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Acta Bio-medica : Atenei Parmensis Jun 2022The high prevalence of obesity and obesity-related comorbidities has reached pandemic proportions, particularly in Western countries. It has been recently recognized as... (Review)
Review
BACKGROUND AND AIM OF THE STUDY
The high prevalence of obesity and obesity-related comorbidities has reached pandemic proportions, particularly in Western countries. It has been recently recognized as a significant risk factor in severe cases of COVID-19 in children and adolescents. Here, we summarize the existing knowledge regarding the pathophysiology of COVID-19 and consider how its various components may be exacerbated by the presence of obesity to investigate the impact of obesity on disease severity among patients with COVID-19 and collaborate for better clinical care of these patients.
METHODS
The literature search was conducted from March 2020 to January 2022. A review of articles was performed via the online database PubMed, combining the terms "obesity," "weight gain," "COVID-19", "children."
RESULTS
Excessive adipose tissue, insulin resistance, dyslipidemia, hypertension, high levels of proinflammatory cytokines are factors that compromise the functioning of organs and systems in obese patients. In obese patients with COVID-19 these changes can increase the risk of death, need for ventilatory assistance, risk of thromboembolism, and perpetuation of inflammatory response.
CONCLUSIONS
Obesity increases the risk for hospitalization, intensive care admission, mechanic ventilation requirement, and death among children and adolescents with COVID-19. These findings emphasize the need for effective actions by health professionals to increase awareness of the risks resulting from obesity and how these are heightened in the current global pandemic.
Topics: Adolescent; COVID-19; Child; Hospitalization; Humans; Obesity; Risk Factors; SARS-CoV-2
PubMed: 35666114
DOI: 10.23750/abm.v93iS3.13075 -
Journal of Clinical Oncology : Official... Jun 2021Severe (grade 3-4) acute graft-versus-host disease (AGVHD) is a major cause of death after unrelated-donor (URD) hematopoietic cell transplant (HCT), resulting in... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Severe (grade 3-4) acute graft-versus-host disease (AGVHD) is a major cause of death after unrelated-donor (URD) hematopoietic cell transplant (HCT), resulting in particularly high mortality after HLA-mismatched transplantation. There are no approved agents for AGVHD prevention, underscoring the critical unmet need for novel therapeutics. ABA2 was a phase II trial to rigorously assess safety, efficacy, and immunologic effects of adding T-cell costimulation blockade with abatacept to calcineurin inhibitor (CNI)/methotrexate (MTX)-based GVHD prophylaxis, to test whether abatacept could decrease AGVHD.
METHODS
ABA2 enrolled adults and children with hematologic malignancies under two strata: a randomized, double-blind, placebo-controlled stratum (8/8-HLA-matched URD), comparing CNI/MTX plus abatacept with CNI/MTX plus placebo, and a single-arm stratum (7/8-HLA-mismatched URD) comparing CNI/MTX plus abatacept versus CNI/MTX CIBMTR controls. The primary end point was day +100 grade 3-4 AGVHD, with day +180 severe-AGVHD-free-survival (SGFS) a key secondary end point. Sample sizes were calculated using a higher type-1 error (0.2) as recommended for phase II trials, and were based on predicting that abatacept would reduce grade 3-4 AGVHD from 20% to 10% (8/8s) and 30% to 10% (7/8s). ABA2 enrolled 142 recipients (8/8s, median follow-up = 716 days) and 43 recipients (7/8s, median follow-up = 708 days).
RESULTS
In 8/8s, grade 3-4 AGVHD was 6.8% (abatacept) versus 14.8% (placebo) ( = .13, hazard ratio = 0.45). SGFS was 93.2% (CNI/MTX plus abatacept) versus 82% (CNI/MTX plus placebo, = .05). In the smaller 7/8 cohort, grade 3-4 AGVHD was 2.3% (CNI/MTX plus abatacept, intention-to-treat population), which compared favorably with a nonrandomized matched cohort of CNI/MTX (30.2%, < .001), and the SGFS was better (97.7% 58.7%, < .001). Immunologic analysis revealed control of T-cell activation in abatacept-treated patients.
CONCLUSION
Adding abatacept to URD HCT was safe, reduced AGVHD, and improved SGFS. These results suggest that abatacept may substantially improve AGVHD-related transplant outcomes, with a particularly beneficial impact on HLA-mismatched HCT.
Topics: Abatacept; Adolescent; Adult; Aged; Child; Cyclosporine; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Tacrolimus; Young Adult
PubMed: 33449816
DOI: 10.1200/JCO.20.01086 -
European Respiratory Review : An... Dec 2022Transbronchial lung cryobiopsy (TBLC) is increasingly being used as an alternative to video-assisted thoracoscopic surgery (VATS) biopsy to establish the histopathologic... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Transbronchial lung cryobiopsy (TBLC) is increasingly being used as an alternative to video-assisted thoracoscopic surgery (VATS) biopsy to establish the histopathologic pattern in interstitial lung disease (ILD).
METHODS
A systematic literature search of the PubMed and Embase databases, from October 2010 to October 2020, was conducted to identify studies that reported on diagnostic yield or safety of VATS or TBLC in the diagnosis of ILD.
RESULTS
43 studies were included. 23 evaluated the diagnostic yield of TBLC after multidisciplinary discussion, with a pooled diagnostic yield of 76.8% (95% confidence interval (CI) 70.6-82.1), rising to 80.7% in centres that performed ≥70 TBLC. 10 studies assessed the use of VATS and the pooled diagnostic yield was 93.5% (95% CI 88.3-96.5). In TBLC, pooled incidences of complications were 9.9% (95% CI 6.8-14.3) for significant bleeding (6.9% for centres with ≥70 TBLC), 5.6% (95% CI 3.8-8.2) for pneumothorax treated with a chest tube and 1.4% (95% CI 0.9-2.2) for acute exacerbation of ILD after TBLC. The mortality rates were 0.6% and 1.7% for TBLC and VATS, respectively.
CONCLUSIONS
TBLC has a fairly good diagnostic yield, an acceptable safety profile and a lower mortality rate than VATS. The best results are obtained from more experienced centres.
Topics: Biopsy; Bronchoscopy; Humans; Lung; Lung Diseases, Interstitial; Thoracic Surgery, Video-Assisted
PubMed: 36198419
DOI: 10.1183/16000617.0280-2021 -
Obstetrics and Gynecology Apr 2022
PubMed: 35594125
DOI: 10.1097/AOG.0000000000004738 -
Nature Medicine Oct 2021Chimeric antigen receptor (CAR) T cells targeting CD19 or CD22 have shown remarkable activity in B cell acute lymphoblastic leukemia (B-ALL). The major cause of...
CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial.
Chimeric antigen receptor (CAR) T cells targeting CD19 or CD22 have shown remarkable activity in B cell acute lymphoblastic leukemia (B-ALL). The major cause of treatment failure is antigen downregulation or loss. Dual antigen targeting could potentially prevent this, but the clinical safety and efficacy of CAR T cells targeting both CD19 and CD22 remain unclear. We conducted a phase 1 trial in pediatric and young adult patients with relapsed or refractory B-ALL (n = 15) to test AUTO3, autologous transduced T cells expressing both anti-CD19 and anti-CD22 CARs (AMELIA trial, EUDRA CT 2016-004680-39). The primary endpoints were the incidence of grade 3-5 toxicity in the dose-limiting toxicity period and the frequency of dose-limiting toxicities. Secondary endpoints included the rate of morphological remission (complete response or complete response with incomplete bone marrow recovery) with minimal residual disease-negative response, as well as the frequency and severity of adverse events, expansion and persistence of AUTO3, duration of B cell aplasia, and overall and event-free survival. The study endpoints were met. AUTO3 showed a favorable safety profile, with no dose-limiting toxicities or cases of AUTO3-related severe cytokine release syndrome or neurotoxicity reported. At 1 month after treatment the remission rate (that is, complete response or complete response with incomplete bone marrow recovery) was 86% (13 of 15 patients). The 1 year overall and event-free survival rates were 60% and 32%, respectively. Relapses were probably due to limited long-term AUTO3 persistence. Strategies to improve CAR T cell persistence are needed to fully realize the potential of dual targeting CAR T cell therapy in B-ALL.
Topics: Adolescent; Adult; Antigens, CD19; Child; Child, Preschool; Female; Humans; Immunotherapy; Immunotherapy, Adoptive; Infant; Male; Pediatrics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Progression-Free Survival; Receptors, Chimeric Antigen; Sialic Acid Binding Ig-like Lectin 2; Young Adult
PubMed: 34642489
DOI: 10.1038/s41591-021-01497-1 -
Journal of Medicine and Life Apr 2022Fibular hemimelia is defined as a partial or complete absence of the fibula. Alongside fibular deformities, there is a wide spectrum of anomalies, foot deformities, and... (Review)
Review
Fibular hemimelia is defined as a partial or complete absence of the fibula. Alongside fibular deformities, there is a wide spectrum of anomalies, foot deformities, and absent rays. A literature review showed only a handful of cases of prenatal diagnosis of fibular hemimelia. It is a rare disorder that might be isolated or associated with visceral anomalies.
Topics: Ectromelia; Female; Fibula; Humans; Pregnancy; Prenatal Diagnosis
PubMed: 35646168
DOI: 10.25122/jml-2021-0397 -
Journal of Pain Research 2020
PubMed: 32904462
DOI: 10.2147/JPR.S265901 -
Redox Biology Jan 20207-Ketocholesterol (7KC) is a toxic oxysterol that is associated with many diseases and disabilities of aging, as well as several orphan diseases. 7KC is the most common... (Review)
Review
7-Ketocholesterol (7KC) is a toxic oxysterol that is associated with many diseases and disabilities of aging, as well as several orphan diseases. 7KC is the most common product of a reaction between cholesterol and oxygen radicals and is the most concentrated oxysterol found in the blood and arterial plaques of coronary artery disease patients as well as various other disease tissues and cell types. Unlike cholesterol, 7KC consistently shows cytotoxicity to cells and its physiological function in humans or other complex organisms is unknown. Oxysterols, particularly 7KC, have also been shown to diffuse through membranes where they affect receptor and enzymatic function. Here, we will explore the known and proposed mechanisms of pathologies that are associated with 7KC, as well speculate about the future of 7KC as a diagnostic and therapeutic target in medicine.
Topics: Humans; Ketocholesterols
PubMed: 31926618
DOI: 10.1016/j.redox.2019.101380