Challenging Treatment of Disseminated Aspergillosis in a Child With Nephrotic Syndrome.

INTRODUCTION: Central nervous system (CNS) aspergillosis is an opportunistic infection with an increasing incidence and a high mortality rate. It is seen in immunocompromised patients as well as in immunocompetent patients. Here, we present disseminated aspergillosis in a child with nephrotic syndrome treated with long-term and aggressive systemic antifungal treatment and intraventricular (IVent) liposomal amphotericin B (L-AmB) as well as surgical excision and drainage due to difficulty in management. CASE REPORT: A 10-year-old boy with nephrotic syndrome on steroid therapy was admitted with limping and weakness. The cranial magnetic resonance imaging showed multiple intraparenchymal scattered abscesses. The largest one was excised and drained. Abscess culture revealed Aspergillus fumigatus and histopathological examination revealed septate hyphae compatible with Aspergillosis. Intravenous (IV) voriconazole was started, and IV L-AmB was added. The size of lesions and perilesional edema continued to increase, and then IVent L-AmB was added. With IVent and systemic antifungal treatment, regression of the lesions was observed. He was followed up with oral voriconazole and weekly IVent L-AmB. After 2 and a half months, he was re-operated because of increased lesion size, number and perilesional edema, and IV voriconazole and other salvage antifungal therapies were started. Since the lesions had decreased and remained stable, IV voriconazole was switched to oral therapy, and he was followed up as an outpatient. Immunodeficiency diseases were excluded by immunological and genetic tests. CONCLUSION: Management of central nervous system aspergillosis can be challenging despite long-term and aggressive systemic and IVent antifungal treatment as well as surgical excision and drainage.

Prolongation of QT interval due to hydroxychloroquine overdose used in COVID-19 treatment.

Hydroxychloroquine is one of the most commonly used drugs in COVID-19 treatment. In this case report, we aimed to present a young patient whose QT interval was prolonged due to hydroxychloroquine overdose which was given for COVID-19 treatment. This is the first reported case of QT interval prolongation at a low dose of 1.600 mg in the literature. A 28-year-old male patient was admitted to the emergency department with the complaints of nausea, diarrhea, and weakness. The patient was diagnosed with COVID-19 a day prior and home isolation was recommended with hydroxychloroquine and oseltamivir P. O. treatment. His complaints started 6 h after accidentally taking 1.600 mg of hydroxychloroquine P. O. at the same time. On physical examination, the Glasgow Coma Scale was 15, and neurological, respiratory, and abdominal examinations were normal. His pulse was 54 beats/min, oxygen saturation was 99%, arterial blood pressure was 122/82 mmHg, and fever was 36.5°C. Electrocardiography (ECG) showed sinus bradycardia and corrected QT interval was calculated as 510 ms. The QT interval prolongation and bradycardia persisted, and the patient was hospitalized for follow-up and treatment. He was discharged on the 3rd day of his hospitalization after the corrected QT interval was detected to be 420 ms and his bradycardia improved. Due to the potential cardiac side effects, patients who are sent to home isolation with treatment should be educated about the use, dosage, and possible side effects of this medicine, and serial ECG monitoring should be provided to patients who are hospitalized.

Splenic Marginal Zone Lymphoma in Turkey: Association with Hepatitis B Instead of Hepatitis C Virus as an Etiologic and Possible Prognostic Factor - A Multicenter Cohort Study

Objective: Chronic antigenic stimulation is frequently blamed in the pathogenesis of extranodal marginal zone lymphomas including splenic marginal zone lymphoma (SMZL). Chronic hepatitis C is frequently observed in SMZL patients in some geographical regions. However, these reports are largely from North America and Europe, and data from other countries are insufficient. In this multicenter study we aimed to identify the clinical characteristics of SMZL patients in Turkey, including viral hepatitis status and treatment details. Materials and Methods: Data were gathered from participating centers from different regions of Turkey using IBM SPSS Statistics 23 for Windows. Hepatitis B virus surface antigen (HBsAg), anti-HBs antibody, anti-HB core antigen antibody (anti-HBcAg), HB viral load, anti-hepatitis C virus (HCV) antibody, HCV viral load results were analyzed. Results: One hundred and four patients were reported. Hepatitis C virus positivity was observed in only one patient. However, hepatitis B virus surface antigen (HBsAg) positivity was observed in 11.2% and HBsAg and/or anti-HB core antigen antibody (anti-HBcAg) positivities were seen in 34.2% of the patients. The median age was 60 years (range=35-87). Median follow-up duration was 21.2 months (range=00.2-212; 23.2 months for surviving patients). Median overall survival was not reached. Estimated 3-year and 10-year survival rates were 84.8% and 68.9%, respectively. Older age, no splenectomy during follow-up, platelet count of <90x103/µL, lower albumin, higher lactate dehydrogenase, higher ß2-microglobulin, and HBsAg positivity were associated with increased risk of death. Only albumin remained significant in multivariable analysis. Conclusion: These results indicate that hepatitis B virus may be a possible risk factor for SMZL in our population. It may also be an indirect prognostic factor.

The Prognosis of Adult Burkitt's Cell Leukemia in Real-Life Clinical Practice.

OBJECTIVE: Many studies reported an improved prognosis in patients with Burkitt's lymphoma obviating the need of stem cell transplantation. However, prognosis of the advanced disease [i.e. Burkitt's cell leukemia (BCL)] has not been reported with current treatment modalities except for a few prospective trials. The aim of this study is to compare the prognoses of BCL patients with similarly treated and nontransplanted patients with other types of acute lymphoblastic leukemia (ALL) and with ALL patients that underwent allogeneic stem cell transplantation (ASCT) in their first remissions. MATERIALS AND METHODS: In this retrospective analysis, BCL patients aged between 16 and 63 who were admitted between 2000 and 2014 to the hospitals of Hacettepe or Gazi University and were treated with intensive therapies aimed at cure were included. All ALL patients who were treated with a similar protocol not including transplantation during the same period (NT-ALL group) and all ALL patients who underwent ASCT in the first complete remission during the same period (T-ALL group) served as control groups. RESULTS: The central nervous system or extramedullary involvement rates, lactate dehydrogenase levels, and white blood cell counts at diagnosis were higher in the BCL group than the NT-ALL group and these differences were significant. BCL patients had disease-free survival (DFS) durations comparable with the T-ALL cohort but NT-ALL patients had significantly shorter DFS durations. Both cumulative relapse incidence and cumulative nonrelapse mortality were higher in NT-ALL patients compared to the T-ALL group and BCL patients. CONCLUSION: DFS in BCL patients treated with a widely accepted modern regimen, R-HyperCVAD, is comparable to results in other ALL patients receiving allogeneic transplantation. Our results are in agreement with a few prospective noncomparative studies suggesting no further need for stem cell transplantation in BCL.

Expression Profiles of the Individual Genes Corresponding to the Genes Generated by Cytotoxicity Experiments with Bortezomib in Multiple Myeloma.

OBJECTIVE: Multiple myeloma (MM) is currently incurable due to refractory disease relapse even under novel anti-myeloma treatment. In silico studies are effective for key decision making during clinicopathological battles against the chronic course of MM. The aim of this present in silico study was to identify individual genes whose expression profiles match that of the one generated by cytotoxicity experiments for bortezomib. MATERIALS AND METHODS: We used an in silico literature mining approach to identify potential biomarkers by creating a summarized set of metadata derived from relevant information. The E-MTAB-783 dataset containing expression data from 789 cancer cell lines including 8 myeloma cell lines with drug screening data from the Wellcome Trust Sanger Institute database obtained from ArrayExpress was "Robust Multi-array analysis" normalized using GeneSpring v.12.5. Drug toxicity data were obtained from the Genomics of Drug Sensitivity in Cancer project. In order to identify individual genes whose expression profiles matched that of the one generated by cytotoxicity experiments for bortezomib, we used a linear regression-based approach, where we searched for statistically significant correlations between gene expression values and IC50 data. The intersections of the genes were identified in 8 cell lines and used for further analysis. RESULTS: Our linear regression model identified 73 genes and some genes expression levels were found to very closely correlated with bortezomib IC50 values. When all 73 genes were used in a hierarchical cluster analysis, two major clusters of cells representing relatively sensitive and resistant cells could be identified. Pathway and molecular function analysis of all the significant genes was also investigated, as well as the genes involved in pathways. CONCLUSION: The findings of our present in silico study could be important not only for the understanding of the genomics of MM but also for the better arrangement of the targeted anti-myeloma therapies, such as bortezomib.

Common variable immune deficiency associated Hodgkin's lymphoma complicated with EBV-linked hemophagocytic lymphohistiocytosis: a case report.

Hemophagocytic syndrome (HPS) is described by an increase in macrophages accountable for extensive phagocytosis of hematopoietic cells. Secondary HPS arises commonly in the presence of infections, neoplasia, autoimmune disorders and immune disorders. Here, we reported a patient with common variable immune deficiency (CVID) and Hodgkin's lymphoma (HL) who later developed EBV linked hemophagocytic lymphohistiocytosis. 42 year old men underwent check-up because of back pain in July 2012. He had known CVID disease. In physical examination he had no lymphadenopathies however his spleen was palpable 3 cm under arcus costa. He had hypogammaglobulinemia with IgG levels around 500 mg/dl. In abdominal computed tomography (CT) multiple lymphadenopathies reaching maximum 26×17 cm size were seen so, PET-CT was performed. Involvement in thorax, abdomen, and bone was detected with maximum SUV max 11.5. He had undergone tru-cut biopsy from lymph node in November 2012 which revealed HL. Bone marrow investigation favored with mix cell type. His cytogenetic analysis was reported as 46 XY. He was considered as stage 4 disease and ABVD (Adriamycin, bleomycin, vincristine and dexamethasone). He was given six cycles of chemotherapy in May 2013 and complete remission was observed in control CT screening in July 2013. However pancytopenia evolved in August 2013. Bone marrow investigation revealed suspicious lymphohistiocytic infiltration. Treatment was planned to apply autologous stem cell transplantation (SCT) after salvage chemotherapy. Control bone marrow investigation again revealed the lymphohistiocytic aggregates with hemophagocytosis. Our patient showed 5 criteria of hemophagocytic syndrome. He had ferritin elevation (>5000 µg/dl), splenomegaly (13 cm) cytopenia, triglyceride elevation and hemophagocytosis. He had unrelated SCT transplantation however he died from transplant related toxicity. The primary and secondary immune deficiency caused by chemotherapy are the major causes for our patient inability to control his EBV infection which eventually lead to hemophagocytic lymphohistiocytosis. To conclude, rare simultaneous manifestation of primary immune deficiencies (PID), Hodgkin's lymphoma and EBV-HLH occurred in our patient which have concordant immunological mechanism that eventually lead poor prognosis in our patient.

Rebound Thrombocytosis following Induction Chemotherapy is an Independent Predictor of a Good Prognosis in Acute Myeloid Leukemia Patients Attaining First Complete Remission.

There are very few data about the relationship between acute myeloid leukemia (AML) prognosis and bone marrow recovery kinetics following chemotherapy. In this study, we aimed to assess the prognostic importance and clinical associations of neutrophil and platelet recovery rates and rebound thrombocytosis (RT) or neutrophilia (RN) in the postchemotherapy period for newly diagnosed AML patients. De novo AML patients diagnosed between October 2002 and December 2013 were evaluated retrospectively. One hundred patients were suitable for inclusion. Cox regression analysis using need for reinduction chemotherapy as a stratification parameter revealed RT as the only parameter predictive of OS, with borderline statistical significance (p = 0.06, OR = 7; 95% CI 0.92-53), and it was the only parameter predictive of DFS (p = 0.024, OR = 10; 95% CI 1.3-75). In order to understand whether RT or RN was related to a better marrow capacity or late consolidation, we considered neutrophil recovery time and platelet recovery time and nadir-first consolidation durations in all patients in the cohort. Both the marrow recovery duration and the time between marrow aplasia and first consolidation were shorter in RT and RN patients. To our knowledge, this is the first study to report a correlation between RT/RN and prognosis in AML.

Clinicopathological associations of acquired erythroblastopenia.

INTRODUCTION: Acquired erythroblastopenia (AE) is a rare clinical situation. It is characterized by the reduction of erythroid precursors in the bone marrow together with the low reticulocyte counts in the peripheral blood. BACKGROUND: Main secondary causes of AE are drugs, Parvovirus B19 and other infectious reasons, lymphoid and myeloid neoplasia, autoimmune diseases, thymoma and pregnancy. The aim of this study is to assess the frequencies and clinical associations of AE via analyzing 12340 bone marrow samples in a retrospective manner. MATERIAL AND METHOD: Bone marrow aspirations which were obtained from patients who applied to Hacettepe University Hematology Clinic between 2002 and 2013, were analyzed retrospectively. RESULTS: Thirty four erythroblastopenia cases were found. Patients ranged in age from 16 to 80 years with a median of 38 years. Fifteen patients were men (44%) and nineteen were women (56%). In these patients, detected causes of erythroblastopenia were MDS, idiopathic pure red cell aplasia (PRCA), parvovirus infection, post chemotherapy aplasia, plasma proliferative diseases, copper deficiency due to secondary amyloidosis, fever of unknown origin, hemophagocytic syndrome, enteric fever and legionella pneumonia. We found that between those reasons the most common causes of erythroblastopenia are MDS (17.7%) and idiopathic PRCA (17.7%). DISCUSSION: As a result, erythroblastopenia in the bone marrow may be an early sign of MDS. In those AE cases possibility of being MDS must be kept in mind as it can be mistaken for PRCA. CONCLUSION: To conclude, in adults MDS without excess blast is one of the most common causes of erythroblastopenia in clinical practice and in case of erythroblastopenia the presence of MDS should be investigated.

The factors affecting early death after the initial therapy of acute myeloid leukemia.

There are some improvements in management of acute myeloid leukemia (AML). However, induction-induced deaths still remain as a major problem. The aim of this study is to assess clinical parameters affecting early death in patients with AML. 199 AML patients, who were treated with intensive, non-intensive or supportive treatment between 2002 and 2014 in Hacettepe Hematology Department, were analyzed retrospectively. In our study early death rate for elderly was found to be lower than previous reports whereas it was similar for those who were under age of 60. Better ECOG performance (ECOG performance score 0 and 1) and non-intensive treatment associated with lower early death rates, however APL-type disease associated with higher early death rates. ECOG performance score at diagnosis was found to be the most related independent factor with higher rate of early death in 15 days after treatment (P<0.001). Therefore we decided to understand the factors which were related with ECOG. WBC count at diagnosis was found to be the only related parameter with ECOG performance score. Leucocyte count at diagnosis appears like to have an indirect effect on early death in AML patients. It maybe suggested that in recent years there is an improvement in early death rates of elderly AML patients. The currently reported findings require prospective validation and would encourage the incorporation of other next generation genomics for the prediction of early death and overall risk status of AML.

Survival analysis of biliary tract cancer cases in Turkey.

BACKGROUND: Because of the relative rarity of biliary tract cancers (BTCs), defining long term survival results is difficult. In the present study, we aimed to evaluate the survival of a series of cases in Turkey. MATERIALS AND METHODS: A totally of 47 patients with billiary tract cancer from Mersin Goverment Hospital, Acibadem Kayseri Hospital and Kayseri Training and Research Hospital were analyzed retrospectively using hospital records between 2006-2012. RESULTS: The median overall survival was 19.3±3.9 months for all patients. The median disease free and overall survivals were 24.3±5.3 and 44.1±12.9 months in patients in which radical surgery was performed , but in those with with inoperable disease they were only 5.3±1.5 and 10.7±3.2 months, respectively. CONCLUSIONS: BTCs have a poor prognosis. Surgery with a microscopic negative margin is still the only curative treatment.

Lack of sunlight exposure influence on primary glioblastoma survival.

BACKGROUND: The prognosis of primary glioblastoma (GBM) is poor. Approximately 2/3 of primary brain tumor diagnoses are GBM, of which 95% are primary lesions. In this study, we aimed to evaluate whether more sunlight exposure has an effect on survival of patients with primary GBM. MATERIALS AND METHODS: A total of 111 patients with primary GBM were enrolled from Kayseri in inner Anatolia which has a cold climate (n: 40) and Mersin in Mediterranean region with a warm climate and more sunlight exposure (n: 71). The patients with primary GBM were divided into two groups as Kayseri and Mersin and compared for progression free survival (PFS) and overall survival (OS). RESULTS: The PFS values were 7.0 and 4.7 months for Kayseri and Mersin groups, respectively (p=0.10) and the respective OS values were 13.3 and 9.4 months (p=0.13). We did not found any significant difference regarding age, sex, comorbidity, smoking, surgery, resurgery, adjuvant chemoradiotherapy and palliative chemotherapy between the groups. CONCLUSIONS: We found that more sunlight exposure had no impact on prognosis of patients with primary GBM, adding inconsistency to the literature about the relationship between sunlight and GBM.

The Optimal Treatment Modality in Patients with T4N2M0 Non-Small Cell Lung Cancer: The Best Choice May Be Definitive Chemoradiotherapy Followed by Consolidation Chemotherapy.

BACKGROUND: Stage IIIB non-small cell lung cancer (NSCLC) consists of T4N2M0 and TXN3M0 NSCLC. In the present study, we aimed to evaluate the efficacy of different treatment strategies on the survival of patients with radiologically confirmed T4N2M0 NSCLC. METHODS: A total of 145 patients were evaluated in three groups according to the treatment protocol: induction chemotherapy followed by chemoradiotherapy (induction group); chemoradiotherapy (CRT group), and chemoradiotherapy followed by consolidation chemotherapy (consolidation group). The groups were compared regarding survival. RESULTS: The median progression-free survival (PFS) was 10.9, 10.8 and 17.1 months for the induction, CRT and consolidation groups, respectively (p = 0.021). The median overall survival (OS) was 17.6, 13.8 and 25.2 months for the induction, CRT and consolidation groups, respectively (p = 0.001). CONCLUSIONS: The patients with T4N2M0 NSCLC who were treated with chemoradiotherapy followed by consolidation chemotherapy had the best outcome in terms of PFS and OS.

The optimal chemotherapy timing in patients with inoperable locally advanced non small cell lung cancer.

BACKGROUND: Only 20% of patients with stage III NSCLC are cured by surgery. There is a disagreement among the oncologists in terms of whether which regimen (induction chemotherapy followed chemoradiotherapy, concurrent chemoradiation or concurrent chemoradiation followed consolidation chemotherapy) is best choice in inoperable LA NSCLC. OBJECTIVE: To evaluate chemotherapy timing in inoperable LA NSCLC (before, only concomitant or after curative chemotherapy). MATERIALS AND METHODS: Total of 74 consecutive patient with LA NSCLC which was inoperable due to medical condition or stage from Kayseri Research and Training Hospital were analyzed retrospectively. The patients were divided into three groups according to treatment protocols: Induction chemotherapy followed chemoradiotherapy (Ind. CTàCRT), chemoradiotherapy (CRT) and chemoradiotherapy followed consolidation chemotherapy (CRTàCons. CT). RESULTS: When evaluating progression free survival (PFS), PFS did not significantly differed among the groups (p=0,078). We found significant difference among groups (p = 0.047) in terms of overall survival. While CRTàCons. CT arm had highest mean and median survival times, Ind. CTàCRT arm had worst OS. CONCLUSIONS: CRTàCons. CT treatment modality seems preferable regimen for treatment of inoperable LA NSCLC.

A case of bismuth intoxication with irreversible renal damage.

Bismuth is a chemical element symbolized as Bi and is a trivalent poor metal, which chemically resembles arsenic and antimony. Colloidal bismuth subcitrate (CBS) and bismuth subsalicylate are the bismuth salts widely used in the treatment of peptic ulcers, functional dyspepsia, and chronic gastritis. Intoxications with CBS are rare. In a few case reports, acute renal failure was described, but the literature review revealed no chronic renal failure related to CBS intoxication. In this case report we present a 21-year old female with chronic renal failure after a one year follow-up of CBS intoxication.

Staging with PET-CT in patients with locally advanced non small cell lung cancer is superior to conventional staging methods in terms of survival.

BACKGROUND: Of patients with non small cell lung cancer (NSCLC), around one third are locally advanced at the time of diagnosis. Because only a proprotion of stage III patients can be cured by surgery, in order to improve the outcomes, sequential or concurrent chemoradiation, or concurrent chemoradiation with induction or consolidation is offered to the patients with locally advanced NSCLC. Today, PET combined with computerized tomography (PET-CT) is accepted as the most sensitive technique for detecting mediastinal lymph node and extracranial metastases from NSCLC. We aimed to compare PET-CT and conventional staging procedures for decisions regarding curative treatment of locally advanced NSCLC. MATERIALS AND METHODS: A total of 168 consecutive patients were included from Acibadem Kayseri Hospital, Acibadem Adana Hospital and Kayseri Research and Training Hospital in this study. RESULTS: While the median PFS was 13.0 ± 1.9 months in the PET-CT group, it was only 6.0 ± 0.9 in the others (p<0.001). The median OS values were 20.5 ± 15.6 and 11.5 ± 1.5 months, respectively (p<0.001). DISCUSSION: As a result, we found that staging with PET CT has better results in terms of survival staging. This superiority leads to survival advantage in patients with locally advanced NSCLC.

Secondline chemotherapy versus best supportive care in patient with malignant pleural mesothelioma: a retrospective study.

INTRODUCTION: Mesothelioma is a rare neoplasm arising from mesothelial surfaces with the malignant pleural mesothelioma (MPM) as the most common form. Secondline chemotherapy in MPM is still controversial and in this study we evaluated whether it is superior to best supportive care. MATERIALS AND METHODS: A total of 51 patients with MPM from Acibadem Kayseri Hospital, Kayseri Training and Research Hospital and Erciyes University were analyzed retrospectively. The patients treated with secondline chemotherapies (SLCT) were compared with those treated with best supportive care (BSC) for overall survival. RESULTS: The median overall survival (OS) for firstline chemotherapy?SLCT and firstline chemotherapy?BSC groups were 20.3 and 14.7 months respectively (p=0.079). After firstline chemotherapy the median OS for SLCT and BSC were 5.9 and 4.7 months (p=0.355). DISCUSSION: Although there was a trend for improvement in overall survival in patients treated with secondline chemotherapy, the difference was not statistically significant. Our results do not support the proposal that secondline chemotherapy could be effective in patients with MPM.

Is season a prognostic factor in breast cancer?

BACKGROUND: Some studies have indicated an inverse relationship between cancer risk and sunlight exposure. Others have reported that the prognosis of some cancers such as prostate, colon, ovarian and non melanoma skin cancer, were affected by the season in which the cancer was diagnosed. In our study, we evaluated whether season is prognostic in Turkish patients with breast cancer. MATERIALS AND METHODS: A total of 517 patients from Kayseri Training and Research Hospital were analysed retrospectively. Patients were divided into 4 groups according to season of cancer diagnosis: winter, spring, summer and autumn. The prognostic factors for disease free survival and overall survival were investigated. RESULTS: No significant differences were found among groups regarding prognostic factors overall. Only estrogen receptor status and lymphovascular invasion were independent prognostic factors (p=0.001 and p=0.001 respectively). We found significantly differences for mean disease free survival among groups (p=0.019). Winter group had better mean DFS while summer group had worse DFS. Mean overall survival was similar in the four groups (p=0.637). CONCLUSIONS: The season is not an independent predictive factor. However, due to interaction with other factors, we think that the season of cancer diagnosis is important for cancer prognosis.