Digital Commons Network^™

Patterns In Use And Transplant Outcomes Among Adult Recipients Of Kidneys From Deceased Donors With Covid-19, Mengmeng Ji, Amanda J Vinson, Su-Hsin Chang, Massini Merzkani, Krista L Lentine, Yasar Caliskan, Kristin Progar, Nicole Nesselhauf, Casey Dubrawka, Tarek Alhamad

2020-Current year OA Pubs

IMPORTANCE: While the COVID-19 pandemic enters a new phase and the proportion of individuals with a previous COVID-19 diagnosis increases, the national patterns in kidney use and medium-term kidney transplant (KT) outcomes among patients receiving kidneys from active or resolved COVID-19-positive donors remain unknown.

OBJECTIVE: To evaluate the patterns in kidney use and KT outcomes among adult recipients of kidneys from deceased donors with active or resolved COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted using national US transplant registry data from 35 851 deceased donors (71 334 kidneys) and 45 912 adult patients who received KTs …

Propranolol Reduces Ifn-Γ Driven Pd-L1 Immunosuppression And Improves Anti-Tumour Immunity In Ovarian Cancer, M Falcinelli, G Al-Hity, S Baron, M Mampay, M C Allen, M Samuels, W Jones, C Cilibrasi, Renee L Flaherty, G Giamas, P H Thaker, M S Flint

2020-Current year OA Pubs

The immune system plays an important role in controlling epithelial ovarian cancer (EOC). EOC is considered to be a "cold tumour," a tumour that has not triggered a strong response by the immune system. However, tumour infiltrating lymphocytes (TILs) and the expression of programmed cell death ligand (PD-L1) are used as prognostic indicators in EOC. Immunotherapy such as PD-(L)1 inhibitors have shown limited benefit in EOC. Since the immune system is affected by behavioural stress and the beta-adrenergic signalling pathway, this study aimed to explore the impact of propranolol (PRO), a beta-blocker, on anti-tumour immunity in both in vitro and …

The Natural History Of Curve Behavior After Brace Removal In Adolescent Idiopathic Scoliosis: A Literature Review, Scott Luhmann, Daphna Zaaroor-Regev, Vidyadhar V Upasani, Harry Shufflebarger

2020-Current year OA Pubs

PURPOSE: Brace treatment is the most common nonoperative treatment to prevent curve progression in adolescent idiopathic scoliosis (AIS). The goal of this review and analysis is to characterize curve behavior after completion of brace treatment and to identify factors that may facilitate the estimation of long-term curve progression.

METHOD: A review of the English language literature was completed using the MEDLINE (PUBMED) database of publications after 1990 until September 2020. Studies were included if they detailed a minimum of 1 year post-brace removal follow-up of AIS patients. Data retrieved from the articles included Cobb angle measurements of the major curves …

Position Paper: Models Of Post-Transplant Care For Individuals With Cystic Fibrosis, Edward Mckone, Joshua Blatter, Ramsey Hachem, Et Al.

2020-Current year OA Pubs

There is no consensus on the best model of care for individuals with CF to manage the non-pulmonary complications that persist after lung transplant. The CF Foundation virtually convened a group of international experts in CF and lung-transplant care. The committee reviewed literature and shared the post-lung transplant model of care practiced by their programs. The committee then developed a survey that was distributed internationally to both the clinical and individual with CF/family audiences to determine the strengths, weaknesses, and preferences for various models of transplant care. Discussion generated two models to accomplish optimal CF care after transplant. The first …

Remote Global Radiation Oncology Education And Training: A Pathway To Increase Access To High-Quality Radiation Therapy Services In Low- And Middle-Income Countries, Awusi Kavuma, Matthew Schmidt, Tianyu Zhao, Hiram Gay, Jeff Michalski, Geoffrey Hugo, Jacaranda Van Rheenen, Baozhou Sun, Et Al.

2020-Current year OA Pubs

PURPOSE: There is a vital need to train radiation therapy professionals in low- and middle-income countries (LMICs) to develop sustainable cancer treatment capacity and infrastructure. LMICs have started to introduce intensity modulated radiation therapy (IMRT), which is the standard of care in high-income countries, because of improved outcomes and reduced toxicities. This work reports the efficacy of a complementary asynchronous plus synchronous virtual-training approach on improving radiation therapy professions' self-confidence levels and evaluating participants' attitudes toward asynchronous and synchronous didactic hands-on learning in 3 LMICs.

METHODS AND MATERIALS: Training was provided to 37 participants from Uganda, Guatemala, and Mongolia, which …

Effects Of A Combination Economic Empowerment And Family Strengthening Intervention On Psychosocial Well-Being Among Ugandan Adolescent Girls And Young Women: Analysis Of A Cluster Randomized Controlled Trial (Suubi4her), Lindsey M Filiatreau, Nhial Tutlam, Rachel Brathwaite, William Byansi, Flavia Namuwonge, Abel Mwebembezi, Ozge Sensoy-Bahar, Proscovia Nabunya, Torsten B Neilands, Patricia Cavazos-Rehg, Mary Mckay, Fred M Ssewamala

2020-Current year OA Pubs

PURPOSE: Economic empowerment and family strengthening interventions have shown promise for improving psychosocial well-being in a range of populations. This study investigates the effect of a combination economic and family strengthening intervention on psychosocial well-being among Ugandan adolescent girls and young women (AGYW).

METHODS: We harnessed data from a three-arm cluster randomized controlled trial among AGYW aged 14-17 years in 47 Ugandan secondary schools. Schools were randomized to either a youth development account intervention (YDA) [N = 16 schools], YDA plus a multiple family group intervention (YDA + MFG) [N = 15 schools], or bolstered standard of care (BSOC) [N …

Circulating Markers Of Microbial Translocation And Host Response To Bacteria With Risk Of Colorectal Cancer: A Prospective, Nested Case-Control Study In Men, Mengyao Shi, Xiaoyu Zong, Jinhee Hur, Brenda M Birmann, Otoniel Martinez-Maza, Marta Epeldegui, Andrew T Chan, Edward L Giovannucci, Yin Cao

2020-Current year OA Pubs

BACKGROUND: Gut microbial dysbiosis contributes to colorectal cancer (CRC) pathogenesis, possibly mediated in part by increased intestinal permeability to endotoxin lipopolysaccharide (LPS), microbial translocation, and subsequent endotoxemia and inflammation. However, epidemiologic evidence linking circulating markers of microbial translocation with CRC risk is limited.

METHODS: We conducted a prospective, nested case-control study of 261 incident CRC cases and 261 controls (matched on age and time of blood draw) among 18,159 men with pre-diagnostic blood specimens in the Health Professionals Follow-Up Study (1993-2009). We examined three complementary markers of microbial translocation and host response to bacteria, including LPS-binding protein (LBP), soluble CD14 …

Sars-Cov-2 Vaccination In The First Year After Allogeneic Hematopoietic Cell Transplant: A Prospective, Multicentre, Observational Study, Joshua A Hill, Peter Westervelt, Et Al.

2020-Current year OA Pubs

BACKGROUND: The optimal timing for SARS-CoV-2 vaccines within the first year after allogeneic hematopoietic cell transplant (HCT) is poorly understood.

METHODS: We conducted a prospective, multicentre, observational study of allogeneic HCT recipients who initiated SARS-CoV-2 vaccinations within 12 months of HCT. Participants were enrolled at 22 academic cancer centers across the United States. Participants of any age who were planning to receive a first post-HCT SARS-CoV-2 vaccine within 12 months of HCT were eligible. We obtained blood prior to and after each vaccine dose for up to four vaccine doses, with an end-of-study sample seven to nine months after enrollment. …

Pregnancy And Neonatal Outcomes Among Women With Early-Onset Colorectal Cancer: A Nationwide Case-Control Study, Yin Cao, Stephanie Zhao, Tomas S Bexelius, Jonas Söderling, Mengyao Shi, Bjorn Roelstraete, Barbara B Warner, Olof Stephansson, Jonas F Ludvigsson

2020-Current year OA Pubs

BACKGROUND: Early-onset colorectal cancer has risen worldwide, leaving more women with colorectal cancer at reproductive ages. We aimed to investigate the risk of adverse pregnancy and neonatal outcomes among women with early-onset colorectal cancer.

METHODS: We conducted a nationwide, matched case-control study of maternal/pregnancy outcomes including pre-eclampsia and Cesarean delivery (C-section) as well as neonatal outcomes including preterm birth among 207 births in women with early-onset colorectal cancer (ages 18-49) and 1019 births in women without colorectal cancer in Sweden (1992-2019). Early-onset colorectal cancer cases were identified through the Cancer Register, and outcome data were retrieved through linkage to Medical …

Cognitive Function Following Diabetic Ketoacidosis In Young Children With Type 1 Diabetes, Simona Ghetti, Kimberly S Quayle, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Young children with type 1 diabetes (T1D) may be at particularly high risk of cognitive decline following diabetic ketoacidosis (DKA). However, studies of cognitive functioning in T1D typically examine school-age children. The goal of this study was to examine whether a single experience of DKA is associated with lower cognitive functioning in young children. We found that recently diagnosed 3- to 5-year-olds who experienced one DKA episode, regardless of its severity, exhibited lower IQ scores than those with no DKA exposure.

METHODS: We prospectively enrolled 46 3- to 5-year-old children, who presented with DKA at the onset of T1D, …

Independent Study Demonstrates Amyloid Probability Score Accurately Indicates Amyloid Pathology, Ilana Fogelman, Randall J Bateman, David M Holtzman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The amyloid probability score (APS) is the model read-out of the analytically validated mass spectrometry-based PrecivityAD

PURPOSE: This study aimed to provide additional independent evidence that the pre-established APS algorithm, along with its cutoff values, discriminates between amyloid positive and negative individuals.

METHODS: The diagnostic performance of the PrecivityAD test was analyzed in a cohort of 200 nonrandomly selected Australian Imaging, Biomarker & Lifestyle Flagship Study of Aging (AIBL) study participants, who were either cognitively impaired or healthy controls, and for whom a blood sample and amyloid PET imaging were available.

RESULTS: In a subset of the dataset aligned …

Immunotherapeutic Approach To Reduce Senescent Cells And Alleviate Senescence-Associated Secretory Phenotype In Mice, Niraj Shrestha, Mark Foster, Lynne Marsala, Pamela Wong, Celia C Cubitt, Jennifer A Foltz, Jennifer Tran, Timothy Schappe, Melissa M Berrien-Elliott, Todd A Fehniger, Et Al.

2020-Current year OA Pubs

Accumulation of senescent cells (SNCs) with a senescence-associated secretory phenotype (SASP) has been implicated as a major source of chronic sterile inflammation leading to many age-related pathologies. Herein, we provide evidence that a bifunctional immunotherapeutic, HCW9218, with capabilities of neutralizing TGF-β and stimulating immune cells, can be safely administered systemically to reduce SNCs and alleviate SASP in mice. In the diabetic db/db mouse model, subcutaneous administration of HCW9218 reduced senescent islet β cells and SASP resulting in improved glucose tolerance, insulin resistance, and aging index. In naturally aged mice, subcutaneous administration of HCW9218 durably reduced the level of SNCs and …

Distinct Effects Of Two Hearing Loss-Associated Mutations In The Sarcomeric Myosin Myh7b, Lindsey A Lee, Samantha K Barrick, Ada E Buvoli, Jonathan Walklate, W Tom Stump, Michael Geeves, Michael J Greenberg, Leslie A Leinwand

2020-Current year OA Pubs

For decades, sarcomeric myosin heavy chain proteins were assumed to be restricted to striated muscle where they function as molecular motors that contract muscle. However, MYH7b, an evolutionarily ancient member of this myosin family, has been detected in mammalian nonmuscle tissues, and mutations in MYH7b are linked to hereditary hearing loss in compound heterozygous patients. These mutations are the first associated with hearing loss rather than a muscle pathology, and because there are no homologous mutations in other myosin isoforms, their functional effects were unknown. We generated recombinant human MYH7b harboring the D515N or R1651Q hearing loss-associated mutation and studied …

Neurosteroids As Stress Modulators And Neurotherapeutics: Lessons From The Retina, Yukitoshi Izumi, Makoto Ishikawa, Toru Nakazawa, Hiroshi Kunikata, Kota Sato, Douglas F. Covey, Charles F. Zorumski

2020-Current year OA Pubs

Neurosteroids are rapidly emerging as important new therapies in neuropsychiatry, with one such agent, brexanolone, already approved for treatment of postpartum depression, and others on the horizon. These steroids have unique properties, including neuroprotective effects that could benefit a wide range of brain illnesses including depression, anxiety, epilepsy, and neurodegeneration. Over the past 25 years, our group has developed ex vivo rodent models to examine factors contributing to several forms of neurodegeneration in the retina. In the course of this work, we have developed a model of acute closed angle glaucoma that involves incubation of ex vivo retinas under hyperbaric …

Bk Channels Of Five Different Subunit Combinations Underlie The De Novo Kcnma1 G375r Channelopathy, Yanyan Geng, Ping Li, Alice Butler, Bill Wang, Lawrence Salkoff, Karl L Magleby

2020-Current year OA Pubs

The molecular basis of a severe developmental and neurological disorder associated with a de novo G375R variant of the tetrameric BK channel is unknown. Here, we address this question by recording from single BK channels expressed to mimic a G375R mutation heterozygous with a WT allele. Five different types of functional BK channels were expressed: 3% were consistent with WT, 12% with homotetrameric mutant, and 85% with three different types of hybrid (heterotetrameric) channels assembled from both mutant and WT subunits. All channel types except WT showed a marked gain-of-function in voltage activation and a smaller decrease-of-function in single-channel conductance, …

Blockade Of Trpv Channels By Intracellular Spermine, Grigory Maksaev, Peng Yuan, Colin G Nichols

2020-Current year OA Pubs

The Vanilloid thermoTRP (TRPV1-4) subfamily of TRP channels are involved in thermoregulation, osmoregulation, itch and pain perception, (neuro)inflammation and immune response, and tight control of channel activity is required for perception of noxious stimuli and pain. Here we report voltage-dependent modulation of each of human TRPV1, 3, and 4 by the endogenous intracellular polyamine spermine. As in inward rectifier K channels, currents are blocked in a strongly voltage-dependent manner, but, as in cyclic nucleotide-gated channels, the blockade is substantially reduced at more positive voltages, with maximal blockade in the vicinity of zero voltage. A kinetic model of inhibition suggests two …

Differential Regulation Of Cardiac Sodium Channels By Intracellular Fibroblast Growth Factors, Paweorn Angsutararux, Amal K Dutta, Martina Marras, Carlota Abella, Rebecca L Mellor, Jingyi Shi, Jeanne M Nerbonne, Jonathan R Silva

2020-Current year OA Pubs

Voltage-gated sodium (NaV) channels are responsible for the initiation and propagation of action potentials. In the heart, the predominant NaV1.5 α subunit is composed of four homologous repeats (I-IV) and forms a macromolecular complex with multiple accessory proteins, including intracellular fibroblast growth factors (iFGF). In spite of high homology, each of the iFGFs, iFGF11-iFGF14, as well as the individual iFGF splice variants, differentially regulates NaV channel gating, and the mechanisms underlying these differential effects remain elusive. Much of the work exploring iFGF regulation of NaV1.5 has been performed in mouse and rat ventricular myocytes in which iFGF13VY is the predominant …

Mitos And King's Staging As Clinical Outcome Measures In Als: A Retrospective Analysis Of The Fortitude-Als Trial, Paulos Gebrehiwet, Lisa Meng, Stacy A Rudnicki, Phil Sarocco, Jenny Wei, Andrew A Wolff, Adriano Chiò, Jinsy A Andrews, Angela Genge, Carlayne E Jackson, Noah Lechtzin, Timothy M Miller, Jeremy M Shefner

2020-Current year OA Pubs

OBJECTIVE: To evaluate the Milano-Torino staging (MiToS) and King's staging systems as potential outcome measures for clinical trials in amyotrophic lateral sclerosis (ALS) by assessing these outcomes in FORTITUDE-ALS.

METHODS: This was a

RESULTS: The full analysis set consisted of 456 patients randomized 3:1 (

CONCLUSION: This exploratory analysis showed the feasibility of MiToS and King's staging as potential outcome measures in ALS. Additional studies of these staging systems are needed to further explore their utility in ALS clinical trials.

Association Of Sex With Neurobehavioral Markers Of Executive Function In 2-Year-Olds At High And Low Likelihood Of Autism, Tanya St John, Natasha Marrus, Kelly N Botteron, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Children with autism and their siblings exhibit executive function (EF) deficits early in development, but associations between EF and biological sex or early brain alterations in this population are largely unexplored.

OBJECTIVE: To investigate the interaction of sex, autism likelihood group, and structural magnetic resonance imaging alterations on EF in 2-year-old children at high familial likelihood (HL) and low familial likelihood (LL) of autism, based on having an older sibling with autism or no family history of autism in first-degree relatives.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study assessed 165 toddlers at HL (n = 110) and LL …

Expanded Directly Binds Conserved Regions Of Fat To Restrain Growth Via The Hippo Pathway, Alexander D Fulford, Leonie Enderle, Jannette Rusch, Didier Hodzic, Maxine V Holder, Alex Earl, Robin Hyunseo Oh, Nicolas Tapon, Helen Mcneill

2020-Current year OA Pubs

The Hippo pathway is a conserved and critical regulator of tissue growth. The FERM protein Expanded is a key signaling hub that promotes activation of the Hippo pathway, thereby inhibiting the transcriptional co-activator Yorkie. Previous work identified the polarity determinant Crumbs as a primary regulator of Expanded. Here, we show that the giant cadherin Fat also regulates Expanded directly and independently of Crumbs. We show that direct binding between Expanded and a highly conserved region of the Fat cytoplasmic domain recruits Expanded to the apicolateral junctional zone and stabilizes Expanded. In vivo deletion of Expanded binding regions in Fat causes …

Tumor-Derived Interleukin-1Α And Leukemia Inhibitory Factor Promote Extramedullary Hematopoiesis, Derek A. G. Barisas, Ashraf Ul Kabir, Jun Wu, Karen Krchma, Minseo Kim, Madhav Subramanian, Bernd H. Zinselmeyer, Colin L. Stewart, Kyunghee Choi

2020-Current year OA Pubs

Extramedullary hematopoiesis (EMH) expands hematopoietic capacity outside of the bone marrow in response to inflammatory conditions, including infections and cancer. Because of its inducible nature, EMH offers a unique opportunity to study the interaction between hematopoietic stem and progenitor cells (HSPCs) and their niche. In cancer patients, the spleen frequently serves as an EMH organ and provides myeloid cells that may worsen pathology. Here, we examined the relationship between HSPCs and their splenic niche in EMH in a mouse breast cancer model. We identify tumor produced IL-1α and leukemia inhibitory factor (LIF) acting on splenic HSPCs and splenic niche cells, …

Capsular Polysaccharide Inhibits Vaccine-Induced O-Antigen Antibody Binding And Function Across Both Classical And Hypervirulent K2:O1 Strains Of Klebsiella Pneumoniae, Paeton L. Wantuch, Cory J. Knoot, Lloyd S. Robinson, Evgeny Vinogradov, Nichollas E. Scott, Christian M. Harding, David A. Rosen

2020-Current year OA Pubs

Klebsiella pneumoniae presents as two circulating pathotypes: classical K. pneumoniae (cKp) and hypervirulent K. pneumoniae (hvKp). Classical isolates are considered urgent threats due to their antibiotic resistance profiles, while hvKp isolates have historically been antibiotic susceptible. Recently, however, increased rates of antibiotic resistance have been observed in both hvKp and cKp, further underscoring the need for preventive and effective immunotherapies. Two distinct surface polysaccharides have gained traction as vaccine candidates against K. pneumoniae: capsular polysaccharide and the O-antigen of lipopolysaccharide. While both targets have practical advantages and disadvantages, it remains unclear which of these antigens included in a vaccine would …

Quantitative Determination Of Slc2a1 Variant Functional Effects In Glut1 Deficiency Syndrome, Naeimeh Tayebi, Brian Leon-Ricardo, Kevin Mccall, Elvisa Mehinovic, Kristin Engelstad, Vincent Huynh, Tychele N Turner, Judy Weisenberg, Liu L Thio, Paul Hruz, Robin S B Williams, Darryl C De Vivo, Vincent Petit, Gabe Haller, Christina A Gurnett

2020-Current year OA Pubs

OBJECTIVE: The goal of this study is to demonstrate the utility of a growth assay to quantify the functional impact of single nucleotide variants (SNVs) in SLC2A1, the gene responsible for Glut1DS.

METHODS: The functional impact of 40 SNVs in SLC2A1 was quantitatively determined in HAP1 cells in which SLC2A1 is required for growth. Donor libraries were introduced into the endogenous SLC2A1 gene in HAP1-Lig4KO cells using CRISPR/Cas9. Cell populations were harvested and sequenced to quantify the effect of variants on growth and generate a functional score. Quantitative functional scores were compared to 3-OMG uptake, SLC2A1 cell surface expression, CADD …

Symptomatic Benefit Of Momelotinib In Patients With Myelofibrosis: Results From The Simplify Phase Iii Studies, Ruben A Mesa, Stephen T Oh, Et Al.

2020-Current year OA Pubs

BACKGROUND: Myelofibrosis (MF)-associated constitutional symptoms can severely impact health-related quality of life. Clinical trials in MF traditionally measure symptom response to treatment as a landmark endpoint of total symptom score (TSS) reduction ≥50% from baseline. However, this dichotomous assessment provides a limited view of clinically relevant symptomatic changes. Herein we evaluated longitudinal change from baseline in TSS over the continuous 24-week period and individual symptom scores to obtain a more comprehensive understanding of symptom benefits experienced by patients with MF receiving therapy.

METHODS: Longitudinal symptom change was evaluated using mixed-effect model repeated measure (MMRM) methodology with individual item-level analyses to …

Provisional Practice Recommendation For The Management Of Myopathy In Vcp-Associated Multisystem Proteinopathy, Bhaskar Roy, Conrad Chris Weihl, Et Al.

2020-Current year OA Pubs

Valosin-containing protein (VCP)-associated multisystem proteinopathy (MSP) is a rare genetic disorder with abnormalities in the autophagy pathway leading to various combinations of myopathy, bone diseases, and neurodegeneration. Ninety percent of patients with VCP-associated MSP have myopathy, but there is no consensus-based guideline. The goal of this working group was to develop a best practice set of provisional recommendations for VCP myopathy which can be easily implemented across the globe. As an initiative by Cure VCP Disease Inc., a patient advocacy organization, an online survey was initially conducted to identify the practice gaps in VCP myopathy. All prior published literature on …

Treatment And Disposal Practices Of Pharmaceutical Effluent Containing Potential Antibiotic Residues In Two States In India And Perceptions Of Various Stakeholders On Contribution Of Pharmaceutical Effluent To Antimicrobial Resistance: A Qualitative Study, Anita Kotwani, Ajita Kapur, Mihir Chauhan, Sumanth Gandra

2020-Current year OA Pubs

BACKGROUND: Antimicrobial resistance (AMR) is a looming pandemic, demanding prompt actions to avert catastrophic consequences. Effluents from pharmaceutical industries containing antimicrobial residues could serve as one of the entry points of these drugs to the environment. This qualitative study explores the treatment and disposal practices of pharmaceutical effluent (PE) containing potential antibiotic residues (ARs) by interviewing major stakeholders. In addition, we assessed their knowledge and perception on contribution of PE to AMR.

METHODS: The study was conducted in the two Indian states, Haryana and Telangana and at the federal level. Data was collected by semi-structured in-depth interviews of 29 participants …

A Phase 1 First-In-Human Study Of Gs-0189, An Anti-Signal Regulatory Protein Alpha (Sirpα) Monoclonal Antibody, In Patients With Relapsed/Refractory (R/R) Non-Hodgkin Lymphoma (Nhl), Mayur Narkhede, Nancy L Bartlett, Sami Ibrahimi, Leslie Popplewell, Anna Seto, Jamie Bates, Yeonju Lee, Vaishnavi Ganti, Ling Han, Tianling Chen, Manish R Patel

2020-Current year OA Pubs

Signal regulatory protein alpha (SIRPα) is the receptor for cluster of differentiation (CD)47, a potent "don't eat me" signal for macrophages. Disruption of CD47-SIRPα signaling in the presence of prophagocytic signals can lead to enhanced phagocytosis of tumor cells, resulting in a direct antitumor effect; agents targeting this pathway have shown efficacy in non-Hodgkin lymphoma (NHL) and other tumor types. GS-0189 is a novel anti-SIRPα humanized monoclonal antibody. Here we report: (1) clinical safety, preliminary activity, and pharmacokinetics of GS-0189 as monotherapy and in combination with rituximab from a phase 1 clinical trial in patients with relapsed/refractory NHL (NCT04502706, SRP001); …

Urinary Tract Infections Trigger Synucleinopathy Via The Innate Immune Response, Wouter Peelaerts, Scott J Hultgren, Tom J Hannan, Et Al.

2020-Current year OA Pubs

Symptoms in the urogenital organs are common in multiple system atrophy (MSA), also in the years preceding the MSA diagnosis. It is unknown how MSA is triggered and these observations in prodromal MSA led us to hypothesize that synucleinopathy could be triggered by infection of the genitourinary tract causing ɑ-synuclein (ɑSyn) to aggregate in peripheral nerves innervating these organs. As a first proof that peripheral infections could act as a trigger in MSA, this study focused on lower urinary tract infections (UTIs), given the relevance and high frequency of UTIs in prodromal MSA, although other types of infection might also …

Transition To Surgery After Pessary Among Female Medicare Beneficiaries With Pelvic Organ Prolapse, Melanie R L Meister, Oyomoare L Osazuwa-Peters, Jerry L Lowder, Victoria L Handa

2020-Current year OA Pubs

BACKGROUND: The American College of Obstetricians and Gynecologists recommends offering a vaginal pessary to women seeking treatment of pelvic organ prolapse. However, single-institution series have suggested that a sizable proportion of women fitted with a pessary will transition to surgery within the first year.

OBJECTIVE: This study aimed to estimate the proportion of female US Medicare beneficiaries with pelvic organ prolapse who undergo surgery after pessary fitting, to describe the median time to surgery from pessary fitting, and to identify factors associated with the transition from pessary to surgery.

STUDY DESIGN: The Medicare 5% Limited Data Set was queried from …

Influence Of Environmental Temperature And Heatwaves On Surgical Site Infection After Hip And Knee Arthroplasty: A Nationwide Study, L Damonti, A Atkinson, L Fontannaz, J P Burnham, P Jent, N Troillet, A Widmer, J Marschall, For Swissnoso, National Center For Infection Control

2020-Current year OA Pubs

BACKGROUND: Previous studies reported higher incidence of surgical site infection (SSI) after procedures performed in summer or with high temperatures. However, no study used detailed climate data to assess this risk after hip and knee arthroplasty, and no study specifically investigated the role of heatwaves.

AIM: To assess the impact of higher environmental temperatures and heatwaves on SSI rates after hip and knee arthroplasty.

METHODS: Data on hip and knee arthroplasty procedures performed between January 2013 and September 2019 in hospitals participating in the Swiss SSI surveillance were linked to climate data extracted from weather stations located in their vicinity. …