Treatment of thalassaemia: a review of the new approaches on transfusion safety and the novel therapeutics

Lifetime red cell concentrate (RCC) transfusions still account for significant iron overload‐related morbidity and mortality despite chelation therapy in thalassaemia. The cumulative risk of transfusion‐transmitted infections is substantial for thalassaemia patients. Pathogen reduction technologies for RCC may imply a proactive approach against new/re‐emerging pathogens and may be an ultimate safeguard for transfusion safety in the developing countries. Red cell alloimmunization may become a significant clinical challenge in thalassaemia. The availability of high‐throughput molecular blood group antigen typing in the donors may allow perfect match transfusion, beyond ABO‐D and CEK antigen‐matched transfusions. Allogeneic stem cell transplantation (A‐SCT) is the only available curative therapy in thalassaemia, but carries a substantial risk of serious adverse events and mortality. Gene addition therapy for correction of the α‐globin chain imbalance overcomes the problems of donor availability and immunological complications of A‐SCT. Gene editing by either gene disruption or correction emerged as a potential alternative to gene addition therapy in beta‐thalassaemia. A new era of novel therapeutics targeting α/β imbalance, ineffective erythropoiesis or iron dysregulation is unfolding in thalassaemia management, and a number of those now have agents in preclinical and clinical development. Hydroxyurea (HU) may improve globin chain imbalance and be beneficial for reducing or omitting transfusion requirement. Ruxolitinib has allowed steady decrease in spleen volume that may serve for avoiding splenectomy in beta‐thalassaemia. Luspatercept may restore normal erythroid differentiation and improve anaemia. Hepcidin mimetics or TMPRSS6 inhibitors may modulate ineffective erythropoiesis by iron restriction and improve anaemia and organ iron loading.     

Bilateral perineal ectopic testes

Perineal testicular ectopia is seen very rarely, bilaterality is even more scarce and three cases have been reported in the literature. Here we present the fourth case with bilateral perineal ectopic testes.     

Neuroleptic malignant syndrome induced by ziprasidone on the second day of treatment.

Neuroleptic malignant syndrome (NMS) is the rarest and most serious of the neuroleptic-induced movement disorders. We describe a case of neuroleptic malignant syndrome (NMS) associated with the use of ziprasidone. Although conventional neuroleptics are more frequently associated with NMS, atypical antipsychotic drugs like ziprasidone may also be a cause. The patient is a 24-year-old male with a history of schizophrenia who developed signs and symptoms of NMS after 2 days of treatment with an 80-mg/day dose of orally administrated ziprasidone. This case is the earliest (second day of treatment) NMS due to ziprasidone reported in the literature.     

Dosimetric evaluation of the effect of dental implants in head and neck radiotherapy.

OBJECTIVE: The aim of the study was to examine the dose enhancement from scattered radiation at bone-dental implant interfaces during simulated head and neck radiotherapy. STUDY DESIGN: Four cylindrical titanium dental implants with 3 different sizes and lengths were implanted into a human mandible in 4 different positions. Ionization measurements for 6 MV X, 25 MV X, and Co-60 gamma rays were done. Thermoluminescent dosimeter (TLD 100 ) chips were used to measure radiation dose enhancement due to the scattered electrons from titanium and electronic disequilibrium at the tissue-metal interface. RESULTS: The results showed that for Co-60, there is a 21% maximum increase in dose to alveolar mandibular bone at the close proximity to the titanium. For 6-MV x-rays the dose enhancement increase was almost the same or slightly lower than for Co-60, while for 25-MV high-energy x-rays, dose enhancement was lower than that of others. This increase in dose enhancement fell off rapidly and became insignificant at 2 mm from the interface. CONCLUSION: Total dose that may lead to osteoradionecrosis risk of the mandible is slightly but not significantly affected by the scattered dose of the dental implants of lower jaw in the radiation field exposed to 3 different radiation beams.     

How do gastric carcinoma classification systems relate to mucin expression patterns? An immunohistochemical analysis in a series of advanced gastric carcinomas

Gastric carcinoma classifications differ in their value for distinguishing tumors according to their morphological pattern, functional properties, and biological significance. In this study we evaluated which of three established classification systems is best correlated with the expression patterns of certain mucins. A total of 160 gastric carcinomas from Turkey and Germany were screened immunohistochemically for the expression of MUC1, MUC2, MUC5AC, and MUC6, and the results were related to the different tumor categories in Lauren's, Carneiro's, and Goseki's classifications. It was found that in all three classifications carcinomas belonging to the gland-forming category most commonly expressed MUC1: 78% of Goseki's grade I carcinomas, 81.1% of Lauren's intestinal type carcinomas, and 82.8% of Carneiro's glandular type. MUC2 was expressed in all Goseki grade II carcinomas, which comprise the mucinous type, while it was not significantly associated with any of the other classifications. MUC5AC was found in all Goseki grade IV carcinomas, i.e., signet ring cell carcinomas. It was also significantly associated with Carneiro's mixed type and isolated cell type carcinomas, while there was no correlation with any of Lauren's types. MUC6 failed to show a relationship with any of the categories of the various classifications. We conclude that Goseki's classification is best correlated with MUC expression patterns because it distinguishes clearly between MUC1-positive gland-forming carcinomas, MUC2-positive mucinous ones, and MUC5AC-positive signet ring cell carcinomas. It is likely that each of these gastric carcinoma types has its own carcinogenesis.     

Nonoliguric renal failure after transurethral resection of prostate

PURPOSE: To define the relation of nonoliguric renal failure to transurethral resection of the prostate (TURP), its clinical importance, and predictive factors. PATIENTS AND METHODS: The files of 439 patients who had undergone TURP at Hacettepe University School of Medicine, Department of Urology, between January 1991 and 1994 were analyzed. The patients were divided into three groups according to postoperative serum creatinine concentration and the presence of clinical signs and symptoms of TUR syndrome (Group I: patients with preoperative and postoperative creatinine in the normal range; Group II: patients suffering nonoliguric renal failure; and Group III: patients with TUR syndrome). The data of the groups were compared in terms of factors influencing nonoliguric renal failure. RESULTS: The mean postoperative concentrations of sodium, blood urea nitrogen, creatinine, and albumin in Groups II and III were statistically different from those in Group I (P < 0.001). There was a moderate relation between hyponatremia and the occurrence of nonoliguric renal failure (r(s) = -0.56). Capsule perforation increased the risk of nonoliguric renal failure 10.6 fold. All of the patients were managed by a conservative approach, and none of the patients died or progressed to end-stage renal disease. They were all discharged with a mean hospitalization period of 7 days and normal renal function tests. CONCLUSION: Nonoliguric renal failure was thought to be an early step in the pathophysiology of TUR syndrome with acute renal failure. It is an asymptomatic clinical picture that is undiagnosed unless laboratory examinations are performed. A conservative therapeutic approach is enough.     

Corrigendum

Corrigendum

Corrigendum