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.     

Reinforcement of the suture line with an ePTFE graft attached with histoacryl glue in duodenal trauma.

BACKGROUND: Most duodenal injuries are managed with primary repair, but the degree of duodenal-wall injury may threaten the integrity of the primary repair. Therefore, we evaluated whether the primary repair site could be reinforced with histoacryl glue (HAG) or HAG with an expanded polytetrafluoroethylene (ePTFE) mesh. METHODS: Grade 3 duodenal injury in the second portion of the rat duodenum was chosen as a standard trauma model. Thirty-three male rats were divided into sham (n = 3), 2-layer primary repair (n = 10), 1-layer primary repair plus HAG application (n = 10) and ePTFE attached with HAG over the 1-layer primary repair site (n = 10) groups. Ten-day survival, adhesion grades and histological assessment were taken as outcome measures. RESULTS: A significant survival advantage was identified in the group that had an ePTFE graft attached with HAG over a 1-layer repair when compared with the group that had a 2-layer primary repair. Adhesion grades were found to be particularly increased in the group that had an ePTFE graft attached with HAG over the primary repair site, moderately increased in the primary repair plus HAG application group and lower in the 2-layer primary repair group. ePTFE graft application was found to be beneficial to coverage of the HAG-dependent empty spaces in the serosal layer. CONCLUSIONS: A primary repair site after duodenal trauma or a difficult duodenal stump can be reinforced with the application of HAG or ePTFE graft implantation with HAG.     

周围性面神经损伤患者对侧神经支配的研究

目的　通过测定面神经损伤患者组及大学生志愿者组面神经各分支对侧神经支配率 ,探讨周围性面肌瘫痪恢复过程中面神经对侧代偿支配的问题。方法　分别测定大学生志愿者 2 2例( 2 2侧 )及 10 8例面神经损伤患者的面神经电图对其对侧神经支配率进行分析其中损伤组又按发病原因不同 ,分为医源性损伤组、Bell氏面瘫组和创伤性损伤组 ,测试损伤支数为Ⅰ支 76支 ,Ⅱ支 81支 ,Ⅲ支 88支 ,Ⅳ支 6 6支。结果　①损伤组 3组间对侧支配率差异无显著性 (P >0 0 5 ) ;②损伤组Ⅰ、Ⅱ支对侧支配率明显高于志愿者组 (P <0 0 0 1) ;③损伤组Ⅰ支对侧支配率明显高于Ⅱ支(P <0 0 0 1)。结论　面神经损伤后 ,存在对侧神经支配功能增强的表现     

Factors leading to hydrocephalus after aneurysmal subarachnoid hemorrhage.

Hydrocephalus is not a rare complication following aneurysmal subarachnoid hemorrhage. Hydrocephalus following subarachnoid hemorrhage can progress acutely (0-3 days), subacutely (4-13 days) or chronically (after 13 days). The predisposing factors leading to hydrocephalus after subarachnoid hemorrhage are not known exactly. This study assessed the predictive factors for the development of this condition. All patients presenting with subarachnoid hemorrhage between 1992-2001 were evaluated. All of them had initial computed tomography (CT) and hydrocephalus was diagnosed on CT scans. Age, gender, preexisting diabetes mellitus and hypertension, neurological state according to the Hunt and Hess scale at admission, Fischer grade on CT, the presence of intraventricular hemorrhage and localization of aneurysm were analyzed to see if there was any meaningful relationship between hydrocephalus and these factors. One hundred and fourteen patients with aneurysmal subarachnoid hemorrhage were evaluated. The incidence of hydrocephalus was 28.1 %. The incidence for acute hydrocephalus was 18.4 %, for subacute 5.2 % and for chronic 4.3 %. Sixty-nine percent of patients with hydrocephalus were graded as 3, 4 or 5 according to the Hunt and Hess scale on admission. Fifty-five percent of patients with hydrocephalus were graded as 3 and 4 according to Fisher grade on initial CT scan. Preexisting diabetes, higher Fisher grade and intraventricular hemorrhage were statistically significant predictors for the development of hydrocephalus. But only preexisting diabetes and higher Fisher grade were independent predictors according to multivariate analyses.     

Point-of-care prothrombin time measurement for professional and patient self-testing use. A multicenter clinical experience. Oral Anticoagulation Monitoring Study Group

We enrolled 386 subjects in a multicenter study of a point-of-care (POC) prothrombin time (PT) testing device. POC tests were performed by health care professionals using venous and finger-stick specimens and by patients using finger-stick specimens. Venous blood also was analyzed in the local hospital laboratory and a national reference laboratory. Accurate POC results were obtained by professionals using both types of specimens. Patients' results were equivalent to those of professionals. The identification of the patient's therapeutic status based on the International Normalized Ratio (INR) was equivalent for POC and local hospital laboratory PT results; 75% of local laboratory results and 77% of POC results were within 0.4 INR of reference laboratory results, while 93% of either system (POC or local laboratory) were within 0.7 INR. Patients overwhelmingly reported satisfaction with the self-test, including the finger stick and device operation. The INR from the POC device is clinically equivalent to the laboratory INR for assessment of anticoagulation status and management decisions in professional and self-testing environments. Patients can learn to perform accurate PT testing, and POC PT testing is feasible in patients' homes.     

狗颌面高速投射伤区小血管病理改变

用光镜、电镜观察狗颌面高速投射伤区小血管的病理变化。实验发现:伤区小血管可见内皮细胞缺失、管壁断裂及细胞内的变性、坏死等病理变化,外径1.0～2,5mm的小血管损伤可远达距伤缘3.0cm处,该处血管7d后基本恢复。提示:临床运用血管化游离组织移植修复颌面部火器伤后的组织缺损时,其血管蒂应与距伤缘3.0cm以外的受区血管吻合,手术最好在伤后7d进行。     

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.     

颌面部狗咬伤的临床处理

目的 结合病例讨论颌面部狗咬伤后特点及临床处理。方法 本组19例,男18例,女1例;13岁以下17例。8天后就诊者给予抗感染及换药治疗,其余均行清创缝合,组织缺损者行拉拢缝合、全厚皮移植、皮瓣转移、唇颊及鼻沟组织瓣转移修复。常规注射破伤风抗毒素及狂犬疫苗。结果 8天后就诊者瘢痕愈合,2例轻度感染,其他均Ⅰ期愈合,无破伤风及狂犬病感染。结论 患者多为儿童,均为撕裂伤,就诊时要注意全身情况,彻底清创的同时,要尽可能保留组织;组织复位要准确,及时修复缺损,防止感染,减轻面部畸形。