Neurological symptoms and natural course of xeroderma pigmentosum

We have prospectively followed 16 Finnish xeroderma pigmentosum (XP) patients for up to 23 years. Seven patients were assigned by complementation analysis to the group XP-A, two patients to the XP-C group and one patient to the XP-G group. Six of the seven XP-A patients had the identical mutation (Arg228Ter) and the seventh patient had a different mutation (G283A). Further patients were assigned to complementation groups on the basis of their consanguinity to an XP patient with a known complementation group. The first sign of the disease in all the cases was severe sunburn with minimal sun exposure in early infancy. However, at the time the diagnosis was made in only two cases. The XP-A patients developed neurological and cognitive dysfunction in childhood. The neurological disease advanced in an orderly fashion through its successive stages, finally affecting the whole nervous system and leading to death before the age of 40 years. Dermatological and ocular damage of the XP-A patients tended to be limited. The two XP-C patients were neurologically and cognitively intact despite mild brain atrophy as seen by neuroimaging. The XP-G patients had sensorineural hearing loss, laryngeal dystonia and peripheral neuropathy. The XP-C patients had severe skin and ocular malignancies that first presented at pre-school age. They also showed immunosuppression in cell-mediated immunity. Neurological disease appears to be associated with the complementation group and the failure of fibroblasts to recover RNA synthesis following UV irradiation, but not necessarily to the severity of the dermatological symptoms, the hypersensitivity of fibroblasts to UVB killing or the susceptibility of keratinocytes to UVB-induced apoptosis

Stroke severity, early recovery and outcome are each related with clinical classification of stroke: Data from the 'Tinzaparin in Acute Ischaemic Stroke Trial (TAIST)

Introduction: Baseline severity and clinical stroke syndrome (Oxford Community Stroke Project, OCSP) classification are predictors of outcome in stroke. We used data from the ‘Tinzaparin in Acute Ischaemic Stroke Trial’ (TAIST) to assess the relationship between stroke severity, early recovery, outcome and OCSP syndrome. Methods: TAIST was a randomised controlled trial assessing the safety and efficacy of tinzaparin versus aspirin in 1,484 patients with acute ischaemic stroke. Severity was measured as the Scandinavian Neurological Stroke Scale (SNSS) at baseline and days 4, 7 and 10, and baseline OCSP clinical classification recorded: total anterior circulation infarct (TACI), partial anterior circulation infarct (PACI), lacunar infarct (LACI) and posterior circulation infarction (POCI). Recovery was calculated as change in SNSS from baseline at day 4 and 10. The relationship between stroke syndrome and SNSS at days 4 and 10, and outcome (modified Rankin scale at 90 days) were assessed. Results: Stroke severity was significantly different between TACI (most severe) and LACI (mildest) at all four time points (p<0.001), with no difference between PACI and POCI. The largest change in SNSS score occurred between baseline and day 4; improvement was least in TACI (median 2 units), compared to other groups (median 3 units) (p<0.001). If SNSS did not improve by day 4, then early recovery and late functional outcome tended to be limited irrespective of clinical syndrome (SNSS, baseline: 31, day 10: 32; mRS, day 90: 4); patients who recovered early tended to continue to improve and had better functional outcome irrespective of syndrome (SNSS, baseline: 35, day 10: 50; mRS, day 90: 2). Conclusions: Although functional outcome is related to baseline clinical syndrome (best with LACI, worst with TACI), patients who improve early have a more favourable functional outcome, irrespective of their OCSP syndrome. Hence, patients with a TACI syndrome may still achieve a reasonable outcome if early recovery occurs

Antidiabetic medication, statins and the risk of endometrioid endometrial cancer in patients with type 2 diabetes

Abstract Objective: To gain further evidence of an association between the incidence of endometrial cancer (EC) and the use of metformin, other antidiabetic medication (ADM) and statins in women with type 2 diabetes (T2D). Methods: A retrospective cohort of 92,366 women with newly diagnosed T2D was obtained from a diabetes register (FinDM). 590 endometrioid ECs were observed during the follow-up time. Poisson regression was utilized to estimate the hazard ratios (HRs) with 95% confidence intervals (95% CIs) of the endometrioid EC in relation to the use of metformin, other oral ADM, insulin and statins. Nested case-control analyses were performed, where up to 20 controls were matched for age and duration of DM for each EC case. The HRs were estimated by conditional logistic regression for never/ever and cumulative use of different forms of ADM and statins. Results: In the case-control analyses the use of metformin (HR 1.24, 95% CI 1.02–1.51) and other oral ADM (HR 1.25, 95% CI 1.04–1.50) was associated with an increased incidence of endometrioid EC compared to no ADM use. No difference was observed between metformin users and those using other oral ADMs. The use of statins was inversely related to the incidence of endometrioid EC (HR 0.78, 95% CI 0.65–0.94). Results from the full cohort analysis supported this finding. Conclusions: In our study the use of metformin or other oral forms of ADM was not associated with a lowered risk of endometrioid EC in women with T2D. Instead statins were observed to be inversely associated with endometrioid EC in this population

Antidiabetic medication, statins and the risk and prognosis of non-endometrioid endometrial cancer in women with type 2 diabetes

Abstract Aim: To determine the incidence and prognosis of non-endometrioid endometrial cancer (EC) in relation to the use of metformin, other antidiabetic medication (ADM) and statins in patients with type 2 diabetes (T2D). Materials and Methods: In order to analyze the incidence and prognosis of non-endometrioid EC, two cohorts were obtained from a nationwide diabetes database (FinDM); 57 non-endometrioid ECs were observed in a cohort of 92,366 women with newly-diagnosed T2D during the follow-up (1996 to 2011) to assess the incidence, and a retrospective cohort of 105 women with T2D diagnosed with non-endometrioid EC (1998 to 2011) was used to estimate cumulative mortality from EC and other causes of death. Hazard ratios (HRs) with 95% confidence intervals (CIs) for EC incidence were estimated in the full-cohort analysis and in the nested case–control analysis, matched for age and duration of T2D. Cumulative mortality was estimated by using the Aalen–Johansen estimator. Cause-specific mortality rates were analyzed by using Cox models regarding the pre-diagnostic use of different forms of ADM and statins. Results: In the nested case–control analysis, the use of metformin was not associated with the risk of non-endometrioid EC (HR=1.09, 95% CI=0.59–2.00), whereas statin use was associated with a lower risk (HR=0.47, 95% CI=0.26–0.84). The results from the full-cohort analysis supported these findings. Mortality from non-endometrioid EC was not different between users of metformin and other types of oral ADM (HR=1.56, 95% CI=0.40–6.07) but was observed to be lower in statin users (HR=0.41, 95% CI=0.20–0.82). Conclusions: Our findings were inconclusive regarding the association of metformin with the risk and prognosis of non-endometrioid EC. However, statin use was associated with a lower incidence and mortality from this disease

The role of metformin and statins in the incidence of epithelial ovarian cancer in type 2 diabetes:a cohort and nested case–control study

Abstract Objective: To obtain evidence of the effects of metformin and statins on the incidence of ovarian cancer in women with type 2 diabetes (T2D). Design: A retrospective cohort study and nested case–control study. Setting: The data were obtained from a diabetes database (FinDM) combining information from several nationwide registers. Population: A cohort of 137 643 women over 40 years old and diagnosed with T2D during 1996–2011 in Finland. Methods: In full cohort analysis Poisson regression was used to estimate the hazard ratios (HR) in relation to ever use of metformin, insulin other oral anti‐diabetic medication or statins. In the nested case–control analysis 20 controls were matched to each case of ovarian cancer. Conditional logistic regression was used to estimate HRs in relation to medication use and cumulative use of different medications. The estimates were adjusted for age and duration of T2D. Main outcome measure: Incidence of ovarian cancer. Results: In all, 303 women were diagnosed with ovarian cancer during the follow up. Compared with other forms of oral anti‐diabetic medication, metformin (HR 1.02, 95% CI: 0.72–1.45) was not found to be associated with the incidence of ovarian cancer. Neither was there evidence for statins to affect the incidence (HR 0.99, 95% CI: 0.78–1.25). In nested case–control analysis the results were essentially similar. Conclusions: No evidence of an association between the use of metformin or statins and the incidence of ovarian cancer in women with T2D was found. Tweetable abstract: No evidence found for metformin or statins reducing the incidence of ovarian cancer