Digital Commons Network^™

Liver Secretin Receptor Predicts Portoenterostomy Outcomes And Liver Injury In Biliary Atresia, Nimish Godbole, Iiris Nyholm, Maria Hukkinen, Joseph R Davidson, Athanasios Tyraskis, Jouko Lohi, Päivi Heikkilä, Katja Eloranta, Marjut Pihlajoki, Mark Davenport, Markku Heikinheimo, Antti Kyrönlahti, Mikko P Pakarinen

Open Access Publications

Biliary atresia (BA) is a chronic neonatal cholangiopathy characterized by fibroinflammatory bile duct damage. Reliable biomarkers for predicting native liver survival (NLS) following portoenterostomy (PE) surgery are lacking. Herein we explore the utility of 22 preidentified profibrotic molecules closely connected to ductular reaction (DR) and prevailing after successful PE (SPE), in predicting PE outcomes and liver injury. We used qPCR and immunohistochemistry in a BA cohort including liver samples obtained at PE (n = 53) and during postoperative follow-up after SPE (n = 25). Of the 13 genes over-expressed in relation to cholestatic age-matched controls at PE, only secretin receptor …

Strategies To Limit Invasive Fungal Infection In A Coronavirus Disease 2019 (Covid-19) Intensive Care Unit: The Role Of Infection Prevention For Renovation And Construction In Resource-Limited Settings, Ornnicha Sathitakorn, Surachai Chaononghin, Panipak Katawethiwong, Thanus Pientong, David J. Weber, David K. Warren, Piyaporn Apisarnthanarak, Anucha Apisarnthanarak

Open Access Publications

No abstract provided.

Digital Mental Health Intervention Plus Usual Care Compared With Usual Care Only And Usual Care Plus In-Person Psychological Counseling For Orthopedic Patients With Symptoms Of Depression Or Anxiety: Cohort Study, Ashwin J Leo, Matthew J Schuelke, Devyani M Hunt, J Philip Miller, Patricia A Areán, Abby L Cheng

Open Access Publications

BACKGROUND: Depression and anxiety frequently coexist with chronic musculoskeletal pain and can negatively impact patients' responses to standard orthopedic treatments. Nevertheless, mental health is not routinely addressed in the orthopedic care setting. If effective, a digital mental health intervention may be a feasible and scalable method of addressing mental health in an orthopedic setting.

OBJECTIVE: We aimed to compare 2-month changes in mental and physical health between orthopedic patients who received a digital mental health intervention in addition to usual orthopedic care, those who received usual orthopedic care only (without a specific mental health intervention), and those who received in-person …

Bhlhe40 Regulates The T-Cell Effector Function Required For Tumor Microenvironment Remodeling And Immune Checkpoint Therapy Efficacy, Avery J Salmon, Alexander S Shavkunov, Qi Miao, Nicholas N Jarjour, Sunita Keshari, Ekaterina Esaulova, Charmelle D Williams, Jeffrey P Ward, Anna M Highsmith, Josué E Pineda, Reshma Taneja, Ken Chen, Brian T Edelson, Matthew M Gubin

Open Access Publications

Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can provoke T cell-dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features that T cells require for efficacious ICT remain to be fully elucidated. Herein, we report that anti-PD-1 and anti-CTLA-4 ICT induce upregulation of the transcription factor BHLHE40 in tumor antigen-specific CD8+ and CD4+ T cells and that T cells require BHLHE40 for effective ICT in mice bearing immune-edited tumors. Single-cell RNA sequencing of intratumoral immune cells in BHLHE40-deficient mice revealed differential …

Oxysterol Compounds In Mouse Mutant Αa- And Αb-Crystallin Lenses Can Improve The Optical Properties Of The Lens, Kehao Wang, Masato Hoshino, Kentaro Uesugi, Naoto Yagi, Barbara K Pierscionek, Usha P Andley

Open Access Publications

Purpose: To investigate how cataract-linked mutations affect the gradient refractive index (GRIN) and lens opacification in mouse lenses and whether there is any effect on the optics of the lens from treatment with an oxysterol compound.

Methods: A total of 35 mice including wild-type and knock-in mutants (Cryaa-R49C and Cryab-R120G) were used in these experiments: 26 mice were treated with topical VP1-001, an oxysterol, in one eye and vehicle in the other, and nine mice were untreated controls. Slit lamp biomicroscopy was used to analyze the lens in live animals and to provide apparent cataract grades. Refractive index in the …

A Novel Methodological Approach To Simultaneously Extract High-Quality Total Rna And Proteins From Cortical And Trabecular Bone, Martina Faraldi, Laura Mangiavini, Caterina Conte, Giuseppe Banfi, Nicola Napoli, Giovanni Lombardi

Open Access Publications

Molecular differences between cortical and trabecular bone, of relevance to understanding the pathophysiological basis of bone diseases, can be determined only through effective isolation methods for RNA and proteins. Here we present a TRIzol-based method, which combines bone pulverization and homogenization to extract simultaneously total RNA and proteins from human cortical and trabecular bone from the same carrot. RNA integrity and purity were determined as the 260/280 nm and 260/230 nm absorbance ratios and the 28S/18S rRNA ratio. Protein integrity and quality were evaluated by Coomassie blue staining. Reverse transcription quantitative polymerase chain reaction and immunoblotting for bone-specific genes and …

Clinical And Molecular Relevance Of Genetic Variants In The Non-Coding Transcriptome Of Patients With Cytogenetically Normal Acute Myeloid Leukemia, Dimitrios Papaioannou, Geoffrey L. Uy, Et Al

Open Access Publications

Expression levels of long non-coding RNA (lncRNA) have been shown to associate with clinical outcome of patients with cytogenetically normal acute myeloid leukemia (CN-AML). However, the frequency and clinical significance of genetic variants in the nucleotide sequences of lncRNA in AML patients is unknown. Herein, we analyzed total RNA sequencing data of 377 younger adults (aged <60 years) with CN-AML, who were comprehensively characterized with regard to clinical outcome. We used available genomic databases and stringent filters to annotate genetic variants unequivocally located in the non-coding transcriptome of AML patients. We detected 981 variants, which are recurrently present in lncRNA that are expressed in leukemic blasts. Among these variants, we identified a cytosine-to-thymidine variant in the lncRNA RP5-1074L1.4 and a cytosine-to-thymidine variant in the lncRNA SNHG15, which independently associated with longer survival of CN-AML patients. The presence of the SNHG15 cytosine-to-thymidine variant was also found to associate with better outcome in an independent dataset of CN-AML patients, despite differences in treatment protocols and RNA sequencing techniques. In order to gain biological insights, we cloned and overexpressed both wild-type and variant versions of the SNHG15 lncRNA. In keeping with its negative prognostic impact, overexpression of the wild-type SNHG15 associated with higher proliferation rate of leukemic blasts when compared with the cytosine-to-thymidine variant. We conclude that recurrent genetic variants of lncRNA that are expressed in the leukemic blasts of CN-AML patients have prognostic and potential biological significance.

Ultrasound-Guided Lumbar Medial Branch Blocks And Intra-Articular Facet Joint Injections: A Systematic Review And Meta-Analysis, Zachary M Ashmore, Michael M Bies, James B Meiling, Rajat N Moman, Leslie C Hassett, Christine L Hunt, Steven P Cohen, W Michael Hooten

Open Access Publications

There is great interest in expanding the use of ultrasound (US), but new challenges exist with its application to lumbar facet-targeted procedures. The primary aim of this systematic review and meta-analysis was to determine the risk of incorrect needle placement associated with US-guided lumbar medial branch blocks (MBB) and facet joint injections (FJI) as confirmed by fluoroscopy or computerized tomography (CT). An a priori protocol was registered, and a database search was conducted. Inclusion criteria included all study types. Risk of bias was assessed using the Cochrane risk of bias tool for randomized controlled trials and the National Heart, Lung, …

Prescription And Acceptance Of Durable Medical Equipment In Fortitude-Als, A Study Of Reldesemtiv In Als: Post Hoc Analyses Of A Randomized, Double-Blind, Placebo-Controlled Clinical Trial, Stacy A Rudnicki, Jinsy A Andrews, Angela Genge, Carlayne Jackson, Noah Lechtzin, Timothy M Miller, Bettina M Cockroft, Fady I Malik, Lisa Meng, Jenny Wei, Andrew A Wolff, Jeremy M Shefner, Fortitude-Als Study Group

Open Access Publications

No abstract provided.

H3k36 Dimethylation Shapes The Epigenetic Interaction Landscape By Directing Repressive Chromatin Modifications In Embryonic Stem Cells, Haifen Chen, Bo Hu, Cynthia Horth, Eric Bareke, Phillip Rosenbaum, Sin Young Kwon, Jacinthe Sirois, Daniel N Weinberg, Faith M Robison, Benjamin A Garcia, Chao Lu, William A Pastor, Jacek Majewski

Open Access Publications

Epigenetic modifications on the chromatin do not occur in isolation. Chromatin-associated proteins and their modification products form a highly interconnected network, and disturbing one component may rearrange the entire system. We see this increasingly clearly in epigenetically dysregulated cancers. It is important to understand the rules governing epigenetic interactions. Here, we use the mouse embryonic stem cell (mESC) model to describe in detail the relationships within the H3K27-H3K36-DNA methylation subnetwork. In particular, we focus on the major epigenetic reorganization caused by deletion of the histone 3 lysine 36 methyltransferase NSD1, which in mESCs deposits nearly all of the intergenic H3K36me2. …

Changes In Marriage, Divorce And Births During The Covid-19 Pandemic In Japan, Cyrus Ghaznavi, Takayuki Kawashima, Yuta Tanoue, Daisuke Yoneoka, Koji Makiyama, Haruka Sakamoto, Peter Ueda, Akifumi Eguchi, Shuhei Nomura

Open Access Publications

INTRODUCTION: Marriage, divorce and fertility are declining in Japan. There is concern that the COVID-19 pandemic may have accelerated the decrease in marriages and births while increasing the number of divorces. Changes in partnership behaviours and fertility have significant implications for mental health, well-being and population demographics.

METHODS: Japanese vital statistical data were collected for December 2011-May 2021. We used the Farrington algorithm on the daily numbers of marriages, divorces and births (per month) in order to determine whether any given month between January 2017 and May 2021 had a significant excess or deficit. Analyses were conducted at the national …

Outcomes Of Diabetic Ketoacidosis In Adults With End-Stage Kidney Disease: Retrospective Study Based On A National Database, Karthik Gangu, Sanket D. Basida, Anitha Vijayan, Sindhu Avula, Aniesh Bobba

Open Access Publications

INTRODUCTION: The prevalence of diabetes mellitus (DM) in the United States has steadily increased over the past few decades. End-stage kidney disease (ESKD) and diabetic ketoacidosis (DKA) are among the most common chronic and acute complications of DM. Guidance on the management of DKA in ESKD is limited by lack of evidence. We investigated the in-hospital outcomes of patients hospitalized for DKA with underlying ESKD. Methods: We carried out a retrospective cohort study and utilized the National Inpatient Sample (NIS) database from 2016 to 2018. International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10 CM) codes were used to identify …

Preoperative And Postoperative Patient-Reported Outcome Measurement Information System Scores In Patients Treated For Benign Versus Malignant Soft Tissue Tumors, Jonathan F. Dalton, Ryan Furdock, Landon Cluts, Bharadwaj Jilakara, Douglas Mcdonald, Ryan Calfee, Cara Cipriano

Open Access Publications

BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS) assesses multiple aspects of patient well-being but has not been thoroughly studied amongst orthopedic oncology patients.

QUESTIONS/PURPOSES: How do preoperative/early postoperative PROMIS scores compare in patients with benign versus malignant soft tissue tumors (STTs) for (1) physical function, (2) pain interference, and (3) depression? Are the differences clinically relevant? What other patient/tumor factors impact PROMIS?

METHODS: This retrospective cohort study included 314 STT patients who underwent resection of a benign (n = 187) or malignant (n = 127) STT over a period of 4.25 years at a single institution. PROMIS physical function, …

Analysis Of X-Inactivation Status In A Rett Syndrome Natural History Study Cohort, Xiaolan Fang, Robin C Ryther, Et Al

Open Access Publications

BACKGROUND: Rett syndrome (RTT) is a rare neurodevelopmental disorder associated with pathogenic MECP2 variants. Because the MECP2 gene is subject to X-chromosome inactivation (XCI), factors including MECP2 genotypic variation, tissue differences in XCI, and skewing of XCI all likely contribute to the clinical severity of individuals with RTT.

METHODS: We analyzed the XCI patterns from blood samples of 320 individuals and their mothers. It includes individuals with RTT (n = 287) and other syndromes sharing overlapping phenotypes with RTT (such as CDKL5 Deficiency Disorder [CDD, n = 16]). XCI status in each proband/mother duo and the parental origin of the …

Evaluating The Efficacy Of Rib-To-Pelvis Growth-Friendly Surgery For The Treatment Of Non-Ambulatory Early-Onset Scoliosis Myelomeningocele Patients, Norman Ramirez, Gerardo Olivella, Ryan E Fitzgerald, John T Smith, Peter F Sturm, Paul D Sponseller, Lawrence I Karlin, Scott J Luhmann, Norberto J Torres-Lugo, Tricia St Hilaire, Pediatric Spine Study Group

Open Access Publications

INTRODUCTION: Early-onset scoliosis (EOS) is a well-known orthopaedic manifestation in patients with myelomeningocele. The rib-based growing system (RBGS) has been proposed as an alternative for these individuals because of the poor outcomes with traditional surgical techniques. We aimed to describe the effect of RBGS in patients with nonambulatory EOS myelomeningocele.

METHODS: We retrospectively reviewed the Pediatric Spine Study Group Multicenter Database for all patients with nonambulatory EOS myelomeningocele treated with RBGS from 2004 to 2019. Demographics, surgical data, radiographic findings, and postoperative complications were obtained. The quality-of-life parameters were assessed postoperatively using the Early-onset Scoliosis Questionnaire-24.

RESULTS: Thirty patients (18 …

Techno-Economic Feasibility Analysis Of A Fully Mobile Radiation Oncology System Using Monte Carlo Simulation, Alex T Price, Casey Canfield, Geoffrey D Hugo, James A Kavanaugh, Lauren E Henke, Eric Laugeman, Pamela Samson, Clair Reynolds-Kueny, Elizabeth A Cudney

Open Access Publications

PURPOSE: Disparities in radiation oncology (RO) can be attributed to geographic location, socioeconomic status, race, sex, and other societal factors. One potential solution is to implement a fully mobile (FM) RO system to bring radiotherapy to rural areas and reduce barriers to access. We use Monte Carlo simulation to quantify techno-economic feasibility with uncertainty, using two rural Missouri scenarios.

METHODS: Recently, a semimobile RO system has been developed by building an o-ring linear accelerator (linac) into a mobile coach that is used for temporary care, months at a time. Transitioning to a more FM-RO system, which changes location within a …

Development And Structure Of An Accurate Machine Learning Algorithm To Predict Inpatient Mortality And Hospice Outcomes In The Coronavirus Disease 2019 Era, Stephen Chi, Aixia Guo, Kevin Heard, Seunghwan Kim, Randi Foraker, Patrick White, Nathan Moore

Open Access Publications

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has challenged the accuracy and racial biases present in traditional mortality scores. An accurate prognostic model that can be applied to hospitalized patients irrespective of race or COVID-19 status may benefit patient care.

RESEARCH DESIGN: This cohort study utilized historical and ongoing electronic health record features to develop and validate a deep-learning model applied on the second day of admission predicting a composite outcome of in-hospital mortality, discharge to hospice, or death within 30 days of admission. Model features included patient demographics, diagnoses, procedures, inpatient medications, laboratory values, vital signs, and substance use …

Baseline Microglial Activation Correlates With Brain Amyloidosis And Longitudinal Cognitive Decline In Alzheimer Disease, Qing Wang, Gengsheng Chen, Suzanne E Schindler, Jon Christensen, Nicole S Mckay, Jingxia Liu, Sicheng Wang, Zhexian Sun, Jason Hassenstab, Shaney Flores, Russ Hornbeck, Lisa Cash, Carlos Cruchaga, Anne M Fagan, Zhude Tu, John C Morris, Yong Wang, Tammie L S Benzinger, Et Al

Open Access Publications

BACKGROUND AND OBJECTIVES: This study aims to quantify microglial activation in individuals with Alzheimer disease (AD) using the 18-kDa translocator protein (TSPO) PET imaging in the hippocampus and precuneus, the 2 AD-vulnerable regions, and to evaluate the association of baseline neuroinflammation with amyloidosis, tau, and longitudinal cognitive decline.

METHODS: Twenty-four participants from the Knight Alzheimer Disease Research Center (Knight ADRC) were enrolled and classified into stable cognitively normal, progressor, and symptomatic AD groups based on clinical dementia rating (CDR) at 2 or more clinical assessments. The baseline TSPO radiotracer [11C]PK11195 was used to image microglial activation. Baseline CSF concentrations of …

Three-Dimensional Quantification Of Cam Resection Using Mri Bone Models: A Comparison Of 2 Techniques, Thomas D Alter, Derrick M Knapik, Martina Guidetti, Alejandro Espinoza, Jorge Chahla, Shane J Nho, Philip Malloy

Open Access Publications

Background: The current clinical standard for the evaluation of cam deformity in femoroacetabular impingement syndrome is based on radiographic measurements, which limit the ability to quantify the complex 3-dimensional (3D) morphology of the proximal femur.

Purpose: To compare magnetic resonance imaging (MRI)-based metrics for the quantification of cam resection as derived using a best-fit sphere alpha angle (BFS-AA) method and using 3D preoperative-postoperative surface model subtraction (PP-SMS).

Study Design: Descriptive laboratory study.

Methods: Seven cadaveric hemipelvises underwent 1.5-T MRI before and after arthroscopic femoral osteochondroplasty, and 3D bone models of the proximal femur were reconstructed from the MRI scans. The …

Sex-Based Differences In Femoroacetabular Impingement Syndrome And The Effect Of Cam Deformity Location On The Extent Of Labral Tearing, Thomas Alter, Derrick Knapik, Fllor Lambers, Martina Guidetti, Jorge Chahla, Philip Malloy, Shane Nho

Open Access Publications

No abstract provided.

Society For Immunotherapy Of Cancer (Sitc) Clinical Practice Guideline On Immunotherapy For The Treatment Of Lung Cancer And Mesothelioma, Ramaswamy Govindan, Charu Aggarwal, Scott J Antonia, Marianne Davies, Steven M Dubinett, Andrea Ferris, Patrick M Forde, Edward B Garon, Sarah B Goldberg, Raffit Hassan, Matthew D Hellmann, Fred R Hirsch, Melissa L Johnson, Shakun Malik, Daniel Morgensztern, Joel W Neal, Jyoti D Patel, David L Rimm, Sarah Sagorsky, Lawrence H Schwartz, Boris Sepesi, Roy S Herbst

Open Access Publications

Immunotherapy has transformed lung cancer care in recent years. In addition to providing durable responses and prolonged survival outcomes for a subset of patients with heavily pretreated non-small cell lung cancer (NSCLC), immune checkpoint inhibitors (ICIs)- either as monotherapy or in combination with other ICIs or chemotherapy-have demonstrated benefits in first-line therapy for advanced disease, the neoadjuvant and adjuvant settings, as well as in additional thoracic malignancies such as small-cell lung cancer (SCLC) and mesothelioma. Challenging questions remain, however, on topics including therapy selection, appropriate biomarker-based identification of patients who may derive benefit, the use of immunotherapy in special populations …

Characterization Of A Novel Microfilarial Antigen For Diagnosis Of Wuchereria Bancrofti Infections, Sarah E. Greene, Kerstin Fischer, Young-Jun Choi, Kurt C. Curtis, Philip J. Budge, Makedonka Mitreva, Christopher L. King, Peter U. Fischer, Gary J. Weil

Open Access Publications

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease caused by the filarial nematodes Wuchereria bancrofti, Brugia malayi and Brugia timori. The Global Program to Eliminate LF uses mass drug administration (MDA) of anti-filarial drugs that clear microfilariae (Mf) from blood to interrupt transmission by mosquitos. New diagnostic tools are needed to assess the impact of MDA on bancroftian filariasis, because available serologic tests can remain positive after successful treatment.

METHODOLOGY/PRINCIPAL FINDINGS: We identified Wb-bhp-1, which encodes a W. bancrofti homologue of BmR1, the B. malayi protein used in the Brugia Rapid antibody test for brugian filariasis. Wb-bhp-1 has a …

Precise Genotyping Of Circular Mobile Elements From Metagenomic Data Uncovers Human-Associated Plasmids With Recent Common Ancestors, Nitan Shalon, David A Relman, Eitan Yaffe

Open Access Publications

Mobile genetic elements with circular genomes play a key role in the evolution of microbial communities. Their circular genomes correspond to circular walks in metagenome graphs, and yet, assemblies derived from natural microbial communities produce graphs riddled with spurious cycles, complicating the accurate reconstruction of circular genomes. We present DomCycle, an algorithm that reconstructs likely circular genomes based on the identification of so-called "dominant" graph cycles. In the implementation, we leverage paired reads to bridge assembly gaps and scrutinize cycles through a nucleotide-level analysis, making the approach robust to misassembly artifacts. We validated the approach using simulated and real sequencing …

Regulation Of Pdf Receptor Signaling Controlling Daily Locomotor Rhythms In Drosophila, Weihua Li, Jennifer S. Trigg, Paul H. Taghert

Open Access Publications

Each day and in conjunction with ambient daylight conditions, neuropeptide PDF regulates the phase and amplitude of locomotor activity rhythms in Drosophila through its receptor, PDFR, a Family B G protein-coupled receptor (GPCR). We studied the in vivo process by which PDFR signaling turns off, by converting as many as half of the 28 potential sites of phosphorylation in its C terminal tail to a non-phosphorylatable residue (alanine). We report that many such sites are conserved evolutionarily, and their conversion creates a specific behavioral syndrome opposite to loss-of-function phenotypes previously described for pdfr. That syndrome includes increases in the amplitudes …

Effect Of Active And Passive Function Of The Posterosuperior Rotator Cuff On Compensatory Muscle Loads In The Shoulder, Philipp Moroder, Aaron Chamberlain, Stefan M Gabriel, Marc C Jacofsky, Mehmet Z Sengun, David B Spenciner, John M Tokish, Lucca Lacheta

Open Access Publications

Background: Irreparable posterosuperior rotator cuff (PSRC) tears have been shown to result in shoulder pain and loss of function.

Purpose/Hypothesis: The purpose of this study was to determine the effect of the loss of active or passive function of the PSRC on compensatory muscle loads in the deltoid and the remaining rotator cuff. It was hypothesized that both deactivation and resection of the PSRC would result in load increases in the remaining muscles and that resection of the PSRC would result in even higher required compensatory forces than would mere deactivation.

Study Design: Controlled laboratory study.

Methods: A total of …

Immunotherapy-Induced Auto-Splenectomy In A Patient Of Malignant Melanoma, Syed Ehsanullah, Azharuddin Muhammad, Syed Hasan, John M. Richart

Open Access Publications

Immune checkpoint inhibitors like programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are biological agents that help in boosting the immune system of the body to fight against cancer cells. These checkpoint inhibitors are now being approved by the Food and Drug Administration (FDA) to treat various malignancies due to remarkable response. Here, we present a rare immune-related adverse event in a 77-year-old female with metastatic melanoma treated with ipilimumab and nivolumab, later presented with auto-splenectomy.

Traumatic Rupture Of A Skull Base Dermoid Cyst Mimicking Chronic Meningitis, Ahmed Taha, Mahmoud A. Abdelrazek, Natalie Manalo, Rabab Elsadek, Scott J. Morrin, Alexander Brodski, Aleksandra Augustynowiczd, Roohallah S. Mollashahi, Anant Shenoy

Open Access Publications

Cranial dermoid cysts are rare, embryologic tumors containing fat, hair, and other ectodermal elements. They occur most frequently in the posterior fossa and are typically diagnosed as incidental findings on brain imaging done for an unrelated reason. Traumatic rupture of a previously unidentified intracranial dermoid cyst can mimic symptoms of post-concussion syndrome and should be ruled out with magnetic resonance imaging (MRI). Surgical intervention after traumatic rupture may not result in complete symptom control due to the persistence of dermoid cyst debris in the subarachnoid space. Here, we present the clinical scenario and radiological features of a ruptured dermoid cyst …

Targeted Treatment For High-Risk Early-Stage Triple-Negative Breast Cancer: Spotlight On Pembrolizumab, Nusayba A Bagegni, Andrew A Davis, Katherine K Clifton, Foluso O Ademuyiwa

Open Access Publications

Triple-negative breast cancer (TNBC) is a biologically aggressive yet heterogeneous disease that disproportionately affects younger women and women of color compared to other breast cancer subtypes. The paucity of effective targeted therapies and the prevalence of chemotherapeutic resistance in high-risk, early-stage TNBC pose significant clinical challenges. Deeper insights into the genomic and immune landscape have revealed key features of TNBC, including intrinsic genomic instability, DNA repair deficiency, and potentially an immunogenic tumor microenvironment. These advances led to landmark trials with immune checkpoint inhibitors in the advanced-stage setting, which subsequently translated into immunotherapy-based clinical trials in the early-stage setting and recent …

Improving Eligibility Criteria For First-Line Trials For Patients With Dlbcl Using A Us-Based Delphi-Method Survey, R Andrew Harkins, Nancy L Bartlett, Amanda F Cashen, Brad S Kahl, Neha Mehta-Shah, Et Al

Open Access Publications

Recent first-line randomized controlled trials (RCTs) for patients with diffuse large B-cell lymphoma (DLBCL) have shown negative results, which may be due in part to onerous eligibility criteria limiting enrollment of poor-risk patients who require immediate treatment. We conducted a Delphi-method survey with lymphoma experts in the United States to define recommendations for essential and potentially unnecessary enrollment criteria for modern first-line DLBCL RCTs aimed at increasing clinical diversity of ensuing study groups. We first tabulated enrollment criteria from 19 DLBCL RCTs spanning the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) era to identify common eligibility criteria from prior DLBCL …

Risk Factors For Severe Covid-19 Differ By Age For Hospitalized Adults, Sevda Molani, Patricia V Hernandez, Ryan T Roper, Venkata R Duvvuri, Andrew M Baumgartner, Jason D Goldman, Nilüfer Ertekin-Taner, Cory C Funk, Nathan D Price, Noa Rappaport, Jennifer J Hadlock

Open Access Publications

Risk stratification for hospitalized adults with COVID-19 is essential to inform decisions about individual patients and allocation of resources. So far, risk models for severe COVID outcomes have included age but have not been optimized to best serve the needs of either older or younger adults. Models also need to be updated to reflect improvements in COVID-19 treatments. This retrospective study analyzed data from 6906 hospitalized adults with COVID-19 from a community health system across five states in the western United States. Risk models were developed to predict mechanical ventilation illness or death across one to 56 days of hospitalization, …