Acta Medica

De-novo use of generic tacrolimus (Adoport) in renal transplant recipients: A single center experience from Türkiye

Neriman Sıla Koç, Tolga Yıldırım, Şeref Rahmi Yılmaz, Yunus Erdem — Thu, 28 Mar 2024 00:00:00 +0000

Objective: Renal transplantation is the best treatment for end-stage kidney disease, and tacrolimus has become an important immunosuppressive treatment for kidney transplant patients since it was introduced. After the first generic tacrolimus has been approved by the FDA, studies have begun to compare the effectiveness and safety of generic tacrolimus with the original tacrolimus. When using generic immunosuppressive therapies, it is also necessary to ensure that it provides adequate immunosuppression and does not cause severe toxicity.

This study aims to compare clinical outcomes, including acute rejection, graft loss and adverse reactions, in patients receiving brand tacrolimus (Prograf, Astellas Pharma, U.S.) or generic tacrolimus (Adoport, Sandoz, UK) from the start of kidney transplant therapy.

Study Design: Renal transplant recipients between 1 January 2015-1 March 2020 were screened retrospectively. All patients receiving de novo generic tacrolimus (n:51) and randomly selected 102 control renal transplant recipients receiving original tacrolimus were included in this study.

Materials and Methods: We evaluated and recorded demographic, clinical and laboratory data including age, gender, primary kidney disease, donor type (live or dead), induction and death regimen, tacrolimus dose, tacrolimus through levels, serum creatinine, biopsy-confirmed acute rejection episodes, delayed transplant function, positive BK polyomavirus in the urine, BK polyomavirus-related nephropathy, cytomegalovirus infection in 1-year follow-up.

Results: Most of the patients were male (64.1%) with a mean age of 38.3 years. There was no significant difference in demographic characteristics between the original and generic tacrolimus groups. No differences were found in terms of creatinine levels, total daily dose of tacrolimus and tacrolimus trough levels at discharge and the first year. Additionally, biopsy-confirmed acute rejection in the following year after transplantation, BKPyV positivity in urine, BKPyVAN, CMV viremia and adverse reactions related to tacrolimus were similar between the two groups.

Conclusion: With this study, we aimed to contribute to the literature with our experience on the use of generic tacrolimus from our country. As a result of our study, we noted that generic tacrolimus can be safely preferred for de-novo use with close drug-level monitoring because it is an immunosuppressant agent with a narrow therapeutic index. There is a continuing need for randomized prospective-designed and multi-centric studies with a wide range of patients.

Eighteen years of the medical scientist training program at Hacettepe University

Şefik Evren Erdener, Alev Özön, Aygün Ertuğrul, Turgay Dalkara — Thu, 28 Mar 2024 00:00:00 +0000

Objective: Medical Scientist Training Program (MSTP) combining acquisition of both MD and PhD degrees, was implemented in 2003 at Hacettepe University. The purpose of this report is to evaluate the program outcomes by assessing the graduates from the first 18 years of the program.

Materials and Methods: A web survey was conducted with the 37 participants who graduated between 2009-2020. Data were analysed using descriptive statistical methods.

Results: About half of the graduates were found to devote a considerable amount of time to scientific research. Although nine participants do not perform any physician duties, about a quarter of graduates concomitantly pursue scientific as well as clinical activities. This implies that the program’s primary goal, to train clinician-scientists in both MD and PhD curriculums have been achieved. 90% of graduates completed their residency in 24 different clinical disciplines. 40% of the graduates have already achieved faculty status at universities in Turkey or abroad. Academic performance indicators of MSTP graduates including the number of publications and citations in leading databases and the number of grants received were notably high.

Conclusion: This study reveals the role of the MSTP at Hacettepe University towards education of highly qualified clinicians with academic and scientific activities.

Clinical results of patients with variceal bleeding and risk analysis of scoring systems

Thu, 28 Mar 2024 00:00:00 +0000

Introduction: Gastroesophageal varices are a common complication of chronic liver disease and the associated portal hypertension. Gastroesophageal variceal bleeding is the most important cause of mortality in cirrhotic patients, and the risk of developing varices and bleeding significantly increases when hepatic venous pressure gradient (HVPG) exceeds 10-12 mmHg.

Aim: In this study, we aimed to determine the most useful scoring system to assess patients with gastric and esophageal variceal bleeding to guide treatment according to the type of varices, to predict the risk of rebleeding and mortality, and to determine the relationship between types of varices, comorbidities, and mortality.

Results: We retrospectively analyzed the files of 566 patients who presented to the Emergency Internal Medicine Department with gastrointestinal hemorrhage. Among these, we recruited 117 patients who were diagnosed with varices. Hematemesis and melena were significantly more common in patients with esophageal variceal bleeding compared to patients with gastric variceal bleeding (p=0.025 and p=0.036, respectively) Among the analyzed scoring systems, the Child-Pugh score most successfully predicted mortality with the highest AUC value (AUC: 0.851, 95% CI: 0.770-0.932, p<0.0001).

Conclusion: Assessment with scoring systems upon admission is useful for risk classification and prediction of mortality risk. In this context, the Child-Pugh score can be used to assess acute variceal hemorrhages.

Investigation of the anticancer, antimigration and antiangiogenesis effects of an oxadiazole derivative in two- and three-dimensional cultured Ishikawa and Huvec cells; in vitro and in silico studies

Thu, 28 Mar 2024 00:00:00 +0000

Introduction: There are various methods used in cases of metastatic endometrial cancer. However, the prognosis is generally poor. Therefore, new anticancer agents are expected to exhibit the potential to prevent metastasis, as well as their effects on the viability of cancer cells. In in vitro conditions, the Ishikawa cell line represents endometrial adenocarcinoma and the Huvec cell line represents human umbilical vein endothelial cells. Oxadiazole derivatives may be promising new agents for endometrial cancer treatments by exhibiting anticancer and antiangiogenic properties.

Objective: The aim of this study was to examine the anticancer, antimigration and antiangiogenic effects of 5-[(4-Phenylpiperazine-1-yl)methyl]-1,3,4-oxadiazol-2-thiol (FP-Oxa) on co-cultured Ishikawa and Huvec cells.

Materials and Methods: In silico molecular docking, ADME and toxicity analyzes were performed for FP-Oxa. The effect on the viability of two- and three-dimensional mono- and co-culture models created with HUVEC and Ishikawa cells was evaluated by MTT analysis and IC50 values were calculated. The effect on the migration of two-dimensional cultured cells was determined by wound healing assay. Changes in VEGF expression in three-dimensional co-culture models were evaluated by immunofluorescence staining.

Results: As a result of in silico analyses, it was determined that FP-Oxa was within the oral bioavailability limits, exhibited class 4 toxicity, and had inhibition potential by binding to VEGR2. While FP-Oxa clearly inhibited migration in two-dimensionally cultured Ishikawa cells, it did not show the same level of success in Huvec and co-cultured cells. It was effective in reducing VEGF expression in three-dimensional co-cultures.

Conclusion: FP-Oxa may have various therapeutic effects on endometrial adenocarcinoma cells. It will be important to conduct biological activity studies in three-dimensional models that mimic the tumor structure created with different types of cancer cells.

The role of PEDF, VEGF, and Ki-67 in tissue invasion and tumor angiogenesis of medullary thyroid carcinoma

Wed, 27 Dec 2023 00:00:00 +0000

Objective: This study investigated the role of pigment epithelium-derived factor (PEDF), vascular endothelial growth factor (VEGF), nuclear factor kappa B (NF-kB), and Ki-67 proliferation index (PI) factors in Medullary thyroid carcinoma (MTC) tissue progression and their relationship with tumor angiogenesis. Immunohistochemical (IHC) analyses of PEDF expression in various human tumor samples and healthy tissues have shown that high levels of PEDF expression are associated with a positive prognosis, and low levels of PEDF suggest a poorer prognosis. With the completion of further studies showing the antitumor effects of PEDF on different types of cancer, PEDF’s potential as a therapeutic agent has become increasingly promising. To the best of our knowledge, the role of PEDF in tumor angiogenesis in MTC has not been previously investigated.

Material and Methods: Thirty-seven tissue samples were retrospectively analyzed and sent/removed for pathology after total or subtotal thyroidectomy and archived between 01.01.2000 and 31.12.2015 in the Pathology Department of Hacettepe University. Relationships between categorical variables are analyzed using Pearson Chi-squared or Fisher’s Exact tests.The correlation between two numerical variables is analyzed using Spearman’s Rho correlation coefficient, and a comparison of numerical variables between two groups is made using the Mann-Whitney U test.

Results: The clinicopathological features of the patients were evaluated as sporadic or hereditary, tumor node metastasis (TNM) staging, single or multifocal focus, recurrence or regional or distant metastasis, progression-free survival time (PFS), and appropriate pathology tissue samples were determined as PEDF, VEGF, NF-kB, Ki-67 staining was compared. As a result of this comparison, a moderate negative correlation was found between VEGF expression level and PFS (rho = - 0,407, p = 0,019). No statistically significant correlation was found between single or multifocal groups and Ki-67 proliferation index (PI) expression levels (p = 0.070), but this is a small p value, a variable that is likely to find significant differences in studies with larger sample groups.The relationship between PEDF, VEGF, NF- kB, Ki-67 PI factors and tumor angiogenesis as reflected by microvessel density (MVD) was also investigated. To this end, we correlated the expression levels of PEDF, VEGF, NF-kB, and Ki-67 staining of suitable pathology tissue samples of the patients with the results obtained from the staining with CD 31. As a result of this comparison, no statistically significant relationship was found.

Conclusions: We demonstrated and described for the first time PEDF expression patterns in MTC tumor tissues. A direct relationship between PEDF expression level and angiogenesis, angiogenetic and clinicopathological factors does not seem to exist, at least as it pertains to the group studied. Further studies are required to fully elucidate mechanisms for tumor angiogenesis and invasion in MTC.

Effects of occupational exposure on the hematologic parameters among welders

Volkan Medeni, Sultan Pınar Çetintepe, Rabia Aygür, Fatma Bozdağ, İrem Medeni — Thu, 28 Mar 2024 00:00:00 +0000

Introduction: The effect of prolonged exposure to welding fumes on blood levels remains an unresolved question. In our study, we aimed to determine the effects of metal fume exposure on various blood parameters in welders.

Materials and Methods: The study was cross-sectional. It included all male welding workers admitted to a health institution, a reference hospital for occupational diseases, for 2021. It was conducted with 254 individuals. The variables examined included age, duration of employment, smoking habit, body mass index, hemoglobin levels, erythrocyte, leukocyte and platelet counts, aspartate aminotransferase, alanine aminotransferase, free prostate-specific antigen, creatinine and manganese levels, and erythrocyte sedimentation rates.

Results: In our study, 40.6% of the welders were between 21-30 years old. 65.7% of the participants have been welding for more than five years. According to body-mass index values, 44.1% of the participants were pre-obese, and 16.9% were obese. 63.8% of the participants were smokers. In 35.8% of participants, hyperglycemia was present, and polycythemia was present in 27.2%. When blood parameters were analyzed, fasting blood glucose, aspartate transaminase, alanine transaminase, and sedimentation rate were lower in those who worked less than five years than those who worked five years or more. The difference was statistically significant. In blood test results, leukocyte, glucose, aspartate transaminase, alanine transaminase, and sedimentation rate values in welders were correlated with total working time.

Conclusion: Welders in our study had a high prevalence of smoking, overweight, and obesity. Working time is correlated with liver enzyme levels and fasting blood glucose values. For healthier workers, employers should fulfill their responsibilities for occupational health and safety.

Does proptosis effect the meibography in patients with thyroid eye disease?

Şule Berk Ergun, Dilmeran Şimşek — Thu, 28 Mar 2024 00:00:00 +0000

Objective: The study aimed to compare the meibographies of the eyes of patients with thyroid eye disease who have varying degrees of proptosis.

Materials and Methods: Charts of patients with thyroid eye disease between January 2019 to January 2022 were retrospectively reviewed. Patients with mild and inactive thyroid eye disease, and with 1 mm or more difference in measurements of Hertel exophthalmometer between the eyes were included in the study. The eye of each patient with higher proptosis was included in the study group while the other eye with lower proptosis was included in the control group. The area of meibomian gland loss was evaluated using meibography (Sirius; CSO, Florence, Italy).

Results: Total of 28 eyes of 14 patients were evaluated. Mean meibomian gland dropout area for the upper eyelid was 17.91± 15.37% in the study group and 14.43± 8.61% in the control group. Mean meibomian gland dropout area for the sum of upper and lower eyelid was 44.76± 23.16% in the study group and 43.03± 21.59% in the control group. Mean meibomian gland dropout area for the upper eyelid and also for the sum of upper and lower eyelid were higher in the study group than the control group; however, these results were not significant (p=0.540 and 0.865, respectively). On the other hand, the Pearson correlation test results suggested a significant correlation between the two groups; for the upper eyelid (p<0.001, r=+0.670) and also for the sum of upper and lower eyelids (p<0.001, r=+0.768).

Conclusion: This study showed differences regarding meibographic changes between control and study group. Further studies with larger series are needed to confirm these results.

The biochemical effect correlated with pulmonary dysfunction and complications in obese patients

Başak Çeltikçi, Esen Sayın Gülensoy — Thu, 28 Mar 2024 00:00:00 +0000

Objective: Obesity, an epidemic metabolic disorder, is associated with various biochemical, inflammatory, oxidative and immunological pathways. We aimed to investigate the biochemical effect correlated with pulmonary dysfunction and complications in overweight and obese patients.

Material and Methods: We aimed to evaluate retrospectively the effect of biochemical parameters on pulmonary dysfunction and complications in 79 overweight and obese patients.

The correlative effect of biochemical values, including CRP, and spirometric measurements, such as forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), on pulmonary dysfunction and complications in 79 overweight and obese patients seen in the outpatient clinic were evaluated. Body mass index (BMI), FEV1 and FVC, and total biochemistry values, including creatinine, AST, ALT and CRP values were correlated among each other.

Results: Low FVC levels, leukocytosis, high AST and ALT levels, and comorbidities of obesity are significantly associated with high BMI values by univariate analysis in these patients. Higher AST levels are significantly correlated with higher leucocyte counts, and both AST and ALT levels are significantly correlated with platelet counts.

Conclusion: We investigated the effect of biochemical parameters on pulmonary dysfunction and complications in obese patients. Obesity can be helpful to categorize high-risk patients with low FVC levels in the context of respiratory diseases and high AST and ALT levels for other comorbidities as steatohepatitis, diabetes mellitus and coronary artery disease. This study sheds light on future research on obese patients for prognosis of these diseases, because of their biochemical profile correlation with pulmonary dysfunction and complications.

Transcatheter mitral valve therapies: A comprehensive review

Riya Bonde, Ulaş Kumbasar — Thu, 28 Mar 2024 00:00:00 +0000

Less invasive approaches offer an optimal treatment option for patients with severe mitral regurgitation who is not a candidate for surgical intervention. Favorable outcomes of transcatheter aortic valve replacement have produced great interest in the development of novel minimally invasive transcatheter technologies for repair and replacement of the mitral valve. In this review we aimed to provide an overview of the current transcatheter technologies used to treat mitral regurgitation and help clinicians in selecting the optimal therapy for their patients. We also wanted to provoke clinicians and researchers on how these technologies could be further developed in the future.

Effects of anemia and peri-operative medication on wound healing in cleft lip and palate patients

Galip Gencay Üstün, Fethiye Damla Menkü Özdemir, Figen Özgür — Thu, 28 Mar 2024 00:00:00 +0000

Introduction: Wound healing complications among cleft lip and palate patients pose risks of additional surgeries, reduced scar quality, and increased patient morbidity. This literature review aims to explore the impact of anemia and drug usage associated with respiratory complications, frequently encountered in these patients, on wound healing.

Materials and Method: We conducted an extensive literature search without time constraints using PubMed and Google Scholar databases. The investigation into the effects of anemia and medications on wound healing was divided into three stages. The first stage examined the general effects of anemia and medications on wound healing. The second and final stages assessed wound healing in craniofacial and cleft lip/palate surgeries, respectively.

Results: Preoperative anemia exerts no substantial influence on wound healing unless hemoglobin levels drop below 5 g/dl. No studies reported detrimental effects of glucocorticoids on wound healing. The impact of salbutamol use on wound healing remains controversial, while data regarding ipratropium usage are insufficient.

Conclusion: Severe anemia is the only significant concern for wound healing, necessitating transfusion or improvement in anemia. It appears that short-term use of glucocorticoids after surgery does not have a negative effect on wound healing.It is worth noting that salbutamol and ipratropium usage may have detrimental effects, and while complete avoidance may not be feasible, their potential impact on wound healing should be considered.

Return to work for cancer survivors: Importance and challenges

Yağmur Kınacı Gümüşçubuk, Nursel Çalık Başaran — Thu, 28 Mar 2024 00:00:00 +0000

The loss of gainful employment can lead to a diminished quality of life, reduced self-esteem, and financial difficulties for cancer survivors. Understanding the factors influencing their ability to re-enter the workforce is crucial. Providing workplace accommodations, reducing workloads, and fostering support from employers and colleagues can incentivize cancer survivors to return to work. Physicians also play a pivotal role in aiding patients through the return-to-work process, thereby enhancing their overall quality of life. Early evaluation and access to social support systems are essential for cancer survivors. In this comprehensive review, we examine the process of cancer survivors returning to work, the associated factors, and the primary challenges, drawing upon current research.