bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Emerging Role of Convalescent Plasma in the Treatment of COVID‐19
Authors: Psaltopoulou Theodora , Sergentanis Theodoros N. , Pappa Vasiliki , Politou Marianna , Terpos Evangelos , Tsiodras Sotirios , Pavlakis George N. , Dimopoulos Meletios A. 
Published: July 2020

AbstractVarious agents are currently under evaluation as potential treatments in the fight against coronavirus disease 2019 (COVID‐19). Plasma from patients that have overcome COVID‐19 infection, referred to as convalescent plasma, is a treatment option with considerable background in viral diseases such as Spanish influenza, H1N1, Ebola, Severe Acute Respiratory Syndrome (SARS), and Middle East Respiratory Syndrome (MERS). Although convalescent plasma has historically proven beneficial in the treatment of some viral diseases, its use is still explorative in the context of COVID‐19. To date, preliminary evidence from case series is favorable as significant clinical, biochemical improvement and hospital discharge have been reported. A detailed overview of randomized as well non‐randomized trials of treatment with convalescent plasma, which have been registered worldwide, is provided in this review. Based on these studies, data from thousands of patients is anticipated in the near future. Convalescent plasma seems to be a safe option, but potential risks such as transfusion‐related acute lung injury and antibody‐dependent enhancement are discussed. Authorities including the Food and Drug Administration (FDA), and scientific associations such as the International Society of Blood Transfusion (ISBT) and the European Blood Alliance (EBA), have provided guidance into the selection criteria for donors and recipients. A debatable, pivotal issue pertains to the optimal timing of convalescent plasma transfusion. This treatment should be administered as early as possible to maximize efficacy, but at the same time be reserved for severe cases. Emerging risk stratification algorithms integrating clinical and biochemical markers to trace the cases at risk of significant deterioration can prove valuable in this direction.
A Phase II Trial of Safety, Tolerability and Immunogenicity of V114, a 15-Valent Pneumococcal Conjugate Vaccine, Compared With 13-Valent Pneumococcal Conjugate Vaccine in Healthy Infants
Authors: Platt Heather L. , Greenberg David , Tapiero Bruce , Clifford Robert A. , Klein Nicola P. , Hurley David C. , Shekar Tulin , Li Jianing , Hurtado Kim , Su Shu-Chih , Nolan Katrina M. , Acosta Camilo J. , McFetridge Richard D. , Bickham Kara , Musey Luwy K. ,   for the V114-008 Study Group
Published: July 2020

Background:
Pneumococcal disease remains a public health priority worldwide. This phase 2 study (V114-008; NCT02987972; EudraCT 2016-001117-25) compared safety and immunogenicity of 2 clinical lots of V114 (investigational 15-valent pneumococcal vaccine: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19F, 19A, 22F*, 23F, 33F*) to 13-valent pneumococcal conjugate vaccine (PCV13) in healthy infants (*serotypes unique to V114).

Methods:
Healthy infants 6–12 weeks old were randomized to receive a 4-dose regimen of V114 Lot 1, V114 Lot 2 or PCV13 at 2, 4, 6 and 12–15 months old. Adverse events were evaluated after each dose. Primary immunogenicity endpoint was to demonstrate noninferiority of V114 Lot 1 and V114 Lot 2 relative to PCV13 based on proportion of infants achieving serotype-specific IgG concentration ≥0.35 µg/mL for 13 serotypes shared with PCV13 at 1 month postdose 3 (PD3). Serotype-specific IgG geometric mean concentrations (GMCs) for all 15 V114 serotypes were measured at PD3, predose 4 and 1 month postdose 4 (PD4).

Results:
Overall, 1044 of 1051 randomized infants received ≥1 dose of vaccine (V114 Lot 1 [n = 350], V114 Lot 2 [n = 347] or PCV13 [n = 347]). Adverse events were generally comparable across groups. At PD3, both V114 lots met noninferiority criteria for all 13 serotypes shared with PCV13. IgG GMCs were comparable among V114 and PCV13 recipients at PD3 and PD4. Serotype 3 responses were higher following receipt of V114 than PCV13. Both V114 lots induced higher GMCs than PCV13 to the 2 unique V114 serotypes.

Conclusions:
Immunogenicity of both V114 lots was noninferior to PCV13 for all 13 shared serotypes between the 2 vaccines and displayed comparable safety and tolerability profiles to PCV13.
Daptomycin for Pediatric Gram-Positive Acute Hematogenous Osteomyelitis
Authors: Bradley John S. , Arrieta Antonio C. , Digtyar Valeri A. , Popejoy Myra W. , Grandhi Anjana , Bokesch Paula , Hershberger Ellie , Dorr Mary Beth , Tan Christopher M. , Murata Yoshihiko , Wolf Dominik J. , Bensaci Mekki 
Published: July 2020

Background:
We prospectively evaluated efficacy and safety of daptomycin versus active comparator in children with acute hematogenous osteomyelitis (AHO).

Methods:
Randomized, controlled, double-blind, global, multicenter, phase 3 trial. Patients 1–17 years of age with suspected/confirmed AHO requiring hospitalization and intravenous therapy were randomized 1:1 to intravenous daptomycin (once-daily, age-adjusted doses) or comparator (vancomycin, nafcillin or equivalent) ≥4 days, followed by oral therapy (14–42 days total). Primary endpoint: protocol-defined clinical improvement by Day 5 in the modified intention-to-treat (MITT) population (confirmed AHO, ≥1 dose of study treatment); differences between study arms were evaluated using a prespecified 15% noninferiority margin for daptomycin.

Results:
Seventy-three patients per arm received treatment. Pathogens were isolated from 62% of patients (83% methicillin-susceptible Staphylococcus aureus, 9% methicillin-resistant S. aureus [MRSA]). Clinical improvement by Day 5 was observed in 55/71 (78%) daptomycin- and 58/70 (83%) comparator-treated MITT patients (95% confidence interval [CI]: −19.4, 7.4). This difference was not statistically significant; however, daptomycin did not meet the prespecified 15% noninferiority margin, since the lower bound of the 95% CI extended below 15%. Overall, 82% of daptomycin and 87% of comparator patients achieved clinical cure at the test-of-cure visit (secondary endpoint). More comparator patients had treatment-emergent (63% vs. 46%) and treatment-related (18% vs. 7%) adverse events.

Conclusions:
Differences between daptomycin and comparator for the primary endpoint were not statistically significant; however, prespecified noninferiority criteria for daptomycin were not met. With insufficient cases of confirmed MRSA, we could not evaluate daptomycin for MRSA AHO. Our nonvalidated protocol design yields valuable information for implementing future trials in AHO (ClinicalTrials.gov NCT01922011).
A transcriptional toolbox for exploring peripheral neuroimmune interactions
Authors: Liang Zhi , Hore Zoe , Harley Peter , Uchenna Stanley Federico , Michrowska Aleksandra , Dahiya Monica , La Russa Federica , Jager Sara E. , Villa-Hernandez Sara , Denk Franziska 
Published: July 2020

Abstract
Correct communication between immune cells and peripheral neurons is crucial for the protection of our bodies. Its breakdown is observed in many common, often painful conditions, including arthritis, neuropathies, and inflammatory bowel or bladder disease. Here, we have characterised the immune response in a mouse model of neuropathic pain using flow cytometry and cell-type-specific RNA sequencing (RNA-seq). We found few striking sex differences, but a very persistent inflammatory response, with increased numbers of monocytes and macrophages up to 3 1/2 months after the initial injury. This raises the question of whether the commonly used categorisation of pain into “inflammatory” and “neuropathic” is one that is mechanistically appropriate. Finally, we collated our data with other published RNA-seq data sets on neurons, macrophages, and Schwann cells in naive and nerve injury states. The result is a practical web-based tool for the transcriptional data mining of peripheral neuroimmune interactions. http://rna-seq-browser.herokuapp.com/
Individuals with chronic pain have the same response to placebo analgesia as healthy controls in terms of magnitude and reproducibility
Authors: Power Andrea , Brown Christopher Andrew , Sivan Manoj , Lenton Ann , Rainey Timothy , El-Deredy Wael , Jones Anthony Kenneth Peter , Watson Alison 
Published: July 2020

Abstract
It is unclear whether a diagnosis of chronic pain is associated with an increase or decrease in the placebo response. The aim of this study was to use an experimental placebo conditioning paradigm to test whether expectancy for pain relief impacts on acute pain perception in individuals with a chronic pain diagnosis of osteoarthritis (OA) or fibromyalgia (FM), compared to healthy individuals (HIs). An inert cream was applied to the dominant forearm of participants (60 OA, 79 FM, and 98 HI), randomly assigned to either a placebo or control group. In both groups, an inactive cream was applied to the dominant forearm. The placebo group was told this may or may not be a local anaesthetic cream, whereas the control group was told the cream was inactive. Laser pain was delivered, and numerical pain intensity ratings collected before, during, and after cream application, along with expectation of pain relief and anxiety. The procedure was repeated 2 weeks later to assess reproducibility. There was a significant reduction in pain in the placebo group, independent of clinical diagnosis. Diagnostic groups (OA, FM, and HI) did not differ in their magnitude of placebo analgesia or expectancy of pain relief. The results were similar in the repeat session. The results demonstrate that individuals with chronic pain respond to experimental placebo analgesia in a similar and reproducible manner as HIs, despite higher levels of psychological comorbidity. This has implications for using placebo analgesia in the treatment of chronic pain.
Quantitative differences in neuronal subpopulations between mouse and human dorsal root ganglia demonstrated with RNAscope in situ hybridization
Authors: Shiers Stephanie , Klein Rebecca M. , Price Theodore J. 
Published: July 2020

Abstract
Next-generation transcriptomics in combination with imaging-based approaches have emerged as powerful tools for the characterization of dorsal root ganglion (DRG) neuronal subpopulations. The mouse DRG has been well characterized by many independently conducted studies with convergent findings, but few studies have directly compared expression of population markers between mouse and human. This is important because of our increasing reliance on the mouse as a preclinical model for translational studies. Although calcitonin gene-related peptide (CGRP) and P2X purinergic ion channel type 3 receptor (P2X3R) have been used to define peptidergic and nonpeptidergic nociceptor subpopulations, respectively, in mouse DRG, these populations may be different in other species. To directly test this, as well as a host of other markers, we used multiplex RNAscope in situ hybridization to elucidate the distribution of a multitude of unique and classic neuronal mRNAs in peptidergic (CGRP-expressing) and nonpeptidergic (P2X3R-expressing) nociceptor subpopulations in mouse and human DRG. We found a large overlapping CGRP and P2X3R neuronal subpopulation in human, lumbar DRG that was not present in mouse. We also found differential expression in a variety of mRNAs for transient receptor potential channels, cholinergic receptors, potassium channels, sodium channels, and other markers/targets. These data offer insights into the spatial and functional organization of neuronal cell subpopulations in the rodent and human DRG and support the idea that sensory system organizational principles are likely different between both species.
Does Midlife Forgetfulness Influence Positive and Negative Aspects of Social Relations at Work?
Authors: Ishtiak-Ahmed Kazi , Hansen Åse Marie , Mortensen Erik Lykke , Garde Anne Helene , Grynderup Matias Brødsgaard , Gyntelberg Finn , Islamoska Sabrina , Lund Rikke , Phung Thien Kieu Thi , Waldemar Gunhild , Nabe-Nielsen Kirsten 
Published: July 2020

Objectives:
We investigated whether midlife forgetfulness was prospectively associated with changes in social relations at work (SRW) among occupationally active individuals in Denmark.

Methods:
We analyzed data of 2339 men and women participating in the first (1990) and second (1995) survey of the Danish Work Environment Cohort Study, responding to questions on working environment, SRW, and forgetfulness. We used multiple linear regression analysis while adjusting for potential confounders.

Results:
At baseline (1990), 517 (22.1%) study participants were categorized as forgetful. Forgetfulness was prospectively associated with a decline in one of the investigated items reflecting a negative aspect of SRW (experiencing teasing, regression coefficient = 0.07, 95% CI: 0.03 to 0.11), while no association was observed with positive aspects of SRW.

Conclusions:
Our findings did not support the hypothesis that memory problems such as midlife forgetfulness negatively affect SRW.
Medullary Pancreatic Carcinoma Due to Somatic POLE Mutation
Authors: Kryklyva Valentyna , ter Linden Esther , Kroeze Leonie I. , de Voer Richarda M. , van der Kolk B. Marion , Stommel Martijn W.J. , Hermans John J. , Luchini Claudio , Wood Laura D. , Hruban Ralph H. , Nagtegaal Iris D. , Ligtenberg Marjolijn J.L. , Brosens Lodewijk A.A. 
Published: July 2020

Abstract
Medullary pancreatic carcinoma (MPC) is a rare histological variant of pancreatic ductal adenocarcinoma (PDAC). Because of its rarity, data on the molecular background of MPC are limited. Previous studies have shown that a subset of MPCs is microsatellite instable due to mismatch repair deficiency. Here, we present a unique case of a female patient in her 60s who is a long-term survivor after surgery for pancreatic cancer. The patient had a microsatellite stable MPC with a somatic mutation of the polymerase epsilon gene (POLE). Both microsatellite instable and POLE-mutated cancers are usually associated with high tumor mutational burden and antigen load, resulting in a prominent antitumor immune response and overall better survival. The current case illustrates that, in addition to mismatch repair deficiency, MPC can develop because of a somatic POLE mutation, resulting in a tumor with a high tumor mutational burden and leading to a better prognosis compared with conventional PDAC. This new finding may have important implications in the management of patients with MPC and calls for further studies on the role of POLE in PDAC.
Improving Mental Health Communication From the Pediatric Emergency Department to Primary Care
Authors: Esposito Jeremy M. , Fein Joel A. , Marshall Jason , Mitchell Christine , Aredas Brenna , Zorc Joseph J. 
Published: July 2020

ObjectivesSuicide is a leading cause of adolescent death, and emergency department (ED) visits are recognized as an opportunity to identify at-risk youth. For patients screening positive for mental health concerns, we implemented a quality improvement initiative to enhance documentation of results and interventions in the ED, increase communication between the ED and primary care providers (PCPs), and increase PCP follow-up.MethodsInterventions included education, feedback, and an alert in our electronic health record. Completion of a Behavioral Health Screen (BHS-ED) initiates an alert that reminds ED providers how to document and communicate results and needed follow-up to the PCP. We reviewed a random monthly sample of ED charts for adolescents 14 to 19 years old presenting with nonpsychiatric complaints who screened positive for severe depression or suicidality. Outcome measures included documentation of BHS-ED results in the ED note, communication of positive results to the PCP, PCP follow-up of results, and ED return visits.ResultsDocumentation of BHS-ED results increased from 73% at baseline to 88% of patients after the intervention. For patients discharged from the ED with nonpsychiatric chief complaints, communication to PCPs increased from 1% at baseline to 40% during the final 3 months of the study. When PCP communication occurred, 67% of in-network PCPs followed up with patients versus 5% when no communication took place from the ED.ConclusionsA multifaceted intervention including education and an electronic health record alert improved ED documentation, communication, and PCP follow-up of issues identified during ED-based mental health screens.
Survey of Current Institutional Practices in the Use of High-Flow Nasal Cannula for Pediatric Patients
Authors: Cheng Amy Y. , Simon Harold K. , Miller Judson , Wetzel Martha , Zmitrovich April , Hebbar Kiran B. 
Published: July 2020

Objectives
High-flow nasal cannula (HFNC) is an oxygen delivery device that provides heated humidified air with higher flow rates. The purpose of this survey is to look at institutional practice patterns of HFNC initiation, weaning, and disposition for pediatric patients across the United States.

Methods
Survey was sent via electronic listservs to pediatric physicians in emergency medicine, hospital medicine, critical care, and urgent care. The questionnaire was divided into demographics and HFNC practices (initiation, management, and weaning). One response per institution was included in the analysis.

Results
Two hundred twenty-four responses were included in the analysis, composed of 40% pediatric emergency medicine physicians, 46% pediatric hospitalists, 13% pediatric intensive care unit (PICU) physicians, and 1% pediatric urgent care physicians. Ninety-eight percent of the participants have HFNC at their institution. Thirty-seven percent of the respondents had a formal guideline for HFNC initiation. Nearly all guideline and nonguideline institutions report HFNC use in bronchiolitis. Guideline cohort is more likely to have exclusion criteria for HFNC (42% in the guideline cohort vs 17% in the nonguideline cohort; P < 0.001) and less frequently mandates PICU admissions once on HFNC (11% in the guideline cohort vs 56% in the nonguideline cohort; P < 0.001). Forty-six percent of guideline cohort had an objective scoring system to help determine the need for HFNC, and 73% had a weaning guideline.

Conclusions
Although there is general agreement to use HFNC in bronchiolitis, great practice variation remains in the initiation, management, and weaning of HFNC across the United States. There is also a discordance on PICU use when a patient is using HFNC.
Sexual Behaviors After PrEP Discontinuation Among HIV Serodiscordant Couples in Kenya and Uganda
Authors: Stalter Randy , Mugwanya Kenneth , Thomas Katherine , Donnell Deborah , Mujugira Andrew , Ngure Kenneth , Celum Connie , Kidoguchi Lara , Bukusi Elizabeth , Baeten Jared , Heffron Renee ,   for the Partners Demonstration Project Team
Published: July 2020

Background:
A strategy of pre-exposure prophylaxis (PrEP) transitioning to treatment as prevention is highly efficacious and cost effective for prevention of HIV transmission within HIV serodiscordant couples. We assessed whether couples who adopted this strategy experienced changes in sexual behaviors after HIV-negative partners discontinued PrEP and transitioned to rely primarily on their partner's adherence to antiretroviral therapy (ART) for prevention.

Setting:
Kenya and Uganda.

Methods:
Data are from the Partners Demonstration Project, a prospective, open-label evaluation of PrEP and ART use for HIV prevention. Using zero-inflated negative binomial models, we assessed changes in the level (ie, intercept) and trend over time (ie, slope) in total and condomless sex acts reported after PrEP discontinuation by HIV-negative partners. We conducted subgroup analyses based on HIV-negative partners' age and sex.

Results:
We included 567 couples where the HIV-negative partner discontinued PrEP because of their partner with HIV using ART for ≥6 months. HIV-negative partners were women in 32.6% of couples and had a median age of 30 years. We observed no change in the level or trend over time in total sex acts [level adjusted rate ratio (aRR) = 0.95, 95% confidence interval (CI): 0.87 to 1.04; trend aRR = 1.00, 95% CI: 0.99 to 1.01] or condomless sex acts (level aRR = 0.97, 95% CI: 0.81 to 1.17; trend aRR = 1.00, 95% CI: 0.98 to 1.03) reported after PrEP discontinuation versus prediscontinuation. No significant changes in behaviors were observed in age and sex subgroups.

Conclusions:
PrEP discontinuation seems to result in no significant changes in couples' sexual behaviors. These data further support a strategy of time-limited PrEP use by serodiscordant couples.
Prospective Evaluation of Outpatient Flexible Sigmoidoscopy in Patients With Deep Infiltrating Endometriosis
Authors: Celentano Valerio , Di Donato Nadine , Buccomino Giusy E. , Candy Katie , Solomon Lemke , Ihezue Chukwumobi , Berry Janet , Tsepov Denis 
Published: July 2020

Introduction:
To study patients’ acceptability of an outpatient flexible sigmoidoscopy (FS) protocol and to assess the diagnostic value of endoscopic assessment in patients with deep endometriosis (DE).

Methods:
All patients with DE and suspected bowel involvement diagnosed were reviewed in the colorectal outpatient clinic before elective surgery following multidisciplinary team meeting discussion. Patients were consented for having the FS performed at the same time of the clinical consultation. Primary outcome was diagnostic value of the FS.

Results:
Sixty patients were included. Fifty-eight (96.7%) patients consented for the outpatient FS, demonstrating a high rate of patients’ acceptability. The sigmoidoscopy demonstrated no abnormalities in 48 patients (82.7%), diverticulosis in 5 patients (8.6%), polyps in 2 patients (3.4%) and mucosal endometriosis in 1 patient only (1.7%).

Conclusions:
Outpatient FS during the preoperative consultation with the colorectal surgeon is feasible in patients with DE affecting the bowel with a high rate of patients’ acceptability but limited additional diagnostic value.
Does the Surgeon’s Caseload Affect the Outcome in Laparoscopic Cholecystectomy for Acute Cholecystitis?
Authors: Terho Petra , Sallinen Ville , Leppäniemi Ari , Mentula Panu 
Published: July 2020

Background:
This study investigated how annual caseloads and the surgeon’s previous experience influence the outcome in laparoscopic cholecystectomy (LCC) for acute cholecystitis.

Methods:
A total of 892 patients treated in Helsinki University Hospital in 2013-2016 were retrospectively analyzed. Surgeons were compared regarding volume—over 5 LCCs for acute cholecystitis a year versus 5 or fewer LCCs a year, and experience—attendings versus residents.

Results:
High-volume surgeons (n=14) operated faster than low-volume surgeons (n=62) (91 vs. 108 min, P<0.001). Examining only procedures with an attending present, high-volume attendings (n=7) converted less (14.9% vs. 32.0%, P<0.001) and operated faster (95 vs. 110 min, P<0.001) compared with low-volume attendings (n=41). The results of residents did not significantly differ from the results of attendings.

Conclusions:
Attending surgeons, performing >5 LCCs for acute cholecystitis a year, have shorter operative times and lower conversion rates.