Rishi Batra

Human papilloma virus positive oropharyngeal squamous cell carcinoma: A growing epidemic

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing despite a decrease in tobacco use. Almost 20-30% of patients with OPSCC do not have the traditional risk factors of smoking and alcohol use and in a vast majority of these patients, the human papilloma virus (HPV) appears to drive the malignant transformation. HPV induced malignant transformation is attributed to two viral oncogenes and their non-structural protein products (E6 and E7). These two proteins appear to affect carcinogenesis by their inhibitory effects on p53 and retinoblastoma proteins (Rb). Patients with HPV mediated OPSCC seem to have a better prognosis compared to their non-HPV counterparts. However, in the absence of strong evidence, standard of care at this time for OPSCC does not differ based on HPV status. Current research is focused on the role of de-escalation of treatment and elucidation of prognostic markers in this unique population. This review focuses on the pathogenesis of HPV mediated OPSCC and details the current evidence in the management of these patients.

A personalized treatment for lung cancer: molecular pathways, targeted therapies, and genomic characterization.

Lung cancer is a heterogeneous, complex, and challenging disease to treat. With the arrival of genotyping and genomic profiling, our simple binary division of lung cancer into non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) is no longer acceptable. In the past decade and with the advent of personalized medicine, multiple advances have been made in understanding the underlying biology and molecular mechanisms of lung cancer. Lung cancer is no longer considered a single disease entity and is now being subdivided into molecular subtypes with dedicated targeted and chemotherapeutic strategies. The concept of using information from a patients tumor to make therapeutic and treatment decisions has revolutionized the landscape for cancer care and research in general.Management of non-small-cell lung cancer, in particular, has seen several of these advances, with the understanding of activating mutations in EGFR, fusion genes involving ALK, rearrangements in ROS-1, and ongoing research in targeted therapies for K-RAS and MET. The next era of personalized treatment for lung cancer will involve a comprehensive genomic characterization of adenocarcinoma, squamous-cell carcinoma, and small-cell carcinoma into various subtypes. Future directions will involve incorporation of molecular characteristics and next generation sequencing into screening strategies to improve early detection, while also having applications for joint treatment decision making in the clinics with patients and practitioners. Personalization of therapy will involve close collaboration between the laboratory and the clinic. Given the heterogeneity and complexity of lung cancer treatment with respect to histology, tumor stage, and genomic characterization, mind mapping has been developed as one of many tools which can assist physicians in this era of personalized medicine. We attempt to utilize the above tool throughout this chapter, while reviewing lung cancer epidemiology, lung cancer treatment, and the genomic characterization of lung cancer.

Effect of Surgical Intervention on Survival of Patients With Clinical N2 Non-Small Cell Lung Cancer: A Veterans' Affairs Central Cancer Registry (VACCR) Database Analysis.

Background:Optimal management of locally advanced non–small cell lung cancer (NSCLC) lacks consensus. A retrospective analysis of patient data entered in the Veterans Affairs Central Cancer Registry was conducted to evaluate these issues. Patients and Methods:Data of patients with cT1-4, cN2, and cM0 NSCLC diagnosed in the VA Health System between 1995 and 2003 were evaluated. Age, sex, race, smoking history, TNM stage, treatment, and overall survival were abstracted. Survival was compared using multivariate Cox proportional hazards regression analysis. Results:Of the 7328 patients analyzed, 7218 (98.5%) were male, 6061 (82.7%) were white, and 321 (4.4%) were never smokers. The treatment received included: none, 23.8%; chemotherapy alone, 14.3%; radiation alone, 23%; and chemoradiation (sequential or concurrent), 31.4%. Only 7.5% of patients had a surgical resection, with or without multimodality therapy. The median survival (months) of these patient groups were: surgery, 19.3; chemoradiation, 13; chemotherapy alone, 9.2; radiation alone, 7.3; and no treatment, 4 (P<0.0001). African Americans had a significantly decreased risk of mortality compared with whites (hazard ratio 0.92; 95% confidence interval, 0.87-0.98). Conclusions:Inclusion of surgical resection as a treatment modality was associated with a better overall survival. Also, African Americans appeared to do better than whites. These hypothesis-generating findings should be useful in the ongoing pursuit of better treatment strategies for locally advanced NSCLC.

Impact of an electronic medical record on the incidence of antiretroviral prescription errors and HIV pharmacist reconciliation on error correction among hospitalized HIV-infected patients.

BACKGROUND Previous review of admissions from 2009-2011 in our institution found a 35.1% error rate in antiretroviral (ART) prescribing, with 55% of errors never corrected. Subsequently, our institution implemented a unified electronic medical record (EMR) and we developed a medication reconciliation process with an HIV pharmacist. We report the impact of the EMR on incidence of errors and of the pharmacist intervention on time to error correction. METHODS Prospective medical record review of HIV-infected patients hospitalized for >24 h between 9 March 2013 and 10 March 2014. An HIV pharmacist reconciled outpatient ART prescriptions with inpatient orders within 24 h of admission. Prescribing errors were classified and time to error correction recorded. Error rates and time to correction were compared to historical data using relative risks (RR) and logistic regression models. RESULTS 43 medication errors were identified in 31/186 admissions (16.7%). The incidence of errors decreased significantly after EMR (RR 0.47, 95% CI 0.34, 0.67). Logistic regression adjusting for gender and race/ethnicity found that errors were 61% less likely to occur using the EMR (95% CI 40%, 75%; P<0.001). All identified errors were corrected, 65% within 24 h and 81.4% within 48 h. Compared to historical data where only 31% of errors were corrected in <24 h and 55% were never corrected, errors were 9.4× more likely to be corrected within 24 h with HIV pharmacist intervention (P<0.001). CONCLUSIONS Use of an EMR decreased the error rate by more than 50% but despite this, ART errors remained common. HIV pharmacist intervention was key to timely error correction.

Premature aortic smooth muscle cell differentiation contributes to matrix dysregulation in Marfan Syndrome

Thoracic aortic aneurysm and dissection are life-threatening complications of Marfan syndrome (MFS). Studies of human and mouse aortic samples from late stage MFS demonstrate increased TGF-β activation/signaling and diffuse matrix changes. However, the role of the aortic smooth muscle cell (SMC) phenotype in early aneurysm formation in MFS has yet to be fully elucidated. As our objective, we investigated whether an altered aortic SMC phenotype plays a role in aneurysm formation in MFS. We describe previously unrecognized concordant findings in the aortas of a murine model of MFS, mgR, during a critical and dynamic phase of early development. Using Western blot, gelatin zymography, and histological analysis, we demonstrated that at postnatal day (PD) 7, before aortic TGF-β levels are increased, there is elastic fiber fragmentation/disorganization and increased levels of MMP-2 and MMP-9. Compared to wild type (WT) littermates, aortic SMCs in mgR mice express higher levels of contractile proteins suggesting a switch to a more mature contractile phenotype. In addition, tropoelastin levels are decreased in mgR mice, a finding consistent with a premature switch to a contractile phenotype. Proliferation assays indicate a decrease in the proliferation rate of mgR cultured SMCs compared to WT SMCs. KLF4, a regulator of smooth muscle cell phenotype, was decreased in aortic tissue of mgR mice. Finally, overexpression of KLF4 partially reversed this phenotypic change in the Marfan SMCs. This study indicates that an early phenotypic switch appears to be associated with initiation of important metabolic changes in SMCs that contribute to subsequent pathology in MFS.

How Can Social Media Get Us in Trouble

&NA; When utilized properly, social media offers several personal and professional benefits for the practicing surgeon, including peer networking, education, e‐mentorship, marketing, recruitment, and patient outreach. However, unprofessional online behavior is common among surgeons, and this improper use of social media can be quite dangerous. This article reviews the dangers of social media and illustrates this with examples of unprofessional behavior and the associated consequences. It also provides recommendations for maintaining a professional and productive online persona. Surgeons must understand the various social media platforms and their target audience while upholding online professionalism at all times.

IL-1β (Interleukin-1β) and TNF-α (Tumor Necrosis Factor-α) Impact Abdominal Aortic Aneurysm Formation by Differential Effects on Macrophage Polarization

Objective— Abdominal aortic aneurysms are inflammatory in nature and are associated with some risk factors that also lead to atherosclerotic occlusive disease, most notably smoking. The purpose of our study was to identify differential cytokine expression in patients with abdominal aortic aneurysm and those with atherosclerotic occlusive disease. Based on this analysis, we further explored and compared the mechanism of action of IL (interleukin)-1&bgr; versus TNF-&agr; (tumor necrosis factor-&agr;) in abdominal aortic aneurysm formation. Approach and Results— IL-1&bgr; was differentially expressed in human plasma with lower levels detected in patients with abdominal aortic aneurysm compared with matched atherosclerotic controls. We further explored its mechanism of action using a murine model and cell culture. Genetic deletion of IL-1&bgr; and IL-1R did not inhibit aneurysm formation or decrease MMP (matrix metalloproteinase) expression. The effects of IL-1&bgr; deletion on M1 macrophage polarization were compared with another proinflammatory cytokine, TNF-&agr;. Bone marrow-derived macrophages from IL-1&bgr;−/− and TNF-&agr;−/− mice were polarized to an M1 phenotype. TNF-&agr; deletion, but not IL-1&bgr; deletion, inhibited M1 macrophage polarization. Infusion of M1 polarized TNF-&agr;−/− macrophages inhibited aortic diameter growth; no inhibitory effect was seen in mice infused with M1 polarized IL-1&bgr;−/− macrophages. Conclusions— Although IL-1&bgr; is a proinflammatory cytokine, its effects on aneurysm formation and macrophage polarization differ from TNF-&agr;. The differential effects of IL-1&bgr; and TNF-&agr; inhibition are related to M1/M2 macrophage polarization and this may account for the differences in clinical efficacy of IL-1&bgr; and TNF-&agr; antibody therapies in management of inflammatory diseases.

Role of Preoperative Biliary Stenting and Preoperative Preparation Before Pancreaticoduodenectomy

Surgical resection remains the only potentially curative treatment option for patients diagnosed with pancreatic cancer. Pancreaticoduodenectomy is a morbid procedure that is fraught with an acceptable mortality rate, but a high morbidity rate. Preoperative biliary stenting can be used as a bridge to surgery for pancreatic cancer, to minimize the risk of developing cholangitis and to facilitate the administration of neoadjuvant therapy in patients with locally advanced pancreatic cancer. It can also be used for palliation in patients with unresectable disease. However, biliary stenting is not recommended for routine use preoperatively and must be individualized to the patient. Prior to pancreaticoduodenectomy, a thorough, systematic, and methodical approach to risk stratification and preoperative planning is mandatory to improve patient selection and optimize outcomes. A multidisciplinary team approach consisting of surgeons, gastroenterologists, medical oncologists, radiation oncologists, and pain specialists helps to deliver comprehensive care to patients in preparation for the operation.

Transesophageal Echocardiogram-Guided Stent Placement in Superior Vena Cava Syndrome Secondary to Granulomatous Lung Disease: A Case Series and Literature Review

Obstruction of the superior vena cava (SVC) is an uncommon, but potentially life-threatening condition due to likely development of edema in the head and neck and potential respiratory compromise. Less than half of those affected by SVC syndrome survive more than a year. Obstruction can be from neoplasms or secondary to benign disease. Treatment for most cases of symptomatic SVC syndrome involves placement of a stent to relieve the stenosis. Serious complications such as stent migration, pulmonary embolism, and cardiac tamponade can occur in 5% to 10% of cases, and inadequate imaging of the SVC–atrial junction by fluoroscopy contributes to these problems. The overlapping contrast in the atrium makes it difficult to precisely place the distal end of the stent, potentially allowing for embolization of the stent to occur. We present a case series of 3 patients wherein transesophageal echocardiography was used for guidance of stent placement in the SVC and significantly aided in placement.

1557Impact of HIV Pharmacist Reconcilation on Correction of Antiretroviral Prescription Errors Among Hospitalized HIV-Infected Patients

Antiretroviral Prescription Errors Among Hospitalized HIV-Infected Patients Rishi Batra, BS; Jane Wolbach-Lowes, PharmD; Susan Swindells, MBBS; Kimberly Scarsi, PharmD; Anthony Podany, PharmD; Harlan Sayles, MS; Uriel Sandkovsky, MD, FACP; College of Medicine, University of Nebraska Medical Center, Omaha, NE; College of Pharmacy, University of Nebraska Medical Center, Omaha, NE; Division of Infectious Diseases, University of Nebraska Medical Center, Omaha, NE; College of Public Health, University of Nebraska Medical Center, Omaha, NE