Publications by authors named "H Girgis"

55 Publications

Sacubitril/Valsartan: A new dawn has begun!: A revisited review.

Curr Cardiol Rev 2021 Aug 31. Epub 2021 Aug 31.

Department of Cardiovascular Science, Mediclinic Hospital, Al Jowhara, Al Ain. United Arab Emirates.

Heart failure (HF) is among the major causes of global morbidity as well as mortality. Increased prevalence, frequent and prolonged hospitalization, rehospitalization, long-term consumption of healthcare resources, absenteeism, and death upsurge the economic burden linked to HF. For decades, Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II Receptor Blockers (ARBs), Beta-Blockers (BBs), and mineralocorticoid receptor antagonists (MRA), have remained the mainstay of the standard of care for HF management. Despite their proven efficacy and cost-effectiveness, HF remains a global pandemic and is still increasing in prevalence. Sacubitril/Valsartan (SAC/VAL) is an Angiotensin Receptor/Neprilysin Inhibitor (ARNI) that proved out to be a game-changer drug in HF treatment. Recent data indicated that SAC/VAL is more efficient and can improve the overall quality of life of HF patients with reduced ejection fraction (HFrEF) with fewer side effects. It is now incorporated in the guidelines as an alternative to ACEIs or ARBs to lower morbidity in addition to mortality in HFrEF patients. This review article will discuss the current guidelines-approved indications and highlight the potential emerging indications, in addition to the currently ongoing clinical trials that will expand the use of SAC/VAL.
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http://dx.doi.org/10.2174/1573403X17666210831142452DOI Listing
August 2021

Improving long-term outcomes in pediatric torcular dural sinus malformations with embolization and anticoagulation: a retrospective review of The Hospital for Sick Children experience.

J Neurosurg Pediatr 2021 Jul 30:1-7. Epub 2021 Jul 30.

1Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto.

Objective: Torcular dural sinus malformations (tDSMs) are rare pediatric cerebrovascular malformations characterized by giant venous lakes localized to the midline confluence of sinuses. Historical clinical outcomes of patients with these lesions were poor, though better prognoses have been reported in the more recent literature. Long-term outcomes in children with tDSMs are uncertain and require further characterization. The goal of this study was to review a cohort of tDSM patients with an emphasis on long-term outcomes and to describe the treatment strategy.

Methods: This study is a single-center retrospective review of a prospectively maintained data bank including patients referred to and cared for at The Hospital for Sick Children for tDSM from January 1996 to March 2019. Each patient's clinical, radiological, and demographic information, as well as their mother's demographic information, was collected for review.

Results: Ten patients with tDSM, with a mean follow-up of 58 months, were included in the study. Diagnoses were made antenatally in 8 patients, and among those cases, 4 families opted for either elective termination (n = 1) or no further care following delivery (n = 3). Of the 6 patients treated, 5 had a favorable long-term neurological outcome, and follow-up imaging demonstrated a decrease or stability in the size of the tDSM over time. Staged embolization was performed in 3 patients, and anticoagulation was utilized in 5 treated patients.

Conclusions: The authors add to a growing body of literature indicating that clinical outcomes in tDSM may not be as poor as initially perceived. Greater awareness of the lesion's natural history and pathophysiology, advancing endovascular techniques, and individualized anticoagulation regimens may lead to continued improvement in outcomes.
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http://dx.doi.org/10.3171/2021.3.PEDS20921DOI Listing
July 2021

Angiographic and Clinical Profile of Patients With COVID-19 Referred for Coronary Angiography During SARS-CoV-2 Outbreak: Results From a Collaborative, European, Multicenter Registry.

Angiology 2021 Jul 28:33197211028760. Epub 2021 Jul 28.

Department of Cardiology, Hospital Universitario La Paz, Madrid, Spain.

Data regarding angiographic characteristics, clinical profile, and inhospital outcomes of patients with coronavirus disease 2019 (COVID-19) referred for coronary angiography (CAG) are scarce. This is an observational study analyzing confirmed patients with COVID-19 referred for CAG from 10 European centers. We included 57 patients (mean age: 66 ± 15 years, 82% male) , of whom 18% had previous myocardial infarction (MI) and 29% had renal insufficiency and chronic pulmonary disease. ST-segment elevation myocardial infarction (STEMI) was the most frequent indication for CAG (58%). Coronavirus disease 2019 was confirmed after CAG in 86% and classified as mild in 49%, with 21% fully asymptomatic. A culprit lesion was identified in 79% and high thrombus burden in 42%; 7% had stent thrombosis. At 40 days follow-up, 16 (28%) patients experienced a major adverse cardiovascular event (MACE): 12 deaths (92% noncardiac), 1 MI, 2 stent thrombosis, and 1 stroke. In an European multicenter registry, patients with confirmed COVID-19 infection referred for CAG during the first wave of the severe acute respiratory syndrome coronavirus 2 pandemic presented mostly with STEMI and were predominantly males with comorbidities. Severity of COVID-19 was in general noncritical and 21% were asymptomatic at the time of CAG. Culprit coronary lesions with high thrombus burden were frequently identified, with a rate of stent thrombosis of 7%. The incidence of MACE at 40 days was high (28%), mostly due to noncardiac death.
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http://dx.doi.org/10.1177/00033197211028760DOI Listing
July 2021

: rapid alignment-free prediction of sequence alignment identity scores using self-supervised general linear models.

NAR Genom Bioinform 2021 Mar 1;3(1):lqab001. Epub 2021 Feb 1.

Department of Mathematics, Vanderbilt University, 1326 Stevenson Center Lane, Nashville, TN 3721, USA.

Pairwise global alignment is a fundamental step in sequence analysis. Optimal alignment algorithms are quadratic-slow especially on long sequences. In many applications that involve large sequence datasets, all what is needed is calculating the identity scores (percentage of identical nucleotides in an optimal alignment-including gaps-of two sequences); there is no need for visualizing how every two sequences are aligned. For these applications, we propose , which produces global identity scores for a large number of pairs of DNA sequences using alignment-free methods and self-supervised general linear models. For the first time, the new tool can predict pairwise identity scores in linear time and space. On two large-scale sequence databases, provided the best compromise between sensitivity and precision while being faster than BLAST, Mash, MUMmer4 and USEARCH by 2-80 times. was the best performing tool when searching for low-identity matches. While constructing phylogenetic trees from about 6000 transcripts, the tree due to the scores reported by was the closest to the reference tree (in contrast to andi, FSWM and Mash). is capable of producing pairwise identity scores of millions-of-nucleotides-long bacterial genomes; this task cannot be accomplished by any global-alignment-based tool. Availability: https://github.com/BioinformaticsToolsmith/Identity.
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http://dx.doi.org/10.1093/nargab/lqab001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850047PMC
March 2021

Single-molecule nanopore sequencing reveals extreme target copy number heterogeneity in arylomycin-resistant mutants.

Proc Natl Acad Sci U S A 2021 01;118(1)

Department of OMNI Bioinformatics, Genentech, South San Francisco, CA 94080;

Tandem gene amplification is a frequent and dynamic source of antibiotic resistance in bacteria. Ongoing expansions and contractions of repeat arrays during population growth are expected to manifest as cell-to-cell differences in copy number (CN). As a result, a clonal bacterial culture could comprise subpopulations of cells with different levels of antibiotic sensitivity that result from variable gene dosage. Despite the high potential for misclassification of heterogenous cell populations as either antibiotic-susceptible or fully resistant in clinical settings, and the concomitant risk of inappropriate treatment, CN distribution among cells has defied analysis. Here, we use the MinION single-molecule nanopore sequencer to uncover CN heterogeneity in clonal populations of and grown from single cells isolated while selecting for resistance to an optimized arylomycin, a member of a recently discovered class of Gram-negative antibiotic. We found that gene amplification of the arylomycin target, bacterial type I signal peptidase LepB, is a mechanism of unstable arylomycin resistance and demonstrate in that amplification instability is independent of RecA. This instability drives the emergence of a nonuniform distribution of CN among cells with a range of 1 to at least 50 copies of identified in a single clonal population. In sum, this remarkable heterogeneity, and the evolutionary plasticity it fuels, illustrates how gene amplification can enable bacterial populations to respond rapidly to novel antibiotics. This study establishes a rationale for further nanopore-sequencing studies of heterogeneous cell populations to uncover CN variability at single-molecule resolution.
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http://dx.doi.org/10.1073/pnas.2021958118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817135PMC
January 2021
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