Uncovering the genomic heterogeneity of multifocal breast cancer

Multifocal breast cancer (MFBC), defined as multiple synchronous unilateral lesions of invasive breast cancer, is relatively frequent and has been associated with more aggressive features than unifocal cancer. Here, we aimed to investigate the genomic heterogeneity between MFBC lesions sharing similar histopathological parameters. Characterization of different lesions from 36 patients with ductal MFBC involved the identification of non‐silent coding mutations in 360 protein‐coding genes (171 tumour and 36 matched normal samples). We selected only patients with lesions presenting the same grade, ER, and HER2 status. Mutations were classified as ‘oncogenic’ in the case of recurrent substitutions reported in COSMIC or truncating mutations affecting tumour suppressor genes. All mutations identified in a given patient were further interrogated in all samples from that patient through deep resequencing using an orthogonal platform. Whole‐genome rearrangement screen was further conducted in 8/36 patients. Twenty‐four patients (67%) had substitutions/indels shared by all their lesions, of which 11 carried the same mutations in all lesions, and 13 had lesions with both common and private mutations. Three‐quarters of those 24 patients shared oncogenic variants. The remaining 12 patients (33%) did not share any substitution/indels, with inter‐lesion heterogeneity observed for oncogenic mutation(s) in genes such as PIK3CA, TP53, GATA3, and PTEN. Genomically heterogeneous lesions tended to be further apart in the mammary gland than homogeneous lesions. Genome‐wide analyses of a limited number of patients identified a common somatic background in all studied MFBCs, including those with no mutation in common between the lesions. To conclude, as the number of molecular targeted therapies increases and trials driven by genomic screening are ongoing, our findings highlight the presence of genomic inter‐lesion heterogeneity in one‐third, despite similar pathological features. This implies that deeper molecular characterization of all MFBC lesions is warranted for the adequate management of those cancers. © 2015 The Authors. Pathological Society of Great Britain and Ireland.     

Treatment of refractory adult lymphoblastic leukemia (ALL) with 4'(9- acridinylamino) methanesulfon-M-anisidide (AMSA)

Twenty-four adults with ALL were treated with AMSA alone or in combination. Twenty-two were treated at time of relapse and two patients after failing primary induction therapy. All had been treated with anthracyclines prior to receiving AMSA. Of the 22 patients with ALL in relapse, 4 achieved a complete remission. Two of these patients have relapsed while receiving maintenance chemotherapy; one died 1 mo after achieving remission due to the occurrence of cholycystitis in the setting of pancytopenia and one patient underwent bone marrow transplantation and is in remission at 8 mo after the second remission. Both patients who failed primary induction therapy remain in remission at 11 and 36 mo, respectively. The use of AMSA should be considered for patients with ALL who fail primary induction as well as those whose leukemia becomes resistant to conventional agents.     

Antinociceptive, anti-inflammatory and antipyretic effects of Solanum nigrum chloroform extract in animal models

AIM: The present study was carried out to evaluate the antinociceptive, anti-inflammatory and antipyretic effects of chloroform extract of Solanum nigrum leaves using various animal models. METHODS: The extract was prepared by soaking (1:20; w/v) the air-dried powdered leaves (20 g) in chloroform for 72 hrs followed by evaporation (40 degrees C) under reduced pressure to dryness (1.26 g) and then dissolved (1:50; w/v) in dimethylsulfoxide (DMSO). The supernatant, considered as the stock solution with dose of 200 mg/kg, was diluted using DMSO to 20 and 100 mg/kg, and all doses were administered (s.c.; 10 ml/kg) in mice/rats 30 min prior to tests. RESULTS: The extract exhibited significant (p<0.05) antinociceptive activity when assessed using the abdominal constriction, hot plate and formalin tests. The extract also produced significant (p<0.05) anti-inflammatory and antipyretic activities when assessed using the carrageenan-induced paw edema and brewer's yeast-induced pyrexia tests. Overall, the activities occurred in a dose-independent manner. CONCLUSION: The present study demonstrated that the lipid-soluble extract of S. nigrum leaves possessed antinociceptive, anti-inflammatory and anti-pyretic properties and confirmed the traditional claims.     

Primary Immunodeficiency Disorders: Survey of Pediatricians in Kuwait

INTRODUCTION: Early diagnosis of primary immunodeficiency disorders (PID) is critical so life saving interventions can be implemented to avoid significant morbidity and mortality. Unfortunately, they are frequently misdiagnosed, which results into significant delay in diagnosis. This study aimed to determine the knowledge and practice of pediatricians in Kuwait about PID. MATERIALS AND METHODS: A 66-item self-administered questionnaire was designed and distributed to the pediatricians working at all six governmental hospitals to measure their knowledge and practice about PID. A total of 244 pediatricians (78.4%; 143 males and 101 females) participated in the study. The mean age of participants was 40 years, and the mean number of years working in pediatrics was 13 years. The mean overall score was 59.6%, whereas the mean score in clinical presentation section was 63%, in associated diseases and syndromes section 58%, and in laboratory investigations section 51%. Only 26% of the participants answered correctly at least 2/3 of the questions (67% of the questions). CONCLUSION: This survey demonstrates that there is universal deficiency in both the knowledge and practice of pediatricians in the field of PID. Implementation of strategies to improve the awareness of pediatricians about PID is critical so early therapeutic interventions can be done to improve the health and prevent morbidity and mortality.     

肌电生物反馈疗法结合部分减重平板运动疗法对脑卒中恢复期患者下肢运动功能的影响

目的:观察肌电生物反馈疗法结合部分减重平板运动疗法对脑卒中偏瘫患者下肢运动功能的影响。方法:脑卒中恢复期偏瘫患者40例随机分为治疗组和对照组各20例。两组患者均给予常规神经内科治疗、综合康复治疗及部分减重平板运动疗法,治疗组加用AM-800神经功能重建仪进行下肢肌电生物反馈疗法,共治疗4周。治疗前后进行功能评估,评估项目包括临床神经功能缺损评分、Fugl-Meyer评定、功能独立性评定(FIM量表)。结果:经治疗后,两组患者神经功能缺损评分均有下降,FIM量表得分及Fugl-Meyer下肢得分均上升,其中治疗组相比对照组神经功能缺损评分下降更显著,Fugl-Meyer下肢得分上升更显著(P均<0.05)。结论:肌电生物反馈疗法结合部分减重平板运动疗法,能有效改善脑卒中患者下肢运动功能,并可降低患者神经缺损程度。     

Hybrid procedure in pseudoaneurysm of the descending thoracic aorta in Hospital Kuala Lumpur

Conventional open repair for Thoracoabdominal aortic aneurysm (TAA) is associated with high morbidity and mortality. Spinal cord ischemia (SCI), renal failure, bowel ischemia and mortality are established complications following this procedure. With the advent of endovascular stent technology, various novel approaches have been described to reduce these complications, namely fenestrated stent graft and hybrid procedure. We present a case of hybrid procedure in a pseudoaneurysm of descending thoracic aorta done in Kuala Lumpur Hospital.     

Symmetrical peripheral digital gangrene following severe Plasmodium falciparum malaria‐induced disseminated intravascular coagulopathy

Ghafoor SZA, MacRae EA, Harding KG, Patel GK. Symmetrical peripheral digital gangrene following severe Plasmodium falciparum malaria‐induced disseminated intravascular coagulopathy. Symmetrical peripheral digital gangrene is a life‐changing complication, caused by a pro‐thrombotic life‐threatening disease, such as disseminated intravascular coagulopathy (DIC) secondary to systemic infection. We describe the unusual case of a woman who developed symmetrical peripheral digital gangrene following DIC because of malaria. While initial treatment led to cure of the infection, in this report we describe also the subsequent management of symmetrical peripheral digital gangrene.