Safety Profile of Intravitreal Injections in the Injection Cabinet: No Cases of Endophthalmitis Seen After 7238 Injections.

Objectives: The present study evaluates the rate of endophthalmitis in intravitreal injections (IVI) performed in a modular injection cabin that could be easily sited in a closet in an office environment, and the performance tests of the cabin in terms of heating, ventilation, and air conditioning (HVAC). Methods: The injections were given over approximately 18 months in the cabin and the demographics of the patients were screened retrospectively, and the cabin was subjected to HVAC tests. Results: A total of 7,238 injections were performed in the defined period, and no cases of endophthalmitis were encountered (0%). The results of the airflow and flow rate, particle count, pressure difference, decontamination time, light, moisture, and heat tests were all found to be above the standard defined by the International Organization for Standardization (ISO). Conclusion: An injection cabin is a practical modular construction that can be easily sited in any space without the need for special climatization, and provides a sterile and safe environment for IVI.

Effects of COVID-19 infection on retinal vascular density and choroidal thickness measured by optical coherence tomography angiography.

AIM: The present study evaluates the possible effects of COVID-19 on choroid thickness, the Foveal Avascular Zone (FAZ) and retinal vascular indices in the same individuals who had Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA) data prior to the COVID-19 pandemic. METHODS: The OCT and OCTA images of the same individuals with no known ophthalmic pathology who developed a COVID-19 infection were obtained were retrieved retrospectively from the database and compared with the repeated images of OCT and OCTA images 1-2 months after COVID-19 infection. RESULTS: Eighty eyes of 40 patients (26 female [65%], 14 male [35%]) who had developed a prior Covid-19 infection were included in the study. When comparing the measurements of the same participants before and after Covid-19 infection, no significant difference was detected in the mean average choroidal thicknesses (p=0.998), average superficial (p=0.425) and deep (p=0.333) retinal vascular densities, and superficial (p=0.991) and deep (p=0.075) FAZ measurements. CONCLUSIONS: No significant effect of COVID-19 on choroid thickness, FAZ or retinal vascular densities was noted in the present study, although there are some studies in literature with equivocal results.

Associations between body mass index and choroidal thickness, superficial and deep retinal vascular indices, and foveal avascular zone measured by OCTA.

AIM: The present study explores the effects of Body Mass Index (BMI) on choroidal thickness, the deep and superficial retinal capillary plexuses, and the foveal avascular zone (FAZ). METHODS: The subjects in this prospective study were divided into five groups based on their calculated BMI. Choroidal thickness, superficial and deep retinal capillary plexuses, and FAZ were measured using enhance depth imaging (EDI) and optical coherence tomography angiography (OCTA). The groups were then compared and correlations with BMI were evaluated. RESULTS: The study included 210 eyes of 105 subjects. The comparison of the BMI groups revealed a significant decrease in the mean choroidal thicknesses in the obese groups (p = 0.001), and a significant negative correlation between BMI and mean choroidal thickness (p = 0.02). The results of the analysis of the mean superficial and deep retinal capillary plexuses did not differ between the groups (p = 0.089, p = 0.808 respectively), while the deep FAZ measurements revealed a significant decrease in the obese groups (p = 0.003). CONCLUSION: Choroidal thickness and deep FAZ are significantly negatively correlated with BMI, suggesting potential choroidal and retinal microvascular effects of obesity.

The Effects of chronic smoking on retinal vascular densities and choroidal thicknesses measured by optical coherence tomography angiography.

PURPOSE: To examine the effects of chronic smoking on vascular density in superficial and deep retinal vascular plexuses and choroidal thicknesses. METHOD: Superficial and deep vessel densities and choroidal thicknesses of smoking volunteers and healthy non-smoking volunteers were measured with the Topcon DRI OCT-1 Tritron® device and compared with each other. RESULTS: This study included 108 eyes of 54 smoking volunteers and 108 eyes of 54 healthy volunteers as a control group. The average superficial vascular density index and deep vascular density indexes of smokers were found to be 39.81 ± 1.5% and 42.53 ± 1.9%, respectively (P = 0.53), while the non-smoking control group was 40.09 ± 1.3% and 41.57 ± 1.6%, respectively (P = 0.006). Average choroidal thicknesses were 284.22 ± 59 in smokers and 270.72 ± 61 in the control group (P = 0.247). Also, smoking quantity per day x years was found to be significantly negatively correlated with average choroidal thicknesses. (P = 0,011). DISCUSSION: In this study, it was determined that chronic smoking increases deep retinal vascular densities on retinal vascular plexus. However, the cumulative effect of smoking was found to be negatively correlated with choroidal thicknesses. Smoking has microvascular effects on vessels such as vasodilatation, vasoconstriction, increased platelet aggregation, endothelial dysfunction. However, studies in the literature are in dispute with the effects of smoking on choroidal and retinal vessels. This study may show that chronic smoking may have different vascular effects on the superficial and deep plexuses and choroidal vessels, as well as different effects from acute use.

Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study.

INTRODUCTION: We aimed to investigate the efficacy and side effects of bendamustine in relapsed/refractory lymphoma patients in Turkey. MATERIAL AND METHODS: In this retrospective study, we included relapsed/refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients who underwent multiple lines of chemotherapy. The primary endpoint was to determine the objective response and toxicity. RESULTS: Ninety-nine patients with a median age of 59.8 years were included in the study. Eighty-one patients had NHL (follicular lymphoma: 10, diffuse large B-cell lymphoma: 27, mantle-cell lymphoma: 18, marginal zone lymphoma: 9, small lymphocytic lymphoma/chronic lymphocytic leukemia: 17) and 18 patients had HL. The patients had previously received a median of three lines of chemotherapy (range: 2-8) except autologous stem cell transplantation (ASCT); 19 patients (HL: 11, NHL: 8) had undergone ASCT. The objective response rate (ORR) was 74.3%, the complete response rate was 57% (= 53), and the partial response rate was 16.6% ( = 19). The overall survival (OS) rate at 1 year was 74.6%. The progression-free survival (PFS) rate at 1 year was 62.5%. The most common side effects were lymphopenia, anemia and neutropenia. Side effects which were observed as grade 3 and higher levels were lymphopenia (14.1%), neutropenia (10.1%) and fatigue (7.1%). CONCLUSIONS: Objective response rate of bendamustine was found to be 74.3% in relapsed/refractory HL and NHL patients. It appears to be an effective option as a salvage treatment for patients who have previously received multiple lines of therapy.

Hematopoietic Stem Cell Transplantation for Patients with Paroxysmal Nocturnal Hemoglobinuria with or without Aplastic Anemia: A Multicenter Turkish Experience

Objective: Although inhibition of the complement system at different steps is a promising therapy modality in patients with paroxysmal nocturnal hemoglobinuria (PNH), allogeneic hematopoietic stem cell transplantation (HCT) is still the only curative therapy, especially for patients with intractable hemolysis or bone marrow failure. The aim of this study is to evaluate the outcomes of allogeneic HCT in PNH patients with aplastic anemia (PNH-AA) or without. Materials and Methods: Thirty-five PNH/PNH-AA patients who were treated with allogeneic HCT in 10 transplantation centers in Turkey were retrospectively analyzed. Results: Sixteen (45.7%) and 19 (54.3%) patients were diagnosed with classical PNH and PNH-AA, respectively. The median age of the patients was 32 (18-51) years. The 2-year overall survival (OS) rate and rate of graft-versus-host disease-free, failure-free survival (GFFS) was 81.2% and 78.1%, respectively. The 2-year OS in cases of classical PNH and PNH-AA was 81.3% and 79.9%, respectively (p=0.87), and 2-year GFFS in cases of PNH and PNH-AA was 79% and 76% (p=0.977), without statistical significance. The OS and GFFS rates also did not differ between transplantations with matched sibling donors (MSDs) and matched unrelated donors (MUDs). Conclusion: Allogeneic HCT with MSDs or MUDs is a good option for selected patients with classical PNH and PNH-AA. In particular, patients with debilitating and refractory hemolysis and patients with bone marrow failure might form an excellent group of candidates for allogeneic HCT.

The effect of religious fasting and dehydration at Ramadan on choroidal thickness and Retinal vessel densities, measured with optical coherence tomography angiography.

AIM: To investigate the effect of religious fasting and dehydration at Ramadan on choroidal thickness and vessel density in the superficial and deep vascular plexuses with OCTA. METHODS: The choroidal thickness, and superficial and deep vessel density indices of fasting healthy subjects were measured with an OCTA device, and compared with non-fasting measurements. RESULTS: The study included 70 eyes of 35 healthy subjects with a mean age of 42.86 ± 8.3 years. The measured choroidal thickness, superficial vessel density index and deep vessel density index were 288.89 ± 67 µm, 40.56% and 41.43%, respectively when measured in the fasting period, compared to 284.62 ± 65 µm, 40.41% and 41.41%, respectively when measured in the non-fasting period. The choroidal thickness under the fovea center was found to be significantly higher in the fasting period than in the non-fasting period (p = 0.014). The mean total choroidal thickness was found to be reduced in the non-fasting period, although not to a statistically significant degree (p > 0.05). An analysis of the mean total superficial and deep vascular plexuses revealed no statistically significant difference (p = 0.368, p = 0.938 respectively). CONCLUSION: Although a significant increase was noted in central choroidal thickness in the fasting period, no significant change due to fasting was observed in the superficial and deep capillary plexuses. The choroidal layer may vary in thickness due to fasting-related metabolic factors, while retinal vessels are more stable against such effects.

Efficacy and safety of ruxolitinib in patients with myelofibrosis: a retrospective and multicenter experience in Turkey

Background/aim: The aim of this study is to assess the efficacy and safety of ruxolitinib in patients with myelofibrosis. Materials and methods: From 15 centers, 176 patients (53.4% male, 46.6% female) were retrospectively evaluated. Results: The median age at ruxolitinib initiation was 62 (28­87) and 100 (56.8%) of all were diagnosed as PMF. Constitutional symptoms were observed in 84.7%. The median initiation dose of ruxolitinib was 30 mg (10­40). Dose change was made in 69 (39.2%) patients. Forty seven (35.6%) and 20 (15.2%) of 132 patients had hematological and nonhematological adverse events, respectively. The mean spleen sizes before and after ruxolitinib treatment were 219.67 ± 46.79 mm versus 199.49 ± 40.95 mm, respectively (p < 0.001). There was no correlation between baseline features and subsequent spleen response. Overall survival at 1-year was 89.5% and the median follow up was 10 (1­55) months. We could not show any relationship between survival and reduction in spleen size (p = 0.73). Conclusion: We found ruxolitinib to be safe, well tolerated, and effective in real-life clinical practice in Turkey. Ruxolitinib dose titration can provide better responses in terms of not only clinical benefit but also for long term of ruxolitinib treatment.

ALTERED BLOOD AND AQUEOUS HUMOR LEVELS OF ASPROSIN, 4-HYDROXYNONENAL, AND 8-HYDROXY-DEOXYGUANOSINE IN PATIENTS WITH DIABETES MELLITUS AND CATARACT WITH AND WITHOUT DIABETIC RETINOPATHY.

PURPOSE: Diabetic retinopathy (DRP) is the formation of edema and small vessels in the retina due to high blood glucose levels. Asprosin is a hormone that stimulates the release of glucose from the liver into the circulation. Considering the relationship between oxidative stress and DRP, our study aimed to determine the levels of the oxidative stress markers 4-hydroxynonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), as well as asprosin, in the blood and aqueous humor (Aq) of patients with and without DRP. METHODS: Thirty patients with single-eye DRP and cataract (DRP + C), 30 patients with diabetes mellitus and cataract without DRP (DM + C), and 30 healthy control (CON) participants were enrolled into this retrospective study. Except for healthy controls, Aq and blood samples were taken from these patients during their cataract operation. Asprosin, 4-HNE, and 8-OHdG concentrations were analyzed using enzyme-linked immunosorbent assays. RESULTS: In patients with DRP, the levels of asprosin, 4-HNE, and 8-OHdG were significantly higher in both Aq and blood samples compared with the group of patients without DRP. CONCLUSION: These findings suggest that the measurement of asprosin, 4-HNE, and 8-OHdG levels may support clinicians in determining the risk of DRP development.

The Turkish experience with therapeutic plasma exchange: A national survey.

Therapeutic plasma exchange (TPE) is used to treat more than 60 diseases worldwide and has drawn growing interest. Little is known about the current situation of TPE activity in Turkey, so we developed a survey to obtain information about this timely topic. We collected data on TPE from 28 apheresis units throughout Turkey. We performed a total of 24,912 TPE procedures with 3203 patients over the past decade. Twenty years ago, the majority of procedures were performed for neurological and hematological disorders, and today, most TPE procedures are done for the same reasons. The only historical change has been an increase in TPE procedures in renal conditions. Currently, renal conditions were more frequently an indication for TPE than rheumatic conditions. Fresh frozen plasma was the most frequently used replacement fluid, followed by 5% albumin, used in 57.9% and 34.6% of procedures, respectively. The most frequently used anticoagulants in TPE were ACD-A and heparin/ACD-A, used with 1671 (52.2%) and 1164 (36.4%) patients, respectively. The frequency of adverse events (AEs) was 12.6%. The most common AEs were hypocalcemia-related symptoms, hypotension, and urticaria. We encountered no severe AEs that led to severe morbidity and mortality. Overall, more than two thirds of the patients showed improvement in the underlying disease. Here, we report on a nationwide survey on TPE activity in Turkey. We conclude that there has been a great increase in apheresis science, and the number of TPE procedures conducted in Turkey has increased steadily over time. Finally, we would like to point out that our past experiences and published international guidelines were the most important tools in gaining expertise regarding TPE.

A multicenter experience of thrombotic microangiopathies in Turkey: The Turkish Hematology Research and Education Group (ThREG)-TMA01 study.

Thrombotic microangiopathies (TMAs) are rare, but life-threatening disorders characterized by microangiopathic hemolytic anemia and thrombocytopenia (MAHAT) associated with multiorgan dysfunction as a result of microvascular thrombosis and tissue ischemia. The differentiation of the etiology is of utmost importance as the pathophysiological basis will dictate the choice of appropriate treatment. We retrospectively evaluated 154 (99 females and 55 males) patients who received therapeutic plasma exchange (TPE) due to a presumptive diagnosis of TMA, who had serum ADAMTS13 activity/anti-ADAMTS13 antibody analysis at the time of hospital admission. The median age of the study cohort was 36 (14-84). 67 (43.5%), 32 (20.8%), 27 (17.5%) and 28 (18.2%) patients were diagnosed as thrombotic thrombocytopenic purpura (TTP), infection/complement-associated hemolytic uremic syndrome (IA/CA-HUS), secondary TMA and TMA-not otherwise specified (TMA-NOS), respectively. Patients received a median of 18 (1-75) plasma volume exchanges for 14 (153) days. 81 (52.6%) patients received concomitant steroid therapy with TPE. Treatment responses could be evaluated in 137 patients. 90 patients (65.7%) achieved clinical remission following TPE, while 47 (34.3%) patients had non-responsive disease. 25 (18.2%) non-responsive patients died during follow-up. Our study present real-life data on the distribution and follow-up of patients with TMAs who were referred to therapeutic apheresis centers for the application of TPE.

Therapeutic apheresis in the treatment of catastrophic antiphospholipid syndrome.

Catastrophic thrombotic syndrome is characterized by occurrence of several thromboembolic occlusions which affect a variety of vascular beds over a short period of time. Catastrophic Antiphospholipid syndrome (CAPS) (1%) is regarded as a rare but severe variant of Antiphospholipid Syndrome. Treatment with anticoagulants, steroids and therapeutic plasma exchange has been shown to give the best results. However, to treat CAPS, the best substitute for plasma is still a debatable issue because there are no standard methods.

Current practice of autologous hematopoietic progenitor cell mobilization in adult patients with multiple myeloma and lymphoma: The results of a survey from Turkish hematology research and education group (ThREG).

Autologous hematopoietic cell transplantation (AHCT) is an established treatment option for adult patients presenting with multiple myeloma (MM), Hodgkin lymphoma (HL) and various subtypes of non-Hodgkin lymphoma (NHL) in upfront and/or relapsed/refractory disease settings. Although there are recently published consensus guidelines addressing critical issues regarding autologous hematopoietic progenitor cell mobilization (HPCM), mobilization strategies of transplant centers show high variability in terms of routine practice. In order to understand the current institutional policies regarding HPCM in Turkey and to obtain the required basic data for preparation of a national positional statement on this issue, Turkish Hematology Research and Education Group (ThREG) conducted a web-based HPCM survey. The survey was designed to include multiple-choice questions regarding institutional practice of HPCM in adults presenting MM, HL, and NHL. The representatives of 27 adult HCT centers participated to the study. Here we report the results of this survey shedding light on the real-world experience in Turkey in terms of autologous HPCM mobilization strategies in patients presenting with MM and lymphoma.

Prognosis estimation under the light of metabolic tumor parameters on initial FDG-PET/CT in patients with primary extranodal lymphoma.

BACKGROUND: Non-Hodgkin's lymphomas arising from the tissues other than primary lymphatic organs are named primary extranodal lymphoma. Most of the studies evaluated metabolic tumor parameters in different organs and histopathologic variants of this disease generally for treatment response. We aimed to evaluate the prognostic value of metabolic tumor parameters derived from initial FDG-PET/CT in patients with a medley of primary extranodal lymphoma in this study. PATIENTS AND METHODS: There were 67 patients with primary extranodal lymphoma for whom FDG-PET/CT was requested for primary staging. Quantitative PET/CT parameters: maximum standardized uptake value (SUVmax), average standardized uptake value (SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were used to estimate disease-free survival and overall survival. RESULTS: SUVmean, MTV and TLG were found statistically significant after multivariate analysis. SUVmean remained significant after ROC curve analysis. Sensitivity and specificity were calculated as 88% and 64%, respectively, when the cut-off value of SUVmean was chosen as 5.15. After the investigation of primary presentation sites and histo-pathological variants according to recurrence, there is no difference amongst the variants. Primary site of extranodal lymphomas however, is statistically important (p = 0.014). Testis and central nervous system lymphomas have higher recurrence rate (62.5%, 73%, respectively). CONCLUSIONS: High SUVmean, MTV and TLG values obtained from primary staging FDG-PET/CT are potential risk factors for both disease-free survival and overall survival in primary extranodal lymphoma. SUVmean is the most significant one amongst them for estimating recurrence/metastasis.

Treatment of Resistant Cyclophosphamide Induced Haemorrhagic Cystitis: Review of Literature and Three Case Reports.

Haemorrhagic Cystitis (HC) is defined as diffuse inflammatory bladder bleeding due to many aetiologies. Massive HC often arises from anticancer chemotherapy or radiotherapy for the treatment of pelvic malignancies. Phosphamides are the anti-cancer drugs used for treating breast cancer, B-cell lymphoma, leukemia, rheumatoid arthritis and systemic lupus erythaematosis by cross-linking strands of DNA and preventing the cell division. They are also used in bone marrow transplantation for prevention of Graft Versus Host Disease (GVHD). Hepatic metabolism of phosphamide forms acrolein, and acrolein makes ulceration, haemorrhage, edema and necrosis of the urothelium during its excretion by the urine. Infectious causes of HC in immunocomprimesed patients are adenovirus, BK polyoma-virus (BK), JC virus, and Cytomegalovirus (CMV). The present article attempts to make a review of literature for the treatment of intractable HC and report three cases with HC.

Influence of indoor and outdoor activities on progression of myopia during puberty.

The purpose of this study was to investigate whether time spent on indoor and outdoor activities or the other possible risk factors including age, gender, parental history, and initial refraction was associated with progression of myopia, during puberty. Fifty eyes of 50 myopic children aged 9-14 years were enrolled in the study. The parents were interviewed to determine the amounts of time in hours per day spent on reading and writing, using computer, watching TV, and outdoor activities (i.e., sports, games, or being outdoor with no activities) on an average day. The annual myopia progression rate (diopters per year) was calculated for each subject and was used in the statistical analyses. The mean initial age of the subjects was 10.9 ± 1.5 (ranging from 9 to 14) years. The mean follow-up period was 33.3 ± 10.3 (ranging from 17 to 55) months. There was a significant increase in the mean myopia value of the subjects after follow-up period (p < 0.001). The mean daily time spent on reading and writing and initial refraction value were independently associated with annual myopic progression rate. On the other hand, age, gender, parental myopia, and the mean daily times spent on computer use, watching TV, and outdoor activities had no correlations with annual myopia progression rate. The present study showed that myopia progression was associated with time spent on reading and writing and initial refraction value, during puberty. However, myopia progression was not associated with parental myopia, age, gender, and daily times spent on using computer, watching TV, and outdoor activities.

The -137G/C Polymorphism in Interleukin-18 Gene Promoter Contributes to Chronic Lymphocytic and Chronic Myelogenous Leukemia Risk in Turkish Patients.

OBJECTIVE: Interleukin-18 (IL-18) is a cytokine that belongs to the IL-1 superfamily and is secreted by various immune and nonimmune cells. Evidence has shown that IL-18 has both anticancer and procancer effects. The aim of this study was to evaluate the relationship between IL-18 gene polymorphisms and susceptibility to chronic lymphocytic leukemias (CLL) and chronic myelogenous leukemias (CML) in Turkish patients. MATERIALS AND METHODS: The frequencies of polymorphisms (rs61667799(G/T), rs5744227(C/G), rs5744228(A/G), and rs187238(G/C)) were studied in 20 CLL patients, 30 CML patients, and 30 healthy individuals. The genotyping was performed by polymerase chain reaction and DNA sequencing analysis. RESULTS: Significant associations were detected between the IL-18 rs187238(G/C) polymorphism and chronic leukemia. A higher prevalence of the C allele was found in CML cases with respect to controls. The GC heterozygous and CC homozygous genotypes were associated with risk of CML when compared with controls. However, prevalence of the C allele was not significantly high in CLL cases with respect to controls. There was only a significant difference between the homozygous CC genotype of CLL patients and the control group; thus, it can be concluded that the CC genotype may be associated with the risk of CLL. Based on our data, there were no significant associations between the IL-18 rs61667799(G/T), rs5744227(C/G), or rs5744228(A/G) polymorphisms and CLL or CML. CONCLUSIONS: IL-18 gene promoter rs187238(G/C) polymorphism is associated with chronic leukemia in the Turkish population. However, due to the limited number of studied patients, these are preliminary results that show the association between -137G/C polymorphism and patients (CLL and CML). Further large-scale studies combined with haplotype and expression analysis are required to validate the current findings.