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Turkish Journal of Medical Sciences

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Individualized Respiratory Exercise Device Originated In Türkiye: Design, Prototype, And First Results, Çi̇ğdem Emi̇rza Ci̇lbi̇r, Özge Ertan Harputlu, Hi̇kmet Uçgun, Büşra Ülker Ekşi̇, Sarper Kaya, Esen Kiyan, Gökşen Kuran Aslan, Buket Akinci

Turkish Journal of Medical Sciences

Background/aim: Respiratory muscle training (RMT) and breathing exercises are crucial components in cardiopulmonary rehabilitation. RMT includes inspiratory muscle training (IMT) and expiratory muscle training (EMT); however, existing RMT devices typically support only one of these. Incentive spirometers, which also provide visual feedback for breathing exercises, are frequently used. Achieving an RMT program requires multiple devices, which increases both the cost and complexity of the training regimen. This study aimed to design, calibrate, and test a novel individualized respiratory exercise device that integrates both IMT and EMT functions into a single unit, thereby offering a cost-effective, user-friendly alternative for comprehensive cardiopulmonary …

Radial Peripapillary Capillary Changes And Retinal Nerve Fiber Layer Alterations In Diabetic Foot Ulcers With Mild-To-Moderate Nonproliferative Diabetic Retinopathy: An Octa Study, Eyüpcan Şensoy, Hi̇kmet Erhan Güven, Mehmet Çitirik

Turkish Journal of Medical Sciences

Background/aim: This study aimed to evaluate the impact of diabetic foot ulcers (DFUs) on retinal microvascular changes, specifically the radial peripapillary capillary (RPC) vessel density and retinal nerve fiber layer (RNFL) thickness in patients with mild-to-moderate nonproliferative diabetic retinopathy (NPDR).

Materials and methods: Ninety participants were enrolled and divided into three groups: 30 patients with DFUs and mild-to-moderate NPDR, 30 patients with NPDR but without DFUs, and 30 healthy controls. RPC density and RNFL thickness were evaluated using optical coherence tomography angiography (OCTA), a noninvasive imaging method. Comparisons between groups were made with statistical adjustments, including optic disc area.

Results: …

Evaluation Of Colonization With Multidrug-Resistant Microorganisms And The Incidence Of Attributable Infections In Patients Undergoing Hematopoietic Stem Cell Transplantation, Burcu Çalişkan Demi̇rkiran, Gülşen İskender, İpek Mumcuoğlu, Duygu Mert, Si̇nan Dal, Tuba Dal, Semra Tunçbi̇lek, Mustafa Ertek, Fevzi̇ Altuntaş

Turkish Journal of Medical Sciences

Background/aim: The global rise in multidrug-resistant organisms (MDROs) has led to an increased incidence of MDRO infections following hematopoietic stem cell transplantation (HSCT), particularly during the preengraftment period. The objective of this study was to evaluate the relationship between pretransplant colonization by MDROs or carbapenem-resistant Enterobacterales (CRE) and the occurrence of infections caused by phenotypically similar microorganisms during the preengraftment period, as well as to assess the clinical outcomes of patients colonized with MDROs prior to transplantation.

Materials and methods: This prospective cohort study included patients diagnosed with hematological malignancies who underwent HSCT at the bone marrow transplant unit of …

The Impact Of Fall History On Instability, Disability, And Anxiety In Patients With Chronic Neck Pain, Bülent Bozyi̇ği̇t, Emre Söylemez, Aydin Si̇nan Apaydin

Turkish Journal of Medical Sciences

Background/aim: This study aimed to investigate the impact of fall history on postural stability, disability, and anxiety in individuals with chronic neck pain (CNP). It was hypothesized that patients with a history of falls would exhibit greater postural instability, perceived disability, and anxiety levels compared with those without a fall history and healthy controls.

Materials and methods: A total of 62 participants were included: 16 CNP patients with a history of falling (Group Ia), 21 CNP patients without falls (Group Ib), and 25 healthy controls. Assessments included the Neck Disability Index (NDI), Beck Anxiety Inventory (BAI), and Visual Analog Scale …

Levothyroxine Poisoning In Children: A Multicenter Study From Türkiye, Kübra Şen Küçük, Şule Demi̇r, Reyhan Deveci̇ Sevi̇m, Fatma Akgül, Gülşen Yalçin, Öznur Eser, Alkan Bal, Eli̇f Ergi̇n, Sercan Öztürk, Ahmet Anik

Turkish Journal of Medical Sciences

Background/aim: This study aimed to investigate the clinical features, laboratory findings, treatment approaches, and follow-up strategies employed in the management of pediatric patients with levothyroxine poisoning.

Materials and methods: This multicenter retrospective study included patients aged ≤18 years who presented with acute, single-episode levothyroxine ingestion to the pediatric emergency departments of six tertiary care centers between 2010 and 2023. Clinical data, laboratory findings, symptom onset and severity, and treatment modalities were extracted from medical records. Thyroid function tests (TFTs) were interpreted according to the age-specific reference ranges of each center. Treatment decisions, including gastric decontamination and pharmacologic therapy, were evaluated …

Effects Of Transversus Abdominis And Erector Spinae Plane Blocks On Postoperative Pain Control And Postpartum Depression After Cesarean Section: A Randomized Prospective Study, Hi̇lal Bi̇radli, Feyza Çalişir, Alev Özer

Turkish Journal of Medical Sciences

Background/aim: Effective postoperative pain management after cesarean section is essential for maternal recovery. Poor pain control can lead to complications, including postpartum depression. This study aimed to compare the postoperative analgesic efficacy of erector spinae plane (ESP) and transversus abdominis plane (TAP) blocks following cesarean section, with a particular focus on their potential impact on postpartum depression.

Materials and methods: Sixty patients were randomly assigned to receive either an ESP block (Group E, n = 30) or a TAP block (Group T, n = 30) after cesarean section. Pain severity was assessed using a visual analog scale (VAS), and the …

Examination Of Sexual Health Literacy And Cyberchondria Levels In Women With Vaginismus, Gonca Türker Ergün, Cemal Ünlü, Ayşe Kuyulu Akman, Elçi̇n İşlek Seçen, Razi̇ye Toksöz

Turkish Journal of Medical Sciences

Background/aim: This study aimed to compare sexual health literacy and cyberchondria levels between women who had been diagnosed with vaginismus and those who had not.

Materials and methods: The research was conducted as a prospective cohort study including 60 women over the age of 18 who were married and unable to engage in sexual intercourse due to primary vaginismus and 60 sexually active married women without vaginismus. Data collection tools included a patient information form, the Cyberchondria Severity Scale (CSS-12-TR), and the Sexual Health Literacy Scale (SHLS).

Results: The median age of the women diagnosed with vaginismus was 27 (21–54) …

Cd20 Molecule Deficiency And Carrier Frequency: A Village-Based Screening Study, Ebru Sümen, Mehmet Ali̇ Karaselek, Serkan Küççüktürk, Tuğçe Duran, Büşra Yüksel, Mustafa Gençeli̇, Ayşe Sümeyra Engi̇n, Muhammed Furkan Erden, Tuğba Esra Pekcandanoğlu, Bi̇lal Bostan, Mahmut Esad Yurtseven, Nazi̇re Nur Onat, Şükrü Nai̇l Güner, Sevgi̇ Keleş, İsmai̇l Rei̇sli̇

Turkish Journal of Medical Sciences

Background/aim: CD20 deficiency is an autosomal recessive inborn error of immunity (IEI), and the only known affected individual worldwide has been under follow-up in our clinic. Because the consanguineous parents of the index patient are putative carriers, we hypothesized that additional individuals with reduced CD20 expression might exist within their village population. This study aimed to evaluate clinical features associated with IEI and to identify individuals displaying CD20 mean fluorescence intensity (MFI) patterns consistent with putative carrier status, while also providing appropriate genetic counseling.

Materials and methods: This cross-sectional screening study was conducted in December 2024 in Çukurbağ village. Participants …

Association Between Frailty Status And Pain, Balance, And Quality Of Life In Patients With Lumbar Spinal Stenosis, Musa Güneş, Aydin Si̇nan Apaydin

Turkish Journal of Medical Sciences

Background/aim: Frailty is a clinical syndrome that affects individuals physically and psychosocially. However, the association between lumbar spinal stenosis (LSS) and frailty remains unclear. This study aimed to compare pain, balance, disability, fear of falling, and quality of life between patients with LSS with and without frailty.

Materials and methods: This cross-sectional study included 43 frail and 48 nonfrail patients with LSS according to the frailty criteria of Fried et al. Pain intensity (numeric rating scale [NRS]), static balance (single leg stance test [SLST]), dynamic balance (Timed Up and Go test [TUG]), disability (Oswestry Disability Index [ODI]), fear of falling …

The Impact Of Covid-19 On Healthcare Workers: Risk Factors, Sources Of Infection, And Sickness Absenteeism, Ezgi̇ Gülten, Güle Çinar, İrem Akdemi̇r, Eli̇f Muki̇me Saricaoğlu, İlkay Taşdan, Emi̇ne Atmaca, Si̇bel Kaymakçi, Fatma Şanal, Di̇lek Sevi̇m Akdaş, Arzu Büyüm, Gülşah Kocaali̇, Safi̇ye Tarakçi, Ati̇lla Hali̇l Elhan, Mehmet Serhat Bi̇rengel, Kemal Osman Memi̇koğlu, Alpay Azap

Turkish Journal of Medical Sciences

Background/aim: Healthcare workers (HCWs) face increased risks of COVID-19 infection due to occupational exposure. Understanding infection sources, risk factors, and workforce losses is crucial for mitigating these impacts in future pandemics. This study aimed to evaluate the risk factors, infection sources, and sickness absenteeism among HCWs diagnosed with SARS-CoV-2 infection, providing insights to enhance infection control strategies.

Materials and methods: The study included 2153 HCWs diagnosed with SARS-CoV-2 between March 2020 and February 2023 at a tertiary care hospital in Türkiye. Demographic, clinical, and professional characteristics, personal protective equipment (PPE) usage, infection sources, and vaccination data were analyzed. Statistical analyses …

Involvement Of Swap-70 In Proteolipid Protein-Induced Experimental Autoimmune Encephalomyelitis, Canan Ulusoy, Gi̇zem Koral, Fatma Akpunar Salman, Meli̇s Şen, Emi̇ne Şekerdağ Kiliç, Recai̇ Türkoğlu, Cem İsmai̇l Küçükali̇, Yasemi̇n Gürsoy Özdemi̇r, Vuslat Yilmaz, Erdem Tüzün

Turkish Journal of Medical Sciences

Background/aim: Multiple sclerosis (MS) is a chronic demyelinating inflammatory disease of the central nervous system. Studies have shown that B cells may play an important role in the induction and progression of MS. Switch-associated protein 70 (SWAP-70) is a signal transduction molecule abundantly expressed in B cells and involved in B-cell polarization, directed migration, endothelial cell adhesion, and tissue homing. B-cell stimuli increase its expression. SWAP-70 has been implicated in the pathogenesis of autoimmune disorders, including MS. This study aims to investigate the effects of acquired SWAP-70 inhibition on immune cell subsets in experimental autoimmune encephalomyelitis (EAE).

Materials and methods: …

Oleanolic Acid–Chitosan Compound Inhibits Mitochondrial Autophagy And Malignant Transformation Of Lung Cancer Through The Pten/Akt Pathway, Abuli̇mi̇ti̇ Abulai̇ti̇, Xi̇aohong Sun, Waresijiang Yibulayin, Dan He, Kemi̇ng Xu, Xi̇ayi̇mai̇erdan Yi̇bulayi̇n

Turkish Journal of Medical Sciences

Background/aim: Oleanolic acid–chitosan compound (OAC) shows potent antinonsmall cell lung cancer (NSCLC) activity, but its mechanisms remain unclear. This study elucidates how OAC modulates autophagy and apoptosis via the Phosphatase and Tensin Homolog/Protein Kinase B (PTEN/AKT) signaling pathway.

Materials and methods: Oleanolic acid was coupled with chitosan to synthesize OAC. A549 and MRC-5 cells were cultured in Dulbecco’s Modified Eagle Medium and Minimum Essential Medium, respectively, supplemented with 10% fetal bovine serum and penicillin–streptomycin. Cells were pretreated with chloroquine before OAC treatment. Cell viability was assessed using the CCK- 8 assay, while 5-bromo-2′-deoxyuridine (BrdU) and colony formation tests were employed …

The Prevalence And Impact Of Workplace Violence In Community Pharmacies: A Mixed-Methods Study, Hi̇lal İlbars, Berna Terzi̇oğlu Bebi̇toğlu, Seyhan Hidiroğlu, Fatma Burcu Doğanç, Yağiz Varol

Turkish Journal of Medical Sciences

Background/aim: Pharmacists and pharmacy technicians employed in community pharmacies face a considerable risk of workplace violence, which can negatively influence their job satisfaction, productivity, and mental well-being. This study examined the prevalence and consequences of workplace violence in community pharmacies in Ankara through a mixed-methods design integrating cross-sectional survey data with qualitative insights.

Materials and methods: The target population included pharmacists and pharmacy technicians. We examined demographic factors, psychological outcomes, and the nature of violent incidents. Data were obtained from a random sample of 355 community pharmacies using a 39-item survey and the depression anxiety stress scales (DASS-21), complemented by …

Preventing Spinal Muscular Atrophy Through The National Premarital Screening Program In Türkiye: An Economic Comparison With Treatment Costs, Gamze Dur, Gülcan Teci̇rli̇, Nurullah Okumuş

Turkish Journal of Medical Sciences

Background/aim: Spinal muscular atrophy (SMA) is a severe neuromuscular disorder with high treatment costs and significant psychosocial burden. In 2021, Türkiye launched a national premarital SMA carrier screening program integrated with in vitro fertilization (IVF) with preimplantation genetic testing (PGT) services for couples identified as carriers. This study aimed to compare the costs associated with the carrier screening and prevention program versus a no-screening (treatment-only) scenario.

Materials and methods: A cost comparison model was developed using data from the Turkish Statistical Institute, the Ministry of Health, and the Social Security Institution. The annual costs of SMA treatment (with nusinersen and …

Contribution Of Adenosine A2a Receptor Agonist And Antagonist On Ovarian Ischemia/Reperfusion Injury In Rats, Azad Mammadov, Abdullah Tuncay Demi̇ryürek, Ahmet Saracaloğlu, Cahi̇t Demi̇rkiran, İsmai̇l Tuncer Deği̇m, Ömer Eronat, Şeni̇z Demi̇ryürek

Turkish Journal of Medical Sciences

Background/aim: To determine the effects of an A2A receptor agonist regadenoson, an A2A receptor antagonist istradefylline, and istradefylline nanosuspension on ovarian ischemia/reperfusion (I/R) injury in rats.

Materials and methods: A total of 80 female rats were divided into 10 groups: sham, ovarian I/R, blank nanosuspension + ovarian I/R, regadenoson (3 μg/kg) + ovarian I/R, regadenoson (30 μg/kg) + ovarian I/R, istradefylline (0.3 mg/kg) + ovarian I/R, istradefylline (3 mg/kg) + ovarian I/R, istradefylline-loaded nanosuspension (3 mg/kg) + ovarian I/R, istradefylline (3 mg/kg) + regadenoson (30 μg/kg) + ovarian I/R, and istradefylline-loaded nanosuspension (3 mg/kg) + regadenoson (30 μg/kg) + ovarian …

Staff Education To Decrease Polypharmacy And Improve Medication Adherence In Older Adults In Primary Healthcare Settings, Nadine Pean Noel

Walden Dissertations and Doctoral Studies

This Doctor of Nursing Practice (DNP) project was a staff education initiative to address polypharmacy and increase medication adherence among older adults in a primary care setting. Polypharmacy is a prevalent and significant safety concern in older adults, increasing the risk for adverse drug events, medication nonadherence, hospitalizations, and decreased quality of life. The purpose of the project was to implement and evaluate a structured staff education focused on evidence-based strategies for medication review, deprescribing, and the integration of smartphone-based adherence tools. The practice-focused question guiding this project was as follows: Will an evidence-based staff education program focused on polypharmacy …

Genetic Analysis And Clinical Effect Of Ace2 Gene Variants (Rs2285666 And Rs4646188) On Coronary Syndrome In Dyslipidaemia Patients, Shaimaa Y. Abdulfattah, Sumaya Saady

Sultan Qaboos University Medical Journal

Objectives: This study aimed to investigate the association of two intronic polymorphisms of the ACE2 gene (rs2285666 and rs4646188) with coronary artery disease (CAD) in Iraqi patients with dyslipidaemia. Methods: This case-control study was conducted from March to September 2023 at the Iraqi Center of Heart Disease, Baghdad, Iraq, and included patients with CAD and dyslipidaemia. Genotyping was performed using TaqMan probes and real-time qPCR. Results: A total of 170 participants were included in this study. Demographic, echocardiographic, and lipid profile data were analysed, revealing significant differences in age, left ventricular ejection fraction %, LV systolic diameter, LV diastolic diameter …

The Enduring Legacy Of Nuclear Tests: Barriers To Managing Type 2 Diabetes Among Marshallese Pacific Islanders In The United States, Bernard A. Muriithi

Occupational Therapy Faculty Scholarship

Introduction / Rationale: Nuclear tests conducted by the United States caused significant damage to the environment and traditional food sources in the Marshall Islands. The Marshall Islanders began to depend on imported processed food, but the change of diet resulted in significant increases in chronic diseases, in addition to cancers and birth defects associated with nuclear radiation. Since the 1986 Compact of Free Association, over 15,000 Marshallese have relocated to the United States, and the majority live in one U.S. state. This community of Marshallese has the highest prevalence rate for type 2 diabetes in the world.

Objectives: identify the …

A Rare And Challenging Polymicrobial Pleural Infection Involving Cupriavidus Pauculus In A Patient With Rheumatoid Arthritis And Multiple Complications, Moiz Ahmed Khan, Syeda Samiya Kamal, Muhammad Muneeb, Summaya Zafar

The University of Louisville Journal of Respiratory Infections

A 58-year-old female with a 15-year history of rheumatoid arthritis (RA) and a history of treatment consisting of methotrexate, hydroxychloroquine, leflunomide, and chronic prednisolone therapy, presented with fever, productive cough, dyspnea, and left leg cellulitis. She developed septic shock complicated by tension pneumothorax requiring emergency thoracostomy and non-ST-elevation myocardial infarction (NSTEMI). Pleural fluid culture grew Cupriavidus pauculus, a rare environmental gram-negative bacillus, alongside Burkholderia cepacia and Candida parapsilosis, indicating polymicrobial infection which was most likely predisposed by patient's immunosuppressed state from RA and prolonged steroid use. Treatment consisted of trimethoprim/sulfamethoxazole, meropenem, fluconazole, and cardiopulmonary support, and culminated in …

Staff Education To Nurses To Lmprove Routine Foot Examinations For Diabetic Patients, Sarah Abrefi

Walden Dissertations and Doctoral Studies

Diabetes-related foot complications remain a significant cause of morbidity, hospitalization, and lower-extremity amputation, despite strong evidence supporting routine preventive assessments. In many outpatient settings, variability in nursing knowledge, skill, and documentation practices contributes to inconsistent implementation of comprehensive diabetic foot examinations. The purpose of this practice-focused quality improvement project was to evaluate the effectiveness of a structured staff education program designed to improve nurses’ knowledge and competency in performing comprehensive diabetic foot assessments in an outpatient diabetes clinic.A pretest–posttest evaluative design was used to measure changes in knowledge following the educational intervention. Ten registered nurses participated in a structured educational …

Sting Activation Induces Cytotoxic And Immune Responses In Meningiomas Via Inflammatory Cell Death Pathways, Mark W Youngblood, Alexander H Stegh, Et Al.

2020-Current year OA Pubs

Meningiomas are common tumors of the central nervous system that are typically treated with surgery or radiation, but lack established systemic therapies. Activation of the stimulator of interferon genes pathway with an agonist such as 8803 can trigger anti-tumor immune responses. Using integrated molecular approaches, here we show that this pathway is targetable in both neoplastic and immune populations within the meningioma microenvironment. Meningioma tumor cells exhibit promoter hypomethylation and increased chromatin accessibility of the STING genomic locus, associated with robust expression of this gene. Treatment of diverse patient meningiomas ex vivo with 8803 induces direct tumor cytotoxicity through inflammatory …

Prevalence And Factors Associated With Delayed Surgery Among Children With Wilms Tumor At Mulago Hospital: A Mixed-Method Study, Lule Daniel, Shamim Nabidda, Abraham Muhwezi, Ronald Naitala, Anne Akullo, Enid Kawala Kagoya, Ruth Namazzi, Nasser Kakembo, Joan N. Kalyango

School of Nursing & Midwifery, East Africa

Introduction:  Wilms tumor (WT) is a highly treatable form of childhood cancer, with five-year survival rates greater than 90% in high-income countries. In low- and middle-income countries, survival is still low. Delayed surgery is one of the leading factors for poor survival, as it leads to tumor complications, making subsequent treatment more complex. However, there is a paucity of information in Uganda on the prevalence and factors associated with delayed surgery. This study aimed to determine the prevalence and factors associated with delayed surgery, and to explore the barriers and facilitators of timely surgery among children with WT at …

Clinical Outcome Of Extremity Arterial Injuries In The Modern Era, Ali̇ Kuşsan, Selçuk Coşkun, Alp Şener, Ferhat İçme, Pinar Köksal Coşkun, Gülhan Kurtoğlu Çeli̇k

Turkish Journal of Medical Sciences

Background/aim: Extremity arterial injuries (EAIs) present a significant clinical challenge due to the risk of limb ischemia, amputation, and mortality. This retrospective cohort study aimed to delineate the clinical course, treatment strategies, and patient outcomes following trauma-induced EAIs, and to identify independent predictors of adverse outcomes.

Materials and methods: Retrospectively analyzed were data from 168 consecutive patients with traumatic EAIs who underwent computed tomography angiography at a tertiary care center between 2019 and 2025. Data extracted from electronic medical records included demographics, injury mechanisms, clinical presentation, laboratory findings, imaging results, treatment modalities (primary repair, grafting, endovascular intervention, conservative management), and …

The Perk Signaling Pathway As A Marker Of The Unfolded Protein Response In Patients With Acute Myeloid Leukemia, Nergi̇z Erkut, Turhan Köksal, Seli̇m Demi̇r, Ahmet Menteşe, Özlen Balta, Mehmet Sönmez

Turkish Journal of Medical Sciences

Background/aim: The protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathway plays a critical role in preventing the accumulation of misfolded or unfolded proteins within the endoplasmic reticulum. In this study, the role of the PERK signaling pathway was evaluated in newly diagnosed, treatment-naïve patients with acute myeloid leukemia (AML).

Materials and methods: Plasma levels of eukaryotic translation initiation factor 2-alpha kinase 3 (eIF2AK3), glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), CCAAT/enhancer-binding protein homologous protein (CHOP), hypoxia-inducible factor-1 alpha (HIF-1α), and caspase 3 were measured by enzyme-linked immunosorbent assay in peripheral blood samples obtained from AML patients and healthy …

Rmzyme: Regulations Of Rna-Modifying Enzymes In Humans, Ruihan Luo, Haixia Xu, Qingbo Zhou, Shanli Ding, Min Qiang, Jianguo Wen, Pora Kim, Xiaojuan Yang, Yunshi Cai, Kunlin Xie, Jiang Zhu, Yungang Xu, Tian Lan, Xiaobo Zhou, Hong Wu

Faculty, Staff and Student Publications

RNA modifications represent a dynamic layer of gene expression regulation, RNA stability, and translation with profound implications for cellular function and disease. However, the critical regulation and functions of RNA-modifying proteins (RMPs) remain poorly understood. Here, we present a large-scale characterization of RMPs through 378 multiomics datasets encompassing genomics, bulk and single-cell transcriptomics, epitranscriptomics, proteomics, and posttranslational modifications (PTMs) across 63 human tissues. Our analysis of experimental perturbations of RMPs revealed dynamic differential modification peaks and expressed genes. We applied nonnegative matrix factorization to annotate RMP-mediated cell types in single-cell transcriptomes. Functional annotations in acute myeloid leukemia (AML) revealed RMPs …

Targeting Oxalate Production By Combining Enzyme Inhibition And Proteolysis Activation: A Novel Therapeutic Approach For Primary Hyperoxaluria Type 1, Fabio Arias, Sumati Rohilla, Yudibeth Sixto-López, Koral S E Richard, Sandeep Das, Sumit K Anand, Pilar Maria Luque-Navarro, Guillermo Bañuelos-Sanchez, Juan Luis Pacheco-García, Reethika Gade, M Peyton Mckinney, Dhananjay Kumar, Jemiah Maxie, W Rylan Corr, Nilesh Pandey, Harpreet Kaur, Jibin Ding, Lin Tan, Elisha Scott, Hyung Nam, Eyal Gottlieb, A Wayne Orr, Nirav Dhanesha, Arif Yurdagul, Angel L Pey, Francisco Franco-Montalbán, José A Gómez Vidal, Oren Rom, Mónica Díaz-Gavilán

Faculty, Staff and Student Publications

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder caused by hepatic oxalate overproduction due to alanine-glyoxylate aminotransferase (AGXT) deficiency. Therapeutic strategies targeting glycolate oxidase (GO) and lactate dehydrogenase A (LDHA), key enzymes in glyoxylate metabolism, have shown promise in reducing oxalate burden. However, recently approved siRNA therapies remain limited by high cost, unfavorable pharmacokinetics, and limited global accessibility. We report the development of compound 2, a dual GO/LDHA inhibitor (K i = 390 and 40 nM, respectively) that also promotes hydrophobic tag-mediated autophagic degradation of LDHA. Its efficacy was evaluated in Agxt –/– mice, both in primary …

Serial False Lumen Patency Evaluation Of A Type B Dissection Represented With Malperfusion Following Medical Management, S Taha Zaidi, Quang Le, Firas Mussa, Akiko Tanaka, S Keisin Wang, Arash Keyhani, Kourosh Keyhani

Faculty, Staff and Student Publications

False lumen evolution in type B aortic dissection, particularly with medical management and anticoagulation, remains incompletely understood. We report a 55-year-old man on apixaban for pulmonary embolism with a subacute zone 3-10L TBAD without malperfusion. He was managed medically initially and represented twice over 2 months with back pain and acute right lower extremity ischemia. Serial imaging demonstrated dynamic remodeling with progression from partial to near-complete thrombosis to full reperfusion with true lumen compression. Urgent endovascular repair was performed successfully. This case illustrates the unpredictable course of medically managed TBAD and need for judicious use of anticoagulation.

Primary Tumor Size And Tumor-Vessel Interface Following Capecitabine And Temozolomide For Pancreatic Neuroendocrine Tumor, Jin Guo, Kever A Lewis, Laura Prakash, Priya Bhosale, Ajaykumar Morani, Matthew H G Katz, Ching-Wei D Tzeng, Naruhiko Ikoma, Rebecca Snyder, Michael P Kim, Chandrikha Chandrasekharan, Arvind Dasari, James C Yao, Jeffrey E Lee, Jessica E Maxwell, Daniel M Halperin

Faculty, Staff and Student Publications

Capecitabine/temozolomide (CAPTEM) is an established regimen for patients with metastatic pancreatic neuroendocrine tumors (PanNET) that is being increasingly used for tumor volume reduction in patients with borderline anatomically resectable disease. We sought to understand the response of the primary tumor, defined as changes in the tumor–vascular interface (TVI). This is a retrospective, single-institution study of patients with locally advanced or metastatic PanNET treated with CAPTEM between 2010 and 2020. RECISTv1.1 measurements and TVI assessments of the primary tumor were performed on pre- and post-therapy images. Patients with locally advanced or metastatic PanNET at presentation (n = 47) were included. …

Tumor-Immune-Neural Circuit Disrupts Energy Homeostasis In Cancer Cachexia, Xiuhui Shi, Alex X Arreola, Zhijun Zhou, Jingxuan Yang, Mingyang Liu, Yang Cai, Yu Ren, Hao Yuan, Qun Chen, Xinjie Chen, Xinyu Yang, Yimei Meng, Jingyi Wang, Wenyi Luo, Michael C Rudolph, Rohan Varshney, Kar-Ming Fung, Chao Xu, Wei R Chen, Michael S Bronze, Lei Zheng, Yi-Ping Li, Courtney W Houchen, Yuqing Zhang, Min Li

Faculty, Staff and Student Publications

Cancer-induced cachexia and anorexia are debilitating complications across many cancers, yet effective treatments remain limited due to a poor understanding of the underlying mechanisms. Here, we identify an uncharacterized tumor-immune-neural circuit driving these syndromes, centered on growth and differentiation factor 15 (GDF15). Using genetically engineered mouse models, we find that loss of GDF15 protects against appetite loss, muscle wasting, and fat loss in pancreatic, lung, and skin cancers. Single-cell RNA sequencing reveals macrophages as a major source of GDF15, induced by tumor-derived colony-stimulating factor 1 (CSF1). GDF15 acts via the central nervous system to enhance β-adrenergic signaling in the tumor …