A prospective cohort study examining medical and social factors associated with engagement in life activities following total hip replacement

Objectives: Studies show limited improvement in the frequency of engaging in life activities after joint replacement. However, there is a paucity of research that has examined factors, including other life events, which influence engagement following total hip replacement (THR). This research sought to identify factors associated with engaging in life activities following THR. Methods: A prospective cohort study was conducted with 376 people who had a THR for osteoarthritis (OA). Data were collected pre-surgery and 1 year post-surgery. The primary outcome was change in frequency in engagement in life activities (Late Life Disability Index (LLDI): higher scores indicate higher frequency of engagement (range 0e80)). Analyses included multivariable regression. Factors considered included: positive/negative life events, a new comorbidity, another joint replacement and complications post-surgery. Results: Participants' mean age was 64 years; 46% were male. 68% of participants had at least one comorbidity pre-surgery; 36% reported at least one new comorbidity after surgery. The mean change in LLDI frequency was an increase of 6.29 (+/- 8.10). 36% reported one or more positive impact life events in the year following surgery; 63% reported one or more negative life events. The number of positive life events (beta=1.24; 95% CI: 0.49, 1.99) was significantly associated with change in LLDI frequency after adjusting for age, sex, education, body mass index (BMI), comorbidities pre-surgery, number of symptomatic joints and pre-surgery pain and function, LLDI limitations and depression. Conclusions: These findings highlight the significant influence of social factors and life circumstances on engagement in life activities following THR. (C) 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype–mismatched hematopoietic transplants

AbstractIn human leukocyte antigen haplotype–mismatched transplantation, extensive T-cell depletion prevents graft-versus-host disease (GVHD) but delays immune recovery. Granulocyte colony-stimulating factor (G-CSF) is given to donors to mobilize stem cells and to recipients to ensure engraftment. Studies have shown that G-CSF promotes T-helper (Th)-2 immune deviation which, unlike Th1 responses, does not protect against intracellular pathogens and fungi. The effect of administration of G-CSF to recipients of mismatched hematopoietic transplants with respect to transplantation outcome and functional immune recovery was investigated. In 43 patients with acute leukemia who received G-CSF after transplantation, the engraftment rate was 95%. However, the patients had a long-lasting type 2 immune reactivity, ie, Th2-inducing dendritic cells not producing interleukin 12 (IL-12) and high frequencies of IL-4– and IL-10–producing CD4+ cells not expressing the IL-12 receptor β2 chain. Similar immune reactivity patterns were observed on exposure of donor cells to G-CSF. Elimination of postgrafting administration of G-CSF in a subsequent series of 36 patients with acute leukemia, while not adversely affecting engraftment rate (93%), resulted in the anticipated appearance of IL-12–producing dendritic cells (1-3 months after transplantation versus > 12 months in transplant recipients given G-CSF), of CD4+ cells of a mixed Th0/Th1 phenotype, and of antifungal T-cell reactivity in vitro. Moreover, CD4+ cell counts increased in significantly less time. Finally, elimination of G-CSF–mediated immune suppression did not significantly increase the incidence of GVHD (< 15%). Thus, this study found that administration of G-CSF to recipients of T-cell–depleted hematopoietic transplants was associated with abnormal antigen-presenting cell functions and T-cell reactivity. Elimination of postgrafting administration of G-CSF prevented immune dysregulation and accelerated functional immune recovery

The development of a short measure of physical function for knee OA KOOS-Physical Function Shortform (KOOS-PS) – an OARSI/OMERACT initiative

SummaryObjectiveTo develop a short measure of physical function for knee osteoarthritis (OA) using multi-national data from individuals with varying degrees of severity of knee OA.MethodsRasch analysis, based on the partial credit model, was conducted on Knee injury and Osteoarthritis Outcome Score and Western Ontario McMaster Universities' Osteoarthritis Index data from individuals with knee OA, ranging from community to pre-total knee replacement samples from five countries. Fit of the data to the Rasch model was evaluated by overall model fit and item-level fit statistics (χ2, size of residual, F-test). Invariance across age, gender and country was evaluated. Unidimensionality was evaluated by factor analysis of residuals. The derived short measure was further tested for fit through re-analyses in individual sub-samples. A nomogram converting raw summed scores to Rasch-derived interval scores was developed.ResultsThirteen data sets were included (n=2145), with an age range of 26–95 years, and a male/female ratio of 1:1.4. The final model included seven of the original 22 items. From easiest to most difficult, the items (logit) were as follows: rising from bed (1.366), putting on socks/stockings (1.109), rising from sitting (0.537), bending to the floor (0.433), twisting/pivoting on injured knee (−0.861), kneeling (−1.292) and squatting (−1.292). Sub-sample analyses confirmed findings.ConclusionBased on the use of accepted Rasch-based measurement methods and the compliment of countries, languages and OA severity represented in this study, our seven item short measure of physical function for knee OA is likely generalizable and widely applicable. This measure has potential for use as the function component in an OA severity scoring system

High-Resolution Genetics Identifies the Lipid Transfer Protein Sec14p as Target for Antifungal Ergolines.

Invasive infections by fungal pathogens cause more deaths than malaria worldwide. We found the ergoline compound NGx04 in an antifungal screen, with selectivity over mammalian cells. High-resolution chemogenomics identified the lipid transfer protein Sec14p as the target of NGx04 and compound-resistant mutations in Sec14p define compound-target interactions in the substrate binding pocket of the protein. Beyond its essential lipid transfer function in a variety of pathogenic fungi, Sec14p is also involved in secretion of virulence determinants essential for the pathogenicity of fungi such as Cryptococcus neoformans, making Sec14p an attractive antifungal target. Consistent with this dual function, we demonstrate that NGx04 inhibits the growth of two clinical isolates of C. neoformans and that NGx04-related compounds have equal and even higher potency against C. neoformans. Furthermore NGx04 analogues showed fungicidal activity against a fluconazole resistant C. neoformans strain. In summary, we present genetic evidence that NGx04 inhibits fungal Sec14p and initial data supporting NGx04 as a novel antifungal starting point

Oral Lactoferrin Supplementation during Induction Chemotherapy Promotes Gut Microbiome Eubiosis in Pediatric Patients with Hematologic Malignancies

Induction chemotherapy is the first-line treatment for pediatric patients with hematologic malignancies. However, several complications may arise, mainly infections and febrile neutropenia, with a strong impact on patient morbidity and mortality. Such complications have been shown to be closely related to alterations of the gut microbiome (GM), making the design of strategies to foster its eubiosis of utmost clinical importance. Here, we evaluated the impact of oral supplementation of lactoferrin (LF), a glycoprotein endowed with anti-inflammatory, immunomodulatory and antimicrobial activities, on GM dynamics in pediatric oncohematologic patients during induction chemotherapy. Specifically, we conducted a double blind, placebo-controlled trial in which GM was profiled through 16S rRNA gene sequencing before and after two weeks of oral supplementation with LF or placebo. LF was safely administered with no adverse effects and promoted GM homeostasis by favoring the maintenance of diversity and preventing the bloom of pathobionts (e.g., Enterococcus). LF could, therefore, be a promising adjunct to current therapeutic strategies in these fragile individuals to reduce the risk of GM-related complications

Consensus on COVID‐19 Vaccination in Pediatric Oncohematological Patients, on Behalf of Infectious Working Group of Italian Association of Pediatric Hematology Oncology

Vaccines represent the best tool to prevent the severity course and fatal consequences of the pandemic by the new Coronavirus 2019 infection (SARS‐CoV‐2). Considering the limited data on vaccination of pediatric oncohematological patients, we developed a Consensus document to support the Italian pediatric hematological oncological (AIEOP) centers in a scientifically correct communication with families and patients and to promote vaccination. The topics of the Consensus were: SARS‐CoV‐2 infection and disease (COVID‐19) in the pediatric subjects; COVID‐19 vaccines (type, schedule); who and when to vaccinate; contraindications and risk of serious adverse events; rare adverse events; third dose and vaccination after COVID‐19; and other general prevention measures. Using the Delphi methodology for Consensus, 21 statements and their corresponding rationale were elaborated and discussed with the representatives of 31 centers, followed by voting. A high grade of Consensus was obtained on topics such as the potential risk of severe COVID‐19 outcome in pediatric oncohematological patients, the need for vaccination as a preventative measure, the type, schedule and booster dose of vaccine, the eligibility of the patients for vaccination, and the timing, definition, and management of contraindications and serious adverse events, and other general prevention measures. All 21 of the statements were approved. This consensus document highlights that children and adolescents affected by hematological and oncological diseases are a fragile category. Vaccination plays an important role to prevent COVID‐ 19, to permit the regular administration of chemotherapy or other treatments, to perform control visits and hospital admissions, and to prevent treatment delays

Favorable outcome of SARS-CoV-2 infection in pediatric hematology oncology patients during the second and third pandemic waves in Italy: a multicenter analysis from the Infectious Diseases Working Group of the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP)

COVID-19 has a mild clinical course with low mortality rate in general pediatric population, while variable outcomes have been described in children with cancer. Infectious diseases working party of the AIEOP collected data on the clinical characteristics and outcomes of SARS-CoV-2 infections in pediatric oncology/hematology patients from April 2020 to May 2021, including the second and the third waves of the pandemic in Italy. Factors potentially associated with moderate, severe, or critical COVID-19 were analyzed. Of the 153 SARS-Cov2 infections recorded, 100 were asymptomatic and 53 symptomatic. The course of COVID-19 was mild in 41, moderate in 2, severe in 5, and critical in 5 children. A total of 40.5% of patients were hospitalized, ten requiring oxygen support and 5 admitted to the intensive care unit. Antibiotics and steroids were the most used therapies. No patient died due to SARS-CoV-2 infection. Infections occurring early (< 60 days) after the diagnosis of the underlying disease or after SCT were associated to moderate, severe, and critical disease compared to infections occurring late (> 60 days) or during maintenance therapy. In the patients on active chemotherapy, 59% withdrew the treatment for a median of 15 days. SARS-CoV-2 presented a favorable outcome in children with cancer in Italy during the pandemic. Modification of therapy represents a major concern in this population. Our findings suggest considering regular chemotherapy continuation, particularly in patients on maintenance therapy or infected late after the diagnosis