Sustainability of C-Reactive Protein Apheresis in Acute Myocardial Infarction-Results from a Supplementary Data Analysis of the Exploratory C-Reactive Protein in Acute Myocardial Infarction-1 Study.

In the multicenter, non-randomized, exploratory C-reactive protein (CRP) Apheresis in Myocardial Infarction (CAMI-1) study, CRP apheresis after ST-Elevation Myocardial Infarction (STEMI) significantly decreased blood CRP concentrations in humans. Cardiac damage was assessed by Cardiac Magnetic Resonance (CMR1) 3−9 d after onset of STEMI symptoms and quantified by myocardial infarct size (IS; %), left ventricular ejection fraction (LVEF; %), circumferential strain (CS) and longitudinal strain (LS). Compared with the control group (n = 34), cardiac damage was significantly lower in the apheresis group (n = 32). These findings suggested improved wound healing due to CRP apheresis already within few days after the STEMI event. In the current supplementary data analysis of CAMI-1, we have tested by a follow-up CMR (CMR2) after an average of 88 (65−177) d whether the effect of CRP apheresis is clinically maintained. After this time period, wound healing in STEMI is considered complete. Whereas patients with low CRP production and a CRP gradient cut off of <0.6 mg/L/h in the hours after STEMI (9 of 32 patients in the CRP apheresis group) did not significantly benefit from CRP apheresis in CMR2, patients with high CRP production and a CRP gradient cut off of >0.6 mg/L/h (23 of 32 patients in the CRP apheresis group) showed significant treatment benefit. In the latter patients, CMR2 revealed a lower IS (−5.4%; p = 0.05), a better LVEF (+6.4%; p = 0.03), and an improved CS (−6.1%; p = 0.005). No significant improvement, however, was observed for LS (−2.9%; p = 0.1). These data suggest a sustained positive effect of CRP apheresis on heart physiology in STEMI patients with high CRP production well beyond the period of its application. The data demonstrate the sustainability of the CRP removal from plasma which is associated with less scar tissue.

C-Reactive Protein Apheresis as Anti-inflammatory Therapy in Acute Myocardial Infarction: Results of the CAMI-1 Study.

Background: C-reactive protein (CRP) is a well-known marker of inflammation. It is less known that CRP mediates tissue damage in acute myocardial infarction (AMI) thus potentially worsening prognosis. A newly developed specific CRP adsorber allows efficient lowering of CRP levels and may improve survival. Objectives: Aim of this multi-center, controlled, non-randomized first-in-man CRP apheresis in Acute Myocardial Infarction study (CAMI-1) was to investigate the relationship between CRP levels (CRP gradient), myocardial infarct size and function as well as safety and efficacy of CRP apheresis in the setting of acute ST-segment Elevation Myocardial Infarction (STEMI) in humans. Methods: Eighty-three patients (45 apheresis, 38 controls) were recruited. CRP apheresis was performed 24 ± 12, 48 ± 12, and optionally 72 ± 12 h after onset of symptoms. First aphereses were performed at a median CRP concentration of 23.0 mg/L (range 9-279). In each apheresis session, 5,900 ± 400 mL plasma was processed via peripheral venous access. Primary study endpoint was a reduction in myocardial infarct size after STEMI as determined by cardiovascular magnetic resonance (CMR). Results: In controls, the CRP concentration significantly correlated with infarct size (p = 0.002) and decreased myocardial function (p ≤ 0.001). The CRP concentration in apheresis patients did not correlate with infarct size (p = 0.66) or left ventricular (LV) function (p = 0.79) and global strains and therefore significantly differed from controls (p = 0.03 and p = 0.002). Three major adverse cardiac events occurred in the control group after 12 months, none occurred in the apheresis group. Mean CRP depletion achieved over all apheresis procedures was 53.0 ± 15.1%. Apheresis sessions were well-tolerated. Reduced infarct size in the apheresis group compared to the control group (primary endpoint) was not achieved according to the original statistical analysis plan. Taking into account the individual CRP levels, however, revealed significant results. Modifications of the analysis plan were introduced in order to recruit a sufficient number of patients. Conclusions: This pilot study in humans reveals a correlation between CRP concentration and myocardial infarct size. CRP concentrations in STEMI can effectively be reduced by CRP apheresis without relevant side effects. CRP apheresis has the potential to interfere with deleterious aspects of STEMI. By lowering CRP levels, it resulted in the loss of correlation of CRP concentrations with myocardial infarct sizes as well as LV function. These results encourage a larger, randomized clinical trial. Clinical Trial Registration: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00008988, DRKS00008988.

Underweight in Nursing Homes: Differences between Men and Women.

OBJECTIVE: In Germany, there is an ongoing concern about the high prevalence of underweight on admission to health-care institutions. In order to assess possible sex-specific differences, the aim of this study is to provide valid figures about the prevalence and risk factors of underweight of men and women in German nursing homes. MATERIAL AND METHODS: A secondary data analysis of 8 annual consecutive cross-sectional studies of 19,686 residents from 280 nursing homes was conducted from 2009 to 2016. Underweight was defined as BMI < 18.5 (<20) for individuals <65 years (≥65 years). For statistical modeling, we used classification and regression trees (CRTs) and random forest in "R." RESULTS: Average prevalence of underweight in nursing home residents was 13.7% (13.2-14.2). Initial descriptive results showed that the prevalence of underweight among women was 15.6% (15.0-16.2) and the prevalence of underweight among men was 7.5% (6.7-8.2). The CRT-based modeling indicated that "loss of appetite" as the most important indicator for low BMI. If "loss of appetite" was present, prevalence of underweight increased from 13.5 to 39.1%. Other important indicators were "very large institutions" and the "resident/nurse ratio." The random forest analysis confirmed the importance of the CRT approach. DISCUSSION/CONCLUSION: The multivariate approach revealed that the role of sex for being underweight in nursing homes is marginal. To avoid higher morbidity and mortality in this group, nutritional intervention by clinical practitioners to increase appetite should be given high priority, especially in large long-term care institutions.

Motor function in survivors of pediatric acute lymphoblastic leukemia treated with chemotherapy-only.

BACKGROUND: Up to 43% of survivors of pediatric acute lymphoblastic leukemia (ALL) may exhibit fine-motor problems. Information on manual dexterity in this cohort is still limited. OBJECTIVES: We tested survivors of childhood ALL treated with chemotherapy-only for fine-motor function in terms of drawing and handwriting abilities using a Digitizing Tablet (DT) with three tasks for drawing and handwriting of varying complexity, for ataxia using the International Cooperative Ataxia Rating Scale (ICARS), and for tremor and hand-eye coordination using the Nine Hole Steadiness Tester (NHST). RESULTS: We examined a cohort of non-irradiated survivors (n = 31) after a median time of 3.5 years after end of therapy. In all tasks of the DT the cohort demonstrated significant (p < 0.05) impairment of speed, automation, and variability in at least two tasks and significantly more pressure. Impaired speed (SPV) inversely correlated with lag time since end of therapy. Dexterity performance of six survivors (19%) lay below the 5th percentile. No survivor exhibited ataxia, tremor, or impaired hand-steadiness. CONCLUSION: Despite the absence of gross ataxia, tremor, and impaired hand-eye coordination, we nevertheless detected significant fine-motor impairment in a relevant number of survivors of childhood ALL. Prospective studies are needed to reveal the pathophysiological underpinnings and genetic risk factors for development of such deficits due to ALL and its treatment.

Efficacy of vitamin D supplementation in multiple sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial.

BACKGROUND: Multiple sclerosis is the most common chronic inflammatory disease of the central nervous system in young adults. Despite the fact that numerous lines of evidence link both the risk of disease development and the disease course to the serum level of 25-hydroxyvitamin D it still remains elusive whether multiple sclerosis patients benefit from boosting the serum level of 25-hydroxyvitamin D, mainly because interventional clinical trials that directly address the therapeutic effects of vitamin D in multiple sclerosis are sparse. We here present the protocol of an interventional clinical phase II study to test the hypothesis, that high-dose vitamin D supplementation of multiple sclerosis patients is safe and superior to low-dose supplementation with respect to beneficial therapeutic effects. METHODS/DESIGN: The EVIDIMS trial is a German multi-center, stratified, randomized, controlled and double-blind clinical phase II pilot study. Eighty patients with the diagnosis of definite multiple sclerosis or clinically isolated syndrome who are on a stable immunomodulatory treatment with interferon-ß1b will be randomized to additionally receive either high-dose (average daily dose 10.200 IU) or low-dose (average daily dose 200 IU) cholecalciferol for a total period of 18 months. The primary outcome measure is the number of new lesions detected on T2-weighted cranial MRI at 3 tesla. Secondary endpoints include additional magnetic resonance imaging and optical coherence tomography parameters for neuroinflammation and -degeneration, clinical parameters for disease activity, as well as cognition, fatigue, depression, and quality of life. Safety and tolerability of high-dose vitamin D supplementation are further outcome parameters. DISCUSSION: In light of the discrepancy between existing epidemiological and preclinical data on the one hand and available clinical data on the other the EVIDIMS trial will substantially contribute to the evaluation of the efficacy of high-dose vitamin D supplementation in MS patients. The study design presented here fulfills the criteria of a high-quality clinical phase II trial in MS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01440062.

Are putative periodontal pathogens reliable diagnostic markers?

Periodontitis is one of the most common chronic inflammatory diseases. A number of putative bacterial pathogens have been associated with the disease and are used as diagnostic markers. In the present study, we compared the prevalence of oral bacterial species in the subgingival biofilm of generalized aggressive periodontitis (GAP) (n = 44) and chronic periodontitis (CP) (n = 46) patients with that of a periodontitis-resistant control group (PR) (n = 21). The control group consisted of subjects at least 65 years of age with only minimal or no periodontitis and no history of periodontal treatment. A total of 555 samples from 111 subjects were included in this study. The samples were analyzed by PCR of 16S rRNA gene fragments and subsequent dot blot hybridization using oligonucleotide probes specific for Aggregatibacter (Actinobacillus) actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, a Treponema denticola-like phylogroup (Treponema phylogroup II), Treponema lecithinolyticum, Campylobacter rectus, Fusobacterium spp., and Fusobacterium nucleatum, as well as Capnocytophaga ochracea. Our data confirm a high prevalence of the putative periodontal pathogens P. gingivalis, P. intermedia, and T. forsythia in the periodontitis groups. However, these species were also frequently detected in the PR group. For most of the species tested, the prevalence was more associated with increased probing depth than with the subject group. T. lecithinolyticum was the only periodontopathogenic species showing significant differences both between GAP and CP patients and between GAP patients and PR subjects. C. ochracea was associated with the PR subjects, regardless of the probing depth. These results indicate that T. lecithinolyticum may be a diagnostic marker for GAP and C. ochracea for periodontal health. They also suggest that current presumptions of the association of specific bacteria with periodontal health and disease require further evaluation.

[Reduction of acute recurrence in patients with chronic recurrent hypertrophic sinusitis by treatment with a bacterial immunostimulant (Enterococcus faecalis Bacteriae of human origin]. / Verminderung der Rezidivhäufigkeit bei Patienten mit chronisch rezidivierender hypertrophischer Sinusitis unter Behandlung mit einem bakteriellen Immunostimulans (Enterococcus faecalis-Bakterien humaner Herkunft).

A double-blind, placebo-controlled multicenter study in 157 patients with chronic recurrent sinusitis investigated the occurrence of acute relapses during treatment of patients with a bacterial immunostimulant (3 x 30 drops/day), comprised of cells and autolysate of human Enterococcus faecalis bacteria (Symbioflor 1, n = 78) in comparison to placebo (n = 79). The study included a treatment period of 6 months and a follow-up period of 8 months. Under verum the occurrence of relapses (50 incidents) was about half (56%) the number observed under placebo (90 incidents). In the Kaplan-Meier test the verum preparation emerged as significantly superior (p = 0.045, log rank test) compared to placebo. This superiority of verum was found during the treatment period with 17 vs. 33 relapses (p = 0.019) as well as during the follow-up observation with 33 vs. 57 relapses (p = 0.013). The time interval to the first relapse was clearly longer under verum (513 days) than under placebo (311 days). The relative risk for a relapse under the test preparation compared to placebo was 49.0% during the treatment and 55.8% during the follow-up period. Severity of the acute relapses was comparable in both groups. However, antibiotic therapy was only required in 2 patients treated with verum compared to 6 patients in the placebo group. Both preparations were well tolerated and serious side effects did not occur in either group. No changes in laboratory tests--hematology and clinical chemistry--were observed. Potential immunomodifying effects of the test preparation in view of the significant reduction in relapses were discussed.