Internal Medicine Commons^™

Lower Respiratory Illnesses In Childhood Are Associated With The Presence Of Air Trapping In Early Adulthood, Francesca Polverino, Debra A Stern, Eric M Snyder, Courtney Wheatley-Guy, Surya P Bhatt, Fernando D Martinez, Stefano Guerra, Wayne J Morgan

Faculty, Staff and Students Publications

Several factors occurring in early life, including lower respiratory tract illnesses (LRIs), are involved in determining lung structure and function in adulthood, but the effects of these factors on lung development remain largely unknown. Hereby, we evaluated the parameters from computed tomography (CT) scans performed at the age of 26 years in 39 subjects from the birth cohort of the Tucson Children's Respiratory Study (TCRS) in order to determine the relationship between early childhood factors and lung structural changes in young adult life. We found that participants with LRIs in childhood had increased air trapping at the age of 26 …

Melatonin Attenuates Mitochondrial Damage In Aristolochic Acid-Induced Acute Kidney Injury, Jian Sun, Jinjin Pan, Qinlong Liu, Jizhong Cheng, Qing Tang, Yuke Ji, Ke Cheng, Rui Wang, Liang Liu, Dingyou Wang, Na Wu, Xu Zheng, Junxia Li, Xueyan Zhang, Zhilong Zhu, Yanchun Ding, Feng Zheng, Jia Li, Ying Zhang, Yuhui Yuan

Faculty, Staff and Students Publications

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro …

Enrollment Of Underrepresented Racial And Ethnic Groups In The Rare And Atypical Diabetes Network (Radiant), Mustafa Tosur, Laura Gandolfo, Ashok Balasubramanyam, Rochelle N Naylor, Toni I Pollin, Neda Rasouli, Sara J Cromer, John B Buse, Maria J Redondo, Radiant Study Group

Faculty, Staff and Students Publications

INTRODUCTION: Diabetes mellitus in underrepresented racial and ethnic groups (URG) is rapidly increasing in incidence and has worse outcomes than diabetes in non-Hispanic White individuals. Rare and Atypical Diabetes Network (RADIANT) established recruitment targets based on the racial and ethnic distribution of the USA to enroll a diverse study population. We examined participation of URG across RADIANT study stages and described strategies to enhance recruitment and retention of URG.

MATERIALS AND METHODS: RADIANT is a multicenter NIH-funded study of people with uncharacterized forms of atypical diabetes. RADIANT participants consent online and progress through three sequential study stages, as eligible.

RESULTS: …

Clinical Characterization Of Data-Driven Diabetes Clusters Of Pediatric Type 2 Diabetes, Mahsan Abbasi, Mustafa Tosur, Marcela Astudillo, Ahmad Refaey, Ashutosh Sabharwal, Maria J Redondo

Faculty, Staff and Students Publications

BACKGROUND: Pediatric Type 2 diabetes (T2D) is highly heterogeneous. Previous reports on adult-onset diabetes demonstrated the existence of diabetes clusters. Therefore, we set out to identify unique diabetes subgroups with distinct characteristics among youth with T2D using commonly available demographic, clinical, and biochemical data.

METHODS: We performed data-driven cluster analysis (K-prototypes clustering) to characterize diabetes subtypes in pediatrics using a dataset with 722 children and adolescents with autoantibody-negative T2D. The six variables included in our analysis were sex, race/ethnicity, age, BMI

RESULTS: We identified five distinct clusters of pediatric T2D, with different features, treatment regimens and risk of diabetes complications: …

Novel Banana Lectin Car-T Cells To Target Pancreatic Tumors And Tumor-Associated Stroma, Mary K Mckenna, Ada Ozcan, Daniel Brenner, Norihiro Watanabe, Maureen Legendre, Dafydd G Thomas, Christopher Ashwood, Richard D Cummings, Challice Bonifant, David M Markovitz, Malcolm K Brenner

Faculty, Staff and Students Publications

BACKGROUND: Cell therapies for solid tumors are thwarted by the hostile tumor microenvironment (TME) and by heterogeneous expression of tumor target antigens. We address both limitations with a novel class of chimeric antigen receptors based on plant lectins, which recognize the aberrant sugar residues that are a 'hallmark' of both malignant and associated stromal cells. We have expressed in T cells a modified lectin from banana, H84T BanLec, attached to a chimeric antigen receptor (H84T-CAR) that recognizes high-mannose (asparagine residue with five to nine mannoses). Here, we tested the efficacy of our novel H84T CAR in models of pancreatic ductal …

Transcriptomic Analyses Of Ovarian Clear-Cell Carcinoma With Concurrent Endometriosis, Kaitlyn E Collins, Xiyin Wang, Yuliya Klymenko, Noah B Davis, Maria C Martinez, Chi Zhang, Kaman So, Aaron Buechlein, Douglas B Rusch, Chad J Creighton, Shannon M Hawkins

Faculty, Staff and Students Publications

INTRODUCTION: Endometriosis, a benign inflammatory disease whereby endometrial-like tissue grows outside the uterus, is a risk factor for endometriosis-associated ovarian cancers. In particular, ovarian endometriomas, cystic lesions of deeply invasive endometriosis, are considered the precursor lesion for ovarian clear-cell carcinoma (OCCC).

METHODS: To explore this transcriptomic landscape, OCCC from women with pathology-proven concurrent endometriosis (n = 4) were compared to benign endometriomas (n = 4) by bulk RNA and small-RNA sequencing.

RESULTS: Analysis of protein-coding genes identified 2449 upregulated and 3131 downregulated protein-coding genes (DESeq2, P< 0.05, log2 fold-change > |1|) in OCCC with concurrent endometriosis compared to endometriomas. Gene set enrichment …

Multiomics In Primary And Metastatic Breast Tumors From The Aurora Us Network Finds Microenvironment And Epigenetic Drivers Of Metastasis, Susana Garcia-Recio, Toshinori Hinoue, Gregory L Wheeler, Benjamin J Kelly, Ana C Garrido-Castro, Tomas Pascual, Aguirre A De Cubas, Youli Xia, Brooke M Felsheim, Marni B Mcclure, Andrei Rajkovic, Ezgi Karaesmen, Markia A Smith, Cheng Fan, Paula I Gonzalez Ericsson, Melinda E Sanders, Chad J Creighton, Jay Bowen, Kristen Leraas, Robyn T Burns, Sara Coppens, Amy Wheless, Salma Rezk, Amy L Garrett, Joel S Parker, Kelly K Foy, Hui Shen, Ben H Park, Ian Krop, Carey Anders, Julie Gastier-Foster, Mothaffar F Rimawi, Rita Nanda, Nancy U Lin, Claudine Isaacs, P Kelly Marcom, Anna Maria Storniolo, Fergus J Couch, Uma Chandran, Michael Davis, Jonathan Silverstein, Alexander Ropelewski, Minetta C Liu, Susan G Hilsenbeck, Larry Norton, Andrea L Richardson, W Fraser Symmans, Antonio C Wolff, Nancy E Davidson, Lisa A Carey, Adrian V Lee, Justin M Balko, Katherine A Hoadley, Peter W Laird, Elaine R Mardis, Tari A King, Charles M Perou

Faculty, Staff and Students Publications

The AURORA US Metastasis Project was established with the goal to identify molecular features associated with metastasis. We assayed 55 females with metastatic breast cancer (51 primary cancers and 102 metastases) by RNA sequencing, tumor/germline DNA exome and low-pass whole-genome sequencing and global DNA methylation microarrays. Expression subtype changes were observed in ~30% of samples and were coincident with DNA clonality shifts, especially involving HER2. Downregulation of estrogen receptor (ER)-mediated cell-cell adhesion genes through DNA methylation mechanisms was observed in metastases. Microenvironment differences varied according to tumor subtype; the ER

Biallelic Prmt7 Pathogenic Variants Are Associated With A Recognizable Syndromic Neurodevelopmental Disorder With Short Stature, Obesity, And Craniofacial And Digital Abnormalities, Elisa Cali, Mohnish Suri, Marcello Scala, Matteo P Ferla, Shahryar Alavi, Eissa Ali Faqeih, Emilia K Bijlsma, Kristen M Wigby, Diana Baralle, Mohammad Y V Mehrjardi, Jennifer Schwab, Konrad Platzer, Katharina Steindl, Mais Hashem, Marilyn Jones, Dmitriy M Niyazov, Jennifer Jacober, Rebecca Okashah Littlejohn, Denisa Weis, Neda Zadeh, Lance Rodan, Alice Goldenberg, François Lecoquierre, Marina Dutra-Clarke, Gabriella Horvath, Dana Young, Naama Orenstein, Shahad Bawazeer, Anneke T Vulto-Van Silfhout, Yvan Herenger, Mohammadreza Dehghani, Seyed Mohammad Seyedhassani, Amir Bahreini, Mahya E Nasab, A Gulhan Ercan-Sencicek, Zahra Firoozfar, Mojtaba Movahedinia, Stephanie Efthymiou, Pasquale Striano, Ehsan Ghayoor Karimiani, Vincenzo Salpietro, Jenny C Taylor, Melody Redman, Alexander P A Stegmann, Andreas Laner, Ghada Abdel-Salam, Megan Li, Mario Bengala, Amelie Johanna Müller, Maria C Digilio, Anita Rauch, Murat Gunel, Hannah Titheradge, Daniela N Schweitzer, Alison Kraus, Irene Valenzuela, Scott D Mclean, Chanika Phornphutkul, Mustafa Salih, Amber Begtrup, Rhonda E Schnur, Erin Torti, Tobias B Haack, Carlos E Prada, Fowzan S Alkuraya, Henry Houlden, Reza Maroofian

Faculty, Staff and Students Publications

PURPOSE: Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with a syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual developmental disability, and seizures. To our knowledge, no comprehensive study describes the detailed clinical characteristics of this syndrome. Thus, we aim to delineate the phenotypic spectrum of PRMT7-related disorder.

METHODS: We assembled a cohort of 51 affected individuals from 39 different families, gathering clinical information from 36 newly described affected individuals and reviewing data of 15 …

Cardiovascular Hemodynamics In Mice With Tumor Necrosis Factor Receptor-Associated Factor 2 Mediated Cytoprotection In The Heart, Andrea G Marshall, Kit Neikirk, Zer Vue, Heather K Beasley, Edgar Garza-Lopez, Larry Vang, Taylor Barongan, Zoe Evans, Amber Crabtree, Elsie Spencer, Josephs Anudokem, Remi Parker, Jamaine Davis, Dominique Stephens, Steven Damo, Thuy T Pham, Jose A Gomez, Vernat Exil, Dao-Fu Dai, Sandra A Murray, Mark L Entman, George E Taffet, Antentor O Hinton, Anilkumar K Reddy

Faculty, Staff and Students Publications

INTRODUCTION: Many studies in mice have demonstrated that cardiac-specific innate immune signaling pathways can be reprogrammed to modulate inflammation in response to myocardial injury and improve outcomes. While the echocardiography standard parameters of left ventricular (LV) ejection fraction, fractional shortening, end-diastolic diameter, and others are used to assess cardiac function, their dependency on loading conditions somewhat limits their utility in completely reflecting the contractile function and global cardiovascular efficiency of the heart. A true measure of global cardiovascular efficiency should include the interaction between the ventricle and the aorta (ventricular-vascular coupling, VVC) as well as measures of aortic impedance and …

Cc16 Drives Vla-2-Dependent Splunc1 Expression, Natalie Iannuzo, Holly Welfley, Nicholas C Li, Michael D L Johnson, Joselyn Rojas-Quintero, Francesca Polverino, Stefano Guerra, Xingnan Li, Darren A Cusanovich, Paul R Langlais, Julie G Ledford

Faculty, Staff and Students Publications

RATIONALE: CC16 (Club Cell Secretory Protein) is a protein produced by club cells and other non-ciliated epithelial cells within the lungs. CC16 has been shown to protect against the development of obstructive lung diseases and attenuate pulmonary pathogen burden. Despite recent advances in understanding CC16 effects in circulation, the biological mechanisms of CC16 in pulmonary epithelial responses have not been elucidated.

OBJECTIVES: We sought to determine if CC16 deficiency impairs epithelial-driven host responses and identify novel receptors expressed within the pulmonary epithelium through which CC16 imparts activity.

METHODS: We utilized mass spectrometry and quantitative proteomics to investigate how CC16 deficiency …

Pemberian Antibiotik Dini Berpengaruh Terhadap Mortalitas Covid-19?, Muchlis Achsan Udji Sofro

Jurnal Penyakit Dalam Indonesia

Coronavirus disease 2019 (COVID-19) merupakan infeksi saluran napas yang diakibatkan oleh severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data di seluruh dunia sampai akhir Juni 2022 menunjukkan bahwa COVID-19 telah menyebabkan 6,2 juta kematian dengan jumlah 530 juta kasus.

Cutaneous Adverse Drug Reaction Among Hiv-Infected Patients Starting Antituberculosis Treatment, Alvina Widhani, Teguh Harjono Karjadi, Evy Yunihastuti, Desi Salwani, Angga Pramudita, Saut Horas Nababan, Mirna Nurasri Praptini, Prionggo Mondrowinduro

Jurnal Penyakit Dalam Indonesia

Introduction. Treatment of tuberculosis (TB) in HIV patients is complicated due to numerous comorbidities and possible adverse effects. One of which is cutaneous adverse drug reaction (CADR). This adverse event is often difficult to manage because of multiple medications the patients get. The objective of this study was to know the prevalence and risk factors of CADR among HIV-infected patients starting anti-TB treatment. Methods. This retrospective study reviewed data from medical records of new patients at Working Group on AIDS outpatient clinic at Cipto Mangunkusumo Hospital, Indonesia in January 2008-December 2010 that had started anti-TB treatment. Risk factors of CADR …

Determinant Factors Of Cognitive Frailty In Elderly Patients, Valencia Santoso, Rensa Rensa

Jurnal Penyakit Dalam Indonesia

Introduction. Physical frailty and cognitive impairment have a strong relationship and there are differences in factors associated with cognitive frailty. This research aimed to determine the prevalence of cognitive frailty and identify factors associated with cognitive frailty in the elderly population in hospital polyclinic. Methods. A cross-sectional study with secondary data on patients aged ≥60 years in the Internal Medicine Polyclinic of Atma Jaya Hospital, Jakarta, from May 2020 to May 2021. The independent variables of this study were age, cardiovascular disease, type 2 diabetes mellitus, dyslipidemia, risk of malnutrition, risk of depression, and functional status. The alternative criteria by …

Effectiveness Of Garlic Extract (Allium Sativum) To Reduce Level Of Malondialdehyde Serum And Improve Quality Of Life In Patients With Chronic Hemodialysis: A Randomized Double-Blind Placebo-Controlled Trial, Amelia Istiqomah, Zulkhair Ali, Irsan Saleh

Jurnal Penyakit Dalam Indonesia

Introduction. Study reported that malondialdehyde (MDA) levels as an in vivo marker of oxidative stress were increased in patients undergoing hemodialysis. Antioxidants allicin compounds contained in garlic (Allium sativum) are known to have antioxidant activity by inducing antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and inhibiting prooxidant enzymes (nitric oxide synthase, xanthine, NADPH oxidase, and cyclooxygenase). This study aimed to investigate the effectiveness of Allium sativum to reduce level of MDA serum and improve quality of life in patients with chronic hemodialysis. Methods. This study was a crossover randomized double-blind placebo-controlled trial. The subjects were 40 chronic kidney …

Effect Of Advance Care Planning On Heart Failure Patients: An Evidence Based Case Report, Hamzah Shatri, Nandika Nurfitria, Dika Sinulingga, Vinandia Irvianita, Edward Faisal, Rudi Putranto, Diah Martina

Jurnal Penyakit Dalam Indonesia

Despite the advances in medical therapy, heart failure remains a disease that requires attention due to the course of the illness; it can lead to unpredictable, progressive, and fatal conditions. Existing therapy aims to improve the condition and prevent disease progression, with a balanced secondary therapy for various conditions that can trigger acute decompensated heart failure. Advances in technology and therapy may increase the prevalence of patients with heart failure, including prolonging the refractory phase of the disease. There are recommendations for advance care planning to support patient therapy and improve the quality of life of patients with heart failure. …

Kecubung Intoxication: A Case Report On A 16-Year-Old Male At Kuningan District, Monica Djaja Saputera, Jessica Djaja Saputera

Jurnal Penyakit Dalam Indonesia

Kecubung (angel’s trumpet) is a plant with hallucinogen effect which contain a tropane alkaloid, which are widely grown in Indonesia and is widely abused by several groups of adolescents aged 18 years in East Nusa Tenggara. Kecubung intoxication is a common case in Indonesia, but rarely reported and hard to make a definitive diagnosis due to lack of the toxicology screening assessment. Besides, an antidote of this case also not available in this country. We present a case of 16-years old male who visited the emergency room with fluctuating level of consciousness accompanied by anxiety, anger, and a visual hallucination. …

Value Of Heart Rate Variability, Neutrophil-Lymphocyte Ratio And Quality Of Life Of Patients With Depressive Symptoms In Acute Myocardial Infarction, Hamzah Shatri, Mizanul Adli, Muhadi Muhadi, Murdani Abdullah, Cosphiadi Irawan, Rudi Putranto, Sukamto Koesnoe, Ika Prasetya Wijaya

Jurnal Penyakit Dalam Indonesia

Introduction. Major depression criteria can be found in more than 20% of coronary heart patients and more than 30% acute coronary syndrome patients have significant depressive symptoms. Several studies have shown that reduction of hearth rate variability (HRV) and enhancement of neutrophil lymphocyte ratio (NLR) can cause enhancement of morbidity and mortality in myocardial infarction patients. On the other hand, depression can cause reduction of HRV, enhancement of NLR and reduction of quality of life. This study aimed to determine differences in HRV, NLR and quality of life between acute myocardial infarction (AMI) patients with depressive symptoms and AMI patients …

Association Between Early Antibiotic Administration And In-Hospital Mortality In Moderate And Severe Covid-19 Patients, Lie Khie Chen, Jason Nathanael, Sharifah Shakinah, Adeline Pasaribu, Robert Sinto, Leonard Nainggolan, Adityo Susilo

Jurnal Penyakit Dalam Indonesia

Introduction. Patients with moderate and severe COVID-19 generally receive antibiotic therapy with consideration of the possibility of co-infection or secondary bacterial infection which clinically is difficult to distinguish from COVID-19 symptoms. Overuse of antibiotics can lead to an increased risk of bacterial resistance to antibiotics which is associated with poor outcomes in COVID-19 patients. This study aimed to assess the effect of early antibiotic administration on mortality in moderate and severe COVID-19 patients. Methods. An observational study with a retrospective cohort design was conducted at Dr. Cipto Mangunkusumo Hospital. Data were obtained from medical records of patients admitted from March …

Second-Line Therapy Tyrosine Kinase Inhibitor For Chronic Phase Chronic Myeloid Leukemia Resistant To Imatinib, Chici Pratiwi, Wulyo Rajabto

Jurnal Penyakit Dalam Indonesia

Since the era of tyrosine kinase inhibitor (TKI) therapy, there has been an increase in the median survival of chronic myeloid leukemia. Nevertheless, nowadays there were several cases of chronic myeloid leukemia that are resistant to the first-line TKIs, so that several second-line TKIs were introduced. Assessment of the therapeutic response was performed using a complete peripheral blood examination, bone marrow aspiration cytogenetic examination, and quantitative BCR-ABL examination. The treatment failure criteria were applied based on the ELN criteria. In selecting the second line TKI should be based on the results of mutation analysis and consider the safety profile of …

Evaluation Of The Efficacy Of The Anti-Ulcer Oral Mucosal Protective Agent Radoralex® In The Prevention And Treatment Of Radiation-Induced Oral Mucosal Reactions Induced During Treatment Of Nasopharyngeal Carcinoma, Jun Yin, Jirui Xie, Jiawei Lin, Chengyin Weng, Shun Lu, Peng Xu, Shuo Zhang, Cheng Luo, Yecai Huang, Lu Li, Jinyi Lang, Mei Feng

Faculty, Staff and Student Publications

The aim of this study was to evaluate the efficacy and safety of antiulcer oral mucosal protectant-RADoralex® in the prevention and treatment of radiation-induced oral mucosal reactions elicited during intensity-modulated radiation therapy (IMRT). for locally advanced nasopharyngeal carcinoma (NPC). A total of 90 patients with locally advanced NPC who developed post-treatment grade 1 oral mucositis were selected for this study. They were randomly assigned to the experimental group (n = 44) treated by mouth rinsing with the RADoralex® during radiochemotherapy and the control group (n = 43) treated by mouth rinsing with sodium bicarbonate solution, and the patients’ oral mucosal …