Peripheral nerve functions may deteriorate parallel to the progression of microangiopathy in diabetic patients

Our aim was to obtain information to help in the early detection of impaired nerve function and to assess the severity of diabetic symmetric polyneuropathy (DPN). Various somatic and autonomic nerve functions in 40 diabetics and 20 age-matched healthy volunteers were evaluated using six objective examinations: nerve conduction study, quantitative vibratory perception threshold, heart rate variability, Valsalva test, head-up tilt and quantitative sudomotor axonal reflex test (QSART). The diabetics were divided into three groups according to the severity of their microangiopathy. The nerve function data and level of impairment were compared between a healthy control and three diabetic groups. The relationships between nerve function data and clinical background were also examined using multivariate analysis. Results were as follows: (1) all nerve dysfunctions seemed to develop parallel to the progression of microangiopathy, (2) reduced nerve conduction velocity and elevated vibratory perception thresholds in the feet might be early detectable signs of DPN, (3) vasomotor and sudomotor sympathetic functions and cardiovagal functions seemed to deteriorate with the appearance of microangiopathy, (4) lowered compound muscle action potential seemed to appear at the advanced microangiopathic condition, (5) hypohydrosis was closely related to diabetic foot ulcers. In conclusion, nerve dysfunction in diabetics might generally progress with microangiopathy from somatic sensory nerve dysfunction to autonomic nerve dysfunction and then to somatic motor nerve dysfunction. Sympathetic sudomotor dysfunction might be a sensitive predictor of diabetic foot ulcer.     

How do the clinical features of brain tumours in childhood progress before diagnosis?

Objectives

To investigate the progression of the clinical features from symptom onset to diagnosis in children with brain tumours. Design: Retrospective case note review. Patients: Sixty children with brain tumours: 27 patients from Nagoya University Hospital diagnosed between February 2004 and April 2008, and 33 patients from Anjo Kosei Hospital diagnosed between April 1995 and December 2008. Results: Various symptoms and signs were observed. The most common initial symptoms or signs were vomiting (24.1%), headache (17.2%), unsteadiness (10.3%), and paresis (10.3%). Sixteen patients were diagnosed based on the initial symptom or sign alone; six, at routine medical check-ups or had perinatal diagnosis; and the remaining 38, based on one or more additional features following the initial symptom. Nine of the 10 patients with headache as the initial symptom subsequently developed either vomiting (in seven) or unsteadiness with cranial nerve palsies (in two). Twelve of the 14 patients with vomiting as the initial symptom subsequently developed headache (in three), unsteadiness (in five), or other manifestations of increased intracranial pressure (in four). The remaining 14 had varied initial symptoms and combinations of symptoms and signs associated with the tumour location. The median pre-diagnosis symptomatic interval was 20.5 days. There was no significant difference in the median symptomatic interval between patients with headache or vomiting as the initial symptom and those with any neurological sign. Conclusion: Paediatric brain tumours present with various initial symptoms and signs. Many are diagnosed as additional symptoms or signs develop. The clinical features exhibit several patterns of progression, which are related to the tumour location.     

Molecular Grade (FGFR3/MIB-1) and EORTC Risk Scores Are Predictive in Primary Non–Muscle-Invasive Bladder Cancer

Background

The European Organization for Research and Treatment of Cancer (EORTC) risk scores are not validated in an independent patient population. Molecular grade (mG) based on fibroblast growth factor receptor 3 (FGFR3) gene mutation status and MIB-1 expression was proposed as an alternative to pathologic grade in bladder cancer (BCa) [1].

Objective

To validate the EORTC risk score and to determine its relation to mG in a series with long-term follow-up as well as to determine reproducibility of pathologic grade and mG.

Design, setting, and participants

In this multicenter study, we included 230 patients with primary non–muscle-invasive BCa (NMIBC).

Measurements

Four uropathologists reviewed the slides. FGFR3 mutation status was examined by two assays. MIB-1 was assessed by immunohistochemistry. The EORTC risk scores for recurrence and progression were determined. Multivariable analyses were used to find prognostic factors.

Results and limitations

Median follow-up was 8.62 yr (interquartile range: 6.6–11.8). FGFR3 mutations were significantly related to favorable disease parameters, whereas altered MIB-1 was frequently seen with pT1, high grade, and high EORTC risk scores. EORTC risk scores were significant in multivariable analyses for recurrence and progression. In multivariable analyses for progression and disease-specific survival, the mG had independent significance. The addition of mG to the multivariable model for progression increased the predictive accuracy from 74.9% to 81.7% (p < 0.001; Mantel-Haenszel test). The mG (89%) was more reproducible than the pathologic grade (41–74%).

Conclusions

We validated the EORTC risk scores for primary NMIBC in a clinical and biomarker setting. Next to EORTC risk score, mG proved highly reproducible and predictive. Our long-term results justify an independent prospective analysis of mG and EORTC risk scores.     

艾滋病腹泻中医药研究进展

艾滋病腹泻是指HIV感染者、艾滋病期患者出现的以腹泻为主要临床表现的一种病症,是艾滋病患者常见的并发症。临床表现大多为慢性腹泻,并常伴有体重减轻、营养不良及消耗综合征,是引起HIV/AIDS患者死亡的主要原因之一。西医认为引起艾滋病腹泻的原因很多,按有无生物因素入侵,可分为感染性和非感染性两大类。而发病机理不明,可能为多种因素共同的结果。中医认为艾滋病腹泻主要病机是脾虚湿盛,脾胃运化功能失调,小肠无以分清泌浊、大肠无以传导变化,水湿内停,合污而下,发生泄泻。在治疗上,根据中医理论辨证论治采用中药和针灸均可取得较好疗效。     

Characterization of host genetic expression patterns in HIV-infected individuals with divergent disease progression

The course of HIV-1 infection shows a variety of clinical phenotypes with an important involvement of host factors. We compare host gene expression patterns in CD3+ T cells from two of these phenotypes: long-term non-progressor patients (LTNP) and matched control patients with standard HIV disease progression. Array analysis revealed over-expression of 322 genes in progressors and 136 in LTNP. Up-regulated genes in progressors were mainly implicated in the regulation of DNA replication, cell cycle and DNA damage stimulus and mostly localized into cellular organelles. In contrast, most up-regulated genes in LTNP were located at the plasmatic membrane and involved in cytokine-cytokine receptor interaction, negative control of apoptosis or regulation of actin cytoskeleton. Regarding gene interactions, a higher number of viral genes interacting with cellular factors were seen in progressors. Our study offers new comparative insights related to disease status and can distinguish differentiated patterns of gene expression among clinical phenotypes.     

Papillary urothelial neoplasm of low malignant potential of the urinary bladder: clinicopathologic and outcome analysis from a single academic center

Few long-term single-center studies have addressed the outcome of patients with papillary urothelial neoplasms of low malignant potential. Our study evaluates the behavior of these tumors occurring as primary urinary bladder lesions. For this purpose, 34 primary in-house cases diagnosed and treated between 1998 and 2008 were identified from our medical records. Upon review, 3 cases were upgraded to noninvasive low-grade urothelial carcinomas and excluded from further evaluation. During follow-up (range, 3-108 months; mean, 42 months), 13 patients developed recurrences; and 9 patients progressed to a noninvasive higher grade lesion (8 to low-grade and 1 to high-grade urothelial carcinomas). None of our patients developed stage progression (>pTa) or died of bladder cancer. Size of the primary tumor was associated with the risk of recurrence (P = .043), whereas the number of episodes of recurrence was associated with the likelihood of grade progression (P = .034). In conclusion, recurrences were observed in 42% of all our patients, with a grade progression rate of 29%. None of our patients developed invasive carcinoma or died as a consequence of their disease. Considering the low but definitive risk of recurrence and grade progression, appropriate clinical follow-up of patients with primary papillary urothelial neoplasm of low malignant potential is warranted.     

Accelerated progression from islet autoimmunity to diabetes is causing the escalating incidence of type 1 diabetes in young children

The incidence of type 1 diabetes is rising worldwide, particularly in young children. Since type 1 diabetes is preceded by autoimmunity to islet antigens, there must be a consequent increase in the incidence of islet autoimmunity in young children or a more rapid rate of progression to diabetes once islet autoimmunity initiates. This study was to determine whether the incidence of islet autoimmunity or the rate of progression from autoimmunity to diabetes onset has changed over a 20-year period in children genetically predisposed to type 1 diabetes. Between 1989 and 2010, children who were first-degree relatives of patients with type 1 diabetes and who were born in Germany were prospectively followed from birth without intervention. A total of 324 children (BABYDIAB study) born between 1989 and 2000 and 216 children (TEDDY study) born between 2004 and 2010 with matched HLA genotypes were recruited before age 3 months and included for analysis. Children were followed for the development of autoantibodies to insulin, GAD, and IA-2, and for progression to diabetes. The cumulative frequency of diabetes by age 4 years was 2.5% (95% CI 0.8-4.2%) in BABYDIAB children and 6.2% (95% CI 2.3-10.1%) in TEDDY children (p = 0.03). The cumulative frequency of islet autoantibodies by age 4 years was similar in the children from both studies (11.3% vs 13.9%). Progression to diabetes from the development of islet autoantibodies was markedly increased in autoantibody-positive children from the more recently recruited TEDDY cohort (50% progression within 85.2 months for BABYDIAB children vs 9.6 months for TEDDY children; p = 0.009), also if children were further selected on the basis of high-risk HLA genotypes or the development of autoantibodies to multiple islet antigens (p = 0.01). The findings suggest that recent increasing incidence of type 1 diabetes in young children could be due to weakening of mechanisms that normally regulate autoimmune destruction of islet beta cells.     

High-grade papillary urothelial carcinoma of the urinary tract: a clinicopathologic analysis of a post-World Health Organization/International Society of Urological Pathology classification cohort from a single academic center

About one half of all bladder neoplasms are noninvasive, and in those, the histologic grade is a crucial prognosticator. Few single-center studies have assessed the recurrence, progression, and cancer-related mortality rates of noninvasive high-grade papillary urothelial carcinomas. With this aim, we evaluated the clinicopathologic and outcome features of 85 patients with high-grade papillary urothelial carcinoma. Median age was 68 years, and 80.5% were men. Tumor size ranged from 0.3 to 13.0 cm (median, 1.6 cm). Recurrence was found in 36.5% of the patients, whereas tumor progression, defined as invasion of lamina propria or beyond, was identified in 40% of all cases. When present, lesion reappearance involved mostly 1 to 2 episodes. Metastasis appeared in 20% of the patients, and 15% died of disseminated bladder cancer. All cancer-related deaths occurred in the group of patients with progression, whereas patients with recurrence showed similar outcomes to those with no recurrence. For patients with tumor progression, clinical stage was significantly associated with outcome (P = .002). As for prognosis, tumor size was strongly associated with progression (P < .01). In conclusion, recurrence, progression, and cancer-specific mortality rates were 36.5%, 40%, and 15%, respectively. All the patients who died of cancer had a history of tumor progression. Patients with recurrences showed similar outcomes to those with no recurrence. Tumor size was strongly associated with tumor progression and cancer-specific survival, whereas clinical stage was significantly associated with outcome in the progression group. In light of the high recurrence and progression rates of high-grade papillary urothelial carcinoma, strict clinical surveillance aimed to detect early recurrent lesions, especially in patients with larger tumors, is warranted.