revascularization (TLR), (4) major amputation, (5) major adverse cardiac events, (6) all-cause death, and (7) bleeding. Studies suggest that DAPT reduces post-surgical restenosis, TLR, and amputation for diabetic patients, without increasing major bleeding incidences, compared to MAPT. Also, AP + AC therapy provides overall superior efficacy, with no difference in bleeding incidences, compared to antiplatelet alone. Additionally, the effects were significant for restenosis, limb salvage, survival rates, and cumulative rate of above ankle amputation or death. These results suggest that treatment with DAPT and AP + AC might provide better outcomes than MAPT following the endovascular intervention for CLI, and that the ideal treatment may be related to the condition of the individual patient. However, the studies were few and heterogenous with small patient populations. Therefore, further large controlled studies are warranted to confirm these outcomes.