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Many patients with advanced type 2 diabetes do not meet their glycated haemoglobin targets and randomised controlled studies comparing the efficacy of pump treatment and multiple daily injections for lowering glucose in insulin-treated patients have yielded inconclusive results. We aimed to resolve this uncertainty with a randomised controlled trial (OpT2mise).We did this multicentre, controlled trial at 36 hospitals, tertiary care centres, and referal centres in Canada, Europe, Israel, South Africa, and the USA. Patients with type 2 diabetes who had poor glycaemic control despite multiple daily injections with insulin analogues were enrolled into a 2-month dose-optimisation run-in period. After the run-in period, patients with glycated haemoglobin of 8·0-12·0% (64-108 mmol/mol) were randomly assigned (1:1) by a computer-generated randomisation sequence (block size 2 with probability 0·75 and size 4 with probability 0·25) to pump treatment or to continue with multiple daily injections. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was change in mean glycated haemoglobin between baseline and end of the randomised phase for the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01182493.495 of 590 screened patients entered the run-in phase and 331 were randomised (168 to pump treatment, 163 to multiple daily injections). Mean glycated haemoglobin at baseline was 9% (75 mmol/mol) in both groups. At 6 months, mean glycated haemoglobin had decreased by 1·1% (SD 1·2; 12 mmol/mol, SD 13) in the pump treatment group and 0·4% (SD 1·1; 4 mmol/mol, SD 12) in the multiple daily injection group, resulting in a between-group treatment difference of -0·7% (95% CI -0·9 to -0·4; -8 mmol/mol, 95% CI -10 to -4, p0·0001). At the end of the study, the mean total daily insulin dose was 97 units (SD 56) with pump treatment versus 122 units (SD 68) for multiple daily injections (p0·0001), with no significant difference in bodyweight change between the two groups (1·5 kg [SD 3·5] vs 1·1 kg [3·6], p=0·322). Two diabetes-related serious adverse events (hyperglycaemia or ketosis without acidosis) resulting in hospital admission occurred in the pump treatment group compared with one in the multiple daily injection group. No ketoacidosis occurred in either group and one episode of severe hypoglycaemia occurred in the multiple daily injection group.In patients with poorly controlled type 2 diabetes despite using multiple daily injections of insulin, pump treatment can be considered as a safe and valuable treatment option.Medtronic.

Despite over 350 million people being safely treated with ivermectin, there have been rare cases of death post-treatment; these events are most often associated with high Loa loa microfilaremia. This first autopsy description of an encephalopathy case following the administration of ivermectin involves a 45-year-old male who became comatose 3 days after treatment. He slowly deteriorated over 5 weeks and died at 54 days after the anthelminthic treatment, probably as a result of a secondary skin or pulmonary infection exacerbated by malnutrition. The major pre- and post-autopsy findings included the presence of high loads of Loa loa, positivity for Plasmodium, the presence of a longstanding respiratory condition, and vascular pathology in the brain. The central nervous system lesions have similarities with those described in previously reported cases of Loa loa-associated death following diethylcarbamazine treatment.

Small B-cell indolent lymphomas postulated to be of a post-germinal center origin include marginal zone lymphomas of the spleen (S-MZL) or lymph nodes (N-MZL) and mucosa-associated lymphoid tissue (MALT) lymphomas and lymphoplasmacytic lymphomas (LPL). The existence of rather aggressive cases stresses the need for new biological prognostic markers. DESIGN AND METHODS: We analyzed 90 tumors (20 LPL, 41 MALT lymphomas, 12 N-MZL, 17 S-MZL), investigating the expression of CD5, CD10, CD20, CD23, CD27, CD38, CD79a, CD138, Bcl6, cyclin D1, IRF4 and Ki67 antigens by immunohistochemistry. Results were compared to the histology, the standard clinical and biological parameters, and the global survival. RESULTS: Tumors were all positive for CD20 and CD79a, occasionally positive for CD5, CD23, CD138 and cyclin D1, and all negative for Bcl-6 and CD10. CD38, CD27 and IRF4 expression was heterogeneous. IRF4 expression was correlated with plasma-cell differentiation (p=0.0017). Ki67 expression was increased mainly in N-MZL (66%) and LPL (45%). In terms of overall survival, Ki67, IRF4 and C-reactive protein levels were found to be the 3 independent parameters associated with a worse outcome. Lack of both Ki67 and IRF4 expression was associated with a longer survival (median overall survival 9.8+/-1.1 years versus 3.6+/-1.3 years in the other group) (p=0.0011). Interpretations and CONCLUSIONS: Absence of expression of both Ki67 and IRF4 is likely to define a group of memory B-cell lymphomas with a better prognosis. This may have an important impact in the staging of patients since expression of these markers is easily assessed in routine diagnosis.

The purpose of this work was to determine the response rate and toxicity of a combination of Carmustine and Cisplatin administered before radiation in patients with newly diagnosed high grade astrocytoma. A good response rate has been published with this association in primary cerebral high grade tumor. This protocol was administered in a homogeneous population of 37 adult patients with measurable tumor on magnetic resonance imaging (MRI) or CT scan. After biopsy or subtotal resection, the patients received BCNU 40 mg/m2/d and CODP 40 mg/m2/d, for 3 days every 28 days for 3 cycles. Evaluation was performed before each cycle. Radiation therapy began 4 weeks after completing the chemotherapy or immediately if there was evidence of tumor progression on chemotherapy. Seven out of 37 (19%) demonstrated tumor regression with a median duration to progression of 11 months. Median survival was 6 months. Myelosuppression was the predominant but manageable toxicity. This work indicated that the first chemotherapy protocol gave poor results in a homogeneous group of patients, with bad prognosis.

Jessner's lymphocytic infiltration of the skin is a rare and benign disorder. Its clinical course is cyclic with remissions and exacerbations. In this disease, photosensitivity was previously noticed by authors and recently demonstrated. We report four new cases with positive photobiological investigation.Four patients (2 males, 2 females), with a mean age 36 years were seen with erythematous papules or discoid plaques on face, arms and upper trunk. The onset of disease occurred after sun exposure in summer. Skin biopsies showed perivascular lymphocytic infiltration in the dermis. All patients relapsed cyclically with incomplete healing during winter. Photobiological investigation elicited skin lesions in a broad spectrum of UV: UVB (2 cases), UVA (1 case), UVA and UVB (1 case). In all patients treatment with oral antimalarials and external photoprotection was effective.Our data suggest that photosensitivity history in patients with Jessner's lymphocytic infiltration of the skin should be searched for, and confirmed by provocative phototesting. This relevant event could guide the therapeutic strategy because antimalarials were effective for the Jessner's lymphocytic infiltration cases with photosensitivity.

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