Diabetes Foot Action GroupThis update on antimicrobial recommendations for diabetic foot ulcer treatment is a consensus statement based on clinical trial evidence, review of international guidelines and expert opinion.In the context of individual treatment decisions, local microbiology results and advice should be paramount in informing responsible clinicians. However, the spectrum of infecting pathogens causing foot infection is consistent and supports the consideration of empirical antibiotic advice. These recommendations are suggested to support clinicians and in conjunction with regional pathogen variations and antibiotic susceptibilities, provide a basis for local guideline development.

AimThis study investigates the relationship between basal insulin regimen and glycaemic outcomes 12 months after skills‐based structured education in the UK Dose Adjustment for Normal Eating (DAFNE) programme for Type 1 diabetes mellitus.MethodRetrospective analysis of data from 892 DAFNE participants from 11 UK centres.ResultsMean HbA1c 12 months after DAFNE was lower in those using twice‐ rather than once‐daily basal insulin after correcting for differences in baseline HbA1c, age and duration of diabetes; difference –2 (95% CI –3 to –1) mmol/mol [–0.2 (–0.3 to –0.1)%], P = 0.009. The greatest fall in HbA1c of –5 (–7 to –3) mmol/mol [–0.4 (–0.6 to –0.3)%], P < 0.001 occurred in those with less good baseline control, HbA1c ≥ 58 mmol/mol, who switched from once‐ to twice‐daily basal insulin. There was no difference in the 12‐month HbA1c between users of glargine, detemir and NPH insulin after correcting for other variables. Relative risk of severe hypoglycaemia fell by 76% and ketoacidosis by 63% 12 months after DAFNE. The rate of severe hypoglycaemia fell from 0.82 to 0.23 events/patient year in twice‐daily basal insulin users. In the group with greatest fall in HbA1c, the estimated relative risk for severe hypoglycaemia in twice‐daily basal insulin users versus once daily at 12 months was 1.72 (0.88–3.36, P = 0.110).ConclusionAfter structured education in adults with Type 1 diabetes mellitus, use of basal insulin twice rather than once daily was associated with lower HbA1c, independent of insulin type, with significant reductions in severe hypoglycaemia and ketoacidosis in all groups.

The data confirm that DAFNE participation improves glycaemic control in Type 1 diabetes with benefits being sustained for 5 years. This study is the first to demonstrate reduced HbA variability after completion of structured education. This is new evidence of the beneficial impact of DAFNE on glycaemic profile.

Ultrastructural immunoreactivity for chromogranin with the LK2H10 antibody was examined in nine cases of breast carcinoma and one example of normal resting breast. These tissues were selected for study on the basis of argyrophilia or LK2H10 immunostaining by light microscopy. In two cases, positive reactivity with the chromogranin antibody was seen in breast neuroendocrine-like dense core granules. In a further six cases chromogranin reactivity was not seen in similar granules that showed the neuroendocrine properties of ultrastructural argyrophilia and uranaffinity. Inability to exhibit the full complement of neuroendocrine characteristics in breast carcinomas contrasts with the facility to demonstrate them in tissues of usual neuroendocrine differentiation. Furthermore, in two mucoid carcinomas and one example of normal resting breast ultrastructural cytoplasmic LK2H10 reactivity was evident, which was not localized to dense core granules, although these were present in two of the cases. Our findings demonstrate the heterogeneity of breast dense core granules and discourage acceptance of such characteristics as evidence of histogenesis of these carcinomas from a neuroendocrine cell type in breast tissue.

In this study breast tissue that contained ultrastructural dense core granules has been examined from 24 patients. The possible neuroendocrine characteristics of the granules were studied using the uranaffin reaction and an ultrastructural argyrophil stain. The tissue included 15 breast carcinomas and nine benign samples. Two types of breast dense core granules can be distinguished on the basis of intracellular distribution patterns and histochemical reactivity. Type I dense core granules are the most common and they were found subluminally distributed in non-pathological tissues and benign lesions as well as carcinomas. They were uranaffin-negative and are unlikely to be of endocrine nature. Type II dense core granules were found only in four carcinomas, where they occurred abundantly throughout the cytoplasm. These granules were uranaffin-positive and argyrophilic and thus exhibited characteristics consistent with neuroendocrine structure.