Observational Study Mortality in Treated Primary Aldosteronism: The German Conn's Registry

In comparison with essential hypertension, primary aldosteronism (PA) is associated with an increased risk of cardiovascular morbidity. To date, no data on mortality have been published. We assessed mortality of patients treated for PA within the German Conn's registry and identified risk factors for adverse outcome in a case-control study. Patients with confirmed PA treated in 3 university centers in Germany since 1994 were included in the analysis. All of the patients were contacted in 2009 and 2010 to verify life status. Subjects from the population-based F3 survey of the Cooperative Health Research in the Region of Augsburg served as controls. Final analyses were based on 600 normotensive controls, 600 hypertensive controls, and 300 patients with PA. Kaplan-Meyer survival curves were calculated for both cohorts. Ten-year overall survival was 95% in normotensive controls, 90% in hypertensive controls, and 90% in patients with PA (P value not significant). In multivariate analysis, age (hazard ratio, 1.09 per year [95% CI, 1.03-1.14]), angina pectoris (hazard ratio, 3.6 [95% CI, 1.04-12.04]), and diabetes mellitus (hazard ratio, 2.55 [95% CI, 1.07-6.09]) were associated with an increase in all-cause mortality, whereas hypokalemia (hazard ratio, 0.41 per mmol/L [95% CI, 0.17-0.99]) was associated with reduced mortality. Cardiovascular mortality was the main cause of death in PA (50% versus 34% in hypertensive controls; P<0.05). These data indicate that cardiovascular mortality is increased in patients treated for PA, whereas all-cause mortality is not different from matched hypertensive controls.     

Using bearing area parameters to quantify early erosive tooth surface changes in enamel: A pilot study

Objectives

Most in vitro studies investigate the erosive process using relatively simple roughness parameters such as roughness average (R_a). In isolation, R_a may misrepresent the surface features. Further, few studies report baseline surface characteristics after sample preparation. This study aimed to test the hypothesis that measuring the bearing area parameters in addition to R_a may be useful when qualifying the surface of enamel at baseline and after an erosive challenge. The null hypothesis for this study was that the bearing area parameters provide no more useful information than R_a alone, when qualifying the surface of enamel at baseline and after an erosive challenge.

Methods

Enamel slabs (n = 20) were prepared from human (n = 2) and bovine (n = 4) incisor teeth and polished with 0.05 μm paste. Roughness average (R_a) and bearing parameters (MR1, MR2, R_pk, R_k, R_vk) were used to record baseline characteristics. Specimens were subjected to erosion with 1% citric acid solution for 1 min. Profilometric characteristics were recorded post-erosion, along with the maximum height changes within the profile. T-tests were carried out in order to compare baseline surface characteristics between tissue types. Post-erosion, analysis of variance (ANOVA) was used to test the effects of tissue type (bovine or human).

Results

There was no significant difference in R_a between human and bovine incisor enamel at baseline (human 0.11 μm, bovine 0.12 μm P > 0.05), and no significant difference was observed post-erosion (human 0.23 μm, bovine 0.20 μm P > 0.05). There were significant differences in bearing parameters at baseline and post-erosion that were not identified by the R_a measurement alone.

Conclusions

The results suggest that if R_a alone is measured, important differences in surface characteristics may be missed. The null hypothesis is rejected, and the recommendation is made that bearing parameters are included within profile measurements in order to further triangulate the results of surface analysis studies.

Clinical relevance

In isolation, R_a may misrepresent the surface features of a profile. These results have shown that the bearing parameters are an important and informative set of measurements. The recommendation is made that bearing parameters are included within profile measurements at baseline and post-erosion, in order to further triangulate the results of surface analysis studies.     

Treatment with Thalidomide and Cyclophosphamide (TCID) is Superior to Vincristine (VID) and to Vinorelbine (VRID) Regimens in Patients with Refractory or Recurrent Multiple Myeloma

Treatment of relapsed or refractory multiple myeloma remains a challenge and novel treatment regimen are required. Here, a matched pair analysis was performed comparing TCID (thalidomide, cyclophosphamide, idarubicin, dexamethasone) treatment to the treatment of patients with VID (vincristine, idarubicin, dexamethasone) or with VRID (vinorelbine, idarubicin, dexamethasone) for relapsed or refractory multiple myeloma. In total, 197 patients were enrolled in multicenter trials. After matching for important prognostic variables 46 matched-pairs (total of 138 patients) could be analysed with regard to survival, toxicity and efficacy. Interestingly, a significant improvement of overall response rate (ORR) for TCID treatment compared to VID and VRID was found. In addition, TCID treatment also led to a significantly higher overall survival (OS) as well as progression-free survival (PFS) compared to VID and VRID. In conclusion, TCID treatment appears to be superior to VRID and VID treatment in patients with progressive or refractory myeloma.     

Nanocomposite liposomes for pH-controlled porphyrin release into human prostate cancer cells

It is both challenging and desirable to have drug sensitizers released at acidic tumor pH for photodynamic therapy in cancer treatment. A pH-responsive carrier was prepared, in which fumed silica-attached 5,10,15,20-tetrakis(4-trimethylammoniophenyl)porphyrin (TTMAPP) was encapsulated into 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) nanocomposite liposomes. The sizes of agglomerates were determined by dynamic light scattering to be 115 nm for silica and 295 nm for silica-TTMAPP-DOPC liposomes. Morphological changes were also found in TEM images, showing liposome formation at pH 8.5 but collapse upon silanol protonation. TTMAPP release is enhanced from 13% at pH 7.5 to 80% at pH 2.3, as determined spectrophotometrically through dialysis membranes. Fluorescence emission of TTMAPP encapsulated in the dry film of liposomes was reduced to half at pH 8.6 when compared to that at pH 5.4, while the production of singlet oxygen was quintupled at pH 5.0 compared to pH 7.6. Upon treatment of human prostate cancer cells with liposomes containing 6.7 μM, 13 μM, 17 μM and 20 μM TTMAPP, the cell viabilities were determined to be 60%, 18%, 20% and 5% at pH 5.4; 58%, 30%, 25% and 10% at pH 6.3; and 90%, 82%, 68% and 35% at pH 7.4, respectively. Light-induced apoptosis in cancerous cells was only observed in the presence of liposomes at pH 6.3 and pH 5.4 but not at pH 7.4, as indicated by chromatin condensation.

Nanocomposite liposomes are relatively stable in weak basic solutions but effectively release porphyrins at acidic pH, as indicated by the difference in fluorescence.     

Long-term follow-up of ruptured intracranial aneurysms treated by microsurgical wrapping with autologous muscle

The purpose of this study is to describe our series of nine unclippable and uncoilable ruptured aneurysms in eight patients treated by microsurgical wrapping with autologous muscle. Records were retrospectively reviewed for rebleeding rate, morbidity and mortality, changes in size or the aneurysm’s configurations, and inflammatory reaction. We conducted a Medline search in the post-microsurgical era, excluding patients in whom wrapping was part of the aneurysm treatment in combination with clipping or coiling. The surgically related morbidity was 12.5 %. Global mortality rate was 25 % due to vasospasm (one case) and rebleeding (one case). Six patients are still alive. Rebleeding rate was 14.3 % within 6 months; then, it was zero. Glasgow outcome scale (GOS) score at discharge was 1 and 4 in one patient, respectively, and 5 in the remaining six. Mean clinical follow-up was 126 months. GOS at last follow-up was 4 and 5 in 50 % of patients, respectively. Mean mRS score was 0.8 at 2 months, and 2.4 at 12 months. Follow-up MR demonstrated persistence of the aneurysm’s sac, without changes in size and configuration. Patients did not describe or exhibit symptoms attributable to complications inherent to the use of muscle. Microsurgical muscle-wrapping of ruptured intracranial aneurysm is safe, is associated with a low rate of acute and delayed postoperative complications and rebleeding, and could be a valid alternative for unclippable and non-amenable to endovascular procedure ruptured aneurysms.     

Why do some trauma patients die while others survive? A matched-pair analysis based on data from Trauma Register DGU®

Purpose: The mortality rate for severely injured patients with the injury severity score (ISS) 16 has decreased in Germany. There is robust evidence that mortality is influenced not only by the acute trauma itself but also by physical health, age and sex. The aim of this study was to identify other possible influences on the mortality of severely injured patients. Methods: In a matched-pair analysis of data from Trauma Register DGU®, non-surviving patients from Germany between 2009 and 2014 with an ISS 16 were compared with surviving matching partners. Matching was performed on the basis of age, sex, physical health, injury pattern, trauma mechanism, conscious state at the scene of the accident based on the Glasgow coma scale, and the presence of shock on arrival at the emergency room. Results: We matched two homogeneous groups, each of which consisted of 657 patients (535 male, average age 37 years). There was no significant difference in the vital parameters at the scene of the accident, the length of the pre-hospital phase, the type of transport (ground or air), pre-hospital fluid management and amounts, ISS, initial care level, the length of the emergency room stay, the care received at night or from on-call personnel during the weekend, the use of abdominal sonographic imaging, the type of X-ray imaging used, and the percentage of patients who developed sepsis. We found a significant difference in the new injury severity score, the frequency of multi-organ failure, hemoglobine at admission, base excess and international normalized ratio in the emergency room, the type of accident (fall or road traffic accident), the pre-hospital intubation rate, reanimation, in-hospital fluid management, the frequency of transfusion, tomography (whole-body computed tomography), and the necessity of emergency intervention. Conclusion: Previously postulated factors such as the level of care and the length of the emergency room stay did not appear to have a significant influence in this study. Further studies should be conducted to analyse the identified factors with a view to optimising the treatment of severely injured patients. Our study shows that there are significant factors that can predict or influence the mortality of severely injured patients.