Treatment of patients with multiple organ dysfunction syndrome (MODS) with an electromagnetic field coupled to biorhythmically defined impulse configuration: the MicrocircMODS study.

BACKGROUND: To potentially improve impaired vasomotion of patients with multiple organ dysfunction syndrome (MODS), we tested whether an electromagnetic field of low flux density coupled with a biorhythmically defined impulse configuration (Physical Vascular Therapy BEMER®, PVT), in addition to standard care, is safe and feasible and might improve disturbed microcirculatory blood flow and thereby improve global haemodynamics. METHODS: In a prospective, monocentric, one-arm pilot study, 10 MODS patients (APACHE II score 20-35) were included. Patients were treated, in addition to standard care, for 4 days with PVT (3 treatment periods of 8 min each day; day 1: field intensity 10.5 µT; day 2:14 µT, day 3:17.5 µT; day 4:21.0 µT). Primary endpoint was the effect of PVT on sublingual microcirculatory perfusion, documented by microvascular flow index (MFI). Patient safety, adverse events, and outcomes were documented. RESULTS: An increase in MFI by approximately 25% paralleled 4-day PVT, with the increase starting immediately after the first PVT and lasting over the total 4-day treatment period. Concerning global haemodynamics (secondary endpoints), halving vasopressor use within 24 h, and haemodynamic stabilisation paralleled 4-day PVT with an increase in cardiac index, stroke volume index, and cardiac power index by 30%-50%. No adverse events (AEs) or serious adverse events (SAEs) were classified as causally related to the medical product (PVT) or study. Three patients died within 28 days and one patient between 28 and 180 days. CONCLUSION: PVT treatment was feasible and safe and could be performed without obstruction of standard patient care. An increase in microcirculatory blood flow, a rapid reduction in vasopressor use, and an improvement in global haemodynamics paralleled PVT treatment. Findings of this pilot study allowed forming a concept for a randomized trial for further proof.

Association of subendocardial viability ratio and mortality in the elderly population: results from the CARdiovascular disease, Living and Ageing in Halle study.

OBJECTIVES: The subendocardial viability ratio (SEVR) reflects the balance of myocardial oxygen supply and demand. Low SEVR indicates a reduced subendocardial perfusion and has been shown to predict mortality in patients with kidney disease and diabetes. The aim of this study is to investigate the association of SEVR and mortality in the elderly population. METHODS: We analysed data from the CARdiovascular disease, Living and Ageing in Halle (CARLA) study. SEVR was estimated noninvasively by radial artery tonometry and brachial blood pressure measurement. The study population was divided into a low (SEVR ≤130%) and normal (SEVR >130%) SEVR group. Cox-regression was used for survival analysis. RESULTS: In total, 1414 participants (635 women, 779 men) aged from 50 to 87 years (mean age 67.3 years) were included in the analysis. The all-cause mortality was 22.7% during a median follow-up of 10.5 years. The unadjusted association of SEVR with all-cause mortality decreased from 3.52 (1.31-9.46) [hazard ratio (95% confidence interval) for low SEVR ≤ 130% versus normal SEVR > 130%] among those younger than 60 years to 0.86 (0.50-1.48) among those older than 80 years and from 1.81 (0.22-14.70) to 0.75 (0.30-1.91) for cardiovascular mortality. Sex-specific unadjusted analyses demonstrated an association of SEVR with all-cause and cardiovascular mortality in men [2.32 (1.61-3.34) and 2.24 (1.18-4.24)], but not in women [1.53 (0.87-2.72) and 1.14 (0.34-3.82)]. CONCLUSION: Our data suggests that SEVR is an age dependent predictor for all-cause mortality, predominantly in men younger than 60 years.

Association of arterial stiffness and heart failure with preserved ejection fraction in the elderly population - results from the CARLA study.

Arterial stiffness has been suspected as a cause of left ventricular diastolic dysfunction and may thereby contribute to the development of heart failure with preserved ejection fraction (HFpEF). However, this association is derived from a small number of studies and application of outdated criteria to diagnose HFpEF. This study aimed to investigate the association of arterial stiffness measured by the augmentation index (AIx) and criteria for diagnosing HFpEF according to the recommended HFA-PEFF score. Our analysis based on data from the first follow-up of the CARdiovascular Disease, Living and Ageing in Halle study. The current analysis included participants with available information about comorbidities and risk factors for HFpEF, parameters for calculation of the HFA-PEFF and noninvasive AIx estimated by applanation tonometry. The association of AIx and HFA-PEFF was investigated through descriptive and inductive statistics. A total of 767 participants were included in the analysis. AIx was associated with E/e', left ventricular wall thickness (LVWT), relative wall thickness, left ventricular mass index (LVMI) and NT-proBNP but not with e' or left atrial volume index. However, after adjustment for confounders, only LVMI and LVWT remained associated with AIx. Males with a high AIx had a 3.2-fold higher likelihood of HFpEF than those with a low AIx. In contrast, that association was not present in females. In summary, AIx is associated with the morphological domain of the HFA-PEFF score represented by LVMI and LVWT. Higher values of AIx are associated with a higher likelihood for HFpEF in elderly males but not in females.

The relationship of skin autofluorescence with diastolic function and HFA-PEFF score in a general population of older people.

BACKGROUND AND AIMS: Advanced glycation end-products accumulation in tissue as measured by Skin autofluorescence (SAF) is related to diastolic function in specific patient populations. This analysis aims at investigating this relationship in a general population of older persons. METHODS AND RESULTS: Based on data from the CARLA cohort at first follow-up, 245 subjects were analyzed and stratified according to cardiovascular risk factors (CVRF). We used linear regression to investigate the association between diastolic function evaluated by echocardiography, HFA-PEFF score, and SAF. Univariable regression analysis showed an association of SAF with septal-E/e' (standardised beta = 1.11, 95% CI = 0.51-1.71) and A (3.42, 95% CI = 0.72-6.12), the former persisting after adjustment for age, sex and CVRF (0.67, 95% CI = 0.05-1.28). Septal-E/e' remained related to SAF only in the high cardiovascular risk stratum (1.16, 95% CI = 0.26-2.06). SAF was related to HFA-PEFF score (0.27, 95% CI = 0.10-0.43) but not after correcting for age and sex (0.16, 95% CI = 0.00-0.32) and CVRF and glomerular filtration rate (0.12, 95% CI = -0.07 - 0.27). SAF was related to the HFA-PEFF score only for participants with high cardiovascular risk (0.23, 95% CI = 0.02-0.45). CONCLUSION: In a general community-dwelling older population, SAF is related to diastolic function as measured by septal-E/e'. Further research is necessary to assess if SAF is a potential screening tool for diastolic dysfunction in advanced age.

Influence of inflammation and cardiac hypertrophy on mechanical properties of human pericardium.

Different devices for mechanical circulatory support (MCS) have been developed for the treatment of refractory cardiogenic shock. However, all of them are associated with direct blood contact, the need for anticoagulation and bleeding complications. To overcome these limitations the pericardial sac got into the focus as a promising implantation site for MCS. For this purpose, further knowledge about the mechanical properties of human pericardium is required. In this prospective, monocentric, experimental pilot study 56 samples of human pericardium were extracted postmortem from 13 critically ill patients. After preparation of test specimens uniaxial tensile tests were performed. The primary end points were load at fracture per sample width and strain at fracture. Acute inflammation was assessed by blood levels of C-reactive protein, white blood count and procalcitonin measured at several times during hospital stay. Inflammatory load was estimated by area under the inflammatory curves. Correlation and regression analysis were used to assess the relationship of primary end points to inflammation, comorbidities and postmortem time to preparation. Human pericardium showed a load at fracture per sample width of 1.95 [1.38-2.94] N/mm (median [inter quartile range]) and a strain at fracture of 89.29 [73.84-135.23] %. Markers of acute inflammation and cardiac hypertrophy did not correlate to load or strain at fracture. However, strain at fracture increased with higher body mass index and an increasing number of postmortem days. In contrast, higher patient age was associated with a lower strain at fracture. Inflammation and cardiac hypertrophy did not influence mechanical properties of human pericardium.

Cardiovascular risk factors, living and ageing in Halle: the CARLA study.

The CARLA study (Cardiovascular Disease, Living and Ageing in Halle) is a longitudinal population-based cohort study of the general population of the city of Halle (Saale), Germany. The primary aim of the cohort was to investigate risk factors for cardiovascular diseases based on comprehensive cardiological phenotyping of study participants and was extended to study factors associated with healthy ageing. In total, 1779 probands (812 women and 967 men, aged 45-83 years) were examined at baseline (2002-2005), with a first and second follow-up performed 4 and 8 years later. The response proportion at baseline was 64.1% and the reparticipation proportion for the first and second follow-up was 86% and 77% respectively. Sixty-four percent of the study participants were in retirement while 25% were full- or partially-employed and 11% were unemployed at the time of the baseline examination. The currently running third follow-up focuses on the assessment of physical and mental health, with an intensive 4 h examination program, including measurement of cardiovascular, neurocognitive, balance and gait parameters. The data collected in the CARLA Study resulted in answering various research questions in over 80 publications, of which two thirds were pooled analyses with other similar population-based studies. Due to the extensiveness of information on risk factors, subclinical conditions and evident diseases, the biobanking concept for the biosamples, the cohort representativeness of an elderly population, and the high level of quality assurance, the CARLA cohort offers a unique platform for further research on important indicators for healthy ageing.

Toxic Epidermal Necrolysis Caused by Allopurinol: A Serious but Still Underestimated Adverse Reaction.

BACKGROUND Allopurinol is the first-line therapy for the treatment of symptomatic hyperuricemia (gout). In clinical practice, there is a tendency to overmedicate asymptomatic patients who have elevated serum urate. Because of this practice, serious and life-threatening reactions such as Stevens-Johnson syndrome (SJS) or the more dramatic toxic epidermal necrolysis (TEN), both frequently caused by uricostatics, may occur. To increase awareness of these complications, we present a case with fulminant TEN caused by allopurinol. CASE REPORT A 75-year-old woman noticed a mildly itching skin rash accompanied by fever, shivering, and weakness approximately 3 weeks after taking newly prescribed allopurinol. The initial clinical examination revealed a generalized maculopapular exanthema. An adverse drug reaction was recognized, and allopurinol was discontinued. Ambulatory supportive therapy using prednisolone and cetirizine was started but failed. The patient developed a progressive exanthema with painful widespread blistering, skin peeling, and mucosal and conjunctival lesions. After recurrent presentations to the Emergency Department, the patient was transferred to our Intensive Care Unit (ICU). The clinical picture confirmed the suspected diagnosis of TEN. Massive fluid replacement, prednisolone, and cyclosporine were used as anti-inflammatory therapy. Polyhexanide and octenidine were applied for local treatment. All treatment measures were guided daily by a multidisciplinary team. After 7 days in the ICU, the patient was transferred to the Dermatology Department and was discharged from the hospital 42 days later. CONCLUSIONS With the prescription of allopurinol, there should be awareness of potentially life-threatening complications such as SJS or TEN. Patients with SJS or TEN should be immediately transferred to an ICU with dermatological expertise and multidisciplinary therapy.

Successful Treatment of an Acute High-Dose Clozapine Poisoning without Detoxication.

BACKGROUND Clozapine is a well-proven atypical antipsychotic drug used for therapy of treatment-resistant schizophrenia. Over the last decades only a few cases of clozapine poisoning have been reported. Hence, guidelines for in-hospital management are currently not available. Most of the reported cases underwent detoxication measures as charcoal therapy and/or gastric lavage. However, there is no evidence for primary detoxication to improve clinical outcome. In contrast, use of therapy with intravenous physostigmine in the case of anticholinergic syndrome is restricted due to concerns about safety and dosing. We present a case of acute high-dose clozapine poisoning without detoxication and complete recovery supported by physostigmine. CASE REPORT We report the case of a 28-year-old man with prior diagnosed schizophrenia who presumably ingested 8 g (regular maximum daily dose 900 mg/d) of clozapine with uncertain intent. Initial computed tomography (CT) showed pulmonary infiltrates and widespread pneumomediastinum and soft-tissue emphysema of unknown genesis. The patient developed a progressive impairment of vigilance and respiratory insufficiency requiring invasive artificial ventilation for 31 h. Afterwards, an anticholinergic syndrome led again to impaired vigilance, tachycardia, and hyperventilation. To avoid risks associated with artificial ventilation, we applied physostigmine. Subsequently, the anticholinergic syndrome and the pneumomediastinum completely regressed and no further artificial ventilation was needed. CONCLUSIONS Based on the presumably ingested dosage, we present the likely highest reported nonfatal overdose of clozapine without detoxication. Additionally, we observed widespread pneumomediastinum as an uncommon complication. Our approach was to refrain from detoxication to minimize complications and to treat early with physostigmine because of anticholinergic syndrome to minimize its impact and to avoid artificial ventilation due do vigilance impairment.