Bariatric Surgery and Inflammatory Bowel Disease: National Trends and Outcomes Associated with Procedural Sleeve Gastrectomy vs Historical Bariatric Surgery Among US Hospitalized Patients 2009-2020.

PURPOSE: The association between bariatric surgery and IBD-related inpatient outcomes is not well characterized. We report, analyze, and compare inpatient trends and outcomes among encounters with a history of bariatric surgery (Hx-MBS) compared to those receiving bariatric surgery during index admission (PR-MBS) admitted from 2009 to 2020. METHODS: Retrospective cohort design: the 2009-2020 National Inpatient Sample (NIS) databases were used to identify hospital encounters with patients aged ≥ 18 years with a history of MBS (Hx-MBS) or with procedure coding indicating MBS procedure (PR-MBS) according to International Classification of Diseases, Ninth (ICD-9-CM/ ICD-9-PCS) or Tenth Revision (ICD-10-CM/ICD-10-PCS) Clinical Modification/Procedure Coding System during index admission (ICD-9-CM: V4586; ICD-10-CM: Z9884; ICD-9-PR: 4382, 4389; ICD-10-PR: 0DB64Z3, 0DB63ZZ). Pearson χ2 analysis, analysis of variance, multivariable regression analyses, and propensity matching on independent variables were conducted to analyze significant associations between variables and for primary outcome inflammatory bowel disease-related admission, and secondary outcomes: diagnosis of nonalcoholic steatohepatitis, nonalcoholic fatty liver disease, or chronic mesenteric ischemia during admission. RESULTS: We identified 3,365,784 (76.20%) Hx-MBS hospitalizations and 1,050,900 hospitalizations with PR-MBS (23.80%). Propensity score matching analysis demonstrated significantly higher odds of inflammatory bowel disease, and chronic mesenteric ischemia for Hx-MBS compared to PR-MBS, and significantly lower odds of nonalcoholic steatohepatitis and nonalcoholic fatty liver disease for Hx-MBS compared to PR-MBS. CONCLUSION: In our study, Hx-MBS was associated with significantly increased odds of inflammatory bowel disease and other GI pathologies compared to matched controls. The mechanism by which this occurs is unclear. Additional studies are needed to examine these findings.

Risk of adverse cardiovascular outcomes among people with HIV and nonalcoholic fatty liver disease.

OBJECTIVE: To examine and compare the risk of major adverse cardiovascular events (MACEs) between people with HIV (PWH) with and without nonalcoholic fatty liver disease (NAFLD). DESIGN: Population-based, multicenter, retrospective cohort study. METHODS: Data on PWH between January 1, 2008, and December 31, 2020 were extracted from the TriNetX database. Primary outcomes were defined as the first incidence of myocardial infarction (MI), MACE, new-onset heart failure (HF), and a composite of cerebrovascular disease. Cox models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: A total of 151 868 patients were identified as having HIV. After exclusions, 4969 patients were identified as having NAFLD. Of them, 4463 (90%) were propensity matched to a non-NAFLD control. Patients with NAFLD were older (42.9 versus 40.8 years). Among the NAFLD cohort, most participants were male and had a smoking history (12.3 versus 9.8%) than non-NAFLD. The mean follow-up was 4.8 ±â€Š1.1 years for the NAFLD group and 5.3 ±â€Š1.2 years for the non-NAFLD group. The risk of all outcomes was statistically significantly higher in NAFLD patients compared to those without NAFLD: MI (HR, 1.49; 95% CI, 1.11-2.01) MACE (HR, 1.49; 95% CI, 1.25-1.79), HF (HR, 1.73; 95% CI 1.37-2.19) and, cerebrovascular diseases (HR, 1.25; 95% CI, 1.05-1.48) and sensitivity analysis showed similar magnitude to the one generated in the primary analysis. CONCLUSIONS: Patients with NAFLD have an elevated risk of adverse cardiovascular events (CVEs). The results indicate the need for targeted efforts to improve awareness of risks factors associated with adverse CVEs risk in PWH with NAFLD.

Clinical characteristics and social determinants of health associated with 30-day hospital readmissions of patients with COVID-19.

COVID-19 readmissions are associated with increased patient mortality and healthcare system strain. This retrospective cohort study of PCR-confirmed COVID-19 positive adults (>18 years) hospitalized and readmitted within 30 days of discharge from index admission was performed at eight Atlanta hospitals from March to December 2020. The objective was to describe COVID-19 patient-level demographics and clinical characteristics, and community-level social determinants of health (SDoH) that contribute to 30-day readmissions. Demographics, comorbidities, COVID-19 treatment, and discharge disposition data were extracted from the index admission. ZIP codes were linked to a demographic/lifestyle database interpolating to community-level SDoH. Of 7155 patients with COVID-19, 463 (6.5%) had 30-day, unplanned, all-cause hospital readmissions. Statistically significant differences were not found in readmissions stratified by age, sex, race, or ethnicity. Patients with a high-risk Charlson Comorbidity Index had higher odds of readmission (OR 4.8 (95% CI: 2.1 to 11.0)). Remdesivir treatment and intensive care unit (ICU) care were associated with lower odds of readmission (OR 0.5 (95% CI: 0.4 to 0.8) and OR 0.5 (95% CI: 0.4 to 0.7), respectively). Patients residing in communities with larger average household size were less likely to be readmitted (OR 0.7 (95% CI: 0.5 to 0.9). In this cohort, patients who received remdesivir, were cared for in an ICU, and resided in ZIP codes with higher proportions of residents with increased social support had lower odds of readmission. These patient-level factors and community-level SDoH may be used to identify patients with COVID-19 who are at increased risk of readmission.

Circulating Tumor DNA-Based Testing and Actionable Findings in Patients with Advanced and Metastatic Pancreatic Adenocarcinoma.

PURPOSE: Recent advances in molecular diagnostic technologies allow for the evaluation of solid tumor malignancies through noninvasive blood sampling, including circulating tumor DNA profiling (ctDNA). Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, often because of late presentation of disease. Diagnosis is often made using endoscopic ultrasound or endoscopic retrograde cholangiopancreatography, which often does not yield enough tissue for next-generation sequencing. With this study, we sought to characterize the ctDNA genomic alteration landscape in patients with advanced PDAC with a focus on actionable findings. MATERIALS AND METHODS: From December 2014 through October 2019, 357 samples collected from 282 patients with PDAC at Mayo Clinic underwent ctDNA testing using a clinically available assay. The majority of samples were tested using the 73-gene panel which includes somatic genomic targets, including complete or critical exon coverage in 30 and 40 genes, respectively, and in some, amplifications, fusions, and indels. Clinical data and outcome variables were available for 165 patients; with 104 patients at initial presentation. RESULTS: All patients included in this study had locally advanced or metastatic PDAC. Samples having at least one alteration, when variants of unknown significance (VUS) were excluded, numbered 266 (75%). After excluding VUS, therapeutically relevant alterations were observed in 170 (48%) of the total 357 cohort, including KRAS (G12C), EGFR, ATM, MYC, BRCA, PIK3CA, and BRAF mutations. KRAS, SMAD, CCND2, or TP53 alterations were seen in higher frequency in patients with advanced disease. CONCLUSION: Our study is the largest cohort to date that demonstrates the feasibility of ctDNA testing in PDAC. We provide a benchmark landscape upon which the field can continue to grow. Future applications may include use of ctDNA to guide treatment and serial monitoring of ctDNA during disease course to identify novel therapeutic targets for improved prognosis. IMPLICATIONS FOR PRACTICE: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis often due to late presentation of disease. Biopsy tissue sampling is invasive and samples are often inadequate, requiring repeated invasive procedures and delays in treatment. Noninvasive methods to identify PDAC early in its course may improve prognosis in PDAC. Using ctDNA, targetable genes can be identified and used for treatment.

Pembrolizumab-axitinib-induced tumor lysis syndrome in a patient with metastatic renal cancer.

Tumor lysis syndrome is uncommon in solid tumors but with the use of immunotherapy (checkpoint inhibitors) their incidence is increasing. Physicians need to take adequate precautions while treating patients with immunotherapy. The findings of our case report will help improve our current understanding of tumor lysis syndrome specially in solid tumors and will help in developing multidisciplinary treatment and prophylaxis strategies for this uncommon, but potentially fatal complication.

Cocaine-Induced Ventilation/Perfusion Mismatch Mimicking Pulmonary Embolism.

Pulmonary complications from cocaine use can range from bronchospasm to vasospasm leading to pulmonary infarction. Profound vasospasm may also lead to perfusion defects presenting as pulmonary embolism on ventilation-perfusion scan. A 65-year-old patient with a past medical history of substance abuse and chronic kidney disease presents to the emergency department with sudden-onset chest pain and shortness of breath. Ventilation-perfusion scan revealed filling defect most notably in the lingual lobe. He was later discharged on warfarin for the management of pulmonary embolism. The patient presented to the emergency department 2 weeks later with similar complaints; the international normalized ratio was subtherapeutic, and urine drug screen was positive for cocaine. Repeat ventilation-perfusion scan revealed no filling defects. Follow-up bilateral venous Doppler of lower extremities and D-dimer were within normal limits.

Safety and efficacy of locoregional therapy for metastatic pancreatic ductal adenocarcinoma to the liver: a single-center experience.

BACKGROUND: Many patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed with liver metastatic disease (mPDAC), and few are surgical candidates. Interventional oncology (IO) locoregional therapies (LRT) have proven beneficial in other primary and metastatic hepatic malignancies. Systemic chemotherapy is the standard of care for patients with mPDAC. This study assessed the safety and efficacy of LRT including thermal ablation, chemoembolization, and radioembolization for mPDAC. METHODS: A retrospective analysis was performed of 28 patients with mPDAC referred to IR clinic for consideration of LRT from 01/2006 to 08/2017, of whom 20 underwent treatment. Laboratory values were analyzed at 0, 3, and 6 months post-treatment. Imaging response was evaluated at 1, 3, and 6 months post-intervention by modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Adverse events (AE) were classified by CTCAE v5.0. Overall survival (OS) from the diagnosis of PDAC, survival from the time of mPDAC diagnosis, and survival from the time of LRT were calculated. RESULTS: Median OS (mOS) was 25 months. Median survival from time of mPDAC diagnosis and post LRT were 16.25 and 9.7 months, respectively. At one month post-intervention, 12 of 17 patients demonstrated disease response (CR or PR per mRECIST). Survival among responders was 9 months vs. 6 months for patients with stable or progressive disease (P=0.08). There were two grade 3 AE which included post-embolization syndrome and transient renal failure. Chemotherapy was briefly delayed in one of these patients, but ultimately resumed. CONCLUSIONS: The use of LRT in patients with mPDAC is safe. Additionally, no significant chemotherapy limiting toxicities were observed. Responders to therapy demonstrated a survival benefit trend in this small and heterogeneous cohort. Further investigations with randomized trials are warranted.

Feasibility of circulating tumor DNA testing in hepatocellular carcinoma.

BACKGROUND: Advancement of technologies enabling clinical assessment of circulating tumor DNA (ctDNA) are allowing for assessment of tumor specific genetic alterations in patients. This holds incredible promise for early detection of disease, serial monitoring of tumor heterogeneity, elucidation of therapeutic targets, and evaluation of treatment response and mechanisms of resistance. Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is often diagnosed late, recurs commonly, and is often diagnosed based upon imaging features alone. A comprehensive evaluation of real-time evaluation of ctDNA in patients with HCC has thus far not been undertaken. METHODS: From January 2015 to February 2018, 35 patients with biliary tract cancer (BTC) at the Mayo Clinic Comprehensive Cancer Center underwent ctDNA testing using a clinically available assay. The majority of samples were tested utilizing the 73-gene panel which includes somatic genomic targets, including complete or critical exon coverage in 30 and 40 genes, respectively; and in some, amplifications, fusions, and indels. RESULTS: A total of 44 samples were collected on these 35 patients, with >70% having stage 3 or 4 disease. Among all samples the median number of alterations per sample, excluding variants of undetermined significance (VUS), was 3.5, with a median allele frequency of 0.65%. A total of 122 unique genetic alterations, excluding VUS or synonymous alterations, were seen. The overall landscape of alterations is described. The top 10 genes altered in this cohort of patients, excluding VUS or synonymous alterations, were TP53 (18%), TERT (14%), CTNNB1 (13%), ARID1A (9%), MYC (5%), BRAF (4%), CCND1 (4%), CDK6 (4%), and MET (4%), and EGFR (3%). CONCLUSIONS: Herein, we describe feasibility of ctDNA testing and results from such testing in HCC patients undergoing ctDNA testing in a real-time clinical context. Patients with these cancers stand to benefit immensely from the use of ctDNA technologies, and concerted efforts at further investigation of such are critically needed.

Aberrant lipid metabolism as a therapeutic target in liver cancer.

INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers. Progress has been made in treatment of HCC; however, improved outcomes are much needed. The increased metabolic needs of cancer cells underscore the importance of metabolic pathways in cancer cell survival. Lipid metabolism has a role in HCC development; aberrant overexpression of several key enzymes is seen in many solid human tumors. Areas covered: We discuss aberrant lipid metabolism and the promise of multiple targets, in particular related to HCC treatment. We searched PubMed and clinicaltrials.gov for published and unpublished studies from 2000 to 2019. These terms were used: lipids, fatty acid metabolism, lipid metabolism, liver cancer, HCC, de novo fatty acid synthesis, ATP citrate lyase, stearoyl CoA denaturase, fatty acid synthase, acetyl coenzyme A carboxylase, CD147, KLF4, monoglyceride lipase, AMP activated protein kinase. Expert opinion: The importance of dysregulation of fatty acid synthesis in cancer is a growing area of research. HCC demonstrates significant alteration in lipid metabolism, representing great potential as a target for novel therapeutics. Various agents have demonstrated promising anti-neoplastic activity. This strategy deserves further development for improved outcomes.

Circulating Tumor DNA Profiling of Advanced Biliary Tract Cancers.

PURPOSE: Recent advances in molecular diagnostic technologies have allowed for the evaluation of solid tumor malignancies via noninvasive blood sampling, including circulating tumor DNA (ctDNA) profiling. We sought to characterize the ctDNA genomic alteration landscape in patients with biliary tract cancers (BTCs). PATIENTS AND METHODS: From January 2015 to February 2018, 124 patients with BTC at the Mayo Clinic Comprehensive Cancer Center underwent ctDNA testing using a clinically available assay. The majority of samples (n = 122) were tested using the 73-gene panel that includes somatic genomic targets, including complete or critical exon coverage in 30 and 40 genes, respectively, and in some, amplifications, fusions, and indels. RESULTS: A total of 138 samples were included, with approximately 70% of patients having intrahepatic BTC. All patients had locally advanced or metastatic BTC. Samples with one or more alterations, when variants of unknown significance were excluded, numbered 105 (76%). Each sample contained, on average, three alterations with a median allelic fraction of 0.52%. The overall landscape of alterations is summarized in Figures 1 and 2. After excluding variants of unknown significance, therapeutically relevant alterations were observed in 76 patients (55%), including BRAF mutations, ERBB2 amplifications, FGFR2 fusions, FGFR2 mutations, and IDH1 mutations seen in 21% of patients. A different spectrum of alterations was observed in patients with early-onset BTC (younger than age 50 years) compared with older patients (older than age 50 years). CONCLUSION: Data on ctDNA in BTC is currently limited. Our study, the largest cohort reported to date to our knowledge, demonstrates the feasibility of ctDNA testing in this disease. We provide a foundation upon which the field can continue to grow.