Publications by authors named "M Tevfik Dorak"

77 Publications

Management of COVID-19 in cancer patients receiving cardiotoxic anti-cancer therapy. Future recommendations for cardio-oncology.

Oncol Rev 2021 Feb 26;15(1):510. Epub 2021 Feb 26.

Department of Pharmacy, School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Penrhyn Road, Kingston Upon Thames.

Cardiotoxicity induced by anti-cancer treatment has become a significant threat as the number of cardiotoxic anti-cancer agents is growing. Cancer patients are at an increased risk of contracting coronavirus disease 2019 (COVID-19) because of immune suppression caused by anti-cancer drugs and/or supportive treatment. Deterioration in lung functions due to COVID-19 is responsible for many cardiac events. The presence of COVID-19 and some of its treatment modalities may increase the chance of cardiotoxicity development in cancer patients receiving potentially cardiotoxic agents. This review provides evidence-based information on the cardiotoxicity risk in cancer patients clinically diagnosed with COVID-19 who are receiving potentially cardiotoxic anti-cancer agents. Proposed strategies relating to the management of this patient cohorts are also discussed.
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http://dx.doi.org/10.4081/oncol.2021.510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967496PMC
February 2021

The Magnitude of Postconvulsive Leukocytosis Mirrors the Severity of Periconvulsive Respiratory Compromise: A Single Center Retrospective Study.

Front Neurol 2019 6;10:1291. Epub 2019 Dec 6.

School of Life Sciences, Pharmacy & Chemistry, Kingston University London, United Kingdom.

Generalized epileptic convulsions frequently exhibit transient respiratory symptoms and non-infectious leukocytosis. While these peri-ictal effects appear to arise independently from one another, the possibility that they stem from a common ictal pathophysiological response has yet to be explored. We aimed to investigate whether peri-ictal respiratory symptoms and postictal leukocytosis coexist. We performed a single center retrospective chart review of 446 patients brought to our emergency department between January 1, 2017 and August 23, 2018 for the care of generalized epileptic convulsions with or without status epilepticus. We included 152 patients who were stratified based on the presence (PeCRC+) or absence (PeCRC-) of overt periconvulsive respiratory compromise (PeCRC). In addition, patients were stratified based on the presence or absence of postconvulsive leukocytosis (PoCL), defined as an initial postconvulsive white blood cell (WBC) count ≥ 11,000 cells/mm. Triage vital signs, and chest x ray (CXR) abnormalities were also examined. Overt PeCRC was observed in 31.6% of patients, 43% of whom required emergent endotracheal intubations. PoCL was observed in 37.5% of patients, and was more likely to occur in PeCRC+ than in PeCRC- patients (79.2 vs. 18.2%; OR = 17.0; 95% CI = 7.2-40.9; < 0.001). Notably, the magnitude of PoCL was proportional to the severity of PeCRC, as the postconvulsive WBC count demonstrated a negative correlation with triage hemoglobin oxygen saturation (R = -0.22; < 0.01; CI = -0.48 to -0.07). Moreover, a receiver operating characteristic analysis of the WBC count's performance as predictor of endotracheal intubation reached a significant area under the curve value of 0.81 (95% CI = 0.71-0.90; < 0.001). Finally, PeCRC+ patients demonstrated frequent CXR abnormalities, and their postconvulsive WBC counts correlated directly with triage heart rate (R = 0.53; < 0.001). Our data support the existence of an ictal pathophysiological response, which induces proportional degrees of PoCL and PeCRC. We suggest this response is at least partially propelled by systemic catecholamines.
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http://dx.doi.org/10.3389/fneur.2019.01291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910016PMC
December 2019

Plasma Free Fatty Acids Metabolic Profile with LC-MS and Appetite-Related Hormones in South Asian and White European Men in Relation to Adiposity, Physical Activity and Cardiorespiratory Fitness: A Cross-Sectional Study.

Metabolites 2019 Apr 13;9(4). Epub 2019 Apr 13.

Applied & Human Sciences, School of Life Sciences, Pharmacy & Chemistry, Kingston University London, Kingston upon Thames KT1 2EE, UK.

South Asians have a greater cardiovascular disease (CVD) and type 2 diabetes (T2D) risk than white Europeans, but the mechanisms are poorly understood. This study examined ethnic differences in free fatty acids (FFAs) metabolic profile (assessed using liquid chromatography-mass spectrometry), appetite-related hormones and traditional CVD and T2D risk markers in blood samples collected from 16 South Asian and 16 white European men and explored associations with body composition, objectively-measured physical activity and cardiorespiratory fitness. South Asians exhibited higher concentrations of five FFAs (laurate, myristate, palmitate, linolenic, linoleate; ≤ 0.040), lower acylated ghrelin (ES = 1.00, = 0.008) and higher leptin (ES = 1.11, = 0.004) than white Europeans; total peptide YY was similar between groups ( = 0.381). South Asians exhibited elevated fasting insulin, C-reactive protein, interleukin-6, triacylglycerol and ratio of total cholesterol to high-density lipoprotein cholesterol (HDL-C) and lower fasting HDL-C (all ES ≥ 0.74, ≤ 0.053). Controlling for body fat percentage (assessed using air displacement plethysmography) attenuated these differences. Despite similar habitual moderate-to-vigorous physical activity (ES = 0.18, = 0.675), V ˙ O was lower in South Asians (ES = 1.36, = 0.001). Circulating FFAs in South Asians were positively correlated with body fat percentage ( = 0.92), body mass ( = 0.86) and AUC glucose ( = 0.89) whereas in white Europeans FFAs were negatively correlated with total step counts ( = 0.96). In conclusion, South Asians exhibited a different FFA profile, lower ghrelin, higher leptin, impaired CVD and T2D risk markers and lower cardiorespiratory fitness than white Europeans.
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http://dx.doi.org/10.3390/metabo9040071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523813PMC
April 2019

Association of HLA-DRB1 shared epitope alleles and immune checkpoint inhibitor-induced inflammatory arthritis.

Rheumatology (Oxford) 2019 03;58(3):476-480

Division of Rheumatology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objective: To evaluate the frequency of HLA class I and II alleles associated with traditional forms of inflammatory arthritis in patients with immune checkpoint inhibitor (ICI)-induced inflammatory arthritis as compared with population controls.

Methods: High-resolution HLA typing was performed on 27 patients with ICI-induced inflammatory arthritis and 726 healthy controls. Genotyping at the shared epitope (SE) locus (HLA DRB1) was performed on 220 RA cases. Allele-positivity rates and frequency of having at least one SE allele were compared using Fisher's exact test between ICI-induced inflammatory arthritis and healthy controls. Frequency of having at least one SE allele was also compared between ICI-induced inflammatory arthritis and RA cases.

Results: Twenty-six patients with ICI-induced inflammatory arthritis were of European descent, and one was African American. In those 26 patients, 16 (61.5%) had at least one SE allele, significantly different from healthy controls of European descent, in whom 299 (41.2%) had at least one SE allele (odds ratio 2.3, P = 0.04). The allele-positivity rate of DRB1*04: 05 was also higher in the ICI-induced inflammatory arthritis group. The ICI-induced inflammatory arthritis population and RA patients of European descent did not differ in frequency of having at least one SE allele, but ICI-induced inflammatory arthritis patients were more likely to be autoantibody-negative for RF and anti-CCP antibodies.

Conclusion: Patients with ICI-induced inflammatory arthritis of European descent were more likely to have at least one SE allele than healthy controls. Further studies are needed to validate these findings and investigate whether a unique immunogenetic framework increases risk for different immune-related adverse events.
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http://dx.doi.org/10.1093/rheumatology/key358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821338PMC
March 2019

What has GWAS done for HLA and disease associations?

Int J Immunogenet 2017 Oct;44(5):195-211

Head of School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Kingston-upon-Thames, UK.

The major histocompatibility complex (MHC) is located in chromosome 6p21 and contains crucial regulators of immune response, including human leucocyte antigen (HLA) genes, alongside other genes with nonimmunological roles. More recently, a repertoire of noncoding RNA genes, including expressed pseudogenes, has also been identified. The MHC is the most gene dense and most polymorphic part of the human genome. The region exhibits haplotype-specific linkage disequilibrium patterns, contains the strongest cis- and trans-eQTLs/meQTLs in the genome and is known as a hot spot for disease associations. Another layer of complexity is provided to the region by the extreme structural variation and copy number variations. While the HLA-B gene has the highest number of alleles, the HLA-DR/DQ subregion is structurally most variable and shows the highest number of disease associations. Reliance on a single reference sequence has complicated the design, execution and analysis of GWAS for the MHC region and not infrequently, the MHC region has even been excluded from the analysis of GWAS data. Here, we contrast features of the MHC region with the rest of the genome and highlight its complexities, including its functional polymorphisms beyond those determined by single nucleotide polymorphisms or single amino acid residues. One of the several issues with customary GWAS analysis is that it does not address this additional layer of polymorphisms unique to the MHC region. We highlight alternative approaches that may assist with the analysis of GWAS data from the MHC region and unravel associations with all functional polymorphisms beyond single SNPs. We suggest that despite already showing the highest number of disease associations, the true extent of the involvement of the MHC region in disease genetics may not have been uncovered.
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http://dx.doi.org/10.1111/iji.12332DOI Listing
October 2017
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