Publications by authors named "A S Seif"

150 Publications

BK Polyomavirus Subtypes II and IV in Hematopoietic Cell Transplant Recipients.

Microbiol Resour Announc 2022 Jan 6;11(1):e0105321. Epub 2022 Jan 6.

Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Symptomatic BK polyomavirus (BKPyV) infections are common and relevant in immunocompromised patients. Here, we present full-length BKPyV genomes from samples from patients who received hematopoietic cell transplants in the United States. These individuals had non-subtype I BKPyV, as determined by amplification, next-generation sequencing, and phylogenetic analysis.
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http://dx.doi.org/10.1128/mra.01053-21DOI Listing
January 2022

Unrelated donor α/β T-cell and B-cell-depleted HSCT for the treatment of pediatric acute leukemia.

Blood Adv 2021 Dec 6. Epub 2021 Dec 6.

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States.

Unrelated donor (URD) hematopoietic stem cell transplant (HSCT) is associated with an increased risk of severe GVHD. TCRαβ/CD19 depletion may reduce this risk, while maintaining graft-versus-leukemia. Outcome data with TCRαβ/CD19 depletion generally describes haploidentical donors, with relatively few URDs. We hypothesized that TCRαβ/CD19-depletion would attenuate the risks of GVHD and relapse for URD HSCT. Sixty pediatric and young adult (YA) patients with hematologic malignancies who lacked a matched-related donor were enrolled at two large pediatric transplantation centers between 10/2014 and 09/2019. All patients with acute leukemia had minimal residual disease testing and DP typing was available for 77%. All patients received myeloablative TBI- or busulfan-based conditioning with no post-transplant immune suppression. Engraftment occurred in 98%. Four-year overall survival was 69% (95%CI 52-81%) and leukemia-free survival was 64% (95%CI 48-76%), with no difference between lymphoid and myeloid malignancies (p=0.6297 and p=0.5441, respectively). One patient (1.7%) experienced primary graft failure. Relapse occurred in 11 patients (3-year cumulative incidence 21%, 95%CI 11-34), and 8 patients (cumulative incidence 15%, 95%CI 6.7-26) experienced non-relapse mortality. Grade III-IV acute GVHD was seen in 8 patients (13%), and 14 patients (26%) developed chronic GVHD, of which 6 (11%) had extensive disease. Non-permissive DP mismatch was associated with higher likelihood of acute GVHD (OR 16.50, 95%CI 1.67-163.42, p=0.0166), but not with the development of chronic GVHD. URD TCRαβ/CD19-depleted peripheral HSCT is a safe and effective approach to transplantation for children/YAs with leukemia. This trial was registered at www.clinicaltrials.gov as #NCT02323867.
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http://dx.doi.org/10.1182/bloodadvances.2021005492DOI Listing
December 2021

Comparative Effect of Vitamin D3 and Carbenoxolone Treatments in Metabolic Syndrome Rats.

Can J Physiol Pharmacol 2021 Dec 2. Epub 2021 Dec 2.

Ain Shams University Faculty of Medicine, 68792, Physiology Department, Cairo, Egypt;

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including central obesity, hypertension, insulin resistance, dyslipidemia, and hyperglyemia. MetS is found to be a positive predictor of cardiovascular morbidity and mortality. The present study was planned to test the efficacy of vitamin D3 supplementation as compared to cortisol inhibition on MetS parameters. Wistar rats were allocated into four groups: controls, untreated MetS, and MetS treated with either vitamin D3 (10 μg/kg), or carbenoxolone (50 mg/kg). MetS was induced by combination of high fat diet and oral fructose. After the induction period (8 weeks), MetS was confirmed and treatment modalities started for a further 4 weeks. Compared to untreated MetS, vitamin D3 and carbenoxolone treated rats showed significant reduction in blood pressure, body mass index, lee index, waist circumference, retroperitoneal fat, and improvement of dyslipidemia. Meanwhile, treatment with carbenoxolone significantly lowered the elevated liver enzymes, vitamin D3 resulted in improved insulin sensitivity, enhanced glucose uptake by muscles and replenished glycogen content in the liver and muscles near control levels. In conclusion, although treatment with vitamin D3 or carbenoxolone reduced the risk factors associated with MetS, vitamin D3 was effective in ameliorating insulin resistance which is the hallmark of MetS.
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http://dx.doi.org/10.1139/cjpp-2021-0400DOI Listing
December 2021

Incidence and risk factors for hypoglycemia during maintenance chemotherapy in pediatric acute lymphoblastic leukemia.

Pediatr Blood Cancer 2021 Nov 22:e29467. Epub 2021 Nov 22.

Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Fasting hypoglycemia is a recognized occurrence among pediatric patients with acute lymphoblastic leukemia (ALL) during maintenance therapy. Existing publications describing this finding are limited to small studies and case reports. Our objective was to determine the incidence of hypoglycemia during maintenance chemotherapy and to investigate the association of age, as well as other potential risk factors, with this outcome in pediatric patients with ALL.

Procedure: This retrospective cohort study included individuals 1 to 21 years of age with ALL treated with antimetabolite-containing maintenance chemotherapy at a large children's hospital between January 2011 and December 2014. The primary endpoint was time to first documented episode of hypoglycemia during maintenance therapy, defined as single measurement of plasma glucose <60 mg/dL. Cox regression was used to evaluate the association with age and identify other potential risk factors.

Results: We identified 126 eligible patients, of whom 63% were documented as White, non-Hispanic, 28% as non-White, non-Hispanic, and 9% as Hispanic. Twenty-eight children (22%) had documented hypoglycemia during maintenance therapy. Younger age at the start of maintenance and hepatotoxicity documented during chemotherapy prior to maintenance initiation were associated with hypoglycemia (adjusted HR age = 0.88; 95% CI, 0.78-0.99; adjusted HR prior hepatotoxicity = 3.50; 95% CI, 1.47-8.36).

Conclusions: Nearly one quarter of children in our cohort had hypoglycemia documented during maintenance chemotherapy. Younger age at maintenance initiation and hepatotoxicity during chemotherapy prior to maintenance initiation emerged as risk factors. These findings highlight the importance of counseling about the risk of, and monitoring for, hypoglycemia, particularly in young children.
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http://dx.doi.org/10.1002/pbc.29467DOI Listing
November 2021

A Systematic Review of Brainstem Contributions to Autism Spectrum Disorder.

Front Integr Neurosci 2021 1;15:760116. Epub 2021 Nov 1.

Brain and Mind Institute, University of Western Ontario, London, ON, Canada.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects one in 66 children in Canada. The contributions of changes in the cortex and cerebellum to autism have been studied for decades. However, our understanding of brainstem contributions has only started to emerge more recently. Disruptions of sensory processing, startle response, sensory filtering, sensorimotor gating, multisensory integration and sleep are all features of ASD and are processes in which the brainstem is involved. In addition, preliminary research into brainstem contribution emphasizes the importance of the developmental timeline rather than just the mature brainstem. Therefore, the purpose of this systematic review is to compile histological, behavioral, neuroimaging, and electrophysiological evidence from human and animal studies about brainstem contributions and their functional implications in autism. Moreover, due to the developmental nature of autism, the review pays attention to the atypical brainstem development and compares findings based on age. Overall, there is evidence of an important role of brainstem disruptions in ASD, but there is still the need to examine the brainstem across the life span, from infancy to adulthood which could lead the way for early diagnosis and possibly treatment of ASD.
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http://dx.doi.org/10.3389/fnint.2021.760116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591260PMC
November 2021
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