ABSTRACT
OBJECTIVE: We aimed to analyze the Health Care Utilization Project's (HCUP) Nationwide Inpatient Sample (NIS) and compare mortality rates in hospitals by month to determine if there is seasonal variability in outcomes associated with venous thromboembolism (VTE). METHODS: The Nationwide Inpatient Sample database was queried from 1998 to 2011. Inclusion criteria were a diagnosis of deep vein thrombosis (DVT) (ICD-9 {International Classification of Diseases, Ninth Revision, Clinical Modification} 453.4, 453.8) and/or VTE (ICD-9 415.1) in patients aged 18 years or more. Admission data was then analyzed to compare mortality rates in teaching and non-teaching hospitals over that time and by month. Demographics, Charlson Comorbidity Index, length of stay (LOS), hospital region, and admission types (emergent/urgent versus elective admissions) were assessed. Linear and logistic models were generated for complex survey design to analyze predictors of mortality and LOS. RESULTS: A total of 1,449,113 DVT/VTE cases were identified in the Nationwide Inpatient Sample (weighted n= 7,150,613), 54.7% female, 56.38% white, 49% in teaching hospitals. Higher mortality was found in the months of November 6.52%, December 6.9%, January 6.94%, and February 6.93% versus overall mortality of 6.4% over 12 months. Higher mortality was noted in these winter months in all regions, along with a significantly increased LOS. Mortality in the total cohort was found to be higher in January, with odds ratio (OR) 1.11 (1.08-1.15), p<0.0001; February, OR 1.11 (1.07-1.15), p<0.0001; and December, OR 1.10 (1.06-1.14), p<0.0001 compared to June. Mortality was significantly lower in the Midwest or North Central regions (OR 0.78 {0.72-0.83}, p<0.0001) and West (OR 0.80 {0.73-0.87}, p<0.0001) compared to the Northeast. Mortality was also significantly higher in teaching hospitals than in non-teaching hospitals (OR 1.16 {1.10-1.22}, p<0.0001), with mortality trending higher in teaching hospitals each month. Emergent/urgent admission, larger hospital size, female sex, age, and urban location were also significantly associated with increased mortality. CONCLUSIONS: This national study identified an increased risk of mortality associated with hospitalizations for DVT/VTE in the winter months, independent of hospital teaching status or region.
ABSTRACT
OBJECTIVES: Pseudomyxoma peritonei (PMP) is a rare malignancy originating from the appendix, characterized by disseminated mucinous tumor implants on peritoneal surfaces. We examined the role of multiplatform molecular profiling to study biomarker-guided treatment strategies for this rare malignancy. METHODS: A total of 54 patients with appendix-derived PMP were included in the study. Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing), protein expression (immunohistochemistry), and gene amplification (C/fluorescent in situ hybridization). RESULTS: Targeted sequencing of 47 genes detected variants in KRAS (81%), GNAS (74%), SMAD4 (16%), and ATM (16%). Mutations were found at low frequencies (n=1 to 2) in APC, BRAF, PIK3CA, MLH1, and TP53. GNAS and KRAS co-occurrence was found in 87%. Protein overexpression was found in epidermal growth factor receptor (83%), cyclooxygenase-2 (73%), cMET (63%), cKIT (58%), and platelet-derived growth factor receptor alpha (58%). Immune checkpoint expression was found in 36% (programmed cell death protein 1) and 18% (programmed death-ligand 1). Surrogate markers of cell proliferation were found at low rates (TLE3 23%, TOP2A 22%), consistent with the slow-growing biology of PMP. Phosophatase and tensin homolog was intact (wild type [100%]) and positive (immunohistochemistry [80%]). Patients exhibited stable microsatellite status and mismatch repair proficiency (93%). Importantly, multidrug resistance protein expression was elevated (100% BCRP, 94% MRP1, 88% PGP). Markers for gemcitabine (RRM1), fluorouracil (TS), oxaliplatin (ERCC1), and irinotecan (TOPO1) chemosensitivities were detected at favorable rates: 93%, 87%, 77% and 65%, respectively. CONCLUSIONS: Molecular profiling by multiple platforms identified potential therapies for the nontargetable KRAS-mutated population. The role of cMET-targeted therapeutics and immune checkpoint inhibitors merits further investigation. Biomarker-guided selection of cytotoxic chemotherapies may facilitate efficacy to systemic treatment.
