Tag: pubmed

J Autoimmun. 2021 Feb 20;119:102610. doi: 10.1016/j.jaut.2021.102610. Online ahead of print.

ABSTRACT

CD4⁺ T cell trafficking is a fundamental property of adaptive immunity. In this study, we uncover a novel role for histone deacetylase 1 (HDAC1) in controlling effector CD4⁺ T cell migration, thereby providing mechanistic insight into why a T cell-specific deletion of HDAC1 protects against experimental autoimmune encephalomyelitis (EAE). HDAC1-deficient CD4⁺ T cells downregulated genes associated with leukocyte extravasation. In vitro, HDAC1-deficient CD4⁺ T cells displayed aberrant morphology and migration on surfaces coated with integrin LFA-1 ligand ICAM-1 and showed an impaired ability to arrest on and to migrate across a monolayer of primary mouse brain microvascular endothelial cells under physiological flow. Moreover, HDAC1 deficiency reduced homing of CD4⁺ T cells into the intestinal epithelium and lamina propria preventing weight-loss, crypt damage and intestinal inflammation in adoptive CD4⁺ T cell transfer colitis. This correlated with reduced expression levels of LFA-1 integrin chains CD11a and CD18 as well as of selectin ligands CD43, CD44 and CD162 on transferred circulating HDAC1-deficient CD4⁺ T cells. Our data reveal that HDAC1 controls T cell-mediated autoimmunity via the regulation of CD4⁺ T cell trafficking into the CNS and intestinal tissues.

PMID:33621930 | DOI:10.1016/j.jaut.2021.102610

Blood Cells Mol Dis. 2021 Feb 18;88:102548. doi: 10.1016/j.bcmd.2021.102548. Online ahead of print.

ABSTRACT

BACKGROUND: Convalescent plasma (CP) is being used as a treatment option in hospitalized patients with COVID-19. Till date, there is conflicting evidence on efficacy of CP in reducing COVID-19 related mortality.

OBJECTIVE: To evaluate the effect of CP on 28-day mortality reduction in patients with COVID-19.

METHODS: We did a multi-centre, retrospective case control observational study from 1st May 2020 to 31st August 2020. A total of 1079 adult patients with moderate and severe COVID-19 requiring oxygen, were reviewed. Of these, 694 patients were admitted to ICU. Out of these, 333 were given CP along with best supportive care and remaining 361 received best supportive care only.

RESULTS: In the overall group of 1079 patients, mortality in plasma vs no plasma group was statistically not significant (22.4% vs 18.5%; p = 0.125; OR = 1.27, 95% CI: 0.94–1.72). However, in patients with COVID-19 admitted to ICU, mortality was significantly lower in plasma group (25.5% vs 33.2%; p = 0.026; OR = 0.69, 95%CI: 0.50-0.96). This benefit of reduced mortality was most seen in age group 60 to 74 years (26.7% vs 43.0%; p = 0.004; OR = 0.48, 95% CI: 0.29-0.80), driven mostly by females of this age group (23.1% vs 53.5%; p = 0.013; OR = 0.26, 95% CI: 0.09-0.78). Significant difference in mortality was observed in patients with one comorbidity (22.3% vs 36.5%; p = 0.004; OR = 0.50, 95% CI: 0.31-0.80). Moreover, patients on ventilator had significantly lower mortality in the plasma arm (37.2% vs 49.3%; p = 0.009; OR = 0.61, 95% CI: 0.42-0.89); particularly so for patients on invasive mechanical ventilation (63.9% vs 82.9%; p = 0.014; OR = 0.37, 95% CI: 0.16-0.83).

CONCLUSION: The use of CP was associated with reduced mortality in COVID-19 elderly patients admitted in ICU, above 60 years of age, particularly females, those with comorbidities and especially those who required some form of ventilation.

PMID:33621948 | DOI:10.1016/j.bcmd.2021.102548

Thromb Res. 2021 Feb 18;201:1-5. doi: 10.1016/j.thromres.2021.02.015. Online ahead of print.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) may be the first symptom of cancer. Statins are suggested to prevent VTE, but the risk of cancer in VTE patients using statins remains poorly understood.

OBJECTIVES: To examine if VTE is a marker of cancer in users of statins.

METHODS: We identified all Danish patients during 1996-2017 with a first-time diagnosis of VTE and a filled prescription for a statin within 90 days prior to the VTE diagnosis. We classified patients as prevalent users if the first filling of a statin occurred more than one year preceding the VTE diagnosis, and as new users if the first filling occurred within the preceding year. We computed cumulative incidences of cancer, with death as a competing risk, and age-, sex-, and calendar-period standardized incidence ratios (SIRs), comparing the observed cancer incidence with the expected based on national cancer statistics.

RESULTS: Among 9280 (85%) prevalent users of statin and 1580 (15%) new users, the one-year cumulative incidence of any cancer was 6.6 (95% CI: 6.1-7.2) for prevalent users and 6.4 (95% CI: 5.2-7.6) for new users; the corresponding SIRs were 3.1 (95% CI: 2.9-3.3) and 3.5 (95% CI: 2.9-4.3). In the second and subsequent years, the SIRs diminished and approached unity for both prevalent (1.1 [95% CI: 1.1-1.2]) and new users (1.1 [95% CI: 0.9-1.3]).

CONCLUSIONS: VTE patients using statins had a 3-fold increased rate of cancer in the first year after diagnosis. A first VTE serves as an important marker of cancer, regardless of statin use.

PMID:33621859 | DOI:10.1016/j.thromres.2021.02.015

Thromb Res. 2021 Feb 18;201:6-14. doi: 10.1016/j.thromres.2021.02.017. Online ahead of print.

ABSTRACT

INTRODUCTION: In heparin-induced thrombocytopenia (HIT), selected patients are treated with therapies directed at the immune response, intravenous immunoglobulin (IVIG) and therapeutic plasma exchange (TPE). To determine IVIG and TPE characteristics and outcomes in HIT, we analyzed the National Inpatient Sample (NIS) database.

METHODS: In a population-based analysis of the NIS, we identified hospital discharges of adult patients with a HIT diagnosis. A two-level statistical analysis was performed comparing cases as follows 1) IVIG or TPE vs. none; and 2) IVIG vs. TPE. For each analysis, the primary outcome was in-hospital mortality. Secondary outcomes were thrombotic events, major bleeding, infections, hospital length of stay, and total charges.

RESULTS: Among 22,152 discharges with a HIT diagnosis, 77 (0.34%) and 52 (0.23%) received TPE and IVIG, respectively. In the first level analysis of TPE or IVIG vs. no treatment, TPE or IVIG treatment was associated with a higher likelihood of in-hospital mortality (OR = 1.85; 95%CI: 1.13-3.03, p = 0.0104), major bleeding (OR = 1.91; 95%CI: 1.25-2.93, p = 0.0030), gastrointestinal bleeding (OR = 1.89; 95%CI: 1.08-3.30, p = 0.0259), and infection (OR = 1.65; 95% CI:1.13-2.41, p = 0.0095). In the second-level analysis comparing IVIG vs. TPE, there were no significant differences in patient characteristics or outcomes in both unadjusted and adjusted analyses.

CONCLUSIONS: In this population-based analysis of HIT, we found similar outcomes of IVIG and TPE-treated cases. Given the small sample size, future studies are needed to confirm this observation.

PMID:33621860 | DOI:10.1016/j.thromres.2021.02.017

Clin Imaging. 2021 Feb 10;77:13-16. doi: 10.1016/j.clinimag.2021.01.038. Online ahead of print.

ABSTRACT

RATIONALE AND OBJECTIVES: Recent evidence suggests an inhomogeneous distribution of intramuscular rotator cuff fat infiltration (FI) in a small sample of individuals with rotator cuff tears, yet clinically just a few slices at the scapular Y-view are used to evaluate FI in patients with rotator cuff tears. The purpose of this study was to determine if assessment of FI using the scapular Y-view is representative of the entire muscle in patients with full-thickness rotator cuff tears, and whether this varies by tear size.

MATERIALS AND METHODS: Patients (N = 25) diagnosed with full-thickness rotator cuff tear and confirmed with magnetic resonance imaging (MRI) were included. Fat-water sequences were used to objectively quantify mean FI (%) in the entire 3D muscle and the mean from 3 slices at the Y-view. Mixed-model 2 × 2 ANOVAs were used to assess for differences between methods, and if results vary by tear-size.

RESULTS: There were no statistically significant differences between mean amount of FI of the entire 3D muscle and mean Y-view in the supraspinatus or infraspinatus muscles (p > 0.05). Additionally, this did not differ across tear size groups (p > 0.05).

CONCLUSION: Results of this study suggest FI assessed in the Y-view is not different (mean difference < 1.0%) from FI of the entire 3D muscle in patients with full-thickness rotator cuff tears. Therefore, the clinical utility of evaluating rotator cuff intramuscular fat infiltration with the Y-view is further supported in patients with full-thickness rotator cuff tears across tear sizes.

PMID:33621862 | DOI:10.1016/j.clinimag.2021.01.038

J Mech Behav Biomed Mater. 2021 Feb 17;117:104406. doi: 10.1016/j.jmbbm.2021.104406. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the efficacy of single and multiple administrations of Poloxamer 188 (P188) in saving meniscal cells following an injurious impact.

METHODS: Meniscal explants were harvested from both the lateral and medial menisci of Flemish Giant rabbits. After a 24-h incubation period, explants were subjected to 50% impact strain to simulate traumatic joint injury, and the explants were then placed in media with or without supplemented P188. Temporal administrations of P188 over a 14-day period were given based on one of 6 different treatments regimes. Over the 14-day period, explants were cyclically loaded to 10% strain at 1 Hz for 1 h per day, five days a week. Cell viability was assessed on day 14, with the remainder of the tissue being fixed to determine cell apoptosis levels and proteoglycan changes via histology.

RESULTS: The injurious impact proved to produce significant levels of cell death in meniscal explants. The ability of P188 to prevent cell death was not affected by the number of P188 doses (single versus multiple). P188 treatment proved to maintain cell viability levels comparable to those from unimpacted explants. There were no significant changes in cell apoptosis or proteoglycan coverage in the tissues over a 14-day period for any group, all treatment groups were statistically similar to the unimpacted explants.

CONCLUSION: A single dose of P188 following impact is all that is necessary to inhibit cell death in the meniscus following a traumatic impact. Thus, orthopaedic surgeons may choose to administer P188 in addition to treating any other acute damage due to a traumatic load to the knee, such as anterior cruciate ligament rupture, although more in depth in vivo studies are necessary.

PMID:33621866 | DOI:10.1016/j.jmbbm.2021.104406

Ultrason Sonochem. 2021 Jan 11;73:105459. doi: 10.1016/j.ultsonch.2020.105459. Online ahead of print.

ABSTRACT

Ultrasonic flotation was an effective method to float fine coal. In this study, the effects of the standing waves with different frequencies on ultrasonic flotation were investigated. The dynamic processes of bubble and coal-bubble were revealed by a high-speed camera. The results showed that under the action of Bjerknes force, bubble aggregates were formed within 450 ms and coal bubble aggregates were formed within 20 ms. The bubble aggregates were statistically analyzed by image processing method. The number of aggregates and small bubbles in the ultrasonic field at 100 kHz was greater than those at 80 and 120 kHz. Besides, 100 kHz ultrasonic flotation achieved the highest yields of clean coal (35.89%) and combustible recovery (45.77%). The cavitation bubbles acted as either a “medium” or an “inclusion”, entrapping and entraining the coal particles in the flotation pulp. It promoted the aggregation of bubbles with coal particles, so the flotation efficiency was effectively improved in the presence of ultrasonic standing waves.

PMID:33621851 | DOI:10.1016/j.ultsonch.2020.105459

Am J Transplant. 2021 Feb 23. doi: 10.1111/ajt.16552. Online ahead of print.

ABSTRACT

Organ procurement organizations (OPO) test potential deceased organ donors for infectious diseases required by policy, but many also perform testing for additional infections. The current state of donor testing in the United States is unknown. We sent an IRB approved survey to all 57 U.S. OPOs using REDCap. Descriptive statistics were performed. From the 57 OPOs, we received 46 (80.7%) unique responses with all 11 United Network of Organ Sharing regions represented. Forty of 46 (87%) OPO respondents consulted an Infectious Diseases physician when needed. Eighteen of 46 (39%) tested for West Nile virus (WNV) and 17 of 18 (94%) tested year-round. Eleven of 46 (23.9%) tested for Strongyloides infection while 17 of 46 (37%) tested for Chagas disease. All OPOs performed prospective nucleic acid testing (NAT) for HIV, hepatitis B and hepatitis C on all donors. OPO testing of additional infections has increased since prior surveys but remains variable. Standardization of organ donor infectious diseases evaluation should be considered.

PMID:33621430 | DOI:10.1111/ajt.16552

ACR Open Rheumatol. 2021 Feb 23. doi: 10.1002/acr2.11229. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the validity of self-reported physician diagnosis of rheumatoid arthritis (RA) using multiple gold-standard measures based on Medicare claims in a nationally representative sample of older adults and to verify whether additional questions about taking medication and having seen a physician in the past two years for arthritis can improve the positive predictive value (PPV) and other measures of the validity of self-reported RA.

METHODS: A total of 3768 Medicare-eligible respondents with and without incident self-reported RA were identified from the 2004, 2008, and 2012 waves of the United States Health and Retirement Study. Self-reported RA was validated using the following three claims-based algorithms: 1) a single International Classification of Diseases, ninth edition, Clinical Modification claim for RA, 2) two or more claims no greater than 2 years apart, and 3) two or more claims with at least one diagnosis by a rheumatologist. Additional self-report questions of medication use and having seen a doctor for arthritis in the past two years were validated against the same criteria.

RESULTS: A total of 345 respondents self-reported a physician diagnosis of RA. Across all three RA algorithms, the PPV of self-report ranged from 0.05 to 0.16., the sensitivity ranged from 0.23 to 0.55., and the κ statistic ranged from 0.07 to 0.15. Additional self-report data regarding arthritis care improved the PPV and other validity measures of self-report; however, the values remained low.

CONCLUSION: Most older adults who self-report RA do not have a Medicare claims history consistent with that diagnosis. Revisions to current self-reported RA questions may yield more valid identification of RA in national health surveys.

PMID:33621434 | DOI:10.1002/acr2.11229

PLoS One. 2021 Feb 23;16(2):e0247683. doi: 10.1371/journal.pone.0247683. eCollection 2021.

ABSTRACT

Essential fructosuria (EF) is a benign, asymptomatic, autosomal recessive condition caused by loss-of-function variants in the ketohexokinase gene and characterized by intermittent appearance of fructose in the urine. Despite a basic understanding of the genetic and molecular basis of EF, relatively little is known about the long-term clinical consequences of ketohexokinase gene variants. We examined the frequency of ketohexokinase variants in the UK Biobank sample and compared the cardiometabolic profiles of groups of individuals with and without these variants alone or in combination. Study cohorts consisted of groups of participants defined based on the presence of one or more of the five ketohexokinase gene variants tested for in the Affymetrix assays used by the UK Biobank. The rs2304681:G>A (p.Val49Ile) variant was present on more than one-third (36.8%) of chromosomes; other variant alleles were rare (<1%). No participants with the compound heterozygous genotype present in subjects exhibiting the EF phenotype in the literature (Gly40Arg/Ala43Thr) were identified. The rs2304681:G>A (p.Val49Ile), rs41288797 (p.Val188Met), and rs114353144 (p.Val264Ile) variants were more common in white versus non-white participants. Otherwise, few statistically or clinically significant differences were observed after adjustment for multiple comparisons. These findings reinforce the current understanding of EF as a rare, benign, autosomal recessive condition.

PMID:33621267 | DOI:10.1371/journal.pone.0247683