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1.
Am J Transplant ; 24(4): 619-630, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37940005

ABSTRACT

The recent shortage of the University of Wisconsin (UW) solution prompted increased utilization of histidine-tryptophan-ketoglutarate (HTK) solution for liver graft preservation. This contemporary study analyzed deceased donor liver transplant outcomes following preservation with HTK vs UW. Patients receiving deceased donor liver transplantations between January 1, 2019, and June 30, 2022, were retrospectively identified utilizing the Organ Procurement and Transplant Network database, stratified by preservation with HTK vs UW, and a propensity score matching analysis was performed. Outcomes assessed included rates of primary nonfunction, graft survival, and patient survival. There were 4447 patients in each cohort. Primary nonfunction occurred in 60 (1.35%) patients in the HTK group vs 25 (0.54%) in the UW group (P < .001). HTK was associated with lower 90-day graft survival (94.39% vs 96.09%; P < .001) and 90-day patient survival (95.97% vs 97.38%; P = .001). Unmatched donation after cardiac death-specific analysis of HTK vs UW demonstrated respective rates of primary nonfunction of 1.63% vs 0.82% (P = .20), 90-day graft survival of 92.50% vs 95.29% (P = .069), and 90-day patient survival of 93.90% vs 96.35% (P = .077). These results suggest that HTK may not be an equivalent preservation solution for deceased donor liver transplantation.


Subject(s)
Liver Transplantation , Organ Preservation Solutions , Humans , Retrospective Studies , Propensity Score , Living Donors , Glucose , Mannitol , Potassium Chloride , Procaine , Insulin , Glutathione , Allopurinol
2.
Hepatology ; 79(2): 380-391, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37548928

ABSTRACT

BACKGROUND AND AIMS: The objective of this study is to determine the diagnostic accuracy of the American College of Radiology Contrast-Enhanced Ultrasound (CEUS) Liver Imaging Reporting and Data System LR-5 characterization for HCC diagnosis in North American or European patients. APPROACH AND RESULTS: A prospective multinational cohort study was performed from January 2018 through November 2022 at 11 academic and nonacademic centers in North America and Europe. Patients at risk for HCC with at least 1 liver observation not previously treated, identified on ultrasound (US), or multiphase CT or MRI performed as a part of standard clinical care were eligible for the study. All participants were examined with CEUS of the liver within 4 weeks of CT/MRI or tissue diagnosis to characterize up to 2 liver nodules per participant using ACR CEUS Liver Imaging Reporting and Data System. Definite HCC diagnosis on the initial CT/MRI, imaging follow-up, or histology for CT/MRI-indeterminate nodules were used as reference standards. A total of 545 nodules had confirmed reference standards in 480 patients, 73.8% were HCC, 5.5% were other malignancies, and 20.7% were nonmalignant. The specificity of CEUS LR-5 for HCC was 95.1% (95% CI 90.1%-97.7%), sensitivity 62.9% (95% CI 57.9%-67.7%), positive predictive value 97.3% (95% CI 94.5%-98.7%), and negative predictive value 47.7% (95% CI 41.7%-53.8%). In addition, benign CEUS characterization (LR-1 or LR-2) had 100% specificity and 100% positive predictive value for nonmalignant liver nodules. CONCLUSIONS: CEUS Liver Imaging Reporting and Data System provides an accurate categorization of liver nodules in participants at risk for HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Prospective Studies , Cohort Studies , Contrast Media , Retrospective Studies , Reproducibility of Results , Magnetic Resonance Imaging/methods , Europe , North America , Sensitivity and Specificity
3.
Cell Rep Med ; 4(12): 101330, 2023 12 19.
Article in English | MEDLINE | ID: mdl-38118415

ABSTRACT

Increased breast cancer (BC) mortality risk posed by delayed surgical resection of tumor after diagnosis is a growing concern, yet the underlying mechanisms remain unknown. Our cohort analyses of early-stage BC patients reveal the emergence of a significantly rising mortality risk when the biopsy-to-surgery interval was extended beyond 53 days. Additionally, histology of post-biopsy tumors shows prolonged retention of a metastasis-permissive wound stroma dominated by M2-like macrophages capable of promoting cancer cell epithelial-to-mesenchymal transition and angiogenesis. We show that needle biopsy promotes systemic dissemination of cancer cells through a mechanism of sustained activation of the COX-2/PGE2/EP2 feedforward loop, which favors M2 polarization and its associated pro-metastatic changes but are abrogated by oral treatment with COX-2 or EP2 inhibitors in estrogen-receptor-positive (ER+) syngeneic mouse tumor models. Therefore, we conclude that needle biopsy of ER+ BC provokes progressive pro-metastatic changes, which may explain the mortality risk posed by surgery delay after diagnosis.


Subject(s)
Breast Neoplasms , Humans , Animals , Mice , Female , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Cell Line, Tumor , Cyclooxygenase 2 , Biopsy, Needle
4.
BMC Bioinformatics ; 24(1): 298, 2023 Jul 22.
Article in English | MEDLINE | ID: mdl-37481512

ABSTRACT

BACKGROUND: Protein biomarkers of cancer progression and response to therapy are increasingly important for improving personalized medicine. Advanced quantitative pathology platforms enable measurement of protein expression in tissues at the single-cell level. However, this rich quantitative cell-by-cell biomarker information is most often not exploited. Instead, it is reduced to a single mean across the cells of interest or converted into a simple proportion of binary biomarker-positive or -negative cells. RESULTS: We investigated the utility of retaining all quantitative information at the single-cell level by considering the values of the quantile function (inverse of the cumulative distribution function) estimated from a sample of cell signal intensity levels in a tumor tissue. An algorithm was developed for selecting optimal cutoffs for dichotomizing cell signal intensity distribution quantiles as predictors of continuous, categorical or survival outcomes. The proposed algorithm was used to select optimal quantile biomarkers of breast cancer progression based on cancer cells' cell signal intensity levels of nuclear protein Ki-67, Proliferating cell nuclear antigen, Programmed cell death 1 ligand 2, and Progesterone receptor. The performance of the resulting optimal quantile biomarkers was validated and compared to the standard cancer compartment mean signal intensity markers using an independent external validation cohort. For Ki-67, the optimal quantile biomarker was also compared to established biomarkers based on percentages of Ki67-positive cells. For proteins significantly associated with PFS in the external validation cohort, the optimal quantile biomarkers yielded either larger or similar effect size (hazard ratio for progression-free survival) as compared to cancer compartment mean signal intensity biomarkers. CONCLUSION: The optimal quantile protein biomarkers yield generally improved prognostic value as compared to the standard protein expression markers. The proposed methodology has a broad application to single-cell data from genomics, transcriptomics, proteomics, or metabolomics studies at the single cell level.


Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Humans , Female , Immunohistochemistry , Ki-67 Antigen , Algorithms
5.
Lab Invest ; 103(8): 100158, 2023 08.
Article in English | MEDLINE | ID: mdl-37088463

ABSTRACT

Current histocytometry methods enable single-cell quantification of biomolecules in tumor tissue sections by multiple detection technologies, including multiplex fluorescence-based immunohistochemistry or in situ hybridization. Quantitative pathology platforms can provide distributions of cellular signal intensity (CSI) levels of biomolecules across the entire cell populations of interest within the sampled tumor tissue. However, the heterogeneity of CSI levels is usually ignored, and the simple mean signal intensity value is considered a cancer biomarker. Here we consider the entire distribution of CSI expression levels of a given biomolecule in the cancer cell population as a predictor of clinical outcome. The proposed quantile index (QI) biomarker is defined as the weighted average of CSI distribution quantiles in individual tumors. The weight for each quantile is determined by fitting a functional regression model for a clinical outcome. That is, the weights are optimized so that the resulting QI has the highest power to predict a relevant clinical outcome. The proposed QI biomarkers were derived for proteins expressed in cancer cells of malignant breast tumors and demonstrated improved prognostic value compared with the standard mean signal intensity predictors. The R package Qindex implementing QI biomarkers has been developed. The proposed approach is not limited to immunohistochemistry data and can be based on any cell-level expressions of proteins or nucleic acids.


Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Humans , Female , Biomarkers , Proteins , Immunohistochemistry , Breast Neoplasms/diagnosis
6.
JCO Precis Oncol ; 7: e2100498, 2023 01.
Article in English | MEDLINE | ID: mdl-36652667

ABSTRACT

PURPOSE: T-cell-mediated cytotoxicity is suppressed when programmed cell death-1 (PD-1) is bound by PD-1 ligand-1 (PD-L1) or PD-L2. Although PD-1 inhibitors have been approved for triple-negative breast cancer, the lower response rates of 25%-30% in estrogen receptor-positive (ER+) breast cancer will require markers to identify likely responders. The focus of this study was to evaluate whether PD-L2, which has higher affinity than PD-L1 for PD-1, is a predictor of early recurrence in ER+ breast cancer. METHODS: PD-L2 protein levels in cancer cells and stromal cells of therapy-naive, localized or locoregional ER+ breast cancers were measured retrospectively by quantitative immunofluorescence histocytometry and correlated with progression-free survival (PFS) in the main study cohort (n = 684) and in an independent validation cohort (n = 273). All patients subsequently received standard-of-care adjuvant therapy without immune checkpoint inhibitors. RESULTS: Univariate analysis of the main cohort revealed that high PD-L2 expression in cancer cells was associated with shorter PFS (hazard ratio [HR], 1.8; 95% CI, 1.3 to 2.6; P = .001), which was validated in an independent cohort (HR, 2.3; 95% CI, 1.1 to 4.8; P = .026) and remained independently predictive after multivariable adjustment for common clinicopathological variables (HR, 2.0; 95% CI, 1.4 to 2.9; P < .001). Subanalysis of the ER+ breast cancer patients treated with adjuvant chemotherapy (n = 197) revealed that high PD-L2 levels in cancer cells associated with short PFS in univariate (HR, 2.5; 95% CI, 1.4 to 4.4; P = .003) and multivariable analyses (HR, 3.4; 95% CI, 1.9 to 6.2; P < .001). CONCLUSION: Up to one third of treatment-naive ER+ breast tumors expressed high PD-L2 levels, which independently predicted poor clinical outcome, with evidence of further elevated risk of progression in patients who received adjuvant chemotherapy. Collectively, these data warrant studies to gain a deeper understanding of PD-L2 in the progression of ER+ breast cancer and may provide rationale for immune checkpoint blockade for this patient group.


Subject(s)
B7-H1 Antigen , Triple Negative Breast Neoplasms , Humans , Programmed Cell Death 1 Receptor , Retrospective Studies
7.
Pathobiology ; 90(2): 114-122, 2023.
Article in English | MEDLINE | ID: mdl-35649384

ABSTRACT

INTRODUCTION: Needle biopsy is essential for definitive diagnosis of breast malignancy. Significant histologic changes due to tissue damage have been reported in solid tumors. This study investigated the association between time from needle biopsy and inflammation in breast tumors. METHODS: A total of 73 stage I-II invasive breast cancer cases diagnosed by image-guided needle biopsy who had surgery as their first definitive treatment were retrospectively analyzed. Time from biopsy to surgical excision ranged from 8 to 252 days. Histological sections of surgically resected tumors with a visible needle tract were reviewed by histologic evaluation. Data were analyzed by McNemar's test for proportional differences, and the Benjamini-Hochberg procedure was used to assess the association between immune cell prevalence and clinical variables. RESULTS: Characteristic histology changes, including foreign body giant-cell reaction, synovial-cell metaplasia, desmoplastic repair changes, granulation tissue, fat necrosis, and inflammation, were frequently detected adjacent to the needle tract. Spatial comparison indicated that a higher proportion of cases had neutrophils, eosinophils, and macrophages adjacent to the needle tract than tumors distant from it. The presence of inflammatory cells adjacent to the needle tract was not associated with time from biopsy or subtype. Still, plasma cells were associated with residual carrier material from biopsy markers. CONCLUSION: Macrophages and eosinophils are highly abundant and retained adjacent to the needle tract regardless of time from the biopsy.


Subject(s)
Breast Neoplasms , Humans , Female , Retrospective Studies , Biopsy, Needle/methods , Breast Neoplasms/pathology , Breast/pathology
8.
J Autism Dev Disord ; 53(12): 4759-4771, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36167886

ABSTRACT

Sensory features are part of the diagnostic criteria for autism and include sensory hypo/hyper reactivity and unusual sensory interest; however, additional sensory differences, namely differences in sensory integration, have not been routinely explored. This study characterized sensory integration differences in a cohort of children (n = 93) with a confirmed diagnosis of autism (5-9 years) using a standardized, norm-referenced battery. Mean z scores, autism diagnostic scores, and IQ are reported. Participants showed substantial deficits in tactile perception, praxis, balance, visual perception, and visual-motor skills. Relationship with autism diagnostic test scores were weak or absent. Findings suggest additional sensory difficulties that are not typically assessed or considered when characterizing sensory features in autism. These data have implications for a greater understanding of the sensory features in the autism phenotype and the development of personalized treatments.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Child , Humans , Autistic Disorder/diagnosis , Autism Spectrum Disorder/diagnosis , Sensation , Visual Perception , Phenotype
9.
Trials ; 23(1): 691, 2022 Aug 19.
Article in English | MEDLINE | ID: mdl-35986303

ABSTRACT

BACKGROUND: The COVID-19 pandemic impacted nearly all facets of our daily lives, and clinical research was no exception. Here, we discuss the impact of the pandemic on our ongoing, three-arm randomized controlled trial (RCT) Sensory Integration Therapy (SIT) in Autism: Mechanisms and Effectiveness (NCT02536365), which investigates the immediate and sustained utility of SIT to strengthen functional daily-living skills and minimize the presence of maladaptive sensory behaviors in autistic children. MAIN TEXT: In this text, we detail how we navigated the unique challenges that the pandemic brought forth between the years 2020 and 2021, including the need to rapidly adjust our study protocol, recruitment strategy, and in-person assessment battery to allow for virtual recruitment and data collection. We further detail how we triaged participants and allocated limited resources to best preserve our primary outcome measures while prioritizing the safety of our participants and study team. We specifically note the importance of open and consistent communication with all participating families throughout the pandemic in ensuring all our protocol adjustments were successfully implemented. CONCLUSIONS: Though the COVID-19 pandemic resulted in an unprecedented interruption to in-person clinical research, clinical trials have always been and will continue to be at risk for unforeseen interruptions, whether from world events or participants' personal circumstances. By presenting our steps to preserving this RCT throughout the pandemic, we offer suggestions for successfully managing unexpected interruptions to research. Ideally, by taking these into account, future RCTs may be increasingly prepared to minimize the impact of these potential interruptions to research.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , COVID-19 , Autism Spectrum Disorder/diagnosis , Autism Spectrum Disorder/therapy , Child , Humans , Pandemics
10.
Cancers (Basel) ; 14(2)2022 Jan 08.
Article in English | MEDLINE | ID: mdl-35053472

ABSTRACT

Tumor-associated macrophages (TAMs) promote progression of breast cancer and other solid malignancies via immunosuppressive, pro-angiogenic and pro-metastatic effects. Tumor-promoting TAMs tend to express M2-like macrophage markers, including CD163. Histopathological assessments suggest that the density of CD163-positive TAMs within the tumor microenvironment is associated with reduced efficacy of chemotherapy and unfavorable prognosis. However, previous analyses have required research-oriented pathologists to visually enumerate CD163+ TAMs, which is both laborious and subjective and hampers clinical implementation. Objective, operator-independent image analysis methods to quantify TAM-associated information are needed. In addition, since M2-like TAMs exert local effects on cancer cells through direct juxtacrine cell-to-cell interactions, paracrine signaling, and metabolic factors, we hypothesized that spatial metrics of adjacency of M2-like TAMs to breast cancer cells will have further information value. Immunofluorescence histo-cytometry of CD163+ TAMs was performed retrospectively on tumor microarrays of 443 cases of invasive breast cancer from patients who subsequently received adjuvant chemotherapy. An objective and automated algorithm was developed to phenotype CD163+ TAMs and calculate their density within the tumor stroma and derive several spatial metrics of interaction with cancer cells. Shorter progression-free survival was associated with a high density of CD163+ TAMs, shorter median cancer-to-CD163+ nearest neighbor distance, and a high number of either directly adjacent CD163+ TAMs (within juxtacrine proximity <12 µm to cancer cells) or communicating CD163+ TAMs (within paracrine communication distance <250 µm to cancer cells) after multivariable adjustment for clinical and pathological risk factors and correction for optimistic bias due to dichotomization.

11.
J Thorac Cardiovasc Surg ; 164(3): 650-657, 2022 09.
Article in English | MEDLINE | ID: mdl-35000683

ABSTRACT

OBJECTIVE: The racial gap in surgical treatment for early-stage non-small cell lung cancer (NSCLC) has been narrowing at the population level, but it is unknown if this trend persists at the facility level. PATIENTS AND METHODS: We queried the National Cancer Database Participant User File from 2006 to 2016 for patients with stage I NSCLC. Facilities were grouped by type, location, and resection volume. The cumulative surgery rate for Black and White patients in each group was calculated, and an incidence rate difference of receipt of surgery was determined. Logistic regression with estimation of marginal effects was used to assess the probability difference of receiving surgery in Black versus White patients in each year. RESULTS: In total, 315,474 patients were included; 287,585 (91.2%) were White and 27,889 (8.8%) were Black. The surgery rate was greater for White patients (60.2% vs 55.8%, P < .001). For most groups, the surgery disparity narrowed over the study period. The disparity widened in community cancer programs; facilities in the New England, West North Central, and Pacific regions; and the lowest volume facilities. The probability difference for receiving surgery was significantly smaller in 2016 versus 2006 in the Middle Atlantic region and community cancer programs; the difference was unchanged for all other groupings. CONCLUSIONS: Trends in disparities in the use of resection for early-stage NSCLC are not universal across facility groupings. As efforts are made toward addressing racial disparities in surgical care for NSCLC, it will be important to remember that population-level analyses may mask lack of progress in certain facility groups.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/surgery , Healthcare Disparities , Humans , Lung Neoplasms/surgery , Racial Groups
12.
Am Heart J Plus ; 24: 100230, 2022 Dec.
Article in English | MEDLINE | ID: mdl-38560637

ABSTRACT

Background: Randomized controlled trials (RCT) of ultrafiltration (UF) have demonstrated conflicting results regarding its efficacy and safety. Objective: We reviewed 10 years of data for adjustable UF during heart failure hospitalizations in a real world cohort. Methods: We performed a retrospective, single center analysis of 335 consecutive patients treated with adjustable rate UF using the CHF Solutions Aquadex Flex Flo System from 2009 to 2019. Results: Compared to previous RCTs investigating UF, our cohort was older, with worse renal impairment and more antecedent HF hospitalizations in the year preceding therapy. Mean fluid removal with UF was 14.6 l. Mean weight loss with UF was 15.6 lbs (range 0.2-57 lbs) and was sustained at 1-2 week follow-up. Mean creatinine change upon stopping UF, at discharge and follow-up (mean 30 days) was +0.11 mg/dl, +0.07 mg/dl and +0.11 mg/dl, respectively. HF rehospitalizations at 30 days, 90 days and 1 year were 12.4 %, 14.9 % and 27.3 % respectively. On average patients had 1.74 fewer hospitalizations for HF in the year following UF when compared to 12 months preceding UF. Major bleeding defined as requiring discontinuation of anticoagulation occurred in 3.6 % of patients. Conclusions: Compared with previous UF trials, our study demonstrates that UF compares favorably for HF rehospitalizations, renal function response, and weight/volume loss. Importantly, our real world experience allowed for the adjustment of UF rate during therapy and we believe this is a major contributor to our favorable outcomes. In clinical practice, UF can be a safe and effective strategy for decongestion.

13.
J Pancreat Cancer ; 7(1): 23-30, 2021.
Article in English | MEDLINE | ID: mdl-34095739

ABSTRACT

Purpose: Current literature reports increased incidence of postpancreaticoduodenectomy (PD) nonalcoholic fatty liver disease (NAFLD), a precursor for nonalcoholic steatohepatitis and cirrhosis. The incidence of and risk factors (RFs) for NAFLD in the PD population, however, are not well elucidated. Methods: A cohort of 421 patients from a single institution who underwent PD for carcinoma and followed for at least 6 months were assessed retrospectively for age, gender, pathology, surgical complications (operative blood loss and length of stay [LOS]), comorbidities (diabetes, hypertension, hyperlipidemia, obesity), tobacco use, pre- and postoperative nutritional status (albumin and body mass index [BMI]), use of pancreatic enzyme replacement, and perioperative laboratory values (hemoglobin and liver function test). Cox proportional hazards model was used to examine these potential RFs as predictors of time to development of post-PD NAFLD. Results: Sixty (14.3%) patients developed post-PD NAFLD. Patients with NAFLD were younger (61.10 vs. 65.01 years old) and had higher preoperative BMI (28.92 vs. 26.61). Multivariate Cox proportional hazard model identified higher preoperative BMI, shorter postoperative LOS, and female gender as RFs for post-PD NAFLD. After excluding 12 patients with rare histology, there was a lower unadjusted hazard of developing NAFLD (p-value = 0.018) in the adenocarcinoma group than in the neuroendocrine and periampullary tumor groups. There was no statistically significant association between post-PD NAFLD and other characteristics. Conclusion: Female gender, higher preoperative BMI, and shorter LOS deserve closer monitoring for earlier detection and management of NAFLD.

14.
Bioinformatics ; 37(10): 1452-1460, 2021 06 16.
Article in English | MEDLINE | ID: mdl-33275142

ABSTRACT

MOTIVATION: Quantitative immunofluorescence is often used for immunohistochemistry quantification of proteins that serve as cancer biomarkers. Advanced image analysis systems for pathology allow capturing expression levels in each individual cell or subcellular compartment. However, only the mean signal intensity within the cancer tissue region of interest is usually considered as biomarker completely ignoring the issue of tumor heterogeneity. RESULTS: We propose using immunohistochemistry image-derived information on the spatial distribution of cellular signal intensity (CSI) of protein expression within the cancer cell population to quantify both mean expression level and tumor heterogeneity of CSI levels. We view CSI levels as marks in a marked point process of cancer cells in the tissue and define spatial indices based on conditional mean and conditional variance of the marked point process. The proposed methodology provides objective metrics of cell-to-cell heterogeneity in protein expressions that allow discriminating between different patterns of heterogeneity. The prognostic utility of new spatial indices is investigated and compared to the standard mean signal intensity biomarkers using the protein expressions in tissue microarrays incorporating tumor tissues from 1000+ breast cancer patients. AVAILABILITY AND IMPLEMENTATION: THE R CODE FOR COMPUTING THE PROPOSED SPATIAL INDICES IS INCLUDED AS SUPPLEMENTARY MATERIAL: . SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Subject(s)
Breast Neoplasms , Biomarkers, Tumor , Female , Humans , Image Processing, Computer-Assisted , Immunohistochemistry , Staining and Labeling
15.
Can J Urol ; 27(3): 10250-10256, 2020 06.
Article in English | MEDLINE | ID: mdl-32544049

ABSTRACT

INTRODUCTION: To evaluate the impact of an 'opt-in' non-narcotic postoperative pain regimen on narcotic utilization and patient-reported pain scores. MATERIALS AND METHODS: A prospective, non-blinded pre- and post-interventional trial was conducted, including a lead-in period for baseline evaluation. The intervention group received a new pain protocol prioritizing non-narcotic medications, an 'opt-in' requirement for opiates, and standardized patient education. Study outcomes included opiate prescription and utilization (measured in Morphine Equivalent Doses) and reported pain scores on postoperative day (POD) 1, discharge and follow up. RESULTS: At discharge, 70% fewer patients were prescribed any opioids (ARR: -0.7; p < 0.001); the amount prescribed was reduced by 95% (pre-intervention 69.3 mg versus post-intervention 3.5 mg, p < 0.001). Mean opioids used following discharge decreased by 76% (14.7 mg versus 3.5 mg, p = 0.011). In a subgroup analysis of robotic prostatectomies, there was a 95% reduction in mean opioids prescribed at discharge (64.6 mg versus 3.2 mg, p < 0.001) and 82% reduction in utilization over entire postoperative course (87.6 mg versus 15.7 mg, p = 0.001). There was no significant difference in pain scores between intervention groups at POD 1, discharge and follow up for patients (entire cohort and post-prostatectomy). CONCLUSION: A standardized pain protocol with 'opt-in' requirements for opiate prescription, emphasis on non-narcotic medications, and patient education, resulted in significant reductions in opioid use. Simple frameshifts in pain management can yield significant gains in the opioid epidemic.


Subject(s)
Analgesics, Opioid/therapeutic use , Drug Prescriptions/statistics & numerical data , Pain, Postoperative/drug therapy , Urologic Neoplasms/surgery , Aged , Female , Humans , Male , Middle Aged , Minimally Invasive Surgical Procedures , Prospective Studies , Urologic Surgical Procedures/methods
16.
Epilepsia ; 61(2): 259-266, 2020 02.
Article in English | MEDLINE | ID: mdl-31912492

ABSTRACT

OBJECTIVE: To determine the incidence of hyperlipidemia after first anticonvulsant treatment for seizures, using a large US administrative claims database. METHODS: We obtained data from the MarketScan Commercial and Medicare databases for 2005-2009 for all adult patients newly treated with an anticonvulsant for seizures who had no previous history of hyperlipidemia or treatment with a lipid-lowering agent. We divided the population based upon whether they were treated with an enzyme-inducing anticonvulsant (phenytoin, carbamazepine, phenobarbital, primidone) or a noninducing anticonvulsant (all others). The primary outcome measure was a new diagnosis of hyperlipidemia during subsequent follow-up. We accounted for a large number of demographic and clinical covariates. RESULTS: Of 11 374 subjects, 8778 (77%) were prescribed noninducers and 2596 (23%) were prescribed inducers. New hyperlipidemia diagnoses were seen in 14.6% of the patients started on inducing anticonvulsants and 10.7% of the patients started on noninducing anticonvulsants (P < .001). Both hyperlipidemia and the use of inducers were significantly associated with older age and male gender. After accounting for covariates, inducer prescription was still associated with 23% higher odds of a subsequent diagnosis of hyperlipidemia (odds ratio = 1.225, 95% confidence interval = 1.066-1.408, P < .001). SIGNIFICANCE: The use of enzyme-inducing anticonvulsants in patients with newly diagnosed epilepsy was associated with a significant increase in subsequent diagnoses of hyperlipidemia, suggesting that the lipid-elevating properties of these agents are of genuine clinical importance. This adds to the body of data demonstrating that these agents are likely associated with additional hassle, cost, and morbidity.


Subject(s)
Anticonvulsants/adverse effects , Hyperlipidemias/chemically induced , Hyperlipidemias/epidemiology , Adult , Age Factors , Aged , Aged, 80 and over , Anticonvulsants/therapeutic use , Databases, Factual , Epilepsy/complications , Epilepsy/drug therapy , Female , Humans , Hyperlipidemias/drug therapy , Hypolipidemic Agents/therapeutic use , Incidence , Male , Medicare , Middle Aged , Population , Seizures/complications , Seizures/drug therapy , Sex Factors , Socioeconomic Factors , Treatment Outcome , United States/epidemiology , Young Adult
17.
Radiology ; 293(1): 223-231, 2019 10.
Article in English | MEDLINE | ID: mdl-31453767

ABSTRACT

Background Overall survival (OS) for patients with uveal melanoma (UM) hepatic metastases is extremely poor. Therefore, stabilization of hepatic metastases is essential to prolonging OS. Purpose To assess the safety and effectiveness of radioembolization (RE) for treatment of UM hepatic metastases. Materials and Methods Enrollment for this prospective phase II trial began November 2011 and concluded January 2017. Treatment-naïve participants (group A) and participants who progressed after immunoembolization (group B) with hepatic tumor burden less than 50% underwent RE. Participants were followed for 1 month and every 3 months for acute and delayed toxicities, respectively. MRI, CT, and PET were performed every 3 months to evaluate for tumor response and extrahepatic disease. Participants were followed for at least 2 years or until death. Kaplan-Meier method and multivariable Cox proportional hazard models were used for data analysis. Results In group A, 24 participants (mean age ± standard deviation, 59 years ± 13; 13 men and 11 women) underwent unilobar (n = 7), fractionated whole-liver (n = 1), or sequential lobar (n = 16) RE. One participant was excluded from the trial. Complete response (n = 0), partial response (n = 9), or stable disease (n = 11) was achieved in 20 of 23 (87.0%; 95% confidence interval [CI]: 66.4%, 97.2%) participants. Median progression-free survival from liver metastasis was 8.1 months (95% CI: 6.4, 11.8; range, 3.3-33.7 months). Median OS was 18.5 months (95% CI: 11.3, 23.5; range, 6.5-73.7 months). In group B, 24 participants (mean age, 58 years ± 10; nine men and 15 women) underwent unilobar (n = 5) or sequential lobar (n = 19) RE. Complete response (n = 0), partial response (n = 8), or stable disease (n = 6) was achieved in 14 of 24 (58.3%; 95% CI: 36.3%, 77.9%) participants. Median progression-free survival from liver metastasis was 5.2 months (95% CI: 3.7, 9.8; range, 2.9-22.0 months). Median OS was 19.2 months (95% CI: 11.5, 24.0; range, 4.8-76.6 months). Grade 3 treatment-related toxicities included transient lymphopenia (group A, n = 1; group B, n = 1), pain (group A, n = 2) and nausea or vomiting (group A, n = 1). Conclusion Radioembolization is a promising treatment for patients with uveal melanoma hepatic metastases. © RSNA, 2019 Online supplemental material is available for this article.


Subject(s)
Embolization, Therapeutic/methods , Liver Neoplasms/radiotherapy , Melanoma/pathology , Neoplasms, Second Primary/radiotherapy , Uveal Neoplasms/pathology , Yttrium Radioisotopes/therapeutic use , Diagnostic Imaging/methods , Female , Humans , Liver/diagnostic imaging , Liver/radiation effects , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/secondary , Male , Middle Aged , Neoplasms, Second Primary/diagnostic imaging , Prospective Studies , Treatment Outcome
18.
Obstet Gynecol ; 134(3): 559-569, 2019 09.
Article in English | MEDLINE | ID: mdl-31403593

ABSTRACT

OBJECTIVE: To evaluate the effects of race and insurance status on the use of brachytherapy for treatment of cervical cancer. METHODS: This is a retrospective cohort study of the National Cancer Database. We identified 25,223 patients diagnosed with stage IB2 through IVA cervical cancer who received radiation therapy during their primary treatment from 2004 to 2015. A univariate analysis was used to assess covariate association with brachytherapy. A multivariable regression model was used to evaluate the effect of race and insurance status on rates of brachytherapy treatment. The Cox proportional hazards model and the multiplicative hazard model were used to evaluate overall survival. P<.05 indicated a statistically significant difference for comparisons of primary and secondary outcomes. RESULTS: Non-Hispanic black patients received brachytherapy at a significantly lower rate than non-Hispanic white patients (odds ratio [OR] 0.93; 95% CI 0.86-0.99; P=.036); Hispanic (OR 0.93; 95% CI 0.85-1.02; P=.115) and Asian (OR 1.13; 95% CI 0.99-1.29; P=.074) patients received brachytherapy at similar rates. Compared with patients with private insurance, those who were uninsured (OR 0.72; 95% CI 0.65-0.79; P<.001), had Medicaid (OR 0.83; 95% CI 0.77-0.89; P<.001) or Medicare insurance (OR 0.85; 95% CI 0.78-0.92; P<.001) were less likely to receive brachytherapy. Brachytherapy was not found to be a mediator of race and insurance-related disparities in overall survival. CONCLUSION: Racial and insurance disparities exist for those who receive brachytherapy, with many patients not receiving the standard of care, but overall survival was not affected.


Subject(s)
Brachytherapy/statistics & numerical data , Healthcare Disparities/statistics & numerical data , Insurance, Health/statistics & numerical data , Racial Groups/statistics & numerical data , Uterine Cervical Neoplasms/radiotherapy , Adult , Black or African American/statistics & numerical data , Aged , Female , Healthcare Disparities/ethnology , Hispanic or Latino/statistics & numerical data , Humans , Insurance Coverage/statistics & numerical data , Middle Aged , Odds Ratio , Proportional Hazards Models , Retrospective Studies , United States , Uterine Cervical Neoplasms/ethnology
19.
Innovations (Phila) ; 14(3): 218-226, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30871400

ABSTRACT

OBJECTIVE: Enhanced recovery pathways reduce length of stay and costs following lung resection. However, many fear that early discharge may lead to increased hospital readmissions. In this study, we aimed to determine whether early discharge was associated with increased readmission following anatomic lung resection. METHODS: Using the lung resection database approved by our institutional review board, we identified all patients undergoing minimally invasive lobectomy and segmentectomy between January 2010 and March 2017 at our institution, where an enhanced recovery pathway is well established. Thirty-day readmissions were compared between patients with short- and average length of stay, defined as 1 to 2 days and 3 to 5 days, respectively. Multivariable logistic regression analysis of patients matched by propensity scores was performed to determine odds of 30-day readmission for each group. Significance was set at P < 0.05. RESULTS: A total of 296 patients met inclusion criteria. Unadjusted analysis revealed a 3-fold increased rate of readmission in the group with average length of stay (9%, n = 12) versus the group with short length of stay (3%, n = 5; P < 0.01). At baseline, patients with average length of stay had increased rates of preoperative chemotherapy (13%, n = 18 vs. 4%, n = 6; P < 0.01) and radiation (12%, n = 16 vs. 3%, n = 5). Patients with average length of stay also had higher rates of lobectomy (95%, n = 127 vs. 86%, n = 140; P = 0.02) and postoperative complications (31%, n = 41 vs. 4%, n = 7; P < 0.01). On multivariable analysis, patients with average length of stay had a 2.3-fold greater odds of readmission, which was not statistically significant (OR = 2.33; 95% CI, 0.60 to 9.02; P = 0.22). CONCLUSIONS: Early discharge following minimally invasive anatomic lung resection does not increase the risk of hospital readmission in patients treated within an enhanced recovery pathway.


Subject(s)
Antineoplastic Agents/therapeutic use , Length of Stay/statistics & numerical data , Lung Neoplasms/surgery , Neoadjuvant Therapy/statistics & numerical data , Patient Readmission/statistics & numerical data , Pneumonectomy/methods , Radiotherapy/statistics & numerical data , Aged , Enhanced Recovery After Surgery , Female , Hospital Costs , Humans , Logistic Models , Lung Neoplasms/pathology , Lymph Node Excision , Male , Middle Aged , Minimally Invasive Surgical Procedures , Multivariate Analysis , Patient Discharge/statistics & numerical data , Postoperative Complications/epidemiology , Robotic Surgical Procedures , Thoracoscopy
20.
Surgery ; 163(4): 819-826, 2018 04.
Article in English | MEDLINE | ID: mdl-29289392

ABSTRACT

BACKGROUND: Laboratory-based evidence of coagulopathy (LC) is observed in 25-35% of trauma patients, but clinically-evident coagulopathy (CC) is not well described. METHODS: Prospective observational study of adult trauma patients transported by helicopter from the scene to nine Level 1 trauma centers in 2015. Patients meeting predefined highest-risk criteria were divided into CC+ (predefined as surgeon-confirmed bleeding from uninjured sites or injured sites not controllable by sutures) or CC-. We used a mixed-effects, Poisson regression with robust error variance to test the hypothesis that abnormalities on rapid thrombelastography (r-TEG) and international normalized ratio (INR) were independently associated with CC+. RESULTS: Of 1,019 highest-risk patients, CC+ (n=41, 4%) were more severely injured (median ISS 32 vs 17), had evidence of LC on r-TEG and INR, received more transfused blood products at 4 hours (37 vs 0 units), and had greater 30-day mortality (59% vs 12%) than CC- (n=978, 96%). The overall incidence of LC was 39%. 30-day mortality was 22% vs 9% in those with and without LC. In two separate models, r-TEG K-time >2.5 min (RR 1.3, 95% CI 1.1-1.7), r-TEG mA <55 mm (RR 2.5, 95% CI 2.0-3.2), platelet count <150 x 109/L (RR 1.2, 95% CI 1.1-1.3), and INR >1.5 (RR 5.4, 95% CI 1.8-16.3) were independently associated with CC+. A combined regression model was not generated because too few patients underwent both r-TEG and INR. CONCLUSION: CC was rare compared to LC. CC was associated with poor outcomes and impairment of both clotting factor and platelet-mediated coagulation components.


Subject(s)
Blood Coagulation Disorders/diagnosis , Emergency Medical Services , International Normalized Ratio , Resuscitation , Thrombelastography , Wounds and Injuries/complications , Adult , Aged , Air Ambulances , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/therapy , Female , Humans , Injury Severity Score , Male , Middle Aged , Phenotype , Poisson Distribution , Prospective Studies , Regression Analysis , Wounds and Injuries/therapy
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