Publications by authors named "Muhittin Akarsu"

3 Publications

  • Page 1 of 1

The impact of hydroxychloroquine and azithromycin on the corrected qt interval in patients with the novel Coronavirus disease 2019.

Rev Assoc Med Bras (1992) 2021 Jul;67(7):979-984

Eskisehir Osmangazi University, Medical Faculty Department of Cardiology - Eskisehir, Turkey.

Objective: With the coronavirus disease 2019 (COVID-19) continuing to spread all over the world, although there is no specific treatment until now, hydroxychloroquine and azithromycin have been reported to be effective in recent studies. Although long-term use of hydroxychloroquine and azithromycin has been reported to cause QT prolongation and malign arrhythmia, there is not enough data about the effect of short-term use on arrhythmia. Therefore, this study aims to assess the effect of hydroxychloroquine alone and hydroxychloroquine + azithromycin on corrected QT (QTc).

Methods: A baseline electrocardiogram and on-treatment baseline electrocardiogram were retrospectively collected in COVID-19 patients who received hydroxychloroquine and/or azithromycin. The QTc interval was calculated, and the baseline and peak QTc intervals were compared. In addition, the peak QTc intervals of monotherapy and combination therapy were compared.

Results: Of the 155 patients included, 102 (65.8%) patients were using hydroxychloroquine, and 53 (34.2%) patients were using hydroxychloroquine + azithromycin combination. The use of both hydroxychloroquine alone and hydroxychloroquine + azithromycin combined therapy significantly prolonged the QTc, and the QTc interval was significantly longer in patients receiving combination therapy. QTc prolongation caused early termination in both groups, 5 (4.9%) patients in the monotherapy group and 6 (11.3%) patients in the combination therapy group.

Conclusion: In this study, patients who received hydroxychloroquine for the treatment of COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc.
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http://dx.doi.org/10.1590/1806-9282.20210380DOI Listing
July 2021

Heterozygous germline mutations increase susceptibility to asbestos and mesothelioma.

Proc Natl Acad Sci U S A 2020 12 14;117(52):33466-33473. Epub 2020 Dec 14.

Thoracic Oncology, University of Hawaii Cancer Center, Honolulu, HI 96813;

Rare biallelic gene mutations cause Bloom syndrome. Whether heterozygous germline mutations ( ) cause human cancer remains unclear. We sequenced the germline DNA of 155 mesothelioma patients (33 familial and 122 sporadic). We found 2 deleterious germline mutations within 2 of 33 families with multiple cases of mesothelioma, one from Turkey (c.569_570del; p.R191Kfs*4) and one from the United States (c.968A>G; p.K323R). Some of the relatives who inherited these mutations developed mesothelioma, while none with nonmutated were affected. Furthermore, among 122 patients with sporadic mesothelioma treated at the US National Cancer Institute, 5 carried pathogenic germline mutations. Therefore, 7 of 155 apparently unrelated mesothelioma patients carried mutations, significantly higher ( = 6.7E-10) than the expected frequency in a general, unrelated population from the gnomAD database, and 2 of 7 carried the same missense pathogenic mutation c.968A>G ( = 0.0017 given a 0.00039 allele frequency). Experiments in primary mesothelial cells from mice and in primary human mesothelial cells in which we silenced revealed that reduced BLM levels promote genomic instability while protecting from cell death and promoted TNF-α release. mice injected intraperitoneally with asbestos had higher levels of proinflammatory M1 macrophages and of TNF-α, IL-1β, IL-3, IL-10, and IL-12 in the peritoneal lavage, findings linked to asbestos carcinogenesis. mice exposed to asbestos had a significantly shorter survival and higher incidence of mesothelioma compared to controls. We propose that germline mutations increase the susceptibility to asbestos carcinogenesis, enhancing the risk of developing mesothelioma.
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http://dx.doi.org/10.1073/pnas.2019652117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7776606PMC
December 2020

The effectiveness and safety of platinum-based pemetrexed and platinum-based gemcitabine treatment in patients with malignant pleural mesothelioma.

BMC Cancer 2015 Jul 9;15:510. Epub 2015 Jul 9.

Lung and Pleural Cancers Research and Clinical Center, Eskisehir Osmangazi University, Eskisehir, Turkey.

Background: We aimed to evaluate the efficiency and safety of cis/carboplatin plus gemcitabine, which was previously used for mesothelioma but with no recorded proof of its efficiency, compared with cis/carboplatin plus pemetrexed, which is known to be effective in mesothelioma, in comparable historical groups of malignant pleural mesothelioma.

Methods: One hundred and sixteen patients received cis/carboplatin plus pemetrexed (group 1), while 30 patients received cis/carboplatin plus gemcitabine (group 2) between June 1999 and June 2012. The two groups were compared in terms of median survival and adverse events to chemotherapy.

Results: The mean ages of groups 1 and 2 were 60.7 and 60.8 years, respectively. Most of the patients (78.1%) had epithelial type tumors, and 47% of the patients had stage IV disease. There was no difference between the two groups in terms of age, gender, asbestos exposure, histology, stage, Karnofsky performance status, presence of pleurodesis, prophylactic radiotherapy, second-line chemotherapy and median hemoglobin and serum albumin levels. The median survival time from diagnosis to death or the last day of follow up with a 95% confidence interval was 12 ± 0.95 months (95% CI: 10.15-13.85) for group 1 and 11.0 ± 1.09 months (95% CI: 8.85-13.15) for group 2 (Log-Rank: 0.142; p = 0.706). The median survival time from treatment to death or the last day of follow-up with a 95% confidence interval was 11.0 ± 0.99 months (95% CI: 9.06-12.94) for group 1 and 11.0 ± 1.52 months (95% CI: 8.02-13.97) for group 2 (Log-Rank: 0.584; p = 0.445). The stage and Karnofsky performance status were found to be significant variables on median survival time by univariate analysis. After adjusting for the stage and Karnofsky performance status, the chemotherapy schema was not impressive on median survival time (OR: 0.837; 95% CI: 0.548-1.277; p = 0.409). The progression free survival was 7.0 ± 0.61 months for group I and 6.0 ± 1.56 months for group II (Log-Rank: 0.522; p = 0.470). The treatment was generally well tolerated, and the side effects were similar in both groups.

Conclusions: The study indicates that platinum-based gemcitabine is effective and a safe schema in malignant pleural mesothelioma. Further research should include large randomized phase III trials comparing these agents.
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http://dx.doi.org/10.1186/s12885-015-1519-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496921PMC
July 2015
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