Medicine and Health Sciences Commons^™

Effect Of Hyperchloremia On Acute Kidney Injury In Critically Ill Septic Patients: A Retrospective Cohort Study, Lenar Yessayan, Javier A. Neyra, Fabrizio Canepa-Escaro, George Vasquez-Rios, Michael Heung, Jerry Yee, Acute Kidney Injury In Critical Illness Study Group

Internal Medicine Faculty Publications

Background: Hyperchloremia is common in critically ill septic patients. The impact of hyperchloremia on the incidence of acute kidney injury (AKI) is not well studied. We investigated the association between hyperchloremia and AKI within the first 72 h of intensive care unit (ICU) admission.

Methods: 6490 ICU adult patients admitted with severe sepsis or septic shock were screened for eligibility. Exclusion criteria included: AKI on admission, baseline estimated glomerular filtration rate (eGFR) < 15 ml/min/1.73 m², chronic renal replacement therapy, absent baseline serum creatinine data, and absent serum chloride data on ICU admission.

Results: A total of 1045 patients were available for …

National Trends In Admission And In-Hospital Mortality Of Patients With Heart Failure In The United States (2001–2014), Emmanuel Akintoye, Alexandros Briasoulis, Alexander Egbe, Shannon M. Dunlay, Sudhir Kushwaha, Diane Levine, Luis Afonso, Dariush Mozaffarian, Jarrett Weinberger

Internal Medicine Faculty Publications

Background-—To investigate heart failure (HF) hospitalization trends in the United States and change in trends after publication of management guidelines.

Methods and Results-—Using data from the National Inpatient Sample and the US Census Bureau, annual national estimates in HF admissions and in-hospital mortality were estimated for years 2001 to 2014, during which an estimated 57.4 million HF-associated admissions occurred. Rates (95% confidence intervals) of admissions and in-hospital mortality among primary HF hospitalizations declined by an average annual rate of 3% (2.5%–3.5%) and 3.5% (2.9%–4.0%), respectively. Compared with 2001 to 2005, the average annual rate of decline in primary HF admissions …

Common Tdp1 Polymorphisms In Relation To Survival Among Small Cell Lung Cancer Patients: A Multicenter Study From The International Lung Cancer Consortium, Pawadee Lohavanichbutr, Lori C. Sakoda, Christopher I. Amos, Susanne M. Arnold, David C. Christiani, Michael P. A. Davies, John K. Field, Eric B. Haura, Rayjean J Hung, Takashi Kohno, Maria Teresa Landi, Geoffrey Liu, Yi Liu, Michael W. Marcus, Grainne M. O'Kane, Matthew B. Schabath, Kouya Shiraishi, Stacey A. Slone, Adonina Tardón, Ping Yang, Kazushi Yoshida, Ruyang Zhang, Xuchen Zong, Gary E. Goodman, Noel S. Weiss, Chu Chen

Internal Medicine Faculty Publications

Background—DNA topoisomerase inhibitors are commonly used for treating small-cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome. In this study, we investigated whether common TDP1 single-nucleotide polymorphisms (SNP) are associated with overall survival among SCLC patients.

Methods—Two TDP1 SNPs (rs942190 and rs2401863) were analyzed in 890 patients from 10 studies in the International Lung Cancer Consortium (ILCCO). The Kaplan–Meier method and Cox regression analyses were used to evaluate genotype associations with overall mortality at 36 months postdiagnosis, adjusting for age, sex, race, and tumor stage. …

Ecog-Acrin (E4805) Randomized Phase Ii Study To Determine The Effect Of 2 Different Doses Of Aflibercept In Patients With Metastatic Renal Cell Carcinoma, Roberto Pili, Opeyemi Jegede, Michael A. Carducci, Judith Manola, David L. Groteluschen, Leonard L. Appleman, Glenn Liu, James C. Shanks, Shaker R. Dakhil, Janice Dutcher, Robert S. Dipaola

Internal Medicine Faculty Publications

Background—Aflibercept is a recombinantly-produced fusion protein that has potent anti-VEGF activity. We tested whether aflibercept has clinical activity in clear cell renal cell carcinoma (ccRCC). The recommended Phase 2 dose was 4 mg/kg but several patients treated at 1 mg/kg demonstrated prolonged progression-free survival (PFS). We therefore tested both doses in a parallel group randomized trial.

Methods—Eligible patients (pts) had histologically confirmed advanced or metastatic ccRCC and previous treatments including prior exposure to a VEGF RTKI. Patients received aflibercept (either 1 mg/kg or 4 mg/kg) day 1 of a 14-day cycle until progression. Patients randomized to 1 mg/kg …

Emergency Department Repair Of Blunt Right Atrial Rupture Utilizing Cardiopulmonary Bypass, Samuel P. Carmichael, Michael C. Bounds, Alexis E. Shafii, Phillip K. Chang

Internal Medicine Faculty Publications

Blunt cardiac injury (BCI) with free wall rupture carries a high risk of pre-hospital death. Cardiopulmonary bypass (CPB) has been utilized as a bridge to repair of cardiac lesions in select patients. We present an interesting case of emergency department repair of right atrial rupture with cardiopulmonary bypass.

Mtor Kinase Inhibition Effectively Decreases Progression Of A Subset Of Neuroendocrine Tumors That Progress On Rapalog Therapy And Delays Cardiac Impairment, Melissa A. Orr-Asman, Zhengtao Chu, Min Jiang, Mariah Worley, Kathleen Lesance, Sheryl E. Koch, Vinicius S. Carreira, Hanan M. Dahche, David R. Plas, Kakajan Komurov, Xiaoyang Qi, Carol A. Mercer, Lowell B. Anthony, Jack Rubinstein, Hala E. Thomas

Internal Medicine Faculty Publications

Inhibition of mTOR signaling using the rapalog everolimus is an FDA-approved targeted therapy for patients with lung and gastroenteropancreatic neuroendocrine tumors (NET). However, patients eventually progress on treatment, highlighting the need for additional therapies. We focused on pancreatic NETs (pNET) and reasoned that treatment of these tumors upon progression on rapalog therapy, with an mTOR kinase inhibitor (mTORKi), such as CC-223, could overcome a number of resistance mechanisms in tumors and delay cardiac carcinoid disease. We performed preclinical studies using human pNET cells in vitro and injected them subcutaneously or orthotopically to determine tumor progression and cardiac function in mice …

Predictors Of In Hospital Mortality In Acute Pancreatitis, David E. Mossad, Brian V. Dinh, Ronald J. Markert, Mustafa N. Musleh, Sangeeta Agrawal

Internal Medicine Faculty Publications

Background and Aims Pancreatitis presents with significant risk for morbidity and mortality acutely. The purpose of this study was to evaluate demographics, comorbidity burden, and hospital characteristics and their effect on in-hospital mortality in patients with acute pancreatitis. Methods Data was collected from The National Hospital Discharge Survey for patients admitted for acute pancreatitis from 2001-2010. Patients were separated into those who suffered in-hospital mortality and those that were discharged. Data was analyzed regarding demographics, length of stay, comorbidity burden, mortality, principal payment, and hospital size. Statistical comparisons were made using SPSS with chi-square and student T tests with a …

Status Of Early-Career Academic Cardiology, A Global Perspective, Carl W. Tong, Meena S. Madhur, Anne K. Rzeszut, Marwah Abdalla, Islam Abudayyeh, Erick Alexanderson, Jonathan Buber, Dmitriy N. Feldman, Rakesh Gopinathannair, Ravi S. Hira, Andrew M. Kates, Thorsten Kessler, Steve W. Leung, Satish R. Raj, Erica S. Spatz, Melanie B. Turner, Anne Marie Valente, Kristin West, Chittur A. Sivaram, Joseph A Hill, Douglas L. Mann, Andrew M. Freeman

Internal Medicine Faculty Publications

Early career academic cardiologists, whom many believe are an important component of the future of cardiovascular care, face a myriad of challenges. The Early Career Section Academic Working Group of the American College of Cardiology (ACC) along with senior leadership support, assessed the progress of this cohort from 2013–2016 with a global perspective. Data consisted of accessing National Heart Lung and Blood Institute (NHLBI) public information, American Heart Association and international organizations providing data, and a membership-wide survey. Although NHBLI increased funding of career development grants, only a small number of early career ACC members have benefited as funding of …

The Influence Of A Kdt501, A Novel Isohumulone, On Adipocyte Function In Humans, Brian S. Finlin, Beibei Zhu, Bernard P. Kok, Cristina Godio, Philip M. Westgate, Neile Grayson, Robert Sims, Jeffrey S. Bland, Enrique Saez, Philip A. Kern

Internal Medicine Faculty Publications

Objective: In a phase II clinical trial in nine obese, insulin-resistant humans, we observed that treatment with KDT501, a novel isohumulone drug, increased total and high-molecular weight (HMW) adiponectin in plasma. The objective was to determine whether KDT501 increased adiponectin secretion from subcutaneous white adipose tissue (SC WAT) and the underlying mechanism(s).

Methods: Nine obese participants with either prediabetes or with normal glucose tolerance plus three features of metabolic syndrome were part of the study. SC WAT biopsies were performed before and after 28 days of KDT501 treatment in a clinical research setting. In addition, a cold stimulus was used …

Cardiac-Specific Inactivation Of Lpp3 In Mice Leads To Myocardial Dysfunction And Heart Failure, Mini Chandra, Diana Escalante-Alcalde, Shenuarin Bhuiyan, Anthony Wayne Orr, Christopher Kevil, Andrew J. Morris, Hyung Nam, Paari Dominic, Kevin J. Mccarthy, Sumitra Miriyala, Manikandan Panchatcharam

Internal Medicine Faculty Publications

Lipid Phosphate phosphatase 3 (LPP3), encoded by the Plpp3 gene, is an enzyme that dephosphorylates the bioactive lipid mediator lysophosphatidic acid (LPA). To study the role of LPP3 in the myocardium, we generated a cardiac specific Plpp3 deficient mouse strain. Although these mice were viable at birth in contrast to global Plpp3 knockout mice, they showed increased mortality ~ 8 months. LPP3 deficient mice had enlarged hearts with reduced left ventricular performance as seen by echocardiography. Cardiac specific Plpp3 deficient mice had longer ventricular effective refractory periods compared to their Plpp3 littermates. We observed that lack of Lpp3 enhanced cardiomyocyte …

Use Of Dark Chocolate For Diabetic Patients: A Review Of The Literature And Current Evidence, Syed Raza Shah, Richard Alweis, Najla Issa Najim, Amin Muhammad Dharani, Muhammad Ahmed Jangda, Maira Shahid, Ahmed Nabeel Kazi, Syed Arbab Shah

Internal Medicine Faculty Publications

Dietary changes are a major lifestyle factor that can influence the progression of chronic diseases such as diabetes. Recently, flavanols, a subgroup of plant-derived phytochemicals called flavonoids, have gained increasing attention, due to studies showing an inverse correlation between dietary intake of flavanols and incidence of diabetes. Flavanoids in the cocoa plant may ameliorate insulin resistance by improving endothelial function, altering glucose metabolism, and reducing oxidative stress. Oxidative stress has been proposed as the main culprit for insulin resistance. The well-established effects of cocoa on endothelial function also points to a possible effect on insulin sensitivity. The relationship between insulin …

Causes, Timing, And Impact Of Dual Antiplatelet Therapy Interruption For Surgery (From The Paris Registry), Mikkel Schoos, Jaya Chandrasekhar, Usman Baber, Aarti Bhasin, Samantha Sartori, Melissa Aquino, Birgit Vogel, Serdar Farhan, Sabato Sorrentino, Annapoorna Kini, Mitchell Kruckoff, David J. Moliterno, Timothy D. Henry, Giora Weisz, C. Michael Gibson, Ioannis Iakovou, Antonio Colombo, P. Gabriel Steg, Bernhard Witzenbichler, Alaide Chieffo, David Cohen, Thomas Stuckey, Cono Ariti, George Dangas, Stuart Pocock, Roxana Mehran

Internal Medicine Faculty Publications

Temporary interruption of dual antiplatelet therapy (DAPT) is not infrequently required in patients undergoing percutaneous coronary intervention (PCI). We sought to describe the procedures and outcomes associated with DAPT interruption in patients treated with DAPT following successful PCI from the Patterns of non-adherence to anti-platelet regimens in stented patients registry (n = 5018). DAPT interruption was prespecified as physician recommended cessation forcohort, 490 patients (9.8%) experienced 594 DAPT interruptions over 2 years following PCI. Only 1 antiplatelet agent was interrupted in 57.2% cases and interruption was frequently recommended by noncardiologists (51.3%). Where type of surgery was reported, majority of DAPT …

Persistence Of Macrocytosis After Discontinuation Of Zidovudine In Hiv-Infected Patients, Inski Yu, Richard N. Greenberg, Timothy N. Crawford, Alice C. Thornton, Thein Myint

Internal Medicine Faculty Publications

The duration of macrocytosis after stopping zidovudine (ZDV) is unknown. Among 104 HIV-infected patients treated with ZDV for more than 1 year, 84 patients had macrocytosis at ZDV discontinuation. The median mean corpuscular volume (MCV) was 114.6 fL (range 100-128 fL). Patients were divided into 2 groups: those who did (resolved macrocytosis, n = 36) and did not (persistent macrocytosis, n = 48) normalize MCV at 3 to 6 months after ZDV discontinuation. Alcohol use (P = .02), smoking (P = .03), and lower (but within normal range) folic acid levels (P = .05) were related to …

Multimodality Therapy Improves Survival In Intramedullary Spinal Cord Metastasis Of Lung Primary, Hayder Saeed, Reema Patel, Jigisha Thakkar, Lames Hamoodi, Li Chen, John L. Villano

Internal Medicine Faculty Publications

Background: Most metastatic spinal cord lesions are located either in the intradural, extramedullary, or in the epidural compartments. Intramedullary spinal cord metastasis (ISCM) is a rare central nervous system spread of cancer. The aim of this report was to evaluate ISCM in the published literature.

Methods: A literature review of PubMed from 1960 to 2016 was undertaken for the publications having demographic, clinical, histological, and outcome data.

Results: A total of 59 relevant papers were identified, showing 128 cases of intramedullary metastasis from lung cancer. The incidence of lung cancer as the primary malignancy with intramedullary metastasis was 56%. The …

Increasing Use Of Allogeneic Hematopoietic Cell Transplantation In Patients Aged 70 Years And Older In The United States, Lori Muffly, Marcelo C. Pasquini, Michael Martens, Ruta Brazauskas, Xiaochun Zhu, Kehinde Adekola, Mahmoud Aljurf, Karen K. Ballen, Ashish Bajel, Frederic Baron, Minoo Battiwalla, Amer Beitinjaneh, Jean-Yves Cahn, Mathew Carabasi, Yi-Bin Chen, Saurabh Chhabra, Stefan Ciurea, Edward Copelan, Anita D'Souza, John Edwards, James Foran, Cesar O. Freytes, Henry C. Fung, Robert Peter Gale, Sergio Giralt, Shahrukh K. Hashmi, Gerhard C. Hildebrandt, Vincent Ho, Ann Jakubowski, Hillard Lazarus

Internal Medicine Faculty Publications

In this study, we evaluated trends and outcomes of allogeneic hematopoietic cell transplantation (HCT) in adults ≥ 70 years with hematologic malignancies across the United States. Adults ≥ 70 years with a hematologic malignancy undergoing first allogeneic HCT in the United States between 2000 and 2013 and reported to the Center for International Blood and Marrow Transplant Research were eligible. Transplant utilization and transplant outcomes, including overall survival (OS), progression-free survival (PFS), and transplant-related mortality (TRM) were studied. One thousand one hundred and six patients ≥ 70 years underwent HCT across 103 transplant centers. The number and proportion of allografts …

The Role Of Sodium Bicarbonate In The Management Of Some Toxic Ingestions, Aibek E. Mirrakhimov, Taha Ayach, Aram Barbaryan, Goutham Talari, Romil Chadha, Adam Gray

Internal Medicine Faculty Publications

Adverse reactions to commonly prescribed medications and to substances of abuse may result in severe toxicity associated with increased morbidity and mortality. According to the Center for Disease Control, in 2013, at least 2113 human fatalities attributed to poisonings occurred in the United States of America. In this article, we review the data regarding the impact of systemic sodium bicarbonate administration in the management of certain poisonings including sodium channel blocker toxicities, salicylate overdose, and ingestion of some toxic alcohols and in various pharmacological toxicities. Based on the available literature and empiric experience, the administration of sodium bicarbonate appears to …

First-In-Human Clinical Trial Of Oral Onc201 In Patients With Refractory Solid Tumors, Mark N. Stein, Joseph R. Bertino, Howard L. Kaufman, Tina M. Mayer, Rebecca A. Moss, Ann W. Silk, Nancy Chan, Jyoti Malhotra, Loma Rodriguez, Joseph Aisner, Robert Aiken, Bruce G. Haffty, Robert S. Dipaola, Tracie Saunders, Andrew Zloza, Sherri Damare, Yasmeen Beckett, Bangning Yu, Saltanat Najmi, Christian Gabel, Sioghan Dickerson, Ling Zheng, Wafik S. El-Deiry, Joshua E. Allen, Martin Stogniew, Wolfgang Oster, Janice M. Mehnert

Internal Medicine Faculty Publications

Purpose: ONC201 is a small-molecule selective antagonist of the G protein–coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D).

Experimental Design: This open-label study treated 10 patients during dose escalation with histologically confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design. An additional 18 patients were treated at the RP2D in an expansion phase to collect additional safety, …

Myo-Inositol Reduces Β-Catenin Activation In Colitis, Emily M. Bradford, Corey A. Thompson, Tatiana Goretsky, Guang-Yu Yang, Luz M. Rodriguez, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

AIM

To assess dietary myo-inositol in reducing stem cell activation in colitis, and validate pβ-catenin^S552 as a biomarker of recurrent dysplasia.

METHODS

We examined the effects of dietary myo-inositol treatment on inflammation, pβ-catenin^S552 and pAkt levels by histology and western blot in IL-10^-/- and dextran sodium sulfate-treated colitic mice. Additionally, we assessed nuclear pβ-catenin^S552 in patients treated with myo-inositol in a clinical trial, and in patients with and without a history of colitis-induced dysplasia.

RESULTS

In mice, pβ-catenin^S552 staining faithfully reported the effects of myo-inositol in reducing inflammation and intestinal stem cell activation. In a …

Higher Mineralized Bone Volume Is Associated With A Lower Plain X-Ray Vascular Calcification Score In Hemodialysis Patients, Teresa Adragao, Anibal Ferreira, Joao M. Frazao, Ana Luisa Papoila, Iola Pinto, Marie-Claude Monier-Faugere, Hartmut H. Malluche

Internal Medicine Faculty Publications

Background and objectives

In dialysis patients, there is an increasing evidence that altered bone metabolism is associated with cardiovascular calcifications. The main objective of this study was to analyse, in hemodialysis patients, the relationships between bone turnover, mineralization and volume, evaluated in bone biopsies, with a plain X-ray vascular calcification score.

Design, setting, participants and measurements

In a cross-sectional study, bone biopsies and evaluation of vascular calcifications were performed in fifty hemodialysis patients. Cancellous bone volume, mineralized bone volume, osteoid volume, activation frequency, bone formation rate/bone surface, osteoid thickness and mineralization lag time were determined by histomorphometry. Vascular calcifications were …

Temperature As A Circadian Marker In Older Human Subjects: Relationship To Metabolic Syndrome And Diabetes, Brianna D. Harfmann, Elizabeth A. Schroder, Jonathan H. England, Natalie J. Senn, Philip M. Westgate, Karyn A. Esser, Philip A. Kern

Internal Medicine Faculty Publications

Background: Circadian rhythms are characterized by approximate 24-hour oscillations in physiological and behavioral processes. Disruptions in these endogenous rhythms, most commonly associated with shift work and/or lifestyle, are recognized to be detrimental to health. Several studies have demonstrated a high correlation between disrupted circadian rhythms and metabolic disease. The aim of this study was to determine which metabolic parameters correlate with physiological measures of circadian temperature amplitude (TempAmp) and stability (TempStab).

Methods: Wrist skin temperature was measured in 34 subjects (ages 50 to 70, including lean, obese, and diabetic subjects) every 10 minutes for 7 consecutive days. Anthropometric measures and …

Endoscopic Resolution And Recurrence Of Gastric Antral Vascular Ectasia After Serial Treatment With Argon Plasma Coagulation, Shashank Garg, Bilal Aslam, Nicholas Nickl

Internal Medicine Faculty Publications

AIM

To evaluate long-term endoscopic resolution and recurrence rate of gastric antral vascular ectasia (GAVE) after argon plasma coagulation (APC) treatment.

METHODS

This was an IRB-approved retrospective single center study that included patients endoscopically treated for GAVE between 1/1/2008 to 12/31/2014. The primary and secondary end points of the study were rate of endoscopic resolution of GAVE after APC treatment and recurrence rate of GAVE after endoscopic resolution, respectively. Endoscopic resolution of GAVE was defined as no endoscopic evidence of GAVE after treatment with APC. Recurrence of GAVE was defined as endoscopic reappearance of GAVE after prior resolution.

RESULTS

Twenty …

Effects Of Kdt501 On Metabolic Parameters In Insulin-Resistant Prediabetic Humans, Philip A. Kern, Brian S. Finlin, Dorothy Ross, Tania Boyechko, Beibei Zhu, Neile Grayson, Robert Sims, Jeffrey S. Bland

Internal Medicine Faculty Publications

Context: KDT501 is an isohumulone drug that has demonstrated beneficial effects on metabolic parameters in mice.

Objective: This study was intended to examine potential improvements in metabolism in humans.

Design and Setting: Changes in carbohydrate and lipid metabolism, along with inflammatory markers, were evaluated in prediabetic humans in a clinical research center.

Participants: Nine obese patients participated. All had prediabetes or normal glucose tolerance plus three features of metabolic syndrome.

Intervention: All participants were treated with escalating doses of KDT501 to a maximum dose of 1000 mg every 12 hours for a total of 28 days.

Outcome Measures: Changes in …

Lisinopril Or Coreg Cr In Reducing Cardiotoxicity In Women With Breast Cancer Receiving Trastuzumab: A Rationale And Design Of A Randomized Clinical Trial, Maya Guglin, Pamela Munster, Angelina Fink, Jeffrey Krischer

Internal Medicine Faculty Publications

Background—Trastuzumab (TZB) is an established therapy for HER2 positive breast cancer. The use of TZB is commonly associated with cardiotoxicity manifesting as asymptomatic decrease in left ventricular ejection fraction (LVEF) or overt heart failure. Several studies demonstrated favorable effects of angiotensin converting enzyme (ACE) inhibitors and beta blockers (BB) in the prevention of chemotherapy-induced cardiotoxicity. We hypothesize that patients, randomized to receive an ACE inhibitor or a beta-blocker during trastuzumab therapy for breast cancer, will maintain a higher LVEF than patients randomized to placebo.

Methods and Results—We designed a prospective, multicenter, randomized, phase II placebo-controlled clinical trial to …

Demographics, Patterns Of Care, And Survival In Pediatric Medulloblastoma, Emily V. Dressler, Therese A. Dolecek, Meng Liu, John L. Villano

Internal Medicine Faculty Publications

We evaluated the American College of Surgeon’s National Cancer Data Base (NCDB) to describe current hospital-based epidemiologic frequency, survival, and patterns of care of pediatric medulloblastoma. We analyzed NCDB 1998–2011 data on medulloblastoma for children ages 0–19 years using logistic and poisson regression, Kaplan–Meier survival estimates, and Cox proportional hazards models. 3647 cases of medulloblastoma in those aged 0–19 years were identified. Chemotherapy was received by 79 and 74% received radiation, with 65% receiving both therapies. Those who received radiation were more likely to be older than four, while those who received chemotherapy were more likely to be age four …

Interdependency Of Egf And Glp-2 Signaling In Attenuating Mucosal Atrophy In A Mouse Model Of Parenteral Nutrition, Yongjia Feng, Farok R. Demehri, Weidong Xiao, Yu-Hwai Tsai, Jennifer C. Jones, Constance D. Brindley, David W. Threadgill, Jens J. Holst, Bolette Hartmann, Terrence A. Barrett, Daniel H. Teitelbaum, Peter J. Dempsey

Internal Medicine Faculty Publications

BACKGROUND & AIMS: Total parenteral nutrition (TPN), a crucial treatment for patients who cannot receive enteral nutrition, is associated with mucosal atrophy, barrier dysfunction, and infectious complications. Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) improve intestinal epithelial cell (IEC) responses and attenuate mucosal atrophy in several TPN models. However, it remains unclear whether these 2 factors use distinct or overlapping signaling pathways to improve IEC responses. We investigated the interaction of GLP-2 and EGF signaling in a mouse TPN model and in patients deprived of enteral nutrition.

METHODS: Adult C57BL/6J, IEC-Egfr^{knock out (KO)} and IEC-pik3r1^KO mice receiving …

Rising Thyroid Cancer Incidence In Southern India: An Epidemic Of Overdiagnosis?, Indu Elizabeth Mathew, Aju Mathew

Internal Medicine Faculty Publications

Background: Thyroid cancer incidence is rising in high-income countries. This increase in disease burden is attributed to the phenomenon of overdiagnosis.

Objective: We aimed to investigate trends in thyroid cancer rates in India, focusing on the state of Kerala in southern India, which has reported a high incidence of the disease.

Design: Population-based study using data from the National Cancer Registry Program.

Participants: We used data from the Population Based Cancer Registries for Thiruvananthapuram (capital of Kerala state), Delhi, Mumbai, Bangalore, and Chennai. We used data for three reporting periods from 2005 to 2014 (represented as 2006, 2009, and 2012). …

Qt Prolongation Is Associated With Increased Mortality In End Stage Liver Disease, Sun Moon Kim, Bennet George, Diego Alcivar-Franco, Charles L. Campbell, Richard Charnigo, Brian P. Delisle, Jonathan Hundley, Yousef Darrat, Gustavo Morales, Samy-Claude Elayi, Alison L. Bailey

Internal Medicine Faculty Publications

AIM

To determine the prevalence of QT prolongation in a large series of end stage liver disease (ESLD) patients and its association to clinical variables and mortality.

METHODS

The QT interval was measured and corrected for heart rate for each patient, with a prolonged QT cutoff defined as QT > 450 ms for males and QT > 470 ms for females. Multiple clinical variables were evaluated including sex, age, serum sodium, international normalized ratio, creatinine, total bilirubin, beta-blocker use, Model for End-Stage Liver Disease (MELD), MELD-Na, and etiology of liver disease.

RESULTS

Among 406 ESLD patients analyzed, 207 (51.0%) had QT prolongation. …

Gastrointestinal Stromal Tumor Induced Hypercalcemia, Aram Barbaryan, Stefania Bailuc, Padma Poddutoori, Aida Richardson, Aibek E. Mirrakhimov

Internal Medicine Faculty Publications

Hypercalcemia in patients with cancer is a common laboratory finding affecting up to 44% of that patient population. 1,25-Dihydroxyvitamin D₃ mediated hypercalcemia is one of the rare mechanisms of this endocrine emergency in cancer patients. It is even rarer for solid organ neoplasms to present with hypercalcemia mediated through the production of 1,25-dihydroxyvitamin D₃. We report a case of a 77-year-old female who presented to the hospital with hypercalcemia and later was found to have metastatic gastrointestinal stromal tumor. There have been only 5 cases of gastrointestinal stromal tumor described in literature resulting in hypercalcemia. In our …

Acute Effects Of Implantable Cardioverter-Defibrillator Shocks On Biomarkers Of Myocardial Injury, Apoptosis, Heart Failure, And Systemic Inflammation, Jordan Brewster, Travis Sexton, Gary Dhaliwal, Richard Charnigo, Gustavo Morales, Kevin Parrott, Yousef Darrat, John C. Gurley, Susan S. Smyth, Claude S. Elayi

Internal Medicine Faculty Publications

Background: Implantable cardioverter‐defibrillator (ICD) shocks are potentially associated with myocardial injury, altered hemodynamics, apoptosis, and inflammatory signaling. Their precise cellular impact can be explored after defibrillation testing (DFT) via biomarkers. We evaluated changes in biomarkers after ICD shocks during DFT.

Methods: We prospectively enrolled outpatients presenting for first implantation of a cardiac device. Biomarkers indicative of myocardial injury, inflammation, and apoptosis were measured before and after implantation, and compared between patients receiving DFT (DFT+) to those not (DFT−).

Results: Sixty‐three patients were enrolled, 40 in the DFT+ group and 23 in the DFT− group. Average levels of troponin I, hsCRP, …

Spotlight On Blisibimod And Its Potential In The Treatment Of Systemic Lupus Erythematosus: Evidence To Date, Aleksander Lenert, Timothy B. Niewold, Petar Lenert

Internal Medicine Faculty Publications

B cells in general and BAFF (B cell activating factor of the tumor necrosis factor [TNF] family) in particular have been primary targets of recent clinical trials in systemic lupus erythematosus (SLE). In 2011, belimumab, a monoclonal antibody against BAFF, became the first biologic agent approved for the treatment of SLE. Follow-up studies have shown excellent long-term safety and tolerability of belimumab. In this review, we critically analyze blisibimod, a novel BAFF-neutralizing agent. In contrast to belimumab that only blocks soluble BAFF trimer but not soluble 60-mer or membrane BAFF, blisibimod blocks with high affinity all three forms of BAFF. …