Medicine and Health Sciences Commons^™

Genetic Effect On Body Mass Index And Cardiovascular Disease Across Generations, Chloé Sarnowski, Matthew P Conomos, Ramachandran S Vasan, James B Meigs, Josée Dupuis, Ching-Ti Liu, Aaron Leong

Faculty, Staff and Student Publications

BACKGROUND: Whether genetics contribute to the rising prevalence of obesity or its cardiovascular consequences in today's obesogenic environment remains unclear. We sought to determine whether the effects of a higher aggregate genetic burden of obesity risk on body mass index (BMI) or cardiovascular disease (CVD) differed by birth year.

METHODS: We split the FHS (Framingham Heart Study) into 4 equally sized birth cohorts (birth year before 1932, 1932 to 1946, 1947 to 1959, and after 1960). We modeled a genetic predisposition to obesity using an additive genetic risk score (GRS) of 941 BMI-associated variants and tested for GRS-birth year interaction …

Emotional Distress, Self-Management, And Glycemic Control Among Participants Enrolled In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness (Grade) Study, Jeffrey S Gonzalez, Heidi Krause-Steinrauf, Ionut Bebu, Gladys Crespo-Ramos, Claire J Hoogendoorn, Aanand D Naik, Andrea Waltje, Elizabeth Walker, Dominic Ehrmann, Janet Brown-Friday, Andrea Cherrington

Faculty, Staff and Student Publications

OBJECTIVE: We examined emotional distress in relation to metformin adherence, overall diabetes self-management, and glycemic control among adults with early type 2 diabetes (T2DM) enrolled in the GRADE study.

METHODS: Linear regression models examined cross-sectional associations of baseline depression symptoms and diabetes distress with adherence to metformin, self-management, and HbA1c, adjusting for covariates. Cognitive-affective (e.g., sadness) and somatic (e.g., sleep/appetite disturbance) depression symptoms and diabetes distress subscales were also examined.

RESULTS: This substudy of 1,739 GRADE participants (56 % Non-Hispanic White, 18 % Non-Hispanic Black, 17 % Hispanic, 68 % male, mean[SD] age = 57.96[10.22] years, diabetes duration = 4.21[2.81] …

Cost Of Failure To Achieve Textbook Outcomes: Association Of Insurance Type With Outcomes And Cumulative Cost For Inpatient Surgery, Michael A Jacobs, Jeongsoo Kim, Jasmine C Tetley, Susanne Schmidt, Bradley B Brimhall, Virginia Mika, Chen-Pin Wang, Laura S Manuel, Paul Damien, Paula K Shireman

Faculty, Staff and Student Publications

Background: Surgical outcome/cost analyses typically focus on single outcomes and do not include encounters beyond the index hospitalization.

Study design: This cohort study used NSQIP (2013-2019) data with electronic health record and cost data risk-adjusted for frailty, preoperative acute serious conditions (PASC), case status, and operative stress assessing cumulative costs of failure to achieve textbook outcomes defined as absence of 30-day Clavien-Dindo level III and IV complications, emergency department visits/observation stays (EDOS), and readmissions across insurance types (private, Medicare, Medicaid, uninsured). Return costs were defined as costs of all 30-day emergency department visits/observation stays and readmissions.

Results: Cases were performed …

Safety And Tolerability Of Ser-109 As An Investigational Microbiome Therapeutic In Adults With Recurrent Clostridioides Difficile Infection: A Phase 3, Open-Label, Single-Arm Trial, Matthew D Sims, Sahil Khanna, Paul Feuerstadt, Thomas J Louie, Colleen R Kelly, Edward S Huang, Elizabeth L Hohmann, Elaine E L Wang, Caterina Oneto, Stuart H Cohen, Charles S Berenson, Louis Korman, Christine Lee, Bret Lashner, Colleen S Kraft, Mayur Ramesh, Michael Silverman, Darrell S Pardi, Ananya De, Asli Memisoglu, David A Lombardi, Brooke R Hasson, Barbara H Mcgovern, Lisa Von Moltke

Faculty, Staff and Student Publications

IMPORTANCE: A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence.

OBJECTIVES: To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks.

DESIGN, SETTING, AND PARTICIPANTS: This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR …

Retrospective Evaluation Of The Role Of Gemcitabine-Docetaxel In Well-Differentiated And Dedifferentiated Liposarcoma, Prapassorn Thirasastr, Heather Lin, Behrang Amini, Wei-Lien Wang, Jeffrey M Cloutier, Elise F Nassif, Emily Z Keung, Christina L Roland, Barry Feig, Dejka Araujo, Robert S Benjamin, Anthony P Conley, John A Livingston, Joseph Ludwig, Shreyaskumar Patel, Ravin Ratan, Vinod Ravi, Maria Alejandra Zarzour, Xiao Zhou, Neeta Somaiah

Faculty, Staff and Student Publications

OBJECTIVE: Well-differentiated (WDLPS) and dedifferentiated liposarcoma (DDLPS) account for the majority of liposarcomas. Although gemcitabine-docetaxel is used as second-line treatment in soft tissue sarcomas, its efficacy in WDLPS/DDLPS is not established. This study retrospectively analyzed the efficacy of gemcitabine regimens in WDLPS/DDLPS.

METHODS: All patients with WDLPS or DDLPS who received gemcitabine-based chemotherapy at our institution between September 2002 and January 2021 were included. Response was evaluated by an independent radiologist using RECIST 1.1. The Kaplan-Meier method was used to estimate distributions of survival outcomes and log-rank tests were used to compare survival outcomes between subgroups.

RESULTS: Sixty-five WDLPS/DDLPS patients …

Smart Start: Rituximab, Lenalidomide, And Ibrutinib In Patients With Newly Diagnosed Large B-Cell Lymphoma, Jason Westin, R Eric Davis, Lei Feng, Fredrick Hagemeister, Raphael Steiner, Hun Ju Lee, Luis Fayad, Loretta Nastoupil, Sairah Ahmed, Alma Rodriguez, Michelle Fanale, Felipe Samaniego, Swaminathan P Iyer, Ranjit Nair, Yasuhiro Oki, Nathan Fowler, Michael Wang, Man Chun John Ma, Francisco Vega, Timothy Mcdonnell, Chelsea Pinnix, Donna Griffith, Yang Lu, Sanjit Tewari, Ryan Sun, David W Scott, Christopher R Flowers, Sattva Neelapu, Michael R Green

Faculty, Staff and Student Publications

PURPOSE: Chemoimmunotherapy for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) is largely unchanged for decades. Both preclinical models and clinical data suggest the combination of lenalidomide and ibrutinib may have synergy in DLBCL, particularly in the non-germinal center B-cell-like subset.

METHODS: We enrolled 60 patients with newly diagnosed non-germinal center B-cell-like DLBCL in this investigator-initiated, single-arm phase II trial of rituximab, lenalidomide, and ibrutinib (RLI) with the sequential addition of chemotherapy (ClinicalTrials.gov identifier: NCT02636322). Patients were treated with rituximab 375 mg/m

RESULTS: The median age was 63.5 years (range, 29-83 years) with 28% age 70 years or older. …

Disparities In Mortality Among Acute Myeloid Leukemia-Related Hospitalizations, Sara Taveras Alam, Deepa Dongarwar, Elyse Lopez, Sarvari Yellapragada, Gustavo Rivero, Quillan Huang, Courtney Miler-Chism, Martha Mims, Hamisu M Salihu

Faculty, Staff and Student Publications

Racial and socioeconomic disparities have become apparent in acute myeloid leukemia (AML) outcomes. We conducted a retrospective cohort study of hospitalizations for adults with a diagnosis of AML from 2009 to 2018 in the Nationwide Inpatient Sample (NIS). We categorized patients' ages in groups of≥60 years and stratified them by reported race/ethnicity. Exposures of interest were patient sociodemographics, hospital characteristics, and Elixhauser-comorbidity Index. Outcome of interest was in-hospital death. Statistical analyses included survey logistic regression to generate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) to quantify the independent associations between patient characteristics and mortality. Of 622,417 AML-related hospitalizations, …

Comparison Of Postoperative Outcomes Of Laparoscopic Vs Open Inguinal Hernia Repair, Jennie Meier, Audrey Stevens, Miles Berger, Konstantinos I Makris, Athanasios Bramos, Joan Reisch, C Munro Cullum, Simon C Lee, Celette Sugg Skinner, Herbert Zeh, Cynthia J Brown, Courtney J Balentine

Faculty, Staff and Students Publications

Importance: Advocates of laparoscopic surgery argue that all inguinal hernias, including initial and unilateral ones, should be repaired laparoscopically. Prior work suggests outcomes of open repair are improved by using local rather than general anesthesia, but no prior studies have compared laparoscopic surgery with open repair under local anesthesia.

Objective: To evaluate postoperative outcomes of open inguinal hernia repair under general or local anesthesia compared with laparoscopic repair.

Design, setting, and participants: This retrospective cohort study identified 107 073 patients in the Veterans Affairs Surgical Quality Improvement Program database who underwent unilateral initial inguinal hernia repair from 1998 to 2019. …

Fixed-Dose Combination Therapy-Based Protocol Compared With Free Pill Combination Protocol: Results Of A Cluster Randomized Trial, Olutobi A Sanuade, Mark D Huffman, Et Al.

2020-Current year OA Pubs

Fixed-dose combination (FDC) therapy is recommended for hypertension management in Nigeria based on randomized trials at the individual level. This cluster-randomized trial evaluates effectiveness and safety of a treatment protocol that used two-drug FDC therapy as the second and third steps for hypertension control compared with a protocol that used free pill combinations. From January 2021 to June 2021, 60 primary healthcare centers in the Federal Capital Territory of Nigeria were randomized to a protocol using FDC therapy as second and third steps compared with a protocol that used the same medications in free pill combination therapy for these steps. …

Lumasiran For Advanced Primary Hyperoxaluria Type 1: Phase 3 Illuminate-C Trial, Mini Michael, Jaap W Groothoff, Hadas Shasha-Lavsky, John C Lieske, Yaacov Frishberg, Eva Simkova, Anne-Laure Sellier-Leclerc, Arnaud Devresse, Fitsum Guebre-Egziabher, Sevcan A Bakkaloglu, Chebl Mourani, Rola Saqan, Richard Singer, Richard Willey, Bahru Habtemariam, John M Gansner, Ishir Bhan, Tracy Mcgregor, Daniella Magen

Faculty, Staff and Students Publications

Rationale & objective: Lumasiran reduces urinary and plasma oxalate (POx) in patients with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function. ILLUMINATE-C evaluates the efficacy, safety, pharmacokinetics, and pharmacodynamics of lumasiran in patients with PH1 and advanced kidney disease.

Study design: Phase 3, open-label, single-arm trial.

Setting & participants: Multinational study; enrolled patients with PH1 of all ages, estimated glomerular filtration rate ≤45 mL/min/1.73 m2 (if age ≥12 months) or increased serum creatinine level (if age < 12 months), and POx ≥20 μmol/L at screening, including patients with or without systemic oxalosis.

Intervention: Lumasiran administered subcutaneously; 3 monthly doses followed by monthly or quarterly weight-based dosing.

Outcome: Primary end point: percent change in POx …

Clinical Importance Of Clonal Hematopoiesis In Metastatic Gastrointestinal Tract Cancers, Bill H Diplas, Kelly Bolton, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Clonal hematopoiesis (CH) has been associated with development of atherosclerosis and leukemia and worse survival among patients with cancer; however, the association with cancer therapy efficacy, in particular immune checkpoint blockade (ICB), and toxicity has not yet been established. Given the widespread use of ICB and the critical role hematopoietic stem cell-derived lymphocytes play in mediating antitumor responses, CH may be associated with therapeutic efficacy and hematologic toxicity.

OBJECTIVE: To determine the association between CH and outcomes, hematologic toxicity, and therapeutic efficacy in patients with metastatic gastrointestinal tract cancers being treated with systemic therapy, both in the first-line metastatic …

A Survey With Interventional Components Delivered On Tablet Devices Versus Usual Care To Increase Pre-Exposure Prophylaxis Uptake Among Cisgender Black Women: A Pilot Randomized Controlled Trial, Mandy J Hill, Angela M Heads, Robert Suchting, Angela L Stotts

Faculty, Staff and Student Publications

BACKGROUND: Cisgender (cis) Black women in the USA are more likely to become HIV positive during their lifetime than other women. We developed and implemented a behavioral intervention, Increasing PrEP (iPrEP), the first pilot randomized controlled trial (RCT) aimed at motivating cis Black women to be willing to use PrEP for HIV prevention and attend an initial PrEP clinic visit following an emergency department visit.

METHODS: Eligible participants were Black cisgender women ages 18-55 years who acknowledged recent condomless sex and substance use. Participants were randomized to iPrEP or usual care (UC). iPrEP is a survey-based intervention designed to raise …

Comparison Of State-Of-The-Art Neural Network Survival Models With The Pooled Cohort Equations For Cardiovascular Disease Risk Prediction, Yu Deng, Lei Liu, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Pooled Cohort Equations (PCEs) are race- and sex-specific Cox proportional hazards (PH)-based models used for 10-year atherosclerotic cardiovascular disease (ASCVD) risk prediction with acceptable discrimination. In recent years, neural network models have gained increasing popularity with their success in image recognition and text classification. Various survival neural network models have been proposed by combining survival analysis and neural network architecture to take advantage of the strengths from both. However, the performance of these survival neural network models compared to each other and to PCEs in ASCVD prediction is unknown.

METHODS: In this study, we used 6 cohorts from …

Ultrasound Assessment Of Spastic Muscles In Ambulatory Chronic Stroke Survivors Reveals Function-Dependent Changes, Javier González-Buonomo, Alexander H Pham, Jaskiran Ghuman, Aila Malik, Nuray Yozbatiran, Gerard E Francisco, Walter R Frontera, Sheng Li

Faculty, Staff and Student Publications

OBJECTIVE: To correlate ultrasound characteristics of spastic muscles with clinical and functional measurements in chronic stroke survivors.

METHODS: Ultrasound assessment and clinical and functional assessments were performed in 28 ambulatory stroke survivors (12 females, mean age 57.8 ± 11.8 years, 76 ± 45 months after stroke).

RESULTS: Muscle thickness in the affected side was decreased compared with the contralateral side (p < 0.001). The decrease was more evident in the upper limb muscles. On the affected side, the modified Heckmatt scale score was lowest (closer to normal) in the rectus femoris (RF) muscle compared with other muscles (biceps brachii (BB), flexor carpi ulnaris (FCU) and medial gastrocnemius (MG)). Muscle thickness and echogenicity of spastic muscles did not correlate with spasticity, as measured with the modified Ashworth scale (MAS), Fugl-Meyer motor assessment scores, age, or time since stroke. There was a significant negative correlation between grip strength and percentage decrease in muscle thickness for the spastic FCU muscle (r = -0.49, p = 0.008). RF muscle thickness correlated with ambulatory function (Timed Up and Go test (r = 0.44, p = 0.021) and 6-metre walk test (r = 0.41, p = 0.032)). There was no significant correlation between echogenicity and functional assessments Conclusion: Ambulatory chronic stroke survivors had function-dependent changes in muscle thickness on the affected side. Muscle thickness and echogenicity of spastic muscles did not correlate with spasticity, Fugl-Meyer motor assessment scores, age, or time since stroke.

Association Of Omega 3 Polyunsaturated Fatty Acids With Incident Chronic Kidney Disease: Pooled Analysis Of 19 Cohorts, Kwok Leung Ong, Matti Marklund, Liping Huang, Kerry-Anne Rye, Nicholas Hui, Xiong-Fei Pan, Casey M Rebholz, Hyunju Kim, Lyn M Steffen, Anniek C Van Westing, Johanna M Geleijnse, Ellen K Hoogeveen, Yun-Yu Chen, Kuo-Liong Chien, Amanda M Fretts, Rozenn N Lemaitre, Fumiaki Imamura, Nita G Forouhi, Nicholas J Wareham, Anna Birukov, Susanne Jäger, Olga Kuxhaus, Matthias B Schulze, Vanessa Derenji De Mello, Jaakko Tuomilehto, Matti Uusitupa, Jaana Lindström, Nathan Tintle, William S Harris, Keisuke Yamasaki, Yoichiro Hirakawa, Toshiharu Ninomiya, Toshiko Tanaka, Luigi Ferrucci, Stefania Bandinelli, Jyrki K Virtanen, Ari Voutilainen, Tharusha Jayasena, Anbupalam Thalamuthu, Anne Poljak, Sonia Bustamante, Perminder S Sachdev, Mackenzie K Senn, Stephen S Rich, Michael Y Tsai, Alexis C Wood, Markku Laakso, Maria Lankinen, Xiaowei Yang, Liang Sun, Huaixing Li, Xu Lin, Christoph Nowak, Johan Ärnlöv, Ulf Risérus, Lars Lind, Mélanie Le Goff, Cécilia Samieri, Catherine Helmer, Frank Qian, Renata Micha, Adrienne Tin, Anna Köttgen, Ian H De Boer, David S Siscovick, Dariush Mozaffarian, Jason Hy Wu

Faculty, Staff and Students Publications

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD).

DESIGN: Pooled analysis.

DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020.

STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate.

DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were …

Examining Stripes On A Herd Of Zebras: Impact Of Genomic Matching For Ultrarare Sarcomas In Phase 1 Clinical Trials (Samba 102), Justin T Moyers, Roberto Carmagnani Pestana, Jason Roszik, David S Hong, Aung Naing, Siqing Fu, Sarina Piha-Paul, Timothy A Yap, Daniel Karp, Jordi Rodon, Andy Livingston, Maria Alejandra Zarzour, Vinod Ravi, Shreyaskumar Patel, Robert S Benjamin, Joseph Ludwig, Cynthia Herzog, Ravin Ratan, Neeta Somaiah, Anthony Conley, Richard Gorlick, Funda Meric-Bernstam, Vivek Subbiah

Faculty, Staff and Student Publications

Purpose: Recently, the Connective Tissue Oncology Society published consensus guidelines for recognizing ultrarare sarcomas (URS), defined as sarcomas with an incidence ≤1 per 1,000,000. We assessed the outcomes of 56 patients with soft tissue, and 21 with bone sarcomas, enrolled in Phase 1 trials.

Experimental design: In this Sarcoma-Matched Biomarker Analysis (SAMBA-102 study), we reviewed records from patients on Phase 1 trials at the University of Texas MD Anderson Cancer Center between January 2013 and June 2021.

Results: Among 587 sarcomas, 106 (18.1%) were classified as URS. Fifty (47%) were male, and the median age was 44.3 years (range, 19-82). …

Prevalence And Geographic Distribution Of Self-Reported Chronic Kidney Disease And Potential Risk Factors In Central America, Erika Figueroa-Solis, David Gimeno Ruiz De Porras, Marianela Rojas-Garbanzo, Lawrence Whitehead, Kai Zhang, George L Delclos

Faculty, Staff and Student Publications

BACKGROUND: Cases for chronic kidney disease of unknown etiology (CKDu) are increasing in specific disease hotspots located in rural agricultural communities over Central America. The goal of the study was to estimate the prevalence and geographic distribution of self-reported work-related CKD and associated risk factors for CKDu by industry sector in Central America.

METHODS: We calculated the prevalence and distribution of self-reported CKD, work-related CKD, and suspected CKDu risk factors among the 9032 workers in the Second Central American Survey of Working Conditions and Health (II ECCTS, 2018). We mapped the distribution of suspected CKDu risk factors to work-related CKDu …

Childhood Adversities And Risk Of Posttraumatic Stress Disorder And Major Depression Following A Motor Vehicle Collision In Adulthood, H N Ziobrowski, S L House, D M Barch, Et Al.

2020-Current year OA Pubs

AIMS: Childhood adversities (CAs) predict heightened risks of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) among people exposed to adult traumatic events. Identifying which CAs put individuals at greatest risk for these adverse posttraumatic neuropsychiatric sequelae (APNS) is important for targeting prevention interventions.

METHODS: Data came from

RESULTS: Most participants (90.9%) reported at least rarely having experienced some CA. Ever experiencing each CA other than emotional neglect was univariably associated with 3-month APNS (RRs = 1.31-1.60). Each CA frequency was also univariably associated with 3-month APNS (RRs = 1.65-2.45). In multivariable models, joint associations of CAs with 3-month …

Prospective Association Of Daily Steps With Cardiovascular Disease: A Harmonized Meta-Analysis, Amanda E Paluch, Shivangi Bajpai, Marcel Ballin, David R Bassett, Thomas W Buford, Mercedes R Carnethon, Ariel Chernofsky, Erin E Dooley, Ulf Ekelund, Kelly R Evenson, Deborah A Galuska, Barbara J Jefferis, Lingsong Kong, William E Kraus, Martin G Larson, I-Min Lee, Charles E Matthews, Robert L Newton, Anna Nordström, Peter Nordström, Priya Palta, Alpa V Patel, Kelley Pettee Gabriel, Carl F Pieper, Lisa Pompeii, Erika Rees-Punia, Nicole L Spartano, Ramachandran S Vasan, Peter H Whincup, Shengping Yang, Janet E Fulton, Steps For Health Collaborative

Faculty, Staff and Students Publications

Background: Taking fewer than the widely promoted "10 000 steps per day" has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose-response relationship between steps per day and CVD can help inform clinical and public health guidelines.

Methods: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional …

Trends And Racial/Ethnic Differences In Predictors Of Cervical Cancer Screening Among Us Women Ages 30-64 Years, Itunu O Sokale, Jane R Montealegre, Abiodun O Oluyomi, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Cervical cancer screening (CCS) participation has decreased in the United States over the last several decades, contributing to cervical cancer's sustained incidence and mortality. This study examined recent trends and racial/ethnic differences in predictors of CCS uptake among US women.

METHODS: We analyzed combined data from the 2016 to 2020 Behavioral Risk Factor Surveillance System (BRFSS) and included 235,713 women ages 30 to 64 years without a hysterectomy. We used simple linear regression to assess trends over time and multivariable logistic regression models to evaluate racial/ethnic differences in predictors of up-to-date CCS.

RESULTS: We found little change in CCS …

Ageanno: A Knowledgebase Of Single-Cell Annotation Of Aging In Human, Kexin Huang, Hoaran Gong, Jingjing Guan, Lingxiao Zhang, Changbao Hu, Weiling Zhao, Liyu Huang, Wei Zhang, Pora Kim, Xiaobo Zhou

Faculty, Staff and Student Publications

Aging is a complex process that accompanied by molecular and cellular alterations. The identification of tissue-/cell type-specific biomarkers of aging and elucidation of the detailed biological mechanisms of aging-related genes at the single-cell level can help to understand the heterogeneous aging process and design targeted anti-aging therapeutics. Here, we built AgeAnno (https://relab.xidian.edu.cn/AgeAnno/#/), a knowledgebase of single cell annotation of aging in human, aiming to provide comprehensive characterizations for aging-related genes across diverse tissue-cell types in human by using single-cell RNA and ATAC sequencing data (scRNA and scATAC). The current version of AgeAnno houses 1 678 610 cells from 28 healthy …

Multimodal Brain Age Estimates Relate To Alzheimer Disease Biomarkers And Cognition In Early Stages: A Cross-Sectional Observational Study, Peter R Millar, Brian A Gordon, Patrick H Luckett, Tammie L S Benzinger, Carlos Cruchaga, Anne M Fagan, Jason J Hassenstab, Richard J Perrin, Suzanne E Schindler, Randall J Bateman, John C Morris, Beau M Ances, Et Al.

2020-Current year OA Pubs

BACKGROUND: Estimates of 'brain-predicted age' quantify apparent brain age compared to normative trajectories of neuroimaging features. The brain age gap (BAG) between predicted and chronological age is elevated in symptomatic Alzheimer disease (AD) but has not been well explored in presymptomatic AD. Prior studies have typically modeled BAG with structural MRI, but more recently other modalities, including functional connectivity (FC) and multimodal MRI, have been explored.

METHODS: We trained three models to predict age from FC, structural (S), or multimodal MRI (S+FC) in 390 amyloid-negative cognitively normal (CN/A-) participants (18-89 years old). In independent samples of 144 CN/A-, 154 CN/A+, …

Comparison Between The Casia Ss-1000 And Pentacam In Measuring Corneal Curvatures And Corneal Thickness Maps, Robert M Feldman, Gene Kim, Alice Z Chuang, Atsushi Shiraishi, Keiichiro Okamoto, Makoto Tsukamoto

Faculty, Staff and Student Publications

PURPOSE: To compare the intra-device repeatability and inter-device reproducibility between two anterior segment imaging instruments, the CASIA SS-1000 (Tomey Corp., Nagoya, Japan) and Pentacam (OCULUS, Arlington, WA) in measuring anterior segment parameters.

METHODS: Single-center, prospective clinical trial. Participants ≥20 years of age were included. One eye was randomly selected, each imaged by three CASIA SS-1000 devices and three Pentacam devices by three different examiners. Each photographer operated a pair of devices, one CASIA SS-1000 and one Pentacam. The image order for each participant was determined by a random permutation table. Three images were taken from each device. A total of …

Effect Of A Muc5ac Antibody (Npc-1c) Administered With Second-Line Gemcitabine And Nab-Paclitaxel On The Survival Of Patients With Advanced Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial, Brandon M Huffman, Atrayee Basu Mallick, Nora K Horick, Andrea Wang-Gillam, Peter Joel Hosein, Michael A Morse, Muhammad Shaalan Beg, Janet E Murphy, Sharon Mavroukakis, Anjum Zaki, Benjamin L Schlechter, Hanna Sanoff, Christopher Manz, Brian M Wolpin, Philip Arlen, Jill Lacy, James M Cleary

Department of Medical Oncology Faculty Papers

Importance: Treatment options are limited for patients with advanced pancreatic ductal adenocarcinoma (PDAC) beyond first-line 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), with such individuals commonly being treated with gemcitabine and nab-paclitaxel.

Objective: To determine whether NPC-1C, an antibody directed against MUC5AC, might increase the efficacy of second-line gemcitabine and nab-paclitaxel in patients with advanced PDAC.

Design, setting, and participants: This multicenter, randomized phase II clinical trial enrolled patients with advanced PDAC between April 2014 and March 2017 whose disease had progressed on first-line FOLFIRINOX. Eligible patients had tumors with at least 20 MUC5AC staining by centralized immunohistochemistry review. Statistical analysis …

Evaluation Of Proton Therapy Reirradiation For Patients With Recurrent Head And Neck Squamous Cell Carcinoma, Anna Lee, Robbie Woods, Amgad Mahfouz, Sarin Kitpanit, Olivia Cartano, Nader Mohamed, Irini Youssef, Kathryn Marqueen, Kevin Sine, Dennis Mah, Brian Neal, Kaveh Zakeri, Jung J Kang, Nadeem Riaz, Yao Yu, Sean M Mcbride, Linda D Chen, C Jillian Tsai, Daphna Y Gelblum, Robert H Press, Loren S Michel, Eric J Sherman, David Pfister, Lara A Dunn, Alan L Ho, James Fetten, Richard J Wong, Jay O Boyle, Bhuvanesh Singh, Jennifer R Cracchiolo, Ian Ganly, Marc A Cohen, Nancy Y Lee

Faculty, Staff and Student Publications

Importance: Use of proton therapy reirradiation (PT-ReRT) for head and neck cancer is increasing; however, reports are heterogenous and outcomes can be difficult to interpret.

Objective: To evaluate outcomes and toxic effects following PT-ReRT in a uniform and consecutive cohort of patients with head and neck squamous cell carcinoma.

Design, setting, and participants: This retrospective cohort study included patients with recurrent primary head and neck squamous cell carcinoma who were treated with PT-ReRT from January 1, 2013, to December 31, 2020, at a single institution. Patient, clinical, and treatment characteristics were obtained, and multidisciplinary review was performed to record and …

Effect Of A Muc5ac Antibody (Npc-1c) Administered With Second-Line Gemcitabine And Nab-Paclitaxel On The Survival Of Patients With Advanced Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial, Brandon M Huffman, Andrea Wang-Gillam, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Treatment options are limited for patients with advanced pancreatic ductal adenocarcinoma (PDAC) beyond first-line 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), with such individuals commonly being treated with gemcitabine and nab-paclitaxel.

OBJECTIVE: To determine whether NPC-1C, an antibody directed against MUC5AC, might increase the efficacy of second-line gemcitabine and nab-paclitaxel in patients with advanced PDAC.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, randomized phase II clinical trial enrolled patients with advanced PDAC between April 2014 and March 2017 whose disease had progressed on first-line FOLFIRINOX. Eligible patients had tumors with at least 20 MUC5AC staining by centralized immunohistochemistry review. Statistical analysis …

Social And Economic Capital As Effect Modifiers Of The Association Between Psychosocial Stress And Oral Health, Abby L J Hensel, Noha Gomaa

Dentistry Publications

OBJECTIVES: To assess the extent of the association of psychosocial stress with oral health in an Ontario population stratified by age groups, and whether any association is modified by indicators of social and economic capital.

METHODS: We retrieved data of 21,320 Ontario adults, aged 30-74 years old, from the Canadian Community Health Survey (CCHS: 2017-2018), which is a Canada-wide, cross-sectional survey. Using binomial logistic regression models that adjusted for age, sex, education, and country of birth, we examined the association of psychosocial stress (indicated by perceived life stress) with inadequate oral health (indicated as having at least one of the …

Leukocytoclastic Vasculitis In A Patient With Crohn Disease: A Case Report., Mark Daniele Bugada, Vamsi K Emani

Ambulatory and Primary Care Articles

Leukocytoclastic vasculitis (LCV) is an idiopathic small vessel vasculitis. Leukocytoclastic vasculitis can be found in a spectrum of diseases and is noted as a rare extraintestinal manifestation of Crohn disease. This case report examines a 55-year-old man with a previous diagnosis of Crohn disease who was admitted after 5 days with a persistent rash. A biopsy confirmed LCV, and the patient followed up with dermatology for outpatient treatment. This study adds to the sparse medical literature on LCV cases relating to Crohn disease.

The Salento Prognostic Model For Limited-Stage Peripheral T-Cell Lymphoma From The International T-Cell Project Network, Greg Hapgood, Monica Civallero, Yana Stepanishyna, Julie M. Vose, Monica Elena Cabrera, Ranjana H Advani, Stefano A. Pileri, Martina Manni, Steven M. Horwitz, Francine M. Foss, Felicitas Hitz, John Radford, Ivan Dlouhy, Carlos Chiattone, Won Seog Kim, Tetiana Skrypets, Arnon Nagler, Judith Trotman, Stefano Luminari, Massimo Federico

Journal Articles: Oncology and Hematology

The natural history of limited-stage peripheral T-cell lymphomas (PTCLs) remains poorly defined. We investigated outcomes and prognostic variables in patients registered in the T-Cell Project (TCP) (#NCT01142674) to develop a model to predict overall survival (OS) for the common nodal PTCL subtypes (PTCL-NOS, AITL, ALCL). The model was validated in an independent data set from Australian and Brazilian registries. 211 patients registered in the TCP between 2006-2018 were studied. The median age was 59 years (range 18-88) and median follow-up was 49 months. One hundred twenty-seven patients (78%) received anthracycline-based regimens, 5 patients (3%) radiotherapy alone (RT), 24 patients (15%) …

High-Grade B-Cell Lymphoma, Not Otherwise Specified: A Multi-Institutional Retrospective Study, Adam S. Zayac, Daniel J. Landsburg, Mitchell E. Hughes, Allison M. Bock, Grzegorz S. Nowakowski, Emily C. Ayers, Mark Girton, Marie Hu, Amy K. Beckman, Shaoying Li, L Jeffrey Medeiros, Julie E. Chang, Adam Stepanovic, Habibe Kurt, Jose Sandoval-Sus, M Ali Ansari-Lari, Shalin K. Kothari, Anna Kress, Mina L. Xu, Pallawi Torka, Suchitra Sundaram, Stephen D. Smith, Kikkeri N. Naresh, Yasmin H. Karimi, Narendranath Epperla, David A. Bond, Umar Farooq, Mahak Saad, Andrew M. Evens, Karan Pandya, Seema G. Naik, Manali Kamdar, Bradley Haverkos, Reem Karmali, Timothy S. Oh, Julie M. Vose, Heather Nutsch, Paul G. Rubinstein, Amina Chaudhry, Adam J. Olszewski

Journal Articles: Oncology and Hematology

In this multi-institutional retrospective study, we examined the characteristics and outcomes of 160 patients with high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS)-a rare category defined by high-grade morphologic features and lack of MYC rearrangements with BCL2 and/or BCL6 rearrangements ("double hit"). Our results show that HGBL-NOS tumors are heterogeneous: 83% of patients had a germinal center B-cell immunophenotype, 37% a dual-expressor immunophenotype (MYC and BCL2 expression), 28% MYC rearrangement, 13% BCL2 rearrangement, and 11% BCL6 rearrangement. Most patients presented with stage IV disease, a high serum lactate dehydrogenase, and other high-risk clinical factors. Most frequent first-line regimens included dose-adjusted cyclophosphamide, …