Efficacy and safety of eculizumab in adult patients with atypical hemolytic uremic syndrome: A single center experience from Turkey.

INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy, which develops as a result of defective activity of the alternative complement pathway and excessive complement activation due to genetic or acquired factors. No satisfactory responses were obtained by plasmapheresis, corticosteroids and fresh frozen plasma (FFP) transfusion. However, promising results are obtained in recent years by eculuzimab treatment, which inhibits C5 activation. OBJECTIVE: To evaluate the efficacy, safety and effect of eculizumab on quality of life of adult aHUS patients followed in our center. MATERIALS AND METHODS: Seven patients who received eculizumab treatment in single center between the years 2012 and 2016 due to aHUS diagnosis were retrospectively evaluated. Patients were diagnosed with aHUS in accordance with certain criteria, after eliminating all the other factors caused by thrombotic microangiopathy. Complement gene mutations were completed in six patients. All patients received eculizumab as recommended (900 mg/per two weeks) following plasmapheresis, FFP, corticosteroid and hemodialysis (HD) treatments. RESULTS: Four out of seven patients were men and three were women; average patient age was 51.1 (26-69) years and average duration of disease was 25.3 (2-45) months. Average period from the initial complaints of the patients up to aHUS diagnosis was 4.2 (2-13) months. Tests were implemented on six patients for complement gene mutations, and complement factor H (CFH) homozygous mutation was identified in three patients. Complete remission was observed in four patients and partial remission in two patients after eculizumab; however, one patient died. Plasmapheresis was discontinued in patients with complete remission, whereas two patients with partial remission continued the HD program, despite normalization in hematologic parameters. Significant improvement was observed in post-treatment quality of life in all six patients who currently continue eculuzimab treatment. No transfusion reaction and/or no serious infections were observed in any of the patients, while URTI (upper respiratory tract infection) was observed in one patient. DISCUSSION: Eculizumab is an effective and safety treatment option in adult aHUS patients. Early diagnosis and initializing eculizumab therapy at an early stage may decrease mortality and morbidity in patients with aHUS. New studies are required on this topic.

The Potential Adverse Impact of Post-Treatment Thrombocytopenia on Clinical Outcomes in Cancer Patients Treated With Immune Checkpoint Inhibitors.

BACKGROUND: The main goal of this study is to explore the prognostic and predictive implications of post-treatment thrombocytopenia on treatment efficacy and clinical outcomes in advanced-stage cancer treated with immune checkpoint inhibitors (ICIs). METHODS: This retrospective study included 102 patients with advanced-stage cancer who were treated with ICIs. The simultaneous administration of chemotherapy and ICIs was omitted; nevertheless, the selection of chemotherapy agents employed in different treatment lines was left to the discretion of the attending clinician. Patients were stratified into distinct cohorts based on their post-treatment platelet counts (evaluated for up to four to six months after the completion of ICI). The primary endpoint of interest was progression-free survival (PFS), and overall survival (OS) was the secondary endpoint. RESULTS: Patients with superior Eastern Cooperative Oncology Group (ECOG) performance status and those who received ICI as second-line treatment displayed markedly elevated incidences of grade 1 thrombocytopenia (p < 0.05). Kaplan-Meier survival analysis confirmed that patients with high-grade thrombocytopenia had significantly shorter PFS (six vs. 13 vs. 19 months, p < 0.0001) and OS (10 vs. 21 vs. 25 months, p < 0.0001) than those with lower grades or without thrombocytopenia, respectively. Multivariate analysis revealed that decreased platelet levels were a negative independent prognostic factor for both PFS and OS in patients with advanced-stage cancer who received ICIs. CONCLUSION: The results of this retrospective study suggest that a decline in platelet levels after treatment represents a dependable adverse prognostic biomarker for clinical outcomes. Moreover, a decrease in platelet levels has been linked to reduced treatment efficacy in advanced-stage cancer patients receiving ICIs, thereby providing valuable prognostic insights for the implementation of personalized treatment strategies in cancer immunotherapy.

[Preferences regarding invasive diagnostic procedures in patients aged 70 years or over presenting with acute coronary syndrome and relationship with short-term mortality]. / Akut koroner sendrom ile basvuran 70 yas ve üzeri hastalarda invaziv tanisal yöntem tercihleri ve bunun erken dönem mortalite ile iliskisi.

OBJECTIVES: We prospectively classified patients presenting with acute coronary syndrome (ACS) into two age groups, <70 years and ≥70 years, and investigated the frequency of cardiac catheterization, the predictors of cardiac catheterization in the older patient population, and determined early mortality in patients treated with or without cardiac catheterization. STUDY DESIGN: The study included 1,101 patients admitted with ACS. The patients were prospectively classified in two age groups, <70 years (n=762; mean age 55±9 years) and ≥70 years (n=339; mean age 76±5 years). Data on demographic characteristics, clinical and laboratory findings, and the presence or absence of cardiac catheterization were recorded. The predictors of cardiac catheterization were assessed in the overall patient group and in those ≥70 years of age, and 30-day mortality rates were determined. RESULTS: Compared with the older group, in younger patients cardiac catheterization was more frequent (74.4% vs. 50.7%, p=0.0001) and earlier (p=0.023), and decision for percutaneous coronary intervention was more common (52.7% vs. 40.7%, p=0.010), whereas coronary bypass grafting was performed more frequently in the older group (43% vs. 31.2%, p=0.010). Overall 30-day mortality rates showed significant differences in both groups between patients treated with or without cardiac catheterization (<70 years: 3.7% vs. 18.3%, p<0.0001; ≥70 years: 5.6% vs. 21%, p<0.0001). Logistic regression analysis showed the following as significant predictors of cardiac catheterization in patients ≥70 years of age: heart failure (OR: 3.853, p=0.017), systolic blood pressure <100 mmHg (OR: 3.602, p=0.008), creatinine clearance <60 ml/min (OR: 2.761, p=0.001), and ST-segment elevation ≥1 mm on the electrocardiogram (OR: 2.817, p=0.0001). CONCLUSION: Invasive diagnostic and therapeutic strategies are implemented less frequently in elderly patients. These procedures, which offer obvious mortality benefit, should be considered in elderly patients after meticulous risk evaluation.