Maria Pritsch

Frequency and predictors of osteoporotic fractures after cardiac or liver transplantation: a follow-up study

BACKGROUND Osteoporosis and related fractures are a major complication after organ transplantation. The aim of this study was to find out the frequency and predictors of osteoporotic fractures after cardiac or liver transplantation. METHODS 235 consecutive patients who had a cardiac transplant (n=105; 88 men, 17 women) or a liver transplant (130; 75 men, 55 women) were followed. Vertebral fractures were assessed by a standardised analysis of spinal radiographs before and annually after transplantation. Clinical and non-vertebral fracture data were noted from hospital records. FINDINGS In the first and second years after transplantation, the proportion of patients (Kaplan-Meier estimates) who had at least one vertebral fracture was slightly higher in the cardiac group (first year 21%, second year 27%) than in the liver group (first year 14%, second year 21%). In the third and fourth years, one third of patients from both groups had had one or more vertebral fractures. Non-vertebral fractures occurred in nine patients (7%) after liver transplantation and avascular necrosis of the hip head in three patients (3%) after cardiac transplantation. In both groups, no dose-dependent effect of immunosuppressive therapy on fracture development could be identified. Independent predictors assessed by multivariate analysis were age (hazard ratio [95% CI] increase of 5 years, 1.71 [1.1-2.7]) and lumbar bone-mineral density (decrease of 1 SD t score, 1.97 [1.2-3.2]) in cardiac transplantation patients, and vertebral fractures before transplantation (6.07 [1.7-21.7]) in the liver group. INTERPRETATION The high frequency of osteoporotic fractures in the 2 years after transplantation and the limitations of reliable fracture-risk predictions, show the need to investigate preventive therapies.

Results of interleukin-2-based treatment in advanced melanoma: a case record-based analysis of 631 patients.

PURPOSE In patients with stage IV melanoma, durable responses have been reported with treatment regimens that involve high-dose interleukin-2 (IL-2). We analyze long-term results of 631 melanoma patients from 12 institutions who had received IL-2 alone, in combination with interferon alfa 2a or 2b (IFNalpha), or with cytotoxic drugs. METHODS Case records that contained pretreatment parameters, response data, and updated survival information were collected. After univariate analysis, the multivariate evaluation of the impact of pretreatment parameters on response and survival was performed by logistic regression and Coxs regression, respectively. RESULTS Patients were divided into four groups according to treatment: IL-2 alone (n=117), IL-2 and chemotherapy (n=49), IL-2 and IFNalpha (n=153), and IL-2, chemotherapy, and IFNalpha (n=312). The median survival of all patients was 10.5 months and the 2- and 5-year survival rates were 19.9% and 10.4%, respectively. Independent prognostic factors for response and survival were entirely different, treatment group being the only significant factor for response, and serum lactate dehydrogenase (LDH), metastatic site, and performance predicting survival. The addition of IFNalpha to IL-2 was associated with prolonged survival, but the effect of additional chemotherapy was less obvious. CONCLUSION Serum LDH, metastatic site, and performance status are useful stratification factors for randomized trials in metastatic melanoma. The improved long-term survival rates observed in melanoma patients treated with IL-2/IFNalpha-containing regimens are notable in contrast to the reported 5-year survival rates of 2% to 6% achieved with chemotherapy, but because selection bias cannot be ruled out, the impact of IL-2, as well as all other components of the treatment regimens, on survival needs to be confirmed in prospective randomized trials.

Early risk factors for miscarriage: a prospective cohort study in pregnant women.

Many pregnancies are lost during early gestation, but clinicians still lack tools to recognize risk factors for miscarriage. Thus, the identification of risk factors for miscarriage during the first trimester in women with no obvious risk for a pregnancy loss was the aim of this prospective cohort trial. A total of 1098 women between gestation weeks 4 and 12 in whom no apparent signs of a threatened pregnancy could be diagnosed were recruited. Demographic, anamnestic, psychometric and biological data were documented at recruitment and pregnancy outcomes were registered subsequently. Among the cases with sufficiently available data, 809 successfully progressing pregnancies and 55 subsequent miscarriages were reported. In this cohort, risk of miscarriage was significantly increased in women at higher age (>33 years), lower body mass index (< or =20 kg/ m(2)) and lower serum progesterone concentrations (< or =12 ng/ml) prior to the onset of the miscarriage. Women with subsequent miscarriage also perceived higher levels of stress/demands (supported by higher concentrations of corticotrophin-releasing hormone) and revealed reduced concentrations of progesterone-induced blocking factor. These risk factors were even more pronounced in the subcohort of women (n = 335) recruited between gestation weeks 4 and 7. The identification of these risk factors and development of an interaction model of these factors, as introduced in this article, will help clinicians to recognize pregnant women who require extra monitoring and who might benefit from therapeutic interventions such as progestogen supplementation, especially during the first weeks of pregnancy, to prevent a miscarriage.

Pattern of Periprosthetic Bone Remodeling Around Stable Uncemented Tapered Hip Stems: A prospective 84-month follow-up study and a Median 156-month Cross-Sectional Study with DXA

Bone resorption in the proximal femur is commonly seen after total hip arthroplasty (THA). With dual energy X-ray absorptiometry (DXA), the amount of bone mass (BMD) after implantation of a total hip stem can be precisely determined. However, prospective evaluation of the change of bone mass around the stem is only available for selected stems and short-term follow-up (up to 36 months). We analyzed BMD in patients who had undergone uncemented THA by DXA. Only patients with good clinical outcome (Merle d’ Aubigné score > 12) were included to obtain normative data for regular bone response. Two separate studies were performed: a prospective longitudinal study over 84 months with baseline values acquired within the first postoperative week (group A) (n = 26 patients) and a separate cross-sectional study, median follow-up 156 (124-178) months (group B) (n = 35 patients). Regions of interest were defined according to Gruen (ROI 1-7) and as net average ROI (net avg) for the periprosthetic femoral bone. After the initial remodeling process (12 months), BMD was compared to the 84-month (longitudinal) and the 156-month (cross-sectional) follow-up values to determine long-term periprosthetic changes of bone mineral density. The longitudinal study (group A), after the initial bone remodeling, showed no relevant further bone loss for women and men with BMD values 1.19 ± 0.15 and 1.40 ± 0.19, respectively, 12 months (women 89.8%, men 93.6%), and 1.19 ± 0.13 and 1.36 ± 0.18, respectively, after 84 months (women 90.0%, men 91.3%) (P = 0.98, P = 0.08,) respectively. The distribution of the BMD around the stem changed during the first 12 months. The ROIs around the proximal stem (ROI 1 and 7) showed the lowest absolute values at the 12-month follow-up and BMD in ROI 7 decreased most during the further follow-up until 84 months. The cross-sectional study (group B) showed no significant difference in BMD (net avg) values at a median of 156 months follow-up compared to the 12-month values (group A) (women: P = 0.77, men: P = 0.44). Initial BMD, implant diameter, and body mass index did not influence BMD loss (net avg) in this study, whereas age showed a weak correlation with BMD loss. The results show that after the initial remodeling process, no relevant further bone loss (net avg) occurs up to 84 months postsurgery, and values after a median of 156 months are similar. Normative long-term changes in the periprosthetic bone can be demonstrated in defined ROIs after implantation of a tapered corundum-blasted titanium stem with a good clinical result.

Enhancer of zeste homolog 2 (EZH2) expression is an independent prognostic factor in renal cell carcinoma

BackgroundThe enhancer of zeste homolog 2 (EZH2) gene exerts oncogene-like activities and its (over)expression has been linked to several human malignancies. Here, we studied a possible association between EZH2 expression and prognosis in patients with renal cell carcinoma (RCC).MethodsEZH2 protein expression in RCC specimens was analyzed by immunohistochemistry using a tissue microarray (TMA) containing RCC tumor tissue and corresponding normal tissue samples of 520 patients. For immunohistochemical assessment of EZH2 expression, nuclear staining quantity was evaluated using a semiquantitative score. The effect of EZH2 expression on cancer specific survival (CSS) was assessed by univariate and multivariate Cox regression analyses.ResultsDuring follow-up, 147 patients (28%) had died of their disease, median follow-up of patients still alive was 6.0 years (range 0-16.1 years). EZH2 nuclear staining was present in tumor cores of 411 (79%) patients. A multivariate Cox regression analysis revealed that high nuclear EZH2 expression was an independent predictor of poor CSS (> 25-50% vs. 0%: HR 2.72, p = 0.025) in patients suffering from non-metastatic RCC. Apart from high nuclear EZH2 expression, tumor stage and Fuhrmans grading emerged as significant prognostic markers. In metastatic disease, nuclear EZH2 expression and histopathological subtype were independent predictive parameters of poor CSS (EZH2: 1-5%: HR 2.63, p = 0.043, >5-25%: HR 3.35, p = 0.013, >25%-50%: HR 4.92, p = 0.003, all compared to 0%: HR 0.36, p = 0.025, respectively).ConclusionsThis study defines EZH2 as a powerful independent unfavourable prognostic marker of CSS in patients with metastatic and non-metastatic RCC.

Vaporization of prostates of ≥80 mL using a potassium-titanyl-phosphate laser: midterm-results and comparison with prostates of <80 mL

To compare the safety and outcome of potassium‐titanyl‐phosphate (KTP) GreenlightTM (Laserscope, AMS, Minnetonka, MN, USA) vaporization for treating benign prostatic hyperplasia (BPH) in prostates of ≥80 vs <80 mL.

Protocol for German trial of Acyclovir and corticosteroids in Herpes-simplex-virus-encephalitis (GACHE): a multicenter, multinational, randomized, double-blind, placebo-controlled German, Austrian and Dutch trial [ISRCTN45122933]

BackgroundThe treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major unsolved problem in Neurology. Current gold standard for therapy is acyclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains up to 15%, less than 20% of patients are able to go back to work, and the majority of patients suffer from severe disability. This is a discouraging, unsatisfactory situation for treating physicians, the disabled patients and their families, and constitutes an enormous burden to the public health services. The information obtained from experimental animal research and from recent retrospective clinical observations, indicates that a substantial benefit in outcome can be expected in patients with HSVE who are treated with adjuvant dexamethasone. But currently there is no available evidence to support the routine use of adjuvant corticosteroid treatment in HSVE. A randomized multicenter trial is the only useful instrument to address this question.DesignGACHE is a multicenter, randomized, double-blind, placebo-controlled, parallel group clinical trial of treatment with acyclovir and adjuvant dexamethasone, as compared with acyclovir and placebo in adults with HSVE. The statistical design will be that of a 3-stage-group sequential trial with potential sample size adaptation in the last stage.Conclusion372 patients with proven HSVE (positive HSV-DNA-PCR), aged 18 up to 85 years; with focal neurological signs no longer than 5 days prior to admission, and who give informed consent will be recruited from Departments of Neurology of academic medical centers in Germany, Austria and The Netherlands. Sample size will potentially be extended after the second interim analysis up to a maximum of 450 patients.Trial RegistrationCurrent Controlled TrialsISRCTN45122933

Uncemented Grit-Blasted Straight Tapered Titanium Stems in Patients Younger than Fifty-five Years of Age: Fifteen to Twenty-Year Results

BACKGROUND Total hip arthroplasty without cement is frequently performed in young active patients, but only limited outcomes data are available after durations of follow-up of more than fifteen years. METHODS We retrospectively evaluated the clinical and radiographic results of a consecutive series of 154 total hip arthroplasties (in 141 patients) performed with an uncemented grit-blasted straight tapered titanium femoral stem combined with a threaded socket in patients under the age of fifty-five years. The median duration of follow-up was seventeen years. Clinical results were evaluated with use of the Harris hip score. The canal fill index was used as the criterion to determine the adequacy of stem sizing. Kaplan-Meier survivorship analysis was performed to predict long-term outcomes. RESULTS The stem was undersized, with a canal fill index of < or =80%, in forty-one hips (27%). Late aseptic loosening of the stem occurred in four femora, and the femoral component was undersized in all four. These four stems were stable for ten years and then underwent progressive subsidence, which was associated with pain. Five stems were revised because of a late postoperative periprosthetic fracture following trauma. Localized proximal femoral osteolysis was seen in seven hips without signs of loosening. Survivorship of the stem with revision for any reason as the end point was estimated to be 90% (95% confidence interval, 87% to 97%) at twenty years. Survivorship with aseptic loosening as the end point was estimated to be 95% (95% confidence interval, 91% to 99%) at twenty years. Sixty-seven (44%) of the threaded uncemented acetabular components were revised during the follow-up period. CONCLUSIONS After a minimum duration of follow-up of fifteen years, the survival of this type of femoral component is excellent in individuals younger than fifty-five years. The main mode of stem failure was a periprosthetic fracture due to trauma, or late aseptic loosening in a small percentage of the hips in which the femoral implant was undersized. The high rate of failure of the acetabular components was attributable to a poor design that is no longer in use.

The enhancer of zeste homolog 2 gene contributes to cell proliferation and apoptosis resistance in renal cell carcinoma cells.

The enhancer of zeste homolog 2 (EZH2) gene has been recently linked to human malignancies where it may serve as a new target for cancer therapy. Here, we analyzed EZH2 expression in primary renal cell carcinoma (RCC) specimens and in nontumorous tissue samples from adult kidney. EZH2 transcripts were detectable in all RCC specimens examined. Expression levels were significantly higher in tumor tissue (p ≤ 0.0001) than in samples from normal adult kidney. Moreover, inhibition of endogenous EZH2 expression in RCC cell lines by RNA interference (RNAi) led to reduced proliferation and increased apoptosis in RCC cells. These data show that EZH2 is overexpressed in RCC. Furthermore, they indicate that the EZH2 gene plays a role for both the proliferation and the apoptosis resistance of RCC cells. Targeted inhibition of EZH2 could therefore represent a novel strategy to improve the therapeutic response of RCC.

Effect of psychotherapy and relaxation on the psychosocial and somatic course of Crohn's disease: main results of the German Prospective Multicenter Psychotherapy Treatment study on Crohn's Disease.

OBJECTIVE Few studies have been published on the influence of psychotherapy on the physical and psychosocial course of Crohns disease (CD). METHODS The present study, a prospective, randomized multicenter investigation conducted with 108 of 488 consecutive CD patients, was designed to investigate the influence of short-term psychodynamic therapy and relaxation in addition to a standardized glucocorticoid therapy on the somatic course of the disease as well as on patient psychosocial status. Based on the same standardized somatic treatment, the psychotherapy and control groups were compared after a 1-year treatment period and a follow-up of another year with regard to somatic course and psychosocial situation. RESULTS A total of 81 (75%) of 108 randomized patients completed the psychosocial follow-up. The comparison between the therapy groups after 1 year showed no significant differences in the four main target criteria of psychosocial status (depression, anxiety, psychosocial-communicative status and health-related quality of life). The mean Becks Depression Inventory (BDI) score at admission was 12.3 in the psychotherapy group and 8.7 in the control group. At the 1-year follow-up, the scores for depression have been 7.8 (psychotherapy group) and 7.8 (control group). In the 2-year follow-up, 84 patients were classified into four groups on the basis of somatic course; 23% of the control group and 30% of the psychotherapy group showed episode-free courses, 29% and 17% respectively underwent surgery due to failure of immunosuppressive or medical therapy, and a further subranking showed no significant differences between the two groups (P=.125). At the 1-year follow-up, the scores for depression of patients with an active episode respective remission were 14.6 vs. 5.8. From the patients point of view, at the end of the 2-year follow-up, the overall subjective evaluation of the effectiveness of psychotherapy was positive. CONCLUSION The patients included showed no psychosocial disturbances of clinical relevance. Although a tendency toward fewer surgical interventions, fewer relapses and reduction of depression was noted, the analysis was unable to demonstrate any benefit from psychosocial intervention on hypothesized parameters of psychosocial status and somatic course. Further studies should be performed to identify patient subgroups that may benefit from psychosocial intervention.