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.     

Abdominal Stab Wounds in Children: an 18-Year Experience

Objective: Evaluation of the diagnosis, management, and the role of selective treatment in children with abdominal stab wounds. Patients and Methods: 59 children (56 male and three female) were included in the study. The patients' median age was 11.8 years (range, 5–14 years). Time between injury and admission was about 3 h. Laparotomy was performed in 44 patients (74%). Solid organ injury was detected in 32 of these patients (73%) and could not be observed in twelve (27%). 15 patients (26%) were treated conservatively, and only one (6.6%) underwent laparotomy during the follow-up. The stomach was the most frequently injured organ (ten patients), followed by the intestines (nine patients). Types of surgical treatment were as follows: primary suture in 28 patients, resection-anastomosis in three, and osteotomy in two. Results: Some prognostic factors such as presence of abdominal organ evisceration and pneumoperitoneum were not significantly correlated with intraabdominal organ injury, whereas some other risk factors such as acute abdomen on admission (p < 0.002) or abdominal clinical and hemodynamic findings (p < 0.001) showed significant correlation with intraabdominal organ injury. The relative risk (odds ratio) of developing an intraabdominal organ injury was > 2 for patients with signs of an acute abdomen on admission. Postoperative complications were observed in five patients with organ injuries. None of our patients died. Conclusions: Conservative treatment can be safely performed in most children with abdominal stab injuries. Signs of major internal hemorrhage or generalized peritonitis are an absolute indication for emergency operation for abdominal stab wounds. Peritoneal penetrations, free air on the abdominal X-ray, and omental or intestinal evisceration are poor indicators of significant organ injuries, and patients presenting these signs shold be closely followed up for developing acute abdominal symptoms. Received: November 2, 2001; revision accepted: February 15, 2002     

Serum lipid levels in psoriasis

A predisposition to occlusive vascular diseases has been reported in patients with psoriasis and it has been suggested that some of these patients have some disorders of lipid metabolism. In this study, serum lipid levels were investigated in psoriatic patients to explore to the knowledge of this relationship. One hundred psoriatic patients and 100 non- psoriatic controls were included in the study. Total cholesterol, triglyceride, high-density lipoprotein-cholesterol (HDL-cholesterol), low-density lipoprotein-cholesterol (LDL-cholesterol), and very low-density lipoprotein-cholesterol (VLDL-cholesterol) levels were measured. In patients with psoriasis, total cholesterol and LDL-cholesterol levels were found to be significantly higher than those of controls. No significant differences were found in the other parameters. We concluded that psoriatic patients should be evaluated and followed up for the risk of hyperlipidemia and obstructive vascular diseases.     

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.     

Corrigendum

Corrigendum

Corrigendum     

Subacute sclerosing panencephalitis: brain stem involvement in a peculiar pattern

The most common pattern in subacute sclerosing panencephalitis, is in the cerebral hemisphere white matter on T2-weighted images with or without atrophy. Brain-stem lesions are rare. We report brain-stem involvement in two children with subacute sclerosing panencephalitis. A peculiar pattern, with involvement of the pons with extension to both middle cerebellar peduncles and substantia nigra but sparing the pontine tegmentum, is suggested. Received: 10 January 2000/Accepted: 18 April 2000     

Intraosseous lipoma of the frontal bone. A case report

Intraosseous lipomas are among the most uncommon bone tumors. They arise most often in the appendicular skeleton. There are very few reported cases of intraosseous lipomas within the skull bones. We report a case of intraosseous lipoma of the frontal bone with conventional radiography and CT findings.     

A cluster of nosocomial Klebsiella oxytoca bloodstream infections in a university hospital.

BACKGROUND: On February 19, 2003, four patients (patients 1-4) in the neurology ward underwent cranial magnetic resonance angiography (MRA) and developed fever within 1 hour afterward. Klebsiella oxytoca was isolated from blood cultures of patients 1 through 3. OBJECTIVE: To identify the source of this cluster of nosocomial K. oxytoca bloodstream infections. DESIGN: Outbreak investigation. SETTING: A 1,000-bed university hospital. METHODS: The infection control team reviewed patient charts and interviewed nursing staff about the preparation and administration of parenteral fluids. The procedure of cranial MRA was observed. Arbitrarily primed polymerase chain reaction (AP-PCR) was performed to show the clonal relationship among these three strains. RESULTS: AP-PCR revealed that three K. oxytoca isolates had the same molecular profile. Cranial MRA was found to be the only common source among these patients. During MRA, before injection of the contrast medium, normal saline solution was infused to check the functioning of the intravenous catheter. Use of the solution for multiple patients was routine, but the access diaphragm of the bottle was not cleansed. The bottle of normal saline solution used on February 19 had already been discarded and the culture sample taken from the solution on the day of observation was sterile. CONCLUSIONS: We speculate that normal saline solution became contaminated during manipulation and that successive uses might have been responsible for this cluster. Poor aseptic techniques employed during successive uses appear to be the most likely route of contamination. Use of parenteral solutions for multiple patients was discontinued.