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INTRODUCTION: Current guidelines for cardiac resynchronization therapy (CRT) device implant are the same across both sexes however women have been traditionally underrepresented in randomized controlled trials (RCTs). We aimed to identify if the number of women included in CRT trials is representative of the real-world burden of heart failure (HF) in women. METHODS: RCTs evaluating the benefit of CRT in HF patients referenced in the 2012 EHRA/HRS expert consensus statement on CRT in HF were included. Studies were evaluated for gender representation, baseline variables, and gender-based analysis of outcomes. RESULTS: A total of 10 CRT trials including 8107 patients were studied. Of the total patient population in these RCTs, only 23% were women. Analysis of outcomes based on sex was reported only in 5 out of 10 trials. Of these five trials reporting sex-based outcomes, multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy (MADIT-CRT) and resynchronization-defibrillation for ambulatory heart failure trial (RAFT) showed a greater benefit in women compared to men. Both MADIT and RAFT trials had a lower ejection fraction (EF) cut-off in the inclusion criteria (EF ≤ 30%) compared to the studies that did not find gender-based differences in the outcome (inclusion criteria: EF ≤ 35% or 40%). Additionally, women had less ischemic cardiomyopathy and more left bundle branch block (LBBB) compared to men in these two trials. CONCLUSION: Women are underrepresented in CRT trials; however, they have been shown to derive a greater benefit from CRT compared to men. Appropriate measures should be taken in future studies to enhance the participation of women in clinical trials for more generalizable evidence.
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Terapia de Ressincronização Cardíaca , Desfibriladores Implantáveis , Insuficiência Cardíaca , Masculino , Feminino , Humanos , Terapia de Ressincronização Cardíaca/efeitos adversos , Resultado do Tratamento , Bloqueio de Ramo/terapia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/epidemiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
PURPOSE: Colon cancer is a leading cause of cancer-related morbidity and mortality in the USA. We sought to better characterize colon cancer among a predominantly Black cohort with and without HIV. METHODS: We retrospectively reviewed all patients (n = 1482) diagnosed with colon cancer between 2015 and 2019 at a large urban tertiary teaching hospital using ICD-9 and ICD-10 codes. In this cohort, 114 (7.7%) of the patients also had HIV. Descriptive summaries were performed for gender, age, race/ethnicity, insurance status, tobacco/alcohol use, and BMI. RESULTS: Among patients with colon cancer only, 50.51% (n = 691) were men and 49.49% (n = 677) were women. Among patients with both HIV and colon cancer, 78.95% (n = 90) were men and 21.05% (n = 24) were women (p-value < 0.001). The mean age of the colon cancer patient sample was 61.62 years for those without HIV and 51.31 years for those with HIV (p-value < 0.001). Persons with both HIV and colon cancer were more likely to have a lower BMI (p-value < 0.001) and a history of smoking and alcohol use (p-value < 0.001), compared to patients with colon cancer only. When accounting for BMI, tobacco, and alcohol use, those with HIV were 10 years younger than those without HIV, 95% CI, 7.3-13; p < 0.001. CONCLUSIONS: In this study, HIV positive status was a risk factor for developing colon cancer at a younger age. Larger observational studies with multivariable analysis should be done to better describe the risk of colon cancer and HIV.
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Neoplasias do Colo , Infecções por HIV , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Estudos de Coortes , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Neoplasias do Colo/epidemiologiaRESUMO
Introduction: To adapt during the coronavirus disease 2019 (COVID-19) pandemic, a large safety-net hospital in Atlanta, Georgia and other hospitals across the United Sates, increased telemedicine (TM) for outpatient visits. The impact on resident physicians, including minority providers, had not yet been reported. We aimed to assess how primary care residents perceived increased TM in clinics during the pandemic, and assess resident burnout. Materials and Methods: An online survey was sent to 60 internal medicine (IM) and 18 family medicine (FM) residents who used TM to treat underserved patients, from March to May 2020, at the onset of the COVID-19 pandemic. The questionnaire included questions on resident demographics, satisfaction with TM, screening capability for COVID-19, effectiveness for patient education on COVID-19, impact on patient interactions and time management. Burnout was assessed with the Abbreviated Maslach Burnout Inventory. Results: A majority (62 of 78) eligible residents (79.5%) responded to the survey. Ninety-one percent of residents agreed that TM was a secure alternative to face-to-face encounters. Seventy-nine percent used it to screen for signs/symptoms of COVID-19 and 93% provided patient education on COVID-19. Average visit length decreased by 10-20 min with TM. Post-TM, scores for overall burnout were decreased (p = 0.0003) and less residents in total exhibited burnout (p = 0.0156). Discussion and Conclusions: IM and FM residents viewed TM as an efficient way to screen for and provide education on COVID-19, as well as a secure alternative to face-to-face encounters. With increased used of TM during COVID-19, there was decreased burnout among primary care residents.
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Esgotamento Profissional , COVID-19 , Internato e Residência , Telemedicina , Esgotamento Profissional/epidemiologia , COVID-19/epidemiologia , Humanos , PandemiasRESUMO
PURPOSE: Recent advances in molecular diagnostic technologies allow for the evaluation of solid tumor malignancies through noninvasive blood sampling, including circulating tumor DNA profiling (ctDNA). Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, often because of late presentation of disease. Diagnosis is often made using endoscopic ultrasound or endoscopic retrograde cholangiopancreatography, which often does not yield enough tissue for next-generation sequencing. With this study, we sought to characterize the ctDNA genomic alteration landscape in patients with advanced PDAC with a focus on actionable findings. MATERIALS AND METHODS: From December 2014 through October 2019, 357 samples collected from 282 patients with PDAC at Mayo Clinic underwent ctDNA testing using a clinically available assay. The majority of samples were tested using the 73-gene panel which includes somatic genomic targets, including complete or critical exon coverage in 30 and 40 genes, respectively, and in some, amplifications, fusions, and indels. Clinical data and outcome variables were available for 165 patients; with 104 patients at initial presentation. RESULTS: All patients included in this study had locally advanced or metastatic PDAC. Samples having at least one alteration, when variants of unknown significance (VUS) were excluded, numbered 266 (75%). After excluding VUS, therapeutically relevant alterations were observed in 170 (48%) of the total 357 cohort, including KRAS (G12C), EGFR, ATM, MYC, BRCA, PIK3CA, and BRAF mutations. KRAS, SMAD, CCND2, or TP53 alterations were seen in higher frequency in patients with advanced disease. CONCLUSION: Our study is the largest cohort to date that demonstrates the feasibility of ctDNA testing in PDAC. We provide a benchmark landscape upon which the field can continue to grow. Future applications may include use of ctDNA to guide treatment and serial monitoring of ctDNA during disease course to identify novel therapeutic targets for improved prognosis. IMPLICATIONS FOR PRACTICE: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis often due to late presentation of disease. Biopsy tissue sampling is invasive and samples are often inadequate, requiring repeated invasive procedures and delays in treatment. Noninvasive methods to identify PDAC early in its course may improve prognosis in PDAC. Using ctDNA, targetable genes can be identified and used for treatment.
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Adenocarcinoma , Carcinoma Ductal Pancreático , DNA Tumoral Circulante , Neoplasias Pancreáticas , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , DNA Tumoral Circulante/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genéticaRESUMO
The United States Food and Drug Administration has approved the wearable cardioverter defibrillator (WCD) for use in patients who are at high risk for sudden cardiac arrest (SCA) and who do not yet have an established indication for an implantation cardioverter defibrillator (ICD) or have contraindications for device implantation for various reasons. The WCD is typically used for primary prevention in (1) high-risk patients with reduced left ventricular ejection fraction (LVEF) ≤35 % after recent acute myocardial infarction (MI) during the 40-day ICD waiting period, (2) before and after coronary artery bypass graft or percutaneous coronary intervention during the 90-day ICD waiting period, (3) after recently diagnosed nonischemic dilated cardiomyopathy (NICM) during the 3- to 9-month medical therapy optimization period, or (4) for those with inherited proarrhythmic conditions such as long QT syndrome or hypertrophic cardiomyopathy. Unlike the automatic external defibrillator, the WCD does not require assistance from bystanders for therapy and conscious patients can delay or avert therapy with the use of response buttons. The WCD exhibits a small risk of inappropriate shock, mostly due to supraventricular tachycardia and/or electrical noise. Multiple non-randomized observational studies have shown high efficacy in detection and appropriate shock therapy for sustained ventricular tachyarrhythmias. This paper discusses the use of the WCD for prevention of SCA in patients with various cardiac substrates.
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Cardiomiopatias/complicações , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores , Infarto do Miocárdio/complicações , Taquicardia Ventricular/terapia , Ponte de Artéria Coronária , Morte Súbita Cardíaca/etiologia , Humanos , Estudos Observacionais como Assunto , Intervenção Coronária PercutâneaRESUMO
OBJECTIVE: To examine and compare the risk of major adverse cardiovascular events (MACEs) between people with HIV (PWH) with and without nonalcoholic fatty liver disease (NAFLD). DESIGN: Population-based, multicenter, retrospective cohort study. METHODS: Data on PWH between January 1, 2008, and December 31, 2020 were extracted from the TriNetX database. Primary outcomes were defined as the first incidence of myocardial infarction (MI), MACE, new-onset heart failure (HF), and a composite of cerebrovascular disease. Cox models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: A total of 151 868 patients were identified as having HIV. After exclusions, 4969 patients were identified as having NAFLD. Of them, 4463 (90%) were propensity matched to a non-NAFLD control. Patients with NAFLD were older (42.9 versus 40.8âyears). Among the NAFLD cohort, most participants were male and had a smoking history (12.3 versus 9.8%) than non-NAFLD. The mean follow-up was 4.8â±â1.1âyears for the NAFLD group and 5.3â±â1.2âyears for the non-NAFLD group. The risk of all outcomes was statistically significantly higher in NAFLD patients compared to those without NAFLD: MI (HR, 1.49; 95% CI, 1.11-2.01) MACE (HR, 1.49; 95% CI, 1.25-1.79), HF (HR, 1.73; 95% CI 1.37-2.19) and, cerebrovascular diseases (HR, 1.25; 95% CI, 1.05-1.48) and sensitivity analysis showed similar magnitude to the one generated in the primary analysis. CONCLUSIONS: Patients with NAFLD have an elevated risk of adverse cardiovascular events (CVEs). The results indicate the need for targeted efforts to improve awareness of risks factors associated with adverse CVEs risk in PWH with NAFLD.
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Doenças Cardiovasculares , Infecções por HIV , Infarto do Miocárdio , Hepatopatia Gordurosa não Alcoólica , Humanos , Masculino , Feminino , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estudos Retrospectivos , Infecções por HIV/complicações , Fatores de Risco , Doenças Cardiovasculares/etiologiaRESUMO
PURPOSE: The association between bariatric surgery and IBD-related inpatient outcomes is not well characterized. We report, analyze, and compare inpatient trends and outcomes among encounters with a history of bariatric surgery (Hx-MBS) compared to those receiving bariatric surgery during index admission (PR-MBS) admitted from 2009 to 2020. METHODS: Retrospective cohort design: the 2009-2020 National Inpatient Sample (NIS) databases were used to identify hospital encounters with patients aged ≥ 18 years with a history of MBS (Hx-MBS) or with procedure coding indicating MBS procedure (PR-MBS) according to International Classification of Diseases, Ninth (ICD-9-CM/ ICD-9-PCS) or Tenth Revision (ICD-10-CM/ICD-10-PCS) Clinical Modification/Procedure Coding System during index admission (ICD-9-CM: V4586; ICD-10-CM: Z9884; ICD-9-PR: 4382, 4389; ICD-10-PR: 0DB64Z3, 0DB63ZZ). Pearson χ2 analysis, analysis of variance, multivariable regression analyses, and propensity matching on independent variables were conducted to analyze significant associations between variables and for primary outcome inflammatory bowel disease-related admission, and secondary outcomes: diagnosis of nonalcoholic steatohepatitis, nonalcoholic fatty liver disease, or chronic mesenteric ischemia during admission. RESULTS: We identified 3,365,784 (76.20%) Hx-MBS hospitalizations and 1,050,900 hospitalizations with PR-MBS (23.80%). Propensity score matching analysis demonstrated significantly higher odds of inflammatory bowel disease, and chronic mesenteric ischemia for Hx-MBS compared to PR-MBS, and significantly lower odds of nonalcoholic steatohepatitis and nonalcoholic fatty liver disease for Hx-MBS compared to PR-MBS. CONCLUSION: In our study, Hx-MBS was associated with significantly increased odds of inflammatory bowel disease and other GI pathologies compared to matched controls. The mechanism by which this occurs is unclear. Additional studies are needed to examine these findings.
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Cirurgia Bariátrica , Doenças Inflamatórias Intestinais , Isquemia Mesentérica , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Humanos , Estudos Retrospectivos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Hepatopatia Gordurosa não Alcoólica/complicações , Obesidade Mórbida/cirurgia , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/cirurgia , Doenças Inflamatórias Intestinais/complicações , Cirurgia Bariátrica/métodos , GastrectomiaRESUMO
COVID-19 readmissions are associated with increased patient mortality and healthcare system strain. This retrospective cohort study of PCR-confirmed COVID-19 positive adults (>18 years) hospitalized and readmitted within 30 days of discharge from index admission was performed at eight Atlanta hospitals from March to December 2020. The objective was to describe COVID-19 patient-level demographics and clinical characteristics, and community-level social determinants of health (SDoH) that contribute to 30-day readmissions. Demographics, comorbidities, COVID-19 treatment, and discharge disposition data were extracted from the index admission. ZIP codes were linked to a demographic/lifestyle database interpolating to community-level SDoH. Of 7155 patients with COVID-19, 463 (6.5%) had 30-day, unplanned, all-cause hospital readmissions. Statistically significant differences were not found in readmissions stratified by age, sex, race, or ethnicity. Patients with a high-risk Charlson Comorbidity Index had higher odds of readmission (OR 4.8 (95% CI: 2.1 to 11.0)). Remdesivir treatment and intensive care unit (ICU) care were associated with lower odds of readmission (OR 0.5 (95% CI: 0.4 to 0.8) and OR 0.5 (95% CI: 0.4 to 0.7), respectively). Patients residing in communities with larger average household size were less likely to be readmitted (OR 0.7 (95% CI: 0.5 to 0.9). In this cohort, patients who received remdesivir, were cared for in an ICU, and resided in ZIP codes with higher proportions of residents with increased social support had lower odds of readmission. These patient-level factors and community-level SDoH may be used to identify patients with COVID-19 who are at increased risk of readmission.
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Tratamento Farmacológico da COVID-19 , Readmissão do Paciente , Adulto , Hospitais , Humanos , Estudos Retrospectivos , Fatores de Risco , Determinantes Sociais da SaúdeRESUMO
Midventricular ballooning syndrome, an atypical variant of takotsubo cardiomyopathy (TCM), is characterized by transient wall motion abnormalities of the midsegment of the left ventricle with apical sparing. In contrast to the typical form of TCM, apical contractility is preserved and may even be hyperkinetic in midventricular TCM. We present a case of atypical TCM in an 86-year-old woman who had chest pain while accompanying her husband in the emergency department as he was evaluated for chest pain.
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Ecocardiografia/métodos , Cardiomiopatia de Takotsubo/diagnóstico por imagem , Idoso de 80 Anos ou mais , Dor no Peito/diagnóstico por imagem , Meios de Contraste , Diagnóstico Diferencial , Eletrocardiografia , Feminino , HumanosRESUMO
In most cases, acute mitral valve regurgitation in the setting of infective endocarditis is caused by the destruction of either the mitral valve leaflets or the chordal apparatus. A 54-year-old woman had development of respiratory failure due to pulmonary oedema from severe acute mitral valve regurgitation in the setting of acute bacterial endocarditis. She was found to have a ruptured anterolateral papillary muscle from occlusion of the circumflex artery by embolic vegetations arising from the aortic valve. Although this occurrence is uncommon, an embolic phenomenon resulting in myocardial infarction and subsequent rupture of papillary muscle must be considered as a cause of acute severe mitral valve regurgitation.
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Valva Aórtica/patologia , Cardiomiopatias/etiologia , Embolia/complicações , Valva Mitral/patologia , Músculos Papilares/patologia , Sepse/complicações , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/cirurgia , Ponte de Artéria Coronária , Ecocardiografia Transesofagiana , Embolia/diagnóstico por imagem , Evolução Fatal , Feminino , Implante de Prótese de Valva Cardíaca , Humanos , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência de Múltiplos Órgãos , Músculos Papilares/diagnóstico por imagem , Músculos Papilares/cirurgia , Ruptura/diagnóstico por imagem , Ruptura/etiologia , Ruptura/cirurgia , Sepse/diagnóstico por imagemRESUMO
Lung cancer is the most common cause of death in both men and women. The United States Preventive Services Task Force (USPSTF) recommends annual lung screening with low-dose computed tomography (LDCT) chest for individuals aged 55-80 who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. We reviewed the electronic medical records of patients visiting our outpatient clinic over a period of one year. We included all eligible individuals according to USPSTF guidelines for LDCT to identify screening rates at our institution. All primary care physicians, including residents and attendings, were given a prepared questionnaire to understand their beliefs and concerns with the implementation of this program. A total of 13,500 patients visited the outpatient clinic and 1178 were eligible for LDCT. Forty-five percent (45%) of patients received LDCT screening, which was higher than the national average of 2%-5%. A total of 50 primary care providers were included in the survey. The majority of the providers were aware of the USPSTF guidelines and believed that patients with multiple comorbidities and insurance issues were barriers in initiating LDCT screening. Lung cancer screening is an important component in cancer preventive strategies. Widespread awareness among the primary care providers and the public is extremely necessary for improving the use of LDCT.
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Pulmonary complications from cocaine use can range from bronchospasm to vasospasm leading to pulmonary infarction. Profound vasospasm may also lead to perfusion defects presenting as pulmonary embolism on ventilation-perfusion scan. A 65-year-old patient with a past medical history of substance abuse and chronic kidney disease presents to the emergency department with sudden-onset chest pain and shortness of breath. Ventilation-perfusion scan revealed filling defect most notably in the lingual lobe. He was later discharged on warfarin for the management of pulmonary embolism. The patient presented to the emergency department 2 weeks later with similar complaints; the international normalized ratio was subtherapeutic, and urine drug screen was positive for cocaine. Repeat ventilation-perfusion scan revealed no filling defects. Follow-up bilateral venous Doppler of lower extremities and D-dimer were within normal limits.
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Cocaína/efeitos adversos , Pulmão/diagnóstico por imagem , Embolia Pulmonar/diagnóstico por imagem , Idoso , Humanos , Masculino , Tomografia Computadorizada de Emissão de Fóton Único , Relação Ventilação-PerfusãoRESUMO
Tumor lysis syndrome is uncommon in solid tumors but with the use of immunotherapy (checkpoint inhibitors) their incidence is increasing. Physicians need to take adequate precautions while treating patients with immunotherapy. The findings of our case report will help improve our current understanding of tumor lysis syndrome specially in solid tumors and will help in developing multidisciplinary treatment and prophylaxis strategies for this uncommon, but potentially fatal complication.
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BACKGROUND: Advancement of technologies enabling clinical assessment of circulating tumor DNA (ctDNA) are allowing for assessment of tumor specific genetic alterations in patients. This holds incredible promise for early detection of disease, serial monitoring of tumor heterogeneity, elucidation of therapeutic targets, and evaluation of treatment response and mechanisms of resistance. Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is often diagnosed late, recurs commonly, and is often diagnosed based upon imaging features alone. A comprehensive evaluation of real-time evaluation of ctDNA in patients with HCC has thus far not been undertaken. METHODS: From January 2015 to February 2018, 35 patients with biliary tract cancer (BTC) at the Mayo Clinic Comprehensive Cancer Center underwent ctDNA testing using a clinically available assay. The majority of samples were tested utilizing the 73-gene panel which includes somatic genomic targets, including complete or critical exon coverage in 30 and 40 genes, respectively; and in some, amplifications, fusions, and indels. RESULTS: A total of 44 samples were collected on these 35 patients, with >70% having stage 3 or 4 disease. Among all samples the median number of alterations per sample, excluding variants of undetermined significance (VUS), was 3.5, with a median allele frequency of 0.65%. A total of 122 unique genetic alterations, excluding VUS or synonymous alterations, were seen. The overall landscape of alterations is described. The top 10 genes altered in this cohort of patients, excluding VUS or synonymous alterations, were TP53 (18%), TERT (14%), CTNNB1 (13%), ARID1A (9%), MYC (5%), BRAF (4%), CCND1 (4%), CDK6 (4%), and MET (4%), and EGFR (3%). CONCLUSIONS: Herein, we describe feasibility of ctDNA testing and results from such testing in HCC patients undergoing ctDNA testing in a real-time clinical context. Patients with these cancers stand to benefit immensely from the use of ctDNA technologies, and concerted efforts at further investigation of such are critically needed.
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INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers. Progress has been made in treatment of HCC; however, improved outcomes are much needed. The increased metabolic needs of cancer cells underscore the importance of metabolic pathways in cancer cell survival. Lipid metabolism has a role in HCC development; aberrant overexpression of several key enzymes is seen in many solid human tumors. Areas covered: We discuss aberrant lipid metabolism and the promise of multiple targets, in particular related to HCC treatment. We searched PubMed and clinicaltrials.gov for published and unpublished studies from 2000 to 2019. These terms were used: lipids, fatty acid metabolism, lipid metabolism, liver cancer, HCC, de novo fatty acid synthesis, ATP citrate lyase, stearoyl CoA denaturase, fatty acid synthase, acetyl coenzyme A carboxylase, CD147, KLF4, monoglyceride lipase, AMP activated protein kinase. Expert opinion: The importance of dysregulation of fatty acid synthesis in cancer is a growing area of research. HCC demonstrates significant alteration in lipid metabolism, representing great potential as a target for novel therapeutics. Various agents have demonstrated promising anti-neoplastic activity. This strategy deserves further development for improved outcomes.
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Carcinoma Hepatocelular/terapia , Metabolismo dos Lipídeos/fisiologia , Neoplasias Hepáticas/terapia , Animais , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/patologia , Sobrevivência Celular , Ácidos Graxos/metabolismo , Humanos , Fator 4 Semelhante a Kruppel , Neoplasias Hepáticas/patologia , Terapia de Alvo MolecularRESUMO
BACKGROUND: Many patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed with liver metastatic disease (mPDAC), and few are surgical candidates. Interventional oncology (IO) locoregional therapies (LRT) have proven beneficial in other primary and metastatic hepatic malignancies. Systemic chemotherapy is the standard of care for patients with mPDAC. This study assessed the safety and efficacy of LRT including thermal ablation, chemoembolization, and radioembolization for mPDAC. METHODS: A retrospective analysis was performed of 28 patients with mPDAC referred to IR clinic for consideration of LRT from 01/2006 to 08/2017, of whom 20 underwent treatment. Laboratory values were analyzed at 0, 3, and 6 months post-treatment. Imaging response was evaluated at 1, 3, and 6 months post-intervention by modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Adverse events (AE) were classified by CTCAE v5.0. Overall survival (OS) from the diagnosis of PDAC, survival from the time of mPDAC diagnosis, and survival from the time of LRT were calculated. RESULTS: Median OS (mOS) was 25 months. Median survival from time of mPDAC diagnosis and post LRT were 16.25 and 9.7 months, respectively. At one month post-intervention, 12 of 17 patients demonstrated disease response (CR or PR per mRECIST). Survival among responders was 9 months vs. 6 months for patients with stable or progressive disease (P=0.08). There were two grade 3 AE which included post-embolization syndrome and transient renal failure. Chemotherapy was briefly delayed in one of these patients, but ultimately resumed. CONCLUSIONS: The use of LRT in patients with mPDAC is safe. Additionally, no significant chemotherapy limiting toxicities were observed. Responders to therapy demonstrated a survival benefit trend in this small and heterogeneous cohort. Further investigations with randomized trials are warranted.
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PURPOSE: Recent advances in molecular diagnostic technologies have allowed for the evaluation of solid tumor malignancies via noninvasive blood sampling, including circulating tumor DNA (ctDNA) profiling. We sought to characterize the ctDNA genomic alteration landscape in patients with biliary tract cancers (BTCs). PATIENTS AND METHODS: From January 2015 to February 2018, 124 patients with BTC at the Mayo Clinic Comprehensive Cancer Center underwent ctDNA testing using a clinically available assay. The majority of samples (n = 122) were tested using the 73-gene panel that includes somatic genomic targets, including complete or critical exon coverage in 30 and 40 genes, respectively, and in some, amplifications, fusions, and indels. RESULTS: A total of 138 samples were included, with approximately 70% of patients having intrahepatic BTC. All patients had locally advanced or metastatic BTC. Samples with one or more alterations, when variants of unknown significance were excluded, numbered 105 (76%). Each sample contained, on average, three alterations with a median allelic fraction of 0.52%. The overall landscape of alterations is summarized in Figures 1 and 2. After excluding variants of unknown significance, therapeutically relevant alterations were observed in 76 patients (55%), including BRAF mutations, ERBB2 amplifications, FGFR2 fusions, FGFR2 mutations, and IDH1 mutations seen in 21% of patients. A different spectrum of alterations was observed in patients with early-onset BTC (younger than age 50 years) compared with older patients (older than age 50 years). CONCLUSION: Data on ctDNA in BTC is currently limited. Our study, the largest cohort reported to date to our knowledge, demonstrates the feasibility of ctDNA testing in this disease. We provide a foundation upon which the field can continue to grow.
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Stroke and thromboembolism are catastrophic complications of atrial fibrillation (AF). Cardiac implantable electronic devices (CIED) with an atrial lead can reliably detect atrial high-rate events (AHRE). However, this correlation may be imperfect because of oversensing and undersensing of atrial signals and spurious arrhythmias. The critical duration, frequency, or overall burden of AHRE that increases stroke risk is still unknown; thus, the threshold level of AHRE (duration and frequency) that warrants anticoagulation in patients with CIED-detected AHRE is still unclear. This article reviews current literature on the risk of stroke with CIED-detected AHRE and raises questions that need further clarification.