Diseases Commons^™

Immunotherapy In Hepatocellular Cancer Patients With Mild To Severe Liver Dysfunction: Adjunctive Role Of The Albi Grade, David J Pinato, Takahiro Kaneko, Anwaar Saeed, Tiziana Pressiani, Ahmed Kaseb, Yinghong Wang, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Chieh-Ju Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Hannah Hildebrand, Yehia I Abugabal, Celina Ang, Thomas U Marron, Uqba Khan, Nicola Personeni, Lorenza Rimassa, Yi-Hsiang Huang

Faculty, Staff and Students Publications

Immune checkpoint inhibitors (ICI) have shown positive results in patients with hepatocellular carcinoma (HCC). As liver function contributes to prognosis, its precise assessment is necessary for the safe prescribing and clinical development of ICI in HCC. We tested the accuracy of the albumin-bilirubin (ALBI) grade as an alternative prognostic biomarker to the Child-Turcotte-Pugh (CTP). In a prospectively maintained multi-centre dataset of HCC patients, we assessed safety and efficacy of ICI across varying levels of liver dysfunction described by CTP (A to C) and ALBI grade and evaluated uni- and multi-variable predictors of overall (OS) and post-immunotherapy survival (PIOS). We studied …

A Counterpoint Paper: Comments On The Electrocardiographic Part Of The 2018 Fourth Universal Definition Of Myocardial Infarction Endorsed By The International Society Of Electrocardiology And The International Society For Holter And Noninvasive Electrocardiology, Yochai Birnbaum, Miguel Fiol, Kjell Nikus, Javier Garcia Niebla, Ljuba Bacharova, Sergio Dubner, Wojciech Zareba, Peter W Macfarlane, Antonio Luiz Ribeiro, Iwona Cygankiewicz, Antoni Bayes De Luna

Faculty, Staff and Students Publications

The Fourth Universal Definition of Myocardial Infarction (FUDMI) focuses on the distinction between nonischemic myocardial injury and myocardial infarction (MI), along with the role of cardiovascular magnetic resonance, in order to define the etiology of myocardial injury. As a consequence, there is less emphasis on updating the parts of the definition concerning the electrocardiographic (ECG) changes related to MI. Evidence of myocardial ischemia is a prerequisite for the diagnosis of MI, and the ECG is the main available tool for (a) detecting acute ischemia, (b) triage, and (c) risk stratification upon presentation. This review focuses on multiple aspects of ECG …

Metformin Enhances Autophagy And Normalizes Mitochondrial Function To Alleviate Aging-Associated Inflammation, Leena P Bharath, Madhur Agrawal, Grace Mccambridge, Dequina A Nicholas, Hatice Hasturk, Jing Liu, Kai Jiang, Rui Liu, Zhenheng Guo, Jude Deeney, Caroline M Apovian, Jennifer Snyder-Cappione, Gregory S Hawk, Rebecca M Fleeman, Riley M F Pihl, Katherine Thompson, Anna C Belkina, Licong Cui, Elizabeth A Proctor, Philip A Kern, Barbara S Nikolajczyk

Faculty, Staff and Student Publications

Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 …

Cardiac Surgery During The Coronavirus Disease 2019 Pandemic: Perioperative Considerations And Triage Recommendations, Vivek Patel, Ernesto Jimenez, Lorraine Cornwell, Trung Tran, David Paniagua, Ali E Denktas, Andrew Chou, Samuel J Hankins, Biykem Bozkurt, Todd K Rosengart, Hani Jneid

Faculty, Staff and Students Publications

The coronavirus disease 2019 pandemic, caused by severe acute respiratory syndrome coronavirus-2, represents the third human affliction attributed to the highly pathogenic coronavirus in the current century. Because of its highly contagious nature and unprecedented global spread, its aggressive clinical presentation, and the lack of effective treatment, severe acute respiratory syndrome coronavirus-2 infection is causing the loss of thousands of lives and imparting unparalleled strain on healthcare systems around the world. In the current report, we discuss perioperative considerations for patients undergoing cardiac surgery and provide clinicians with recommendations to effectively triage and plan these procedures during the coronavirus disease …

Low Yield Of Hepatitis C Infection In An Outreach Screening Program In Harris County, Texas, Hyun-Seok Kim, Rosalia Guerrero, Shane W Reader, Maria Daheri, Maya Balakrishnan, Catherine L Troisi, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

A community outreach hepatitis C virus (HCV) infection screening program provided low yield of detecting HCV-infected patients, linking them to our hepatology clinic for treatment. Our data underscore that most of the yield was related to addiction centers and birth cohort; these groups should be targeted by future interventions.

Burden-Of-Illness Associated With Bleeding-Related Hospitalizations In Atrial Fibrillation Patients: Findings From The Nationwide Readmission Database, Benjamin Miao, Monique Miller, Belinda Lovelace, Anne Beaubrun, Kelly Mcneil-Posey, Mark J Alberts, William Frank Peacock, Olivia S Costa, Charles Michael White, Craig I Coleman

Faculty, Staff and Students Publications

Introduction  A paucity of contemporary data examining bleeding-related hospitalization outcomes in atrial fibrillation (AF) patients exists.

Methods  Adults in the Nationwide Readmissions Database (January 2016–November 2016) with AF and hospitalized for intracranial hemorrhage (ICH), gastrointestinal, genitourinary, or other bleeding were identified. Association between bleed types and outcomes were assessed using multivariable regression (gastrointestinal defined as referent) and reported as crude incidences and adjusted odds ratios (ORs) or mean differences with 95% confidence intervals (CIs).

Results  In total, 196,878 index bleeding-related hospitalizations were identified in this AF cohort (CHA2DS2VASc score ≥2 in 95.1%), with 70.8% classified as gastrointestinal. The overall incidences …

Impact Of Covid-19 On Pediatric Gastroenterology Fellow Training In North America, Daniel Mallon, John F Pohl, Uma P Phatak, Melissa Fernandes, John M Rosen, Sarah S Lusman, Cade M Nylund, Candi S Jump, Aliza B Solomon, Arvind Srinath, Andrew Singer, Rula Harb, Norberto Rodriguez-Baez, Kristin L Whitfield Van Buren, Shifra Koyfman, Riha Bhatt, Dellys M Soler-Rodriguez, Mamata Sivagnanam, Christine K Lee, Naspghan Training Committee Covid-19 Survey Working Group

Faculty, Staff and Students Publications

BACKGROUND: The COVID-19 pandemic has drastically changed healthcare systems and training around the world. The Training Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition sought to understand how COVID-19 has affected pediatric gastroenterology fellowship training.

METHODS: A 21 question survey was distributed to all 77 pediatric gastroenterology fellowship program directors (PDs) in the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition program director database via email on April 7. Responses collected through April 19, 2020 were analyzed using descriptive statistics.

RESULTS: Fifty-one of 77 (66%) PDs from the United States, Canada, and Mexico responded to …

Glycemic Control And Infections Among Us Hemodialysis Patients With Diabetes Mellitus, Jinnie J Rhee, Yuanchao Zheng, Sai Liu, Maria E Montez-Rath, Richard J Hamill, Julie H Ishida, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

INTRODUCTION: Patients with diabetes mellitus (DM) on hemodialysis (HD) may be particularly vulnerable to infections.

METHODS: We used merged data from the United States Renal Data System and electronic health records data from a large US dialysis provider to retrospectively examine the association between glycemic control and infections in these patients. Adult patients with DM aged ≥18 years who initiated in-center maintenance HD treatment from 2006 to 2011 and survived >90 days were included. Quarterly mean time-averaged hemoglobin A1c (HbA1c) values were categorized into

RESULTS: In a cohort of 33,753 eligible patients, those with higher HbA1c levels had higher rates …

Association Analysis Of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci With 20,871 Lung Cancer Cases And 15,971 Controls, Yuzhuo Wang, Olga Y Gorlova, Ivan P Gorlov, Meng Zhu, Juncheng Dai, Demetrius Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Gary E Goodman, Stig E Bojesen, Maria Teresa Landi, Mattias Johansson, Angela Risch, Heunz-Erich Wichmann, Heike Bickeboller, David C Christiani, Gad Rennert, Susanne M Arnold, Paul Brennan, John K Field, Sanjay Shete, Loïc Le Marchand, Olle Melander, Hans Brunnstrom, Geoffrey Liu, Rayjean J Hung, Angeline S Andrew, Lambertus A Kiemeney, Shanbeh Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil E Caporaso, Penella J Woll, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Victoria L Stevens, Hongxia Ma, Guangfu Jin, Zhibin Hu, Christopher I Amos, Hongbing Shen

Faculty, Staff and Students Publications

BACKGROUND: A substantial proportion of cancer driver genes (CDG) are also cancer predisposition genes. However, the associations between genetic variants in lung CDGs and the susceptibility to lung cancer have rarely been investigated.

METHODS: We selected expression-related single-nucleotide polymorphisms (eSNP) and nonsynonymous variants of lung CDGs, and tested their associations with lung cancer risk in two large-scale genome-wide association studies (20,871 cases and 15,971 controls of European descent). Conditional and joint association analysis was performed to identify independent risk variants. The associations of independent risk variants with somatic alterations in lung CDGs or recurrently altered pathways were investigated using data …

Combined Lenvatinib And Pembrolizumab As Salvage Therapy In Advanced Adrenal Cortical Carcinoma, Sara Bedrose, Kevin Charles Miller, Lina Altameemi, Mohamed S Ali, Sameh Nassar, Naveen Garg, Marilyne Daher, Keith D Eaton, Jeffrey Thomas Yorio, Davey B Daniel, Matthew Campbell, Keith C Bible, Mabel Ryder, Ashish V Chintakuntlawar, Mouhammed Amir Habra

Faculty, Staff and Students Publications

BACKGROUND: There is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC.

METHODS: A retrospective case series describing the use of LEN/PEM …

Renal Trajectory Patterns Are Associated With Postdischarge Mortality In Patients With Cirrhosis And Acute Kidney Injury, Ayse L Mindikoglu, Ruben Hernaez, Yan Liu, Jennifer R Kramer, Thomas Taylor, Abbas Rana, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Little is known about long-term outcomes of acute kidney injury (AKI) in patients with cirrhosis. Outcomes can vary with stage of AKI, chronic kidney disease, and trajectory of renal function.

METHODS: We collected data from the Department of Veterans Affairs and identified 6917 patients with cirrhosis who developed AKI during hospitalization at any of its 127 hospitals, from 2004 through 2014. We used latent class analysis of serial creatinine measurements during the index hospitalization to determine trajectories of renal function.

RESULTS: Overall, 32% of patients died within 90 days of discharge from the hospital and 48% of …

Dynamic Ultrasound Uniquely Reveals Anterior Capsular Tear Communicating With Vastus Intermedius Fibers, Shiv J Patel, Jasvinder A Singh, Max H Epstein, Prathap Jayaram

Faculty, Staff and Students Publications

We present a case of an anterior capsular tear of the right knee in a previously healthy, active individual. The patient was a 31-year-old male seen one month after the onset of throbbing anterior right knee pain, which progressed to sharp suprapatellar pain over the next three months. Both dynamic ultrasound (US) and MRI were obtained. Dynamic US revealed a tear of the anterior capsule of the right knee complicated by a suprapatellar effusion communicating into the vastus intermedius fibers of the quadriceps tendon. However, these findings were not evident on MRI. In addition to discussing this unique pathology, we …

Dermatology Resident Training On Depression Screening: A Cross-Sectional Survey, Kaitlyn L Streight, Harry Dao, Soo Jung Kim

Faculty, Staff and Students Publications

Background

Many dermatologic diseases are implicated in the development of depression. Currently, there is no literature addressing the extent of dermatology residency training on depression screening.

Objective

Our study aimed to determine the extent of dermatology residency training on depression screening to potentially improve education in this area.

Methods

We designed a 12-question survey to assess the level of resident training and comfort in depression screening for patients with acne vulgaris, atopic dermatitis, psoriasis, hidradenitis suppurativa, and skin cancer. Fifty-six residents completed the survey, and data for each question was analysed in aggregate.

Results

Participants found depression screening most important …

Highlights Of Studies In Cardiovascular Disease Prevention Presented At The 2020 American College Of Cardiology Annual Scientific Session, Xiaoming Jia, Mahmoud Al Rifai, Jing Liu, Anandita Agarwala, Martha Gulati, Salim S Virani

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: The review highlights selected studies related to cardiovascular disease (CVD) prevention that were presented at the American College of Cardiology 2020 Virtual Scientific Session (ACC.20)/World Cardiology Congress (WCC).

RECENT FINDINGS: The studies reviewed include clinical trials on the efficacy and safety of alirocumab (Study in Participants with Homozygous Familial Hypercholesterolemia [ODYSSEY HoFH]) and evinacumab in the treatment of homozygous familial hypercholesterolemia (HoFH); Evaluating the Efficacy of E-cigarettes for Smoking Cessation (E3); the use of renal denervation in the treatment of hypertension (SPYRAL HTN-OFF MED PIVOTAL); and the assessment of vericiguat in the treatment of heart failure (A …

Acute Tubular Injury In A Patient On A Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor, June K Pickett, Maulin Shah, Michael Gillette, Peter Jones, Salim Virani, Christie Ballantyne, Vijay Nambi

Faculty, Staff and Students Publications

A 72-year-old man with coronary artery disease, statin intolerance, and chronic kidney disease stage IIIa was initiated on alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, and developed acute kidney injury. A kidney biopsy was performed and suggested acute tubular injury. The serum creatinine returned to baseline after discontinuation of alirocumab. (Level of Difficulty: Intermediate.)

Multi-Community Cardiopulmonary Resuscitation Education By Medical Students, Kenton L Anderson, Kian Niknam, Larry Laufman, Stefanie S Sebok-Syer, Sara Andrabi

Faculty, Staff and Students Publications

Introduction One purpose of the hands-only cardiopulmonary resuscitation (HOCPR) program is to simplify CPR instruction to encourage more bystanders to take action during cardiac arrest. Although the program has been successfully implemented in traditional classroom settings, the utility of large-scale training events has not been well-explored. We hypothesized that CPR knowledge and comfort levels would increase through a large-scale, multi-community HOCPR training event. We also explored what effect this training event had on perceived barriers to bystander-performed CPR. Methods A convenience sample participated in HOCPR training on a single day across 10 Texas cities. A sub-sample completed training questionnaires, including …

A Genome-Wide Association Study Identifies Two Novel Susceptible Regions For Squamous Cell Carcinoma Of The Head And Neck, Sanjay Shete, Hongliang Liu, Jian Wang, Robert Yu, Erich M Sturgis, Guojun Li, Kristina R Dahlstrom, Zhensheng Liu, Christopher I Amos, Qingyi Wei

Faculty, Staff and Students Publications

To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which 434,839 typed and 7,423,250 imputed SNPs as the discovery. SNPs with P <1×10–3 were further validated in the OncoArray study of oral and pharynx cancer (5,205 cases and 3,232 controls of European ancestry) from dbGaP. Meta-analysis of the discovery and replication studies identified one novel locus 6p22.1 (P = 2.96×10–9 for the leading rs259919) and two cancer susceptibility loci 6p21.32 (rs3135001, HLA-DQB1) and 6p21.33 (rs1265081, CCHCR1) associated with SCCHN risk. Further stratification by tumor site revealed four known cancer loci (5p15.33, 6p21.32, 6p21.33, and 2p23.1) associated with oral cavity cancer risk and oropharyngeal cancer risk, respectively. In addition, one novel locus 18q22.2 (P = 2.54×10–9 for the leading SNP rs142021700) was identified for hypo-pharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and eQTL analysis. Collectively, our identification of four reported loci (2p23.1, 5p15.33, 6p21.32, and 6p21.33) and two novel loci (6p22.1 and 18q22.2) for SCCHN risk highlight the importance of HLA loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN.

Systemic Proteome Alterations Linked To Early Stage Pancreatic Cancer In Diabetic Patients, Hong Peng, Sheng Pan, Yuanqing Yan, Randall E Brand, Gloria M Petersen, Suresh T Chari, Lisa A Lai, Jimmy K Eng, Teresa A Brentnall, Ru Chen

Faculty, Staff and Students Publications

BACKGROUND: Diabetes is a risk factor associated with pancreatic ductal adenocarcinoma (PDAC), and new adult-onset diabetes can be an early sign of pancreatic malignancy. Development of blood-based biomarkers to identify diabetic patients who warrant imaging tests for cancer detection may represent a realistic approach to facilitate earlier diagnosis of PDAC in a risk population.

METHODS: A spectral library-based proteomic platform was applied to interrogate biomarker candidates in plasma samples from clinically well-defined diabetic cohorts with and without PDAC. Random forest algorithm was used for prediction model building and receiver operating characteristic (ROC) curve analysis was applied to evaluate the prediction …

Wolff-Parkinson-White Syndrome: De Novo Variants And Evidence For Mutational Burden In Genes Associated With Atrial Fibrillation, Zeynep H Coban-Akdemir, Wu-Lin Charng, Mahshid Azamian, Ingrid S Paine, Jaya Punetha, Christopher M Grochowski, Tomasz Gambin, Santiago O Valdes, Bryan Cannon, Gladys Zapata, Patricia P Hernandez, Shalini Jhangiani, Harsha Doddapaneni, Jianhong Hu, Fatima Boricha, Donna M Muzny, Eric Boerwinkle, Yaping Yang, Richard A Gibbs, Jennifer E Posey, Xander H T Wehrens, John W Belmont, Jeffrey J Kim, Christina Y Miyake, James R Lupski, Seema R Lalani

Faculty, Staff and Student Publications

BACKGROUND: Wolff-Parkinson-White (WPW) syndrome is a relatively common arrhythmia affecting ~1-3/1,000 individuals. Mutations in PRKAG2 have been described in rare patients in association with cardiomyopathy. However, the genetic basis of WPW in individuals with a structurally normal heart remains poorly understood. Sudden death due to atrial fibrillation (AF) can also occur in these individuals. Several studies have indicated that despite ablation of an accessory pathway, the risk of AF remains high in patients compared to general population.

METHODS: We applied exome sequencing in 305 subjects, including 65 trios, 80 singletons, and 6 multiple affected families. We used de novo analysis, …

Ipledge Must Abstain From Abstinence, Kami Lowery, Theodore Rosen, Janet Malek

Faculty, Staff and Students Publications

Isotretinoin has unmatched efficacy in the treatment of acne. However, because isotretinoin is a teratogen that can cause profound birth defects, the iPLEDGE program regulates the drug's distribution in the United States. To minimize fetal exposure to isotretinoin, the program requires that female patients capable of becoming pregnant use two forms of contraception or commit to abstinence while using this therapy. This manuscript argues that iPLEDGE should be revised to remove abstinence as an acceptable contraceptive option in the face of evidence that disputes its efficacy. All patients, regardless of reported sexual activity, should be required to use data-proven contraception. …

Our Duty Of Care In Pandemic Times, Perryn Ng

The Texas Heart Institute Journal

No abstract provided.

Incidental Cannulation Of Left Ventricular Thebesian Vein, Kalyan Chakravarthy Potu, Jay N Patel, Majd Ibrahim, Sujitha Sree Ketineni, Sudhir Mungee

The Texas Heart Institute Journal

No abstract provided.

Surgical Endoepicardial Linear Ablation For Ventricular Tachycardia With Postinfarction Left Ventricular Aneurysm, Changcheng Liu, Zhaoping Su, Liangshan Wang, Bo Li, Jin Wang, Yang Yu, Chengxiong Gu

The Texas Heart Institute Journal

This retrospective study evaluated the feasibility of surgical endoepicardial linear ablation for ventricular tachycardia in patients with postinfarction left ventricular aneurysm. Sixty-four patients with multivessel coronary artery disease and left ventricular aneurysm but no mural thrombosis of the aneurysm or valve disease were treated at our institution from March 2012 through July 2015. All underwent off-pump coronary artery bypass grafting and left ventricular aneurysm repair by linear plication. Twenty-three patients (35.9%) had ventricular tachycardia and underwent surgical endoepicardial linear ablation on the beating heart guided by epicardial substrate mapping with the Carto 3 system. The remaining 41 patients (64.1%) composed …

Altered Mental Status And Hyponatremia After 20 Hours Of Amiodarone Therapy, Andrea Qi, John C Moscona, Justin Reed, Thierry H Le Jemtel

The Texas Heart Institute Journal

A 66-year-old woman with no relevant medical history presented at the emergency department with new-onset atrial fibrillation. We initiated intravenous amiodarone therapy. At 20 hours, the patient experienced severe neurologic symptoms, hyponatremia, and syndrome of inappropriate antidiuretic hormone. We discontinued amiodarone, infused saline solution, and restricted the patient's fluid intake. She recovered in 3 days. This case illustrates that amiodarone-induced syndrome of inappropriate antidiuretic hormone with hyponatremia can occur far earlier than expected during acute amiodarone therapy.

Cardiac Involvement By Burkitt Lymphoma In A 49-Year-Old Man, Kainat Khalid, Nadeen Faza, Nasser M Lakkis, Rashed Tabbaa

The Texas Heart Institute Journal

Malignant metastases are among the most common cardiac masses. We report a rare case of cardiac involvement by Burkitt lymphoma in a 49-year-old man who presented with a 2-month history of dyspnea and palpitations. A transthoracic echocardiogram revealed 2 intracardiac masses in the right atrium (one of which partially encased the tricuspid valve), myocardial infiltration, and pericardial disease. Results of pleural fluid cytology and flow cytometry confirmed involvement by Burkitt lymphoma. Subsequent chemotherapy markedly reduced the intracardiac tumor burden and resolved the patient's presenting symptoms. Our case highlights the importance of cardiac imaging in diagnosing systemic illness, initiating early and …

Optimizing P2 Neochordal Length And Stability In Mitral Valve Repair With Use Of A Polypropylene Loop, Anil Ozen, Ertekin Utku Unal, Hamdi Mehmet Ozbek, Gorkem Yigit, Hakki Zafer Iscan

The Texas Heart Institute Journal

Determining the optimal length of artificial chordae tendineae and then effectively securing them is a major challenge in mitral valve repair. Our technique for measuring and stabilizing neochordae involves tying a polypropylene suture loop onto the annuloplasty ring. We used this method in 4 patients who had moderate-to-severe mitral regurgitation from degenerative posterior leaflet (P2) prolapse and flail chordae. Results of intraoperative saline tests and postoperative transesophageal echocardiography revealed only mild insufficiency. One month postoperatively, echocardiograms showed trivial regurgitation in all 4 patients. We think that this simple, precise method for adjusting and stabilizing artificial chordae will be advantageous in …

Discovery Of A Selective Inhibitor Of Doublecortin Like Kinase 1, Fleur M Ferguson, Behnam Nabet, Srivatsan Raghavan, Yan Liu, Alan L Leggett, Miljan Kuljanin, Radha L Kalekar, Annan Yang, Shuning He, Jinhua Wang, Raymond W S Ng, Rita Sulahian, Lianbo Li, Emily J Poulin, Ling Huang, Jost Koren, Nora Dieguez-Martinez, Sergio Espinosa, Zhiyang Zeng, Cesear R Corona, James D Vasta, Ryoma Ohi, Taebo Sim, Nam Doo Kim, Wayne Harshbarger, Jose M Lizcano, Matthew B Robers, Senthil Muthaswamy, Charles Y Lin, A Thomas Look, Kevin M Haigis, Joseph D Mancias, Brian M Wolpin, Andrew J Aguirre, William C Hahn, Kenneth D Westover, Nathanael S Gray

Faculty, Staff and Students Publications

Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vivo-compatible chemical probe of the DCLK1 kinase domain, DCLK1-IN-1. We demonstrate activity of DCLK1-IN-1 against clinically relevant patient-derived PDAC organoid models and use a combination of RNA-sequencing, proteomics and phosphoproteomics analysis to reveal that DCLK1 inhibition modulates proteins and pathways associated with cell motility in this context. DCLK1-IN-1 will serve as a versatile tool …

Myeloma Cells Shift Osteoblastogenesis To Adipogenesis By Inhibiting The Ubiquitin Ligase Murf1 In Mesenchymal Stem Cells, Zhiqiang Liu, Huan Liu, Jin He, Pei Lin, Qiang Tong, Jing Yang

Faculty, Staff and Students Publications

The suppression of bone formation is a hallmark of multiple myeloma. Myeloma cells inhibit osteoblastogenesis from mesenchymal stem cells (MSCs), which can also differentiate into adipocytes. We investigated myeloma-MSC interactions and the effects of such interactions on the differentiation of MSCs into adipocytes or osteoblasts using single-cell RNA sequencing, in vitro co-culture, and subcutaneous injection of MSCs and myeloma cells into mice. Our results revealed that the α4 subunit of integrin on myeloma cells stimulated vascular cell adhesion molecule 1 (VCAM1) on MSCs, leading to the activation of protein kinase C β1 (PKCβ1) signaling and repression of the muscle ring-finger …

A Rare Clinical Presentation Of Metastatic Crohn's Disease, Kaitlyn L Streight, Tara L Braun, Nicholas Lowe, Soo Jung Kim

Faculty, Staff and Students Publications

A 31-year-old female with a history of systemic lupus erythematous, IgA nephropathy, and psoriasis presented with a one-month history of a painful, pruritic rash under the bilateral breasts and in the genital region. Cutaneous examination revealed a large, tender ulcer under the left breast with a shiny erythematous base and peripheral hypertrophic changes. Small ulcers were present on the bilateral inguinal folds, and the labia majora were edematous with multiple erythematous papules. Histological examination of the left breast revealed ulceration with granulomatous dermatitis, consistent with a diagnosis of metastatic Crohn's disease. Metastatic Crohn's disease is a rare cutaneous manifestation of …

Surgical Management And Outcome Of Newly Diagnosed Glioblastoma Without Contrast Enhancement (Low-Grade Appearance): A Report Of The Rano Resect Group, Ameya A Jategaonkar, Vivian F Kaul, Eric Lee, Eric M Genden

Faculty, Staff and Student Publications

The palatomaxillary structure plays critical roles in both form and function of the midface. Surgical defects of the palate and maxilla can be associated with significant morbidity and deformity. Various defect classification systems have been used to assist in reconstruction and rehabilitation. Reconstructive options include prosthetic rehabilitation, local flaps, and free tissue transfer. Here, we review the functional and surgical anatomy of the palatomaxillary complex, defect classification systems, and provide an overview of reconstructive options.