Band Ligation Resolves Esophageal Adenocarcinoma Overlying Esophageal Varix.

When early-stage esophageal cancer overlies an esophageal varix, endoscopic mucosal resection is not safe because of risk of variceal bleeding. We report a 59-year-old man with alcohol-related liver cirrhosis and an 8 mm Stage I adenocarcinoma in the distal esophagus overlying a large varix. After a multidisciplinary review, we performed band ligation of the nodular adenocarcinoma and varix. On follow-up upper endoscopy 2 months after banding, no evidence of residual adenocarcinoma was visualized. Pathologic biopsies returned negative for malignancy. Band ligation of early-stage esophageal adenocarcinoma may prove an effective option for patients who have nodular malignancies overlying an esophageal varix.

Germline Cancer Susceptibility Gene Testing in Unselected Patients With Colorectal Adenocarcinoma: A Multicenter Prospective Study.

BACKGROUND & AIMS: Hereditary factors play a role in the development of colorectal cancer (CRC). Identification of germline predisposition can have implications on treatment and cancer prevention. This study aimed to determine the prevalence of pathogenic germline variants (PGVs) in CRC patients using a universal testing approach, association with clinical outcomes, and the uptake of family variant testing. METHODS: We performed a prospective multisite study of germline sequencing using a more than 80-gene next-generation sequencing platform among CRC patients (not selected for age or family history) receiving care at Mayo Clinic Cancer Centers between April 1, 2018, and March 31, 2020. RESULTS: Of 361 patients, the median age was 57 years (SD, 12.4 y), 43.5% were female, 82% were white, and 38.2% had stage IV disease. PGVs were found in 15.5% (n = 56) of patients, including 44 in moderate- and high-penetrance cancer susceptibility genes. Thirty-four (9.4%) patients had incremental clinically actionable findings that would not have been detected by practice guideline criteria or a CRC-specific gene panel. Only younger age at diagnosis was associated with the presence of PGVs (odds ratio, 1.99; 95% CI, 1.12-3.56). After a median follow-up period of 20.7 months, no differences in overall survival were seen between those with or without a PGV (P = .2). Eleven percent of patients had modifications in their treatment based on genetic findings. Family cascade testing was low (16%). CONCLUSIONS: Universal multigene panel testing in CRC was associated with a modest, but significant, detection of heritable mutations over guideline-based testing. One in 10 patients had changes in their management based on test results. Uptake of cascade family testing was low, which is a concerning observation that warrants further study.

Depiction of Resuscitation on Medical Dramas: Proposed Effect on Patient Expectations.

The public has unrealistic views regarding the success of cardiopulmonary resuscitation, and one potential source of misinformation is medical dramas. Prior research has shown that depictions of resuscitation on television are skewed towards younger patients with acute injuries, while most cardiac arrests occur in older patients as a result of medical comorbidities. Additionally, the success rate of televised resuscitations on older shows has vastly exceeded good outcomes in the real world. We sought to understand resuscitation outcomes on current medical dramas and to review the literature for evidence that media affects patient decision-making. We reviewed medical dramas to evaluate the demographics of cardiac arrest victims and the success rate of resuscitations and compared the results to outcomes for real-world patients. Medical dramas continue to focus on trauma as the main cause of cardiac arrest and portray favorable outcomes more frequently than should be expected. Patients who believe the overly optimistic prognoses portrayed on television may be more likely to desire aggressive medical care in the face of serious illness. Healthcare workers should anticipate the need to counter misinformation when discussing patient goals of care and end-of-life planning.

Efficacy of Endoscopic Submucosal Dissection for Superficial Gastric Neoplasia in a Large Cohort in North America.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is a widely accepted treatment option for superficial gastric neoplasia in Asia, but there are few data on outcomes of gastric ESD from North America. We aimed to evaluate the safety and efficacy of gastric ESD in North America. METHODS: We analyzed data from 347 patients who underwent gastric ESD at 25 centers, from 2010 through 2019. We collected data on patient demographics, lesion characteristics, procedure details and related adverse events, treatment outcomes, local recurrence, and vital status at the last follow up. For the 277 patients with available follow-up data, the median interval between initial ESD and last clinical or endoscopic evaluation was 364 days. The primary endpoint was the rate of en bloc and R0 resection. Secondary outcomes included curative resection, rates of adverse events and recurrence, and gastric cancer-related death. RESULTS: Ninety patients (26%) had low-grade adenomas or dysplasia, 82 patients (24%) had high-grade dysplasia, 139 patients (40%) had early gastric cancer, and 36 patients (10%) had neuroendocrine tumors. Proportions of en bloc and R0 resection for all lesions were 92%/82%, for early gastric cancers were 94%/75%, for adenomas and low-grade dysplasia were 93%/ 92%, for high-grade dysplasia were 89%/ 87%, and for neuroendocrine tumors were 92%/75%. Intraprocedural perforation occurred in 6.6% of patients; 82% of these were treated successfully with endoscopic therapy. Delayed bleeding occurred in 2.6% of patients. No delayed perforation or procedure-related deaths were observed. There were local recurrences in 3.9% of cases; all occurred after non-curative ESD resection. Metachronous lesions were identified in 14 patients (6.9%). One of 277 patients with clinical follow up died of metachronous gastric cancer that occurred 2.5 years after the initial ESD. CONCLUSIONS: ESD is a highly effective treatment for superficial gastric neoplasia and should be considered as a viable option for patients in North America. The risk of local recurrence is low and occurs exclusively after non-curative resection. Careful endoscopic surveillance is necessary to identify and treat metachronous lesions.

Comparison of Universal Genetic Testing vs Guideline-Directed Targeted Testing for Patients With Hereditary Cancer Syndrome.

IMPORTANCE: Hereditary factors play a key role in the risk of developing several cancers. Identification of a germline predisposition can have important implications for treatment decisions, risk-reducing interventions, cancer screening, and germline testing. OBJECTIVE: To examine the prevalence of pathogenic germline variants (PGVs) in patients with cancer using a universal testing approach compared with targeted testing based on clinical guidelines and the uptake of cascade family variant testing (FVT). DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter cohort study assessed germline genetic alterations among patients with solid tumor cancer receiving care at Mayo Clinic cancer centers and a community practice between April 1, 2018, and March 31, 2020. Patients were not selected based on cancer type, disease stage, family history of cancer, ethnicity, or age. EXPOSURES: Germline sequencing using a greater than 80-gene next-generation sequencing platform. MAIN OUTCOMES AND MEASURES: Proportion of PGVs detected with a universal strategy compared with a guideline-directed approach and uptake of cascade FVT in families. RESULTS: A total of 2984 patients (mean [SD] age, 61.4 [12.2] years; 1582 [53.0%] male) were studied. Pathogenic germline variants were found in 397 patients (13.3%), including 282 moderate- and high-penetrance cancer susceptibility genes. Variants of uncertain significance were found in 1415 patients (47.4%). A total of 192 patients (6.4%) had incremental clinically actionable findings that would not have been detected by phenotype or family history-based testing criteria. Of those with a high-penetrance PGV, 42 patients (28.2%) had modifications in their treatment based on the finding. Only younger age of diagnosis was associated with presence of PGV. Only 70 patients (17.6%) with PGVs had family members undergoing no-cost cascade FVT. CONCLUSIONS AND RELEVANCE: This prospective, multicenter cohort study found that universal multigene panel testing among patients with solid tumor cancer was associated with an increased detection of heritable variants over the predicted yield of targeted testing based on guidelines. Nearly 30% of patients with high-penetrance variants had modifications in their treatment. Uptake of cascade FVT was low despite being offered at no cost.

Intravenous Access in Gastrointestinal Hemorrhage: A Multidisciplinary Quality Improvement Initiative Led by Emergency Department Nurses and Internal Medicine Physicians.

BACKGROUND: The management of acute gastrointestinal hemorrhage (GIH) is focused on early resuscitation through 2 large-bore intravenous (2LBIV) catheters, although adherence to this recommendation is low. LOCAL PROBLEM: Of 100 patients hospitalized with GIH in 2017, only 14 received 2LBIV access. The goal of this study was to improve this measure. METHODS: A multidisciplinary team used the DMAIC (define, measure, analyze, improve, and control) framework to perform a quality improvement initiative. INTERVENTIONS: The team used quality tools including a stakeholder survey, swimlane diagram, and fishbone diagram. The first intervention involved education of the hospitalists directing admissions, and the second intervention involved education of emergency department (ED) physicians and nurses regarding the importance of 2LBIV placement. RESULTS: Following the second intervention, there was a substantial increase in 2LBIV placement to 37 of 86 (43%). CONCLUSIONS: Carefully directed education of ED physicians and nurses with monthly feedback was effective in improving appropriate intravenous placement in patients with GIH.

Successful Use of Intragastric Balloon Therapy as a Bridge to Heart Transplantation.

Obesity is an important limiting factor for heart transplantation (HT) in patients with congestive heart failure (CHF). Achieving substantial weight loss is challenging in this population due to activity limitations and fluid retention. Endoscopic bariatric therapies (EBTs) including intragastric balloons (IGB) are effective primary weight loss therapies. IGBs have also been successfully utilized as a bridge therapy prior to liver transplantation and, in one case report, prior to HT. Potential advantages of IGBs in this population include low bleeding risk and less invasiveness as compared to other EBTs and surgery. We report the successful use of IGB as a bridge therapy in two patients with class II obesity and end-stage CHF requiring left ventricular assist devices (LVAD), anticoagulation, antiplatelet, and inotrope therapy.

Removal of a Large Stone in the Upper Thoracic Esophagus.

Ingestion of a foreign body is a common occurrence. Flexible endoscopy is most commonly used for treatment, but certain large foreign bodies are more easily retrieved with rigid endoscopy. We present a technically challenging case of intentional ingestion of a large stone that required retrieval from the upper thoracic esophagus using rigid endoscopy. This case highlights the importance of alternative methods to manage large foreign bodies and of collaboration of medical subspecialties.

Glucose-dependent trans-plasma membrane electron transport and p70S6k phosphorylation in skeletal muscle cells.

The reduction of extracellular oxidants by intracellular electrons is known as trans-plasma membrane electron transport (tPMET). The goal of this study was to characterize a role of tPMET in the sensing of glucose as a physiological signal. tPMET from C2C12 myotubes was monitored using a cell-impermeable extracellular electron acceptor, water-soluble tetrazolium salt-1 (WST-1). Superoxide dismutase in the incubation medium or exposure to an NADPH oxidase (NOX) isoform 1/4 inhibitor suppressed WST-1 reduction by 70%, suggesting a role of NOXs in tPMET. There was a positive correlation between medium glucose concentration and WST-1 reduction, suggesting that tPMET is a glucose-sensing process. WST-1 reduction was also decreased by an inhibitor of the pentose phosphate pathway, dehydroepiandrosterone. In contrast, glycolytic inhibitors, 3PO and sodium fluoride, did not affect WST-1 reduction. Thus, it appears that glucose uptake and processing in the pentose phosphate pathway drives NOX-dependent tPMET. Western blot analysis demonstrated that p70S6k phosphorylation is glucose-dependent, while the phosphorylation of AKT and MAPK did not differ in the presence or absence of glucose. Further, phosphorylation of p70S6k was dependent upon NOX enzymes. Finally, glucose was required for full stimulation of p70S6k by insulin, again in a fashion prevented by NOX inhibition. Taken together, the data suggest that muscle cells have a novel glucose-sensing mechanism dependent on NADPH production and NOX activity, culminating in increased p70S6k phosphorylation.

HIV infection and clinical spectrum of associated vasculitides.

Various infections have been causative in the pathogenesis of systemic vasculitides, and HIV infection is not spared. In an immunocompromised host, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, herpes simplex virus, hepatitis B and hepatitis C virus, and mycobacteria, along with HIV infection can cause vasculitis. Herein we emphasize the spectrum of vasculitides, their pathogenesis, presentation, course, and therapy in the HIV-infected population. Every spectrum and size of the blood vessel involvement have been seen in HIV-associated vasculitides. We review each spectrum in detail and describe our experience with polyarteritis nodosa, the most common presentation occurring in HIV-infected patients. We also discuss the differences in HIV, hepatitis B, and hepatitis C- related polyarteritis nodosa in detail.

HIV infection and rheumatic diseases: the changing spectrum of clinical enigma.

In this article, the authors discuss the occurrence and prevalence of rheumatic syndromes before and after highly active antiretroviral therapy became the usual mode of treatment. The immunologic, environmental, and genetic factors behind the combination of HIV infection and rheumatic manifestation contribute to the complexity of these diseases. Miscellaneous case reports are discussed in relation to HIV infection. The authors conclude that geriatric care of HIV patients is on the horizon as more people have access to newer, more effective therapy and mortality is on the decline. Younger HIV patients will be committed to a lifetime of therapy to address bone disease and other chronic problems. In the future, newer agents may steer the clinical scenario in unforeseen directions.