Rising Events and Improved Outcomes of Gastrointestinal Bleed With Shock in USA: A 12-year National Analysis.

OBJECTIVE: Limited information is available based on single-center studies on trends of incidence and outcomes in gastrointestinal (GI) bleed with shock. METHODS: We analyzed data from 2002 to 2013 National Inpatient Sample. Using ICD-9 codes we identified 6.4 million hospital discharges of GI bleed from National Inpatient Sample database. Events were analyzed based on type of GI bleed, in-hospital mortality, hemodynamic status, and use of blood products. RESULTS: GI bleed with shock results in higher hospital mortality (20.77% with shock vs. 2.6% without shock). Between 2002 and 2013, there has been an increase in the percentage of upper and lower GI bleed with shock (1.35% to 4.92% and 1.49% to 3.06%) along with a reduction in mortality in both upper GI bleed with shock (26.9% to 13.8%) and lower GI bleed with shock (54.7% to 19.7%). Consistent with the rise in GI bleed with shock was an increase in blood product utilization. Packed red blood cell (pRBC) transfusion was associated with reduction in mortality in both nonvariceal upper GI bleed with shock (18.3% without pRBC vs. 13.9% receiving pRBC) and lower GI bleed with shock (36.05% without pRBC vs. 22.13% receiving pRBC), but did not affect mortality in variceal upper GI bleed with shock (31.79% vs. 32.22%). CONCLUSIONS: GI bleed with shock carries a higher mortality and have been steadily increasing from 2002 to 2013. pRBC transfusion was associated in improved mortality in GI bleed with shock except variceal bleed.

Trends in Incidence and Outcomes of Clostridium difficile Colitis in Hospitalized Patients of Febrile Neutropenia: A Nationwide Analysis.

INTRODUCTION: Clostridium difficile infection (CDI) has been attracting attention lately as the most common hospital acquired infection. Patients with neutropenia because of malignancy seem to be at an increased risk for developing CDI. There is currently limited data that assesses the national burden and outcomes of CDI in Febrile Neutropenia (FN). METHODS: We analyzed the National Inpatient Sample (NIS) database for all subjects with discharge diagnosis of FN with or without CDI (ICD-9 codes 288.00, 288.03,780.60, and 008.45) as primary or secondary diagnosis during the period from 2008 to 2014. All analyses were performed with SAS, version 9.4 (SAS Institute). RESULTS: From 2008 to 2014 there were total 19422 discharges of FN patients with CDI. There was a rising incidence of CDI in patients with FN from 4.11% (in 2008) to 5.83% (in 2014). The In-hospital mortality showed a decreasing trend from 7.79% (in 2008) to 5.32% (in 2014), likely because of improvements in diagnostics and treatment. The overall mortality (6.37% vs. 4.61%), length of stay >5 days (76.45% vs. 50.98%), hospital charges >50,000 dollars (64.43% vs. 40.29%), colectomy and colostomy (0.35% vs. 0.15%), and discharge to skilled nursing facility (10.47% vs. 6.43%) was significantly more in FN patients with CDI versus without CDI over 7 years (2008 to 2014). Age above 65 years, Hispanic race, hematological malignancies, urban hospital settings, and sepsis were significant predictors of mortality in febrile neutropenia patients with CDI. DISCUSSION: Despite the significant decrease in mortality, the incidence of CDI is rising in hospitalized FN patients with underlying hematological malignancies. Risk factor modification, with the best possible empiric antibiotic regimen is imperative for reducing mortality and health care costs in this cohort.

Recent Trends in Electively Treated Unruptured Intracranial Aneurysms.

BACKGROUND AND PURPOSE: To determine recent treatment and outcome trends in patients undergoing elective surgical clipping (SC) or endovascular therapy (EVT) for unruptured intracranial aneurysms (UIAs) in the United States. METHODS: Data were extracted and analyzed from the National Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality for all patients admitted for elective EVT or SC of UIAs between 2011 and 2014. Treatment trends, in-hospital mortality, complication rates, length of stay (LOS) and total hospital costs were evaluated and analyzed. RESULTS: A total of 31,070 patients with UIAs were included in our analysis, of which 14,411 and 16,659 underwent elective SC and EVT, respectively. There was no significant difference in in-hospital mortality rates between the 2 groups. EVT was associated with lower in-hospital complication rates, decreased median LOS (.8 days versus 3.3 days, P ≤ .0001), and an increased likelihood of discharge to home (92.9% versus 72.9%, P = .0001). Median total hospital charges were similar in both treatment cohorts. Independent predictors of mortality in the elective population were age over 40 years (P ≤ .0001), weekend treatment (P ≤ .0001), and high co-morbidity status (P ≤ .0001). CONCLUSIONS: In-hospital mortality rates were similar in elective EVT and SC UIA patients; however, EVT was associated with lower in-hospital complication rates and shorter LOS.

Predicting In-Hospital Mortality After Acute Myeloid Leukemia Therapy: Through Supervised Machine Learning Algorithms.

PURPOSE: Despite careful patient selection, induction chemotherapy for acute myeloid leukemia (AML) is associated with a considerable risk for treatment-related mortality (5%-20%). We evaluated machine learning (ML) algorithms trained using factors available at the time of admission for AML therapy to predict death during the hospitalization. METHODS: We included AML discharges with age > 17 years who received inpatient chemotherapy from State Inpatient Database from Arizona, Florida, New York, Maryland, Washington, and New Jersey for years 2008-2014. The primary objective was to predict inpatient mortality in patients undergoing chemotherapy using covariates present before initiation of chemotherapy. ML algorithms logistic regression (LR), decision tree, and random forest were compared. RESULTS: 29,613 hospitalizations for patients with AML were included in the analysis each with 4,177 features. The median age was 58.9 (18-101) years, 13,689 (53.7%) were male, and 20,203 (69%) were White. The mean time from admission to chemotherapy was 3 days (95% CI, 2.9 to 3.1), and 2,682 (9.1%) died during the hospitalization. Both LR and random forest models achieved an area under the curve (AUC) score of 0.78, whereas decision tree achieved an AUC of 0.70. The baseline LR model with age yielded an AUC of 0.62. To clinically balance and minimize false positives, we selected a decision threshold of 0.7 and at this threshold, 51 of our test set of 5,923 could have potentially averted treatment-related mortality. CONCLUSION: Using readily accessible variables, inpatient mortality of patients on track for chemotherapy to treat AML can be predicted through ML algorithms. The model also predicted inpatient mortality when tested on different data representations and paves the way for future research.

Length of Stay and Hospital Costs for Patients Undergoing Allogeneic Stem-Cell Transplantation.

PURPOSE: Patients who undergo allogeneic hematopoietic stem-cell transplantation (allo-HSCT) usually require a prolonged hospital stay that varies greatly across patients. Limited information exists on the factors associated with hospital length of stay (LOS) after allo-HSCT and the impact on transplant-related costs. The objective of this study was to determine predictors for longer LOS for allo-HSCT and to assess their impact on the cost of transplant stay. METHODS: Using the National Inpatient Sample database, adult patients hospitalized for allo-HSCT were identified using International Classification of Diseases, Ninth Revision, primary and secondary procedure codes. RESULTS: Between 2002 and 2015, 68,296 hospitalizations for allo-HSCT were identified. Peripheral blood was the most common stem-cell source (80%) followed by bone marrow (15%) and cord blood (5%). Median LOS was 25.8 days (interquartile range [IQR], 21-34.0 days), and the overall inpatient mortality rate was 8%. Stem-cell source was a significant predictor for longer LOS, being significantly longer for cord blood (median, 36.9 days; IQR, 26.7-49.9 days) compared with bone marrow (median, 27.2 days; IQR, 21.5-35.2 days) and peripheral blood (median 25.4 days; IQR, 20.8-32.7 days). Other predictors for longer LOS were patient characteristics such as age and race, transplant/post-transplant characteristics, and complications such as total body irradiation use, acute graft-versus-host disease, and infections. Longer LOS was also found to be associated with higher hospital costs. CONCLUSION: In patients who undergo allo-HSCT, LOS can be predicted using patient- and transplant-related characteristics as well as post-transplant complications. LOS is also a driver for increased cost, and further efforts are needed to mitigate transplant complications and resource utilization.

Association between spinal stenosis and wild-type ATTR amyloidosis.

Age-related cardiac amyloidosis results from deposits of wild-type tranthyretin amyloid (ATTRwt) in cardiac tissue. ATTR may play a role in carpal tunnel syndrome (CTS) and in spinal stenosis (SS), indicating or presaging systemic amyloidosis. We investigated consecutive patients undergoing surgery for SS for ATTR deposition in the resected ligamentum flavum (LF) and concomitant risk of cardiac amyloidosis. Each surgical specimen (LF) was stained with Congo red, and if positive, the amyloid deposits were typed by mass spectrometry. Patients with positive specimens underwent standard of care evaluation with fat pad aspirates, serum and urine protein electrophoresis with immunofixation, free light-chain assay, TTR gene sequencing and technetium 99 m-pyrophosphate-scintigraphy. In 2018-2019, 324 patients underwent surgery for SS and 43 patients (13%) had ATTR in the LF with wild-type TTR gene sequences. Two cases of ATTRwt cardiac amyloidosis were diagnosed and received treatment. In this large series, ATTRwt was identified in 13% of the patients undergoing laminectomy for SS. Patients with amyloid in the ligamentum flavum were older and had a higher prevalence of CTS, suggesting a systemic form of ATTR amyloidosis involving connective tissue. Further prospective study of patients with SS at risk for systemic amyloidosis is warranted.

Prospective Evaluation of Effect of Metformin on Activation of AMP-activated Protein Kinase (AMPK) and Disease Control in a Sub-group Analysis of Patients with GI Malignancies.

BACKGROUND: Observational studies have demonstrated association of metformin with reduced cancer incidence and mortality in multiple cancer types, including gastrointestinal (GI) malignancies. Anti-neoplastic effects of metformin are believed through many mechanisms including activation of AMP-activated protein kinase, which controls mammalian target of rapamycin (mTOR) growth regulatory pathway. METHODS: In a pilot, delayed-start randomized study, non-diabetic patients with GI cancers were randomized to 2 arms, Stage 1: concurrent metformin (500mg twice daily) plus chemotherapy vs. chemotherapy alone followed by cross over to metformin plus chemotherapy arm in Stage 2, while adverse events (DLT) were assessed by CTCAE v.3.0. As a translational correlate, we used phosphorylation of AMPKα at Thr172 to measure AMPK activation by western blot technique in PBMCs isolated from patients before and after receiving M. These levels were correlated with radiological (RECIST 1.1) and tumor marker outcomes by descriptive analysis. In this study, we present the sub-group analysis of patients with GI cancers. RESULTS: 41 patients with GI cancers (colorectal: 22, pancreatic: 12, gastroesophageal: 4, biliary: 2, others: 1) were treated in this trial. Mean duration of metformin therapy was 85 days (range: 9-443). There was no significant difference in grade 3 or above DLT in metformin plus chemotherapy vs. chemotherapy arm (14% vs. 12% respectively). Gel band density analysis on 19 patients showed that 63% patients had increased phosphorylation of AMPKα after metformin (ratio of phospho-AMPKα after and before metformin > 1) with mean = 1.227 (± 0.134). RECIST 1.1 restaging showed disease control in 55% patients and 45% patients had decline in tumor markers. Of note, 60% of patients with disease control also showed increase in phosphorylation of AMKα. CONCLUSIONS: This group of patients treated with metformin prospectively demonstrates the impact of metformin on AMPKα phosphorylation, and correlates with clinical benefit in patients with GI cancers when metformin was added to systemic chemotherapy of varying types. We aim to perform a dose-escalation of metformin in our next study with additional metabolomics correlates.

Capecitabine for the treatment of pancreatic cancer.

INTRODUCTION: Capecitabine is an oral prodrug of 5-fluorouracil (5-FU) which is converted to 5FU by a series of reactions catalyzed by different enzymes, the last of the enzymes being thymidine phosphorylase (TP). TP is found to be elevated in tumor cells in comparison to normal cells, which consequently tumor-localizes the production of 5-FU, thereby limiting its systemic toxicity. Today, capecitabine is extensively used for the treatment of many solid malignancies, with a particular focus in breast and gastrointestinal tumors, but also in pancreatic cancer. Areas covered: This review summarizes the pharmacology and the clinical evidence relevant to the use of capecitabine in the treatment of pancreas cancer. The authors provide, furthermore, provide their expert perspectives on its use. Expert opinion: Capecitabine has the advantage over other therapeutics in so much that it has both convenient oral administration and a favorable toxicity profile. Current data has promised the use of capecitabine in all stages of pancreatic cancer. However, predictive markers for outcome and toxicity remain to be validated.

The safety of lanreotide for neuroendocrine tumor.

INTRODUCTION: Lanreotide autogel is a synthetic somatostatin analogue which has been FDA and EMA approved for unresectable, well to moderately differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumor. Its action is mediated by its affinity to somatostatin receptors, especially sst2 and sst5 receptors. Its longer half-life offers the convenience of 4-week dosing over the need for frequent injections of short-acting somatostatin analogues. Areas covered: Lanreotide ATG offers progression-free survival benefit in locally advanced or metastatic neuroendocrine tumor (NET) compared to placebo, reflecting a strong antiproliferative signal. As lanreotide is commonly used for management of NET, it is imperative to recognize and appropriately manage any drug-related toxicities. In this review, we will provide an overview of the toxicity with lanreotide and its management. Expert opinion: Lanreotide is highly effective in managing carcinoid symptoms and has a robust anti-tumor effect in NET. Overall, it is well tolerated with low rates of treatment discontinuation due to toxicity. It's toxicity profile is mostly predictable, and patients should be informed of the transient nature of some of the upfront toxicities.