Eight-week, multimodal exercise counteracts a progress of chemotherapy-induced peripheral neuropathy and improves balance and strength in metastasized colorectal cancer patients: a randomized controlled trial.

PURPOSES: Physical activity is supposed to decrease mortality of colorectal cancer (CRC) and is suggested to reduce side-effects of the disease and its treatment. However, the knowledge about the influence of exercise interventions on patients suffering from CRC and metastasized CRC (mCRC) is still sparse. One frequently observed side effect in mCRC is chemotherapy-induced peripheral neuropathy (CIPN). This randomized controlled trial investigated the influence of a supervised exercise program on CIPN in mCRC. METHODS: Thirty patients (stage IV) undergoing outpatient palliative treatment including a median of 23.5 chemotherapy cycles of various regimens were randomly assigned to an intervention or control group (IG, n = 17; CG, n = 13). The IG participated in an eight-week supervised exercise program, including endurance, resistance and balance training (2×/week for 60 min) whereas the CG received written standard recommendations to obtain physical fitness. CIPN was assessed using the FACT/GOG-NTX questionnaire. Moreover, endurance capacity (6MWT), strength (h1RM) and balance (GGT-Reha) were evaluated before (t 0) and after (t 1) the intervention as well as after 4 weeks follow-up (t2). RESULTS: Neuropathic symptoms remained stable in the IG over time, while CIPN significantly worsened in the CG from t 0 to t 1 and t 0 to t 2. In contrast to the CG, the IG significantly improved in strength and balance function. Changes in CIPN correlated with changes in balance. CONCLUSIONS: This is the first investigation showing positive effects of a multimodal exercise program on CIPN, balance and strength on mCRC patients in a palliative setting, thereby consequently increasing patients` quality of life. The results support earlier findings stating a positive influence of balance exercise on CIPN.

Rates of cardiovascular events and deaths are associated with advanced stages of HIV-infection: results of the HIV HEART study 7, 5 year follow-up.

INTRODUCTION: Cardiovascular diseases are increasing in aging HIV-positive patients (HIV+). Impact of traditional cardiovascular risk factors, HIV-specific parameters and antiretroviral therapy (ART) on the incidence of cardiovascular events (CVE) and on the mortality rate are investigated in different HIV+ cohorts. METHODS: The HIV HEART (HIVH) study is an ongoing prospective observational cohort study in the German Ruhr area to assess the frequency and clinical course of cardiac disorders in 1481 HIV+ by standardized non-invasive cardiovascular screening. CVE were defined as diagnosed or documented myocardial infarction, coronary heart disease, arterial coronary intervention, stent implantation, bypass operation and stroke. RESULTS: 1481 HIV+ subjects (mean age: 49.3±10.7 years (y), female: 15.6%) were included. 130 CVE and 90 deaths were documented until the end of 7, 5 year follow-up of HIVH. Mean duration of the HIV-infection was 12.9±6.8 y. HIV+ were treated with ART on average for 8.6±6.8 y. According to the CDC classification of the HIV-infection, HIV+ were distributed over the clinical categories (A:34.6%; B:31.4% and C:33.9%) while more than the half had an advanced immunodeficiency (I:8.3%; II:41.1%; III:50.7%). Advanced clinical and immunological stages were significantly (p<0.001) associated with higher incidences of deaths (A:16.7%; B:26.7%; C:56.7% and I:6.7%; II:27.7%; III:65.6%) and CVE (A:17.7%; B:33.1%; C:49.2% and I:3.1%; II:32.3%; III:64.6%) but not with the duration of HIV-infection (per y: Hazard ratio (HR): 0.91 [0.88-0.94]) and ART (per y: HR: 0.81 [0.79-0.84]) adjusted for age. The proportion of deceased HIV+ with HIV-RNA ≥50 copies/mL and lower CD4-cell counts at their last visit is significantly higher compared with living HIV+ without CVE (HIV-RNA ≥50 copies/mL: 25.6% vs 14.7%). Median CD4-cells: 286.5 cells/µL (IQR: 168.8-482.8) versus 574 cells/µL (IQR: 406-786). 96.1% of the living HIV+ with CVE had HIV-RNA<50 copies/mL and median CD4-cells 542.5 cells/µL (IQR: 370-793.5). CONCLUSIONS: Advanced clinical and immunological stages of HIV-infection, but not the duration of ART, were associated with higher incidences of CVE and deaths in the HIVH cohort. These observations support an earlier initiation of ART in HIV+. Special cardiovascular risk calculations for HIV+ should consider immunological and clinical categories of the HIV-infection.

Expression of ribosomal and translation-associated genes is correlated with a favorable clinical course in chronic lymphocytic leukemia.

B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease with a highly variable clinical course. Recent studies have shown that CD38 surface expression on the malignant cell clone may serve as a prognostic marker in that CD38(+) patients with B-CLL are characterized by advanced disease stage, lesser responsiveness to chemotherapy, and shorter survival than CD38(-) patients. To further investigate the molecular phenotype of these 2 clinical subgroups, we compared the gene expression profiles of CD38(+) (n = 25) with CD38(-) (n = 45) B-CLL patients using oligonucleotide-based DNA chip microarrays representative of approximately 5600 genes. The results showed that B-CLLs display a common gene expression profile that is largely independent of CD38 expression. Nonetheless, the expression of 14 genes differed significantly between the 2 groups, including genes that are involved in the regulation of cell survival. Furthermore, unsupervised hierarchical cluster analysis of 76 B-CLL samples led to the separation of 2 major subgroups, comprising 20 and 56 patients. Clustering to the smaller group was due in part to the coordinate high expression of a large number of ribosomal and other translation-associated genes, including elongation factors. Importantly, we found that patients with high expression of translation factors were characterized by a more favorable clinical course with significantly longer progression-free survival and reduced chemotherapy requirements than the remaining patients (P <.05). Our data show that gene expression profiling can help identify B-CLL subtypes with different clinical characteristics. Furthermore, our results suggest a role of translation-associated genes in the pathogenesis of B-CLL.

Fluorescence in situ hybridization shows spatial distribution of as yet uncultured treponemes in biopsies from digital dermatitis lesions.

Fluorescence in situ hybridization (FISH) was performed on sections of plastic-embedded tissue using 16S rRNA-directed oligonucleotide probes to visualize uncultured treponemes in skin biopsies of cows with digital dermatitis. Plastic as embedding material allowed sectioning of hard and soft tissue with a defined thickness, avoiding the risk of dragging bacteria into the tissue while sectioning. furthermore, it provided a good signal-to-noise ratio. Using this method the spatial distribution of three different bacterial phylotypes was visualized simultaneously within the tissue. Whereas debris covering the ulcers contained a mixture of different micro-organisms, a layering of certain treponemal phylotypes was observed deeper in the epidermis. Confocal laser scanning microscopy and subsequent three-dimensional reconstruction of series of optical sections confirmed that the treponemes migrated intercellularly around the cells, most of them directed towards the dermis. In situ hybridization on tissue embedded in plastic proved to be a useful method to study mixed bacterial infections since it combines excellent histological conservation of tissue with identification of bacterial species by simultaneous use of probes labelled with different fluorescent dyes. This technique may have implications for in situ detection, identification and localization of microorganisms in veterinary as well as in human medicine.