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1.
NPJ Digit Med ; 7(1): 130, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760474

ABSTRACT

Determining acute ischemic stroke (AIS) etiology is fundamental to secondary stroke prevention efforts but can be diagnostically challenging. We trained and validated an automated classification tool, StrokeClassifier, using electronic health record (EHR) text from 2039 non-cryptogenic AIS patients at 2 academic hospitals to predict the 4-level outcome of stroke etiology adjudicated by agreement of at least 2 board-certified vascular neurologists' review of the EHR. StrokeClassifier is an ensemble consensus meta-model of 9 machine learning classifiers applied to features extracted from discharge summary texts by natural language processing. StrokeClassifier was externally validated in 406 discharge summaries from the MIMIC-III dataset reviewed by a vascular neurologist to ascertain stroke etiology. Compared with vascular neurologists' diagnoses, StrokeClassifier achieved the mean cross-validated accuracy of 0.74 and weighted F1 of 0.74 for multi-class classification. In MIMIC-III, its accuracy and weighted F1 were 0.70 and 0.71, respectively. In binary classification, the two metrics ranged from 0.77 to 0.96. The top 5 features contributing to stroke etiology prediction were atrial fibrillation, age, middle cerebral artery occlusion, internal carotid artery occlusion, and frontal stroke location. We designed a certainty heuristic to grade the confidence of StrokeClassifier's diagnosis as non-cryptogenic by the degree of consensus among the 9 classifiers and applied it to 788 cryptogenic patients, reducing cryptogenic diagnoses from 25.2% to 7.2%. StrokeClassifier is a validated artificial intelligence tool that rivals the performance of vascular neurologists in classifying ischemic stroke etiology. With further training, StrokeClassifier may have downstream applications including its use as a clinical decision support system.

2.
Res Sq ; 2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37961532

ABSTRACT

Determining the etiology of an acute ischemic stroke (AIS) is fundamental to secondary stroke prevention efforts but can be diagnostically challenging. We trained and validated an automated classification machine intelligence tool, StrokeClassifier, using electronic health record (EHR) text data from 2,039 non-cryptogenic AIS patients at 2 academic hospitals to predict the 4-level outcome of stroke etiology determined by agreement of at least 2 board-certified vascular neurologists' review of the stroke hospitalization EHR. StrokeClassifier is an ensemble consensus meta-model of 9 machine learning classifiers applied to features extracted from discharge summary texts by natural language processing. StrokeClassifier was externally validated in 406 discharge summaries from the MIMIC-III dataset reviewed by a vascular neurologist to ascertain stroke etiology. Compared with stroke etiologies adjudicated by vascular neurologists, StrokeClassifier achieved the mean cross-validated accuracy of 0.74 (±0.01) and weighted F1 of 0.74 (±0.01). In the MIMIC-III cohort, the accuracy and weighted F1 of StrokeClassifier were 0.70 and 0.71, respectively. SHapley Additive exPlanation analysis elucidated that the top 5 features contributing to stroke etiology prediction were atrial fibrillation, age, middle cerebral artery occlusion, internal carotid artery occlusion, and frontal stroke location. We then designed a certainty heuristic to deem a StrokeClassifier diagnosis as confidently non-cryptogenic by the degree of consensus among the 9 classifiers, and applied it to 788 cryptogenic patients. This reduced the percentage of the cryptogenic strokes from 25.2% to 7.2% of all ischemic strokes. StrokeClassifier is a validated artificial intelligence tool that rivals the performance of vascular neurologists in classifying ischemic stroke etiology for individual patients. With further training, StrokeClassifier may have downstream applications including its use as a clinical decision support system.

3.
Sci Rep ; 13(1): 17171, 2023 10 11.
Article in English | MEDLINE | ID: mdl-37821520

ABSTRACT

Although a decrease in stroke admissions during the SARS-CoV-2 pandemic has been observed, detailed analyses of the evolution of stroke metrics during the pandemic are lacking. We analyzed changes in stroke presentation, in-hospital systems-of-care, and treatment time metrics at two representative Comprehensive Stroke Centers (CSCs) during the first year of Coronavirus disease 2019 pandemic. From January 2018 to May 2021, data from stroke presentations to two CSCs were obtained. The study duration was split into: period 0 (prepandemic), period 1 (Wave 1), period 2 (Lull), and period 3 (Wave 2). Acute stroke therapies rates and workflow times were compared among pandemic and prepandemic periods. Analyses were adjusted for age, sex, comorbidities, and pre-morbid care needs. There was a significant decrease in monthly hospital presentations of stroke during Wave 1. Both centers reported declines in reperfusion therapies during Wave 1, slowly catching up but never to pre pandemic numbers, and dropping again in Wave 2. Both CSCs experienced in-hospital workflow delays during Waves 1 and 2, and even during the Lull period. Our results highlight the need for proactive strategies to reduce barriers to workflow and hospital avoidance for stroke patients during crisis periods.


Subject(s)
COVID-19 , Stroke , Humans , COVID-19/epidemiology , SARS-CoV-2 , Pandemics , Stroke/epidemiology , Stroke/therapy , Comorbidity , Retrospective Studies
4.
Semin Neurol ; 42(1): 3-11, 2022 02.
Article in English | MEDLINE | ID: mdl-35576926

ABSTRACT

For over two decades, telestroke has been utilized as a means for improving acute access to a stroke specialist when this expertise is otherwise unavailable. During this time, telestroke use has increased and improvements in care metrics have been widely reported. Several telestroke model variations are utilized; each has different workflow implications. A successful telestroke system should include adequate protocols and training, equipment, documentation system, and tracking of quality metrics. Upfront costs of needed technology and devices, credentialing hurdles, and limited reimbursement are all reported barriers to the utilization of telestroke. Emphasis on safety measures during the COVID-19 pandemic resulted in the dramatic upscaling of telehealth utilization, although overall stroke volumes declined in many areas in the early phases of the pandemic. Going forward, continued reduction in cost of required devices and broadband connections, increased use of automated and advanced analytical software, and a universal licensing and credentialing system are needed to continue the expansion of telestroke use.


Subject(s)
COVID-19 , Stroke , Telemedicine , Humans , Pandemics , Stroke/drug therapy , Stroke/therapy , Telemedicine/methods , Thrombolytic Therapy
5.
NPJ Digit Med ; 5(1): 47, 2022 Apr 08.
Article in English | MEDLINE | ID: mdl-35396454

ABSTRACT

Electronic health record (EHR) datasets are statistically powerful but are subject to ascertainment bias and missingness. Using the Mass General Brigham multi-institutional EHR, we approximated a community-based cohort by sampling patients receiving longitudinal primary care between 2001-2018 (Community Care Cohort Project [C3PO], n = 520,868). We utilized natural language processing (NLP) to recover vital signs from unstructured notes. We assessed the validity of C3PO by deploying established risk models for myocardial infarction/stroke and atrial fibrillation. We then compared C3PO to Convenience Samples including all individuals from the same EHR with complete data, but without a longitudinal primary care requirement. NLP reduced the missingness of vital signs by 31%. NLP-recovered vital signs were highly correlated with values derived from structured fields (Pearson r range 0.95-0.99). Atrial fibrillation and myocardial infarction/stroke incidence were lower and risk models were better calibrated in C3PO as opposed to the Convenience Samples (calibration error range for myocardial infarction/stroke: 0.012-0.030 in C3PO vs. 0.028-0.046 in Convenience Samples; calibration error for atrial fibrillation 0.028 in C3PO vs. 0.036 in Convenience Samples). Sampling patients receiving regular primary care and using NLP to recover missing data may reduce bias and maximize generalizability of EHR research.

6.
J Neurol ; 269(1): 307-315, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34052896

ABSTRACT

INTRODUCTION: Sex-specific differences in ischemic stroke outcomes are prevalent. We sought to investigate sex differences in the determinants of reperfusion and functional outcomes after endovascular thrombectomy (EVT) for emergent large vessel occlusion ischemic stroke (ELVO). METHODS: Patients presenting to a single referral center with an anterior circulation ELVO that underwent EVT from 2011 to 2019 were included in this retrospective analysis. Sex differences in history, presentation, adequate reperfusion (TICI 2b-3), and 90-day good outcome [delta modified Rankin Scale (mRS) ≤ 2 from pre-stroke] were examined. Multivariable logistic regression analyses were performed to assess sex-specific associations with outcomes. RESULTS: Three hundred and eighty-one consecutive ELVO patients were identified. Women (N = 193) were older (75 vs 64 years, p < 0.0001), had more pre-stroke disability (17% vs 9%, p = 0.032), more atrial fibrillation (41% vs 30%, p = 0.033), but less carotid atherosclerosis (8% vs 16%, p = 0.027). Rates of TICI 2b-3 and good outcome were similar between sexes. Carotid atherosclerosis (OR 0.315, 95% CI 0.130, 0.762) and dissection (OR 0.124, 95% CI 0.027, 0.569) independently decreased the odds of TICI 2b-3 among men but not women. Older age, more severe stroke, and not achieving TICI 2b-3 independently decreased the odds of good outcome among both sexes, while prior stroke (OR 0.258, 95% CI 0.083, 0.797) and hemorrhagic transformation (OR 0.111, 0.021, 0.592) were determinants exclusive to men. CONCLUSION: In a real-world analysis of ELVO stroke patients treated with EVT, we found that despite advanced age and more pre-stroke disability, women have comparable reperfusion rates and functional outcomes compared to men. Sex-specific determinants of reperfusion and functional outcome were identified that require further study.


Subject(s)
Brain Ischemia , Endovascular Procedures , Ischemic Stroke , Stroke , Aged , Brain Ischemia/complications , Brain Ischemia/epidemiology , Female , Humans , Male , Retrospective Studies , Sex Characteristics , Stroke/epidemiology , Stroke/surgery , Thrombectomy , Treatment Outcome
7.
J Am Heart Assoc ; 10(21): e022363, 2021 11 02.
Article in English | MEDLINE | ID: mdl-34666503

ABSTRACT

Background Performance of existing atrial fibrillation (AF) risk prediction models in poststroke populations is unclear. We evaluated predictive utility of an AF risk model in patients with acute stroke and assessed performance of a fully refitted model. Methods and Results Within an academic hospital, we included patients aged 46 to 94 years discharged for acute ischemic stroke between 2003 and 2018. We estimated 5-year predicted probabilities of AF using the Cohorts for Heart and Aging Research in Genomic Epidemiology for Atrial Fibrillation (CHARGE-AF) model, by recalibrating CHARGE-AF to the baseline risk of the sample, and by fully refitting a Cox proportional hazards model to the stroke sample (Re-CHARGE-AF) model. We compared discrimination and calibration between models and used 200 bootstrap samples for optimism-adjusted measures. Among 551 patients with acute stroke, there were 70 incident AF events over 5 years (cumulative incidence, 15.2%; 95% CI, 10.6%-19.5%). Median predicted 5-year risk from CHARGE-AF was 4.8% (quartile 1-quartile 3, 2.0-12.6) and from Re-CHARGE-AF was 16.1% (quartile 1-quartile 3, 8.0-26.2). For CHARGE-AF, discrimination was moderate (C statistic, 0.64; 95% CI, 0.57-0.70) and calibration was poor, underestimating AF risk (Greenwood-Nam D'Agostino chi-square, P<0.001). Calibration with recalibrated baseline risk was also poor (Greenwood-Nam D'Agostino chi-square, P<0.001). Re-CHARGE-AF improved discrimination (P=0.001) compared with CHARGE-AF (C statistic, 0.74 [95% CI, 0.68-0.79]; optimism-adjusted, 0.70 [95% CI, 0.65-0.75]) and was well calibrated (Greenwood-Nam D'Agostino chi-square, P=0.97). Conclusions Covariates from an established AF risk model enable accurate estimation of AF risk in a poststroke population after recalibration. A fully refitted model was required to account for varying baseline AF hazard and strength of associations between covariates and incident AF.


Subject(s)
Atrial Fibrillation , Ischemic Stroke , Stroke , Aged , Aged, 80 and over , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Humans , Incidence , Middle Aged , Risk Assessment/methods , Risk Factors , Stroke/diagnosis , Stroke/epidemiology , Stroke/etiology
8.
Drugs Today (Barc) ; 57(9): 559-569, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34586104

ABSTRACT

The identification of oncogenic drivers and the subsequent development of targeted therapies have been established as biomarker-based care for metastatic non-small cell lung cancer (NSCLC) patients. Rearranged during transfection (RET) events have been reported to be oncogenic drivers in NSCLC and were more common in patients who i) were young; ii) had adenocarcinoma histology; and iii) had never smoked. Phase II studies indicated the limited efficacy of multi-targeted tyrosine kinase inhibitors in patients with NSCLC that have a confirmed RET event. Consequently, there has been ongoing research to develop more potent and specific RET tyrosine kinase inhibitors. Recently, a novel and specific RET inhibitor, pralsetinib (BLU-667), has been reported to have excellent efficacy and low off-target toxicity in RET cancer patients. In this review, we summarize the clinical data regarding the use of pralsetinib in NSCLC patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Lung Neoplasms/drug therapy , Proto-Oncogene Proteins c-ret , Pyrazoles , Pyridines , Pyrimidines
10.
Drugs Today (Barc) ; 57(6): 377-385, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34151904

ABSTRACT

Small cell lung cancer (SCLC) is a rapidly progressive, aggressive metastatic and lethal subtype of lung cancer. Unfortunately, there has been little progress regarding the development of novel treatments for SCLC. However, lurbinectedin, a transcriptional inhibitor, has emerged as a potential novel treatment for cancer. It produces antitumor efficacy by inhibiting oncogenic transcription activity, inducing the accumulation of DNA double-strand breaks and modulating the tumor microenvironment (TME). Data from phase I/II trials indicates that lurbinectedin has significant antitumor efficacy and tolerable adverse effects in SCLC patients. Furthermore, lurbinectedin is efficacious in platinum-sensitive and platinum-resistant SCLC patients and in those with SCLC relapse after second-line treatment. In 2020, the U.S. Food and Drug Administration (FDA) approved lurbinectedin for the treatment of adult patients with metastatic SCLC or for patients that have received platinum-based chemotherapy. In this review, we discuss the molecular profile and the preclinical and clinical studies of lurbinectedin in the treatment of SCLC patients.


Subject(s)
Lung Neoplasms , Small Cell Lung Carcinoma , Adult , Carbolines , Heterocyclic Compounds, 4 or More Rings , Humans , Lung Neoplasms/drug therapy , Neoplasm Recurrence, Local , Small Cell Lung Carcinoma/drug therapy , Tumor Microenvironment
12.
Neurology ; 96(15): e1999-e2005, 2021 04 13.
Article in English | MEDLINE | ID: mdl-33637632

ABSTRACT

OBJECTIVE: To determine whether providing teleneurology (TN) consultations aiding in determination of death by neurologic criteria (DNC) to a bedside intensivist is feasible and whether timely access and expert input increase the quality of the DNC examination and identification of potential organ donors, we reviewed retrospective data related to outcomes of such consultations. METHODS: Between November 2017 and March 2019, TN consults were requested for sequential comatose patients in the intensive care unit (ICU). We recorded patients' demographic information, causes leading to coma or suspected DNC, and the results of TN consultations. We obtained data on the number of referrals to the organ bank and number of organ donors. RESULTS: Ninety-nine consults were performed with a median time from request to start of the consult of 20.2 minutes (interquartile range 5.4-65.3 minutes). Eighty consults were requested for determination of prognosis, whereas 19 consults were requested for supervision of the DNC examination. In 1 of 80 (1.2%) prognostication consults, the patient was determined by the neurologist to require assessment of DNC and was found to meet DNC criteria; determination of DNC occurred in 11 of the 19 (57.9%) consultations for a supervised DNC examination. In a comparison of the pre-TN (94 months) and post-TN (17 months) periods, there was 2.56-fold increase in the proportion of patients meeting DNC criteria who were medically suitable for donation (pre-TN 8.9% vs post-TN 21.1%, p = 0.02) and a 2.12-fold increase in the proportion of donors (pre-TN 6.14% vs post-TN 13.1%, p = 0.14). CONCLUSIONS: It is feasible to perform TN consultations for patients with severe neurologic damage and to allow expert supervision for DNC examination. Having a teleneurologist as part of the ICU assessment team helped differentiate severe neurologic deficits from DNC and was associated with increase in organ donation.


Subject(s)
Brain Death/diagnosis , Neurologic Examination/methods , Neurology/methods , Referral and Consultation , Telemedicine/methods , Aged , Female , Heart Arrest/complications , Humans , Male , Middle Aged , Retrospective Studies , Tissue Donors/supply & distribution
13.
Expert Rev Cardiovasc Ther ; 18(5): 277-287, 2020 May.
Article in English | MEDLINE | ID: mdl-32323590

ABSTRACT

INTRODUCTION: Since approval by the United States Food and Drug Administration in 1996, alteplase utilization rates for acute ischemic stroke have increased. Despite its efficacy for improving stroke outcomes, however, the majority of ischemic stroke patients still do not receive alteplase. To address this issue, different methods for improving access to alteplase have been tested with varying degrees of success. AREAS COVERED: This article gives an overview of the recent approaches pursued to improve access to alteplase for acute ischemic stroke patients. Utilization of stroke systems of care, quality metrics, and quality-improvement initiatives to improve alteplase treatment rates are discussed. The implementation of Telestroke networks to improve access and timely evaluation by a stroke specialist are also reviewed. Lastly, this review discusses the use of neuroimaging techniques to identify alteplase candidates in stroke of unknown symptom onset or beyond the 4.5-h treatment window. EXPERT COMMENTARY: Expanding access to alteplase therapy for acute ischemic stroke is a multi-faceted approach. Specific considerations based on region, population, and health-care resources should be considered for each strategy. Neuroimaging approaches to identify alteplase-eligible patients beyond the 4.5-h treatment window are a recent development in acute stroke care that holds promise for increasing alteplase treatment rates.


Subject(s)
Brain Ischemia/drug therapy , Stroke/drug therapy , Tissue Plasminogen Activator/therapeutic use , Administration, Intravenous , Fibrinolytic Agents/therapeutic use , Humans , Thrombolytic Therapy/methods , Treatment Outcome , United States , United States Food and Drug Administration
14.
Leukemia ; 33(7): 1713-1722, 2019 07.
Article in English | MEDLINE | ID: mdl-30573775

ABSTRACT

The iliac crest is the sampling site for minimal residual disease (MRD) monitoring in multiple myeloma (MM). However, the disease distribution is often heterogeneous, and imaging can be used to complement MRD detection at a single site. We have investigated patients in complete remission (CR) during first-line or salvage therapy for whom MRD flow cytometry and the two imaging modalities positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) were performed at the onset of CR. Residual focal lesions (FLs), detectable in 24% of first-line patients, were associated with short progression-free survival (PFS), with DW-MRI detecting disease in more patients. In some patients, FLs were only PET positive, indicating that the two approaches are complementary. Combining MRD and imaging improved prediction of outcome, with double-negative and double-positive features defining groups with excellent and dismal PFS, respectively. FLs were a rare event (12%) in first-line MRD-negative CR patients. In contrast, patients achieving an MRD-negative CR during salvage therapy frequently had FLs (50%). Multi-region sequencing and imaging in an MRD-negative patient showed persistence of spatially separated clones. In conclusion, we show that DW-MRI is a promising tool for monitoring residual disease that complements PET and should be combined with MRD.


Subject(s)
Diffusion Magnetic Resonance Imaging/methods , Flow Cytometry/methods , Hematopoietic Stem Cell Transplantation/adverse effects , Multiple Myeloma/therapy , Neoplasm, Residual/diagnosis , Positron-Emission Tomography/methods , Biomarkers, Tumor/genetics , Follow-Up Studies , Humans , Multiple Myeloma/pathology , Neoplasm, Residual/diagnostic imaging , Neoplasm, Residual/etiology , Prognosis , Remission Induction , Survival Rate , Transplantation, Autologous , Exome Sequencing
15.
Nat Commun ; 8(1): 268, 2017 08 16.
Article in English | MEDLINE | ID: mdl-28814763

ABSTRACT

In multiple myeloma malignant plasma cells expand within the bone marrow. Since this site is well-perfused, a rapid dissemination of "fitter" clones may be anticipated. However, an imbalanced distribution of multiple myeloma is frequently observed in medical imaging. Here, we perform multi-region sequencing, including iliac crest and radiology-guided focal lesion specimens from 51 patients to gain insight into the spatial clonal architecture. We demonstrate spatial genomic heterogeneity in more than 75% of patients, including inactivation of CDKN2C and TP53, and mutations affecting mitogen-activated protein kinase genes. We show that the extent of spatial heterogeneity is positively associated with the size of biopsied focal lesions consistent with regional outgrowth of advanced clones. The results support a model for multiple myeloma progression with clonal sweeps in the early phase and regional evolution in advanced disease. We suggest that multi-region investigations are critical to understanding intra-patient heterogeneity and the evolutionary processes in multiple myeloma.In multiple myeloma, malignant cells expand within bone marrow. Here, the authors use multi-region sequencing in patient samples to analyse spatial clonal architecture and heterogeneity, providing novel insight into multiple myeloma progression and evolution.


Subject(s)
Bone Marrow/pathology , Multiple Myeloma/genetics , Plasma Cells/metabolism , 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics , Aged , Aged, 80 and over , Cyclin-Dependent Kinase Inhibitor p18/genetics , Disease Progression , Female , Fibroblast Growth Factors/genetics , Humans , Male , Middle Aged , Mitogen-Activated Protein Kinases/genetics , Multiple Myeloma/pathology , Mutation , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , STAT3 Transcription Factor/genetics , Sequence Analysis, DNA , Tumor Suppressor Protein p53/genetics
16.
Blood Cancer J ; 7(2): e535, 2017 02 24.
Article in English | MEDLINE | ID: mdl-28234347

ABSTRACT

The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant abnormalities and novel prognostic markers. Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1, CDKN2C and TP53 where they have prognostic significance.


Subject(s)
Multiple Myeloma/genetics , Retinoblastoma Binding Proteins/genetics , Ubiquitin-Protein Ligases/genetics , Humans , Multiple Myeloma/pathology , Neoplasm Recurrence, Local , Prognosis , Retinoblastoma Protein/genetics
17.
J Clin Pharm Ther ; 42(1): 115-118, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27813106

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: Paritaprevir/ritonavir/ombitasvir+dasabuvir (PrOD) is a direct-acting antiviral (DAA) approved for the treatment of chronic hepatitis C virus. We report on a probable interaction between PrOD with ribavirin and warfarin. CASE DESCRIPTION: Two weeks after the start of PrOD with ribavirin, the patient's international normalized ratio (INR) became subtherapeutic. Eleven weeks into therapy and following a 125% total increase in the weekly warfarin dose, therapeutic INR was achieved. Thirteen days after DAA therapy was completed and discontinued, the patient's INR became critically supratherapeutic. WHAT IS NEW AND CONCLUSION: Patients on PrOD plus ribavirin with warfarin should have INR followed closely upon initiation and discontinuation of therapy due to a probable drug interaction.


Subject(s)
Anilides/adverse effects , Anticoagulants/therapeutic use , Carbamates/adverse effects , Macrocyclic Compounds/adverse effects , Ribavirin/therapeutic use , Ritonavir/adverse effects , Sulfonamides/adverse effects , Uracil/analogs & derivatives , Warfarin/therapeutic use , 2-Naphthylamine , Anilides/therapeutic use , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , Carbamates/therapeutic use , Cyclopropanes , Drug Interactions , Drug Therapy, Combination/adverse effects , Hepatitis C, Chronic/drug therapy , Humans , Lactams, Macrocyclic , Macrocyclic Compounds/therapeutic use , Male , Middle Aged , Proline/analogs & derivatives , Ritonavir/therapeutic use , Sulfonamides/therapeutic use , Uracil/adverse effects , Uracil/therapeutic use , Valine
18.
Ann Thorac Surg ; 79(4): 1110-5; discussion 1110-5, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15797034

ABSTRACT

BACKGROUND: Barrett's esophagus, high-grade dysplasia (HGD), and invasive cancer are steps in the progression of esophageal adenocarcinoma. While surgery is recommended for resectable invasive adenocarcinoma, a number of treatment modalities are advocated for HGD. The purpose of this study is to determine the outcomes after surgery for HGD. METHODS: We identified cases of HGD based on endoscopic biopsy in a single institution's databases from 1980 through 2001. Records were reviewed for patient characteristics, treatments, staging, and outcomes. RESULTS: In a 22-year period, 869 cases of esophageal adenocarcinoma and 1,614 cases of Barrett's esophagus were diagnosed. Of these, 115 had HGD without pretreatment evidence of invasion. Forty-nine patients with HGD underwent resection (mean age, 59 years) as initial treatment. Forty-seven had endoscopic treatment (mean age, 70 years) by photodynamic therapy or endoscopic mucosal resection. Seven of the endoscopically treated patients failed, with three undergoing surgery and four observation. Nineteen patients were initially observed, with six eventually having surgery. For the 49 initially treated surgically, one (2%) operative mortality occurred. Invasive adenocarcinoma was present in 18 (37%). The five-year survival was 83% for all resected HGD patients (91% for those without invasion, 68% with invasion). Three of the eight deaths in those with invasion were from recurrent adenocarcinoma. CONCLUSIONS: Surgical resection of esophageal HGD can be performed with low mortality and allows long-term survival. A significant percentage with an initial diagnosis of HGD will have invasive disease at resection. Surgery is the optimal treatment for HGD unless contraindicated by severe comorbidities.


Subject(s)
Barrett Esophagus/surgery , Esophageal Neoplasms/surgery , Esophagus/pathology , Adenocarcinoma/etiology , Adenocarcinoma/surgery , Adult , Aged , Barrett Esophagus/mortality , Barrett Esophagus/pathology , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophagectomy , Esophagoscopy , Female , Humans , Male , Middle Aged , Neoplasm Staging , Survival Rate
19.
Ann Surg ; 240(3): 535-44; discussion 544-6, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15319725

ABSTRACT

OBJECTIVES: Carotid endarterectomy (CEA) is supported by level 1 evidence as the standard treatment of severe carotid stenosis in both symptomatic and asymptomatic patients. As interventional techniques are emerging for treatment of this disease, this study was undertaken to provide a contemporary surgical standard for comparison to carotid stenting. PATIENTS AND METHODS: During the interval 1989 to 1999, 2236 isolated CEAs were performed on 1897 patients (62% male, 36% symptomatic, 4.6% reoperative procedures). Study endpoints included perioperative events, patient survival, late incidence of stroke, anatomic durability of CEA, and resource utilization changes during the study. Variables associated with complications, long-term and stroke free survival, restenosis, and resource utilization were analyzed by univariate and multivariate analysis. RESULTS: Perioperative complications occurred in 5.5% of CEA procedures, including any stroke/death (1.4%), neck hematoma (1.7%), cardiac complications (0.5%), and cranial nerve injury (0.4%). Actuarial survival at 5 and 10 years was 72.4% (95% confidence interval [CI] 69.3-73.5) and 44.7% (95% CI 41.7-47.9) respectively, with coronary artery disease (P < 0.0018), chronic obstructive pulmonary disease (P < 0.00018) and diabetes mellitus (P < 0.0011) correlating with decreased longevity. The age- and sex-adjusted incidence of any stroke during follow-up was reduced by 22% (upper 0.35, lower 0.08) of predicted with the patient classification of hyperlipidemia (P < 0.0045) as the only protective factor. Analysis of CEA anatomic durability during a median follow-up period of 5.9 years identified a 7.7% failure rate (severe restenosis/occlusion, 4.5%; or reoperative CEA, 3.2%) with elevated serum cholesterol (P < 0.017) correlating with early restenosis. Resource utilization diminished (first versus last 2-year interval periods) for average hospital length of stay from 10.3 +/- 1.5 days to 4.3 +/- 0.7 days (P < 0.01) and preoperative contrast angiography from 87% +/- 1.4% to 10.3% +/- 4%. CONCLUSIONS: These data delineate the safety, durability, and effectiveness in long-term stroke prevention of CEA. They provide a standard to which emerging catheter-based therapies for carotid stenosis should be compared.


Subject(s)
Carotid Stenosis/surgery , Endarterectomy, Carotid , Aged , Angioplasty, Balloon , Carotid Stenosis/complications , Carotid Stenosis/mortality , Carotid Stenosis/therapy , Endarterectomy, Carotid/adverse effects , Endarterectomy, Carotid/mortality , Female , Humans , Male , Risk Factors , Stents , Stroke/etiology , Stroke/prevention & control , Survival Rate , Treatment Outcome
20.
Ann Vasc Surg ; 18(1): 79-85, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14508664

ABSTRACT

Popliteal artery embolism has been a focus of study at the Massachusetts General Hospital for over 60 years. It is a formidable vascular problem with significant limb loss and mortality. To assess the impact of advances in cardiac and vascular therapies, we reviewed our outcomes over 12 years. A retrospective review from our databases identified 66 patients with 72 popliteal artery emboli between January 1989 and October 2000. Patients undergoing nonsurgical therapy or with in situ atherosclerotic thrombosis were excluded. Demographics, comorbidities, presentation, duration, etiology, treatment, and outcomes were analyzed. Patients were classified into those with acute (AP; symptoms <7 days; 59 of 72, 82%) or delayed (DP; symptoms >7 days; 13 of 72, 18%) presentation. The presentation was typically acute ischemia (85%) in the AP group and claudication (69%), rest pain (15.5%), or gangrene (15.5%) in the DP group. The most common etiology was embolism secondary to atrial fibrillation (17 of 72, 24%). Femoral artery access (15 of 72, 21%) was more prevalent than in our prior experience. In the AP group, 9 of 59 (15%) were treated with a femoral artery approach, 44 of 59 (75%) with a popliteal artery approach, and 6 of 59 (10%) with bypass. In the DP group, 11 of 13 (85%) were treated with a popliteal approach and 2 of 13 (15%) with bypass. Completion angiography was done in 17 cases (24%). Limb salvage rate was 88% (88% AP, 85% DP); the rate was 94% with angiography and 85% without it (p > 0.1). There were seven deaths (10%). The mortality rate was 33% after amputation and 7% after limb salvage (p < 0.05). Except for a greater prevalence of femoral artery access as an etiology, the demographics of patients with popliteal embolism were similar to those of prior reports. Although a femoral approach may be appropriate in select AP cases, a popliteal approach is preferred in most patients and is necessary in DP cases. Completion angiography should be performed to ensure adequacy of the embolectomy. Outcomes are unchanged. Future therapies should aim to improve limb salvage and mortality rates.


Subject(s)
Aneurysm/surgery , Popliteal Artery/surgery , Vascular Surgical Procedures/methods , Vascular Surgical Procedures/trends , Aged , Female , Humans , Limb Salvage/methods , Male , Retrospective Studies , Treatment Outcome
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