All-cause and cause-specific mortality following non-traumatic spinal cord injury: evidence from a population-based cohort study in Switzerland.

STUDY DESIGN: Observational cohort study. OBJECTIVE: To benchmark all-cause and cause-specific mortality following NTSCI to the general population (GP). SETTING: Specialized rehabilitation centers in Switzerland. METHODS: Longitudinal data from the Swiss Spinal Cord Injury (SwiSCI) Medical Record study were probabilistically linked with cause of death (CoD) information from the Swiss National Cohort. Standardized mortality ratios (SMRs) were estimated for all-cause and cause-specific mortality. Competing risk frameworks were used to estimate the probability of death due to specific CoD. RESULTS: One thousand five hundred and one individuals were admitted for first rehabilitation with NTSCI between 1990-2011; CoD information was available for 454 individuals of the 525 individuals that died. Overall, the mortality rate for persons with NTSCI was 1.6 times greater than that of the GP. Deaths due to cardiovascular disease (39.8%), neoplasms (22%), and infection (9.9%) were most often reported. Individuals with an SCI due to a vascular etiology indicated the greatest burden of mortality from infection compared with the GP (SMR 5.4; 95% CI, 3.1 to 9.2). CONCLUSIONS: Cause-specific SMRs varied according to etiology. This supports the need for targeted clinical care and follow-up. Cardiovascular disease, neoplasms, and infection, emerged as main causes of death following NTSCI and should thus be targets for future research and differential clinical management approaches.

Survival after non-traumatic spinal cord injury: evidence from a population-based rehabilitation cohort in Switzerland.

STUDY DESIGN: Observational cohort study. OBJECTIVE: To investigate survival and life expectancy after NTSCI in Switzerland according to etiology. SETTING: Specialized rehabilitation centers in Switzerland. METHODS: Longitudinal data from the Swiss Spinal Cord Injury (SwiSCI) medical records study were used. Adjusted hazard ratios (HRs) and life expectancies were estimated using flexible parametric survival modeling. RESULTS: One thousand four hundred and fifty individuals were admitted to first rehabilitation for NTSCI between 1990 and 2011, contributing 6137 cumulative person-years at risk and 528 deaths. With reference to persons with a degenerative disc disorder, the HR for mortality in individuals with NTSCIs from infections was 1.42 (95% CI 0.99-2.04), while risk in those with NTSCIs from vascular disorders was 1.28 (95% CI 0.97-1.68). Mortality risk was most pronounced in individuals with NTSCIs from malignant neoplasms (HR 6.32, 95% CI 4.79-8.34). Exemplified for males with an attained age of 60 years, a malignant etiology was associated with 1.7 life years remaining (LYR), as compared to 10.1 LYR for non-malignant etiologies. Males with an attained age of 60 years and a degenerative disc etiology were estimated to have 12.9 LYR. CONCLUSIONS: This study contributes an evidence base for risk factors of mortality after NTSCI, reducing a considerable knowledge gap in survival after NTSCI. Survival and life expectancy estimates were highly differential between etiological groups, indicating a need for a heterogeneous clinical approach and dynamic health-care provisions for this growing population.

Differences between Parkinson's and Huntington's diseases and their role for prioritization of stem cell-based treatments.

The problems of allocation of scarce resources and priority setting in health care have so far not been much studied in the context of stem cell-based therapeutic applications. If and when competitive cost effective stem cell-based therapies are available, the problem of priority setting - to whom should stem cellbased therapies be offered and on what grounds - is discussed in this article using the examples of Parkinson's Disease (PD) and Huntington's Disease (HD). The aim of this paper is to examine the presently known differences between PD and HD and analyze the role of these differences for setting priorities of stem cell-based therapeutic applications to treat these diseases. To achieve this aim, we (1) present the theoretical framework used in the analysis; (2) compare PD and HD in terms of health related and non-health related consequences of these diseases for patients, their relatives and third parties; (3) analyze the ethical relevance of observed differences for priority setting given different values and variables; (4) compare PD and HD in terms of social justice related consequences of stem cell-based therapies; and (5) analyze the ethical relevance of these differences for priority setting given different values and variables. We argue that the steps of analysis applied in this paper could be helpful when setting priorities among treatments of other diseases with similar differences as those between PD and HD.

Late stent thrombosis in the absence of prior intracoronary brachytherapy.

Late stent thrombosis has not been reported in the absence of prior coronary brachytherapy. We reviewed our experience in 1,855 consecutive patients who received at least one stent and did not receive coronary brachytherapy. Half of all stent thromboses occurred within the first week and nearly 65% (22) occurred within 15 days. The incidence of stent thrombosis within this traditional time frame was 1.2%. An additional 12 patients, however, presented with stent thrombosis between 33 and 270 days post-procedure (mean = 72.9 +/- 23 days). The true incidence of stent thrombosis was therefore 1.8% (34/1,855). There were three bypass operations, one stroke and two deaths in the late stent thrombosis group. Late stent thrombosis is an unusual but serious complication in patients who have not received coronary brachytherapy. Intracoronary radiation may potentiate a phenomenon that already occurs after stent deployment. Prolonged treatment (6-12 months) with anti-platelet agents should be considered after percutaneous intervention with coronary stents.

Precise mapping of t(12;14) leiomyoma breakpoint on chromosome 14 between D14S298 and D14S540.

Uterine leiomyoma is a common tumor of smooth muscle cell origin often characterized by the presence of a balanced t(12;14)(q13-15;q24.1) chromosomal translocation. This breakpoint on chromosome 14 had previously been placed between the markers SPTB and D14S77, a region estimated to span 7 cM. In this study we have used a meiotic breakpoint mapping panel to construct a high resolution genetic map of this interval. Markers that mapped within this interval were used to analyze DNA from a somatic cell hybrid containing the t(12;14) translocated chromosome. The results of this analysis localize the t(12;14) breakpoint on chromosome 14 between D14S298 and D14S540, between which no meiotic recombination was detected. This sets the stage for identifying the gene(s) disrupted by the chromosomal translocation by defining the markers that flank the translocation breakpoint.

Physical mapping of the uterine leiomyoma t(12;14)(q13-15;q24.1) breakpoint on chromosome 14 between SPTB and D14S77.

Uterine leiomyoma is the most common tumor of smooth muscle cell origin and is often associated with the recurrent balanced translocation t(12;14)(q13-15;q24). As an initial step toward finding the gene or genes that are interrupted by the translocation breakpoint, a somatic cell hybrid carrying the derivative 14 as the single t(12;14) translocated chromosome was constructed from a leiomyoma cell line with this translocation. Sequence tagged sites (STS) whose locations on the genetic map of chromosome 14 were known were used to map the breakpoint in the translocated chromosomes. The results of this analysis place the translocation breakpoint on the long arm of chromosome 14 between the proximal marker SPTB and the distal marker D14S77, narrowing the chromosomal translocation breakpoint to a region of approximately 7 cM. The identification of flanking markers on chromosome 14 lays the foundation for efforts to clone the breakpoint and to identify the genes involved in the formation of leiomyoma.

Importance of L3T4+ and Lyt-2+ cells in the immunologic control of infection with Mycobacterium bovis strain bacillus Calmette-Guérin in mice. Assessment by elimination of T cell subsets in vivo.

The course of infection after injection of small doses of bacillus Calmette-Guérin (BCG) was studied in mice which were depleted in vivo of T cell subsets by administration of either anti-L3T4 or anti-Lyt-2 mAb. The results presented herein strongly suggest that the L3T4+ subpopulation play a pivotal role in the immunologic control of BCG infection because the depletion of L3T4+ cells led to a dramatic increase in the number of viable bacteria. Depletion of Lyt-2+ cells had no significant effect on the course of infection. These results were confirmed by using adoptive transfer experiments which showed that protective immunity was mediated by L3T4+ cells generated in the spleen as a result of infection. Moreover, T cells capable of controlling the recurrence of BCG multiplication from residual bacteria remaining in organs after the recovery from infection were shown to belong to the L3T4+ subpopulation.

Murine T lymphocyte specificity for African trypanosomes. II. Suppression of the T lymphocyte proliferative response to Trypanosoma brucei by systemic trypanosome infection.

Previously, we described a system allowing the study of murine T cell-dependent proliferative responses to Trypanosoma brucei antigens. It was observed that T. brucei-specific T cells could be demonstrated in the regional lymph nodes of primed mice for only 2 to 3 weeks following priming. The results of the present study indicate that this inability to demonstrate a long-lived memory response is due to an immunosuppressive effect of the resulting T. brucei infection. The exact mechanism of the suppression is not known, and appears to function in the absence of demonstrable suppressor cells. Since the T cell responses are strictly dependent on the presence of macrophages, we have investigated whether the loss in responsiveness is due to a defect in the T cell population, or to a loss of macrophage function. Our results show that T cells taken from mice 3 weeks after priming with T. brucei are unable to mount a proliferative response in the presence of a normal macrophage population, and conversely that macrophages taken 3 weeks after infection with T. brucei are unable to elicit a normal proliferative response using a competent primed T cell population. Thus these results indicate that both populations are affected by the parasite infection.