[Glucose metabolism in older patients]. / Glukosestoffwechsel im fortgeschrittenen Lebensalter.

Current guidelines for specialized treatment of diabetes mellitus in the elderly (>65 years old) are primarily based on epidemiologic studies and geriatric assessment of functional health. Yet, age-dependent alterations of glucose metabolism and homeostasis are highly relevant to the pathophysiology of diabetes in the elderly. In this review, we focus on age-related alterations in metabolic pathways and their relevance for the specialized diabetic care in the elderly. We review the role of increasing insulin resistance, age-related ß­cell dysfunction and incretin secretion. The clinical relevance of these effects will also be discussed in regard to the central geriatric syndrome of sarcopenia and antidiabetic drug therapy.

Crystal arthritides - gout and calcium pyrophosphate arthritis : Part 2: clinical features, diagnosis and differential diagnostics.

Gout develops in four stages beginning with an asymptomatic increase in blood levels of uric acid. An acute gout attack is an expression of an underlying inflammatory process, which in the course of time is self-limiting. Without therapy monosodium urate crystals remain in the synovial fluid and synovial membrane and trigger more acute attacks. In the course of the disease monosodium urate crystals form deposits (tophi) leading in severe forms to irreversible joint deformities with loss of functionality. In 20% of cases gout leads to involvement of the kidneys. Overproduction of uric acid can cause nephrolithiasis. These stones can be composed of uric acid or calcium phosphate. Another form of kidney disease caused by gout is uric acid nephropathy. This is a form of abacterial chronic inflammatory response with deposition of sodium urate crystals in the medullary interstitium. Acute obstructive nephropathy is relatively rare and characterized by renal failure due to uric acid precipitation in the tubules because of rapid cell lysis that occurs, for example, with chemotherapy. There is a causal interdependence between the occurrence of hyperuricemia and hypertension. Uric acid activates the renin-angiotensin-aldosterone (RAA) system and inhibits nitric oxide (NO) with the possible consequence of a rise in systemic vascular resistance or arteriolar vasculopathy; however, uric acid is also an apparently independent risk factor for atherosclerosis. In contrast to young patients, the diagnosis of an acute gout attack in the elderly can be a challenge for the physician. Polyarticular manifestations and obscure symptoms can make it difficult to differentiate it from rheumatoid arthritis and calcium pyrophosphate deposition disease (CPPD). Aspiration of synovial fluid with visualization of urate crystals using compensated polarized light microscopy is the gold standard for diagnosis of acute gout. Moreover, analysis of synovial fluid enables a distinction from septic arthritis by Gram staining and bacterial culture. Soft tissue ultrasonography is useful to detect affected synovial tissue and monosodium urate crystals within the synovial fluid. Involvement of bone occurs relatively late in the disease so that x­ray images are not useful in the early stages but might be helpful in differential diagnostics. Dual energy computed tomography (CT) and magnetic resonance imaging (MRI) can be used for certain indications.

Crystal arthritides - gout and calcium pyrophosphate arthritis : Part 1: Epidemiology and pathophysiology.

Gout and calcium pyrophosphate deposition disease (CPPD, pseudogout) are still the most frequent inflammatory arthritides in multimorbid elderly patients. Gout and CPPD are different diseases and based on different pathophysiological principles. Gout is closely associated with the metabolic syndrome and is an independent risk factor for cardiovascular mortality. The prevalence of asymptomatic hyperuricemia is estimated to be 10-20% of adults in industrial nations and prevalence is strongly associated with age. More than 7% of persons aged over 65 years suffer from clinically manifest gout. The underlying pathophysiological principle is an imbalance between the formation and elimination of uric acid. The degradation of the purine bases adenine and guanosine to uric acid is catalysed by xanthine oxidase and genetic polymorphisms and mutations play an important role in absorption and excretion processes. Furthermore, carrier proteins, such as URAT-1 or OAT-4 also have an influence on these processes. An imbalance of the physiological processes results in the solubility product being exceeded, which in consequence leads to crystallization of urate. This induces a cascade of massive inflammatory reactions at the molecular and cellular level with the activation of cytokines. The inflammatory process can be stopped by neutrophil extracellular traps (NETs) that modulate aggregation and degradation of chemokines and cytokines and partitioning of crystallized urate against immune cells. Calcium pyrophosphate dehydrate (CPP) crystals are formed in the cartilage and CPP deposition can be found in 30% of people aged over 80 years. Inorganic pyrophosphate (PPi) is synthesized in chondrocytes and plays an important part in the formation of calcium pyrophosphate crystals. The degradation is catalyzed by inorganic pyrophosphatases. If there is dysregulation of this homeostasis more PPi is produced, which ultimately contributes to the formation of the CPP crystals.

Crystal arthritides - gout and calcium pyrophosphate arthritis : Part 3: Treatment.

The treatment of gout is based on several principles. Symptom control and termination of the inflammatory process are important early goals, whereas the urate level should be lowered in the long term to prevent further gout attacks and complications. The non-pharmacological approach is based on individually informing the patient on dietary measures and changes of life style. Besides physical measures, such as cold applications on the affected joint, various medications are available for treatment of an acute gout attack. The choice of drug depends on the individual risk profile. If non-steroidal anti-inflammatory drugs (NSAID) and coxibs are chosen it should be taken into account that the use is restricted in patients with renal insufficiency. Moreover, these drugs may have gastrointestinal side effects and are associated with increased cardiovascular morbidity and mortality. Colchicine has gastrointestinal side effects at high dosages but can also be used for differential diagnostics if there is a quick response to treatment. Steroids are an effective alternative and can be given orally or parenterally in patients with dysphagia. Moreover, steroids can be used in cases of renal insufficiency. After symptoms of the acute attack have subsided, urate lowering therapy should be initiated to prevent further attacks. Low-dose urate lowering therapy can be started during an acute gout attack when acute therapy is initiated. Allopurinol is still the medication of choice but its use is restricted in patients with renal insufficiency. A rare but serious side effect is allopurinol hypersensitivity syndrome. Febuxostat can be an alternative in patients who do not tolerate allopurinol. In February 2016, lesinurad, an URAT-1 and OAT-4 inhibitor, was approved in combination with allopurinol or febuxostat. Data on the effectiveness and safety of synthetic uricases and biologicals are still sparse for elderly patients. These substances are reserved for severe cases of gout.

[Liquid Biopsy: Detection of Molecular Markers for Treatment Decisions in Lung Cancer]. / "Liquid biopsy": Analyse molekularer Marker aus Blutproben zur Therapiesteuerung beim Lungenkarzinom.

Personalized, individualized, targeted therapy has successfully found entrance in the palliative treatment of lung cancer as they enable a personalized and individualized strategy going ahead with biomarker testing. Due to the crescending amount of predictive molecular and immunhistochemical analyses at different time points during therapy the need for more and actual tumor tissue increases; however these samples cannot always be obtained without major discomfort for the patients. Therefore, analyses from blood, the so called "liquid biopsy", is an alternative or additional method. Activating mutations in the EGFR gene and the inhibitory mutation T790 M can already be detected from blood during clinical routine. This review presents the status of liquid biopsy for diagnosis, prognosis and as predictive parameter during the course of therapy in lung cancer and gives an outlook on future developments.

Olive oil attenuates the cholesterol-induced development of nonalcoholic steatohepatitis despite increased insulin resistance in a rodent model.

It is indefinite whether nonalcoholic steatohepatitis (NASH) results as by-product from general metabolic perturbations and adipokine dysregulations or whether defined dietary factors also play a pathogenetic role. Here, we examine the effects of a modification of dietary lipids in a NASH inducing diet on metabolic changes as well as hepatic steatosis, inflammation, and fibrosis in rats. Male Wistar rats were fed with variations of the atherogenic diet (AD), which induces pathophysiological changes resembling human NASH. Dietary variants (AD without cholesterol, cholate, or choline; change of neutral fat to olive oil or coconut oil) were fed for 8 weeks. Insulin resistance, adipokine profile, liver histology, and lipid content as well as expression of proinflammatory and profibrogenic genes were examined. AD led to clear signs of hepatic steatosis and inflammation together with an increase in TNF and collagen type 1 expression. AD without cholesterol showed markedly less liver damage without changes of insulin action and adipokine profile. AD with olive oil and AD without cholate clearly attenuated hepatic inflammation, whereas fat deposition and features of the metabolic syndrome were increased in these animals. Insulin resistance and hepatic fat deposition per se do not cause significant hepatic inflammation in this rodent model. However, dietary cholesterol is an important causal agent for the development of NASH. Olive oil plays a protective role in this respect, which might be due to the high content of monounsaturated fatty acids.

European proficiency study with control serum for the tumor marker CA 19-9 measured on different test systems.

BACKGROUND: Reliable and precise CA 19-9 testing is required for the long-term follow-up of patients with pancreatic carcinoma during therapy. The aim of this longitudinal proficiency study was to evaluate the comparability, linearity, and precision of CA 19-9 determinations performed in different laboratories using currently available test systems under routine conditions. METHODS: During the one year study period, 15 laboratories applied 7 different tests and included a liquid BIOREF control serum with pancreatic carcinoma derived CA 19-9 in their routine testing and quality control procedures. The results were collected centrally and evaluated statistically. RESULTS: The comparability of CA 19-9 results is limited especially when different tests are used, albeit, some tests show a good correlation: The CA 19-9 values obtained by different laboratories using different test systems vary up to a factor of 2. The precision of CA 19-9 determinations was acceptable in most laboratories with coefficients of variation ranging between very low 3.2% and high 17.8%. The imprecision was slightly increased when automatic dilution procedures of the analysers were used. CONCLUSIONS: The comparability of CA 19-9 test results must be improved. The precision is acceptable in most cases. In order to monitor key performance parameters, every laboratory should participate in external quality assessment schemes and should perform a routine internal quality control with a control serum independent from the test kit manufacturer.

[Reversal of aging and lifespan elongation. Current biomedical key publications and the implications for geriatrics]. / Alternsumkehr und Lebensspannenverlängerung : Aktuelle biomedizinische Schlüsselpublikationen und ihre Implikationen für die Geriatrie.

Biological aging means a time-dependent accumulation of changes to which a living organism is being exposed during its lifetime. Biological aging normally concurs with chronological aging the time frame of which is set by an upper limit, the lifespan (in humans approximately 120 years). New findings in experimental biogerontology are challenging both the dogma of irreversibility of biological aging and the preset species-specific limitations of life. The present overview first explains the general principle of rejuvenation and reversal of biological aging with paradigms from stem cell research. Secondly, recent key publications on artificial telomerase elongation and (alleged) lifespan enhancement by sirtuins and resveratrol will be discussed with an emphasis on the implications for (future) geriatric medicine.

[Translational research in geriatrics? A plea based on current biomedical key publications]. / Translationale Forschung in der Geriatrie? : Ein Plädoyer anhand aktueller biomedizinischer Schlüsselpublikationen.

Contemporary geriatric research focuses mainly on observational clinical studies and epidemiological surveys and the translation of basic scientific results from biogerontology into a clinical context is often neglected. Following a definition of translational research the article gives an overview of recent key publications in experimental biogerontology with a special emphasis on their relevance for clinical geriatrics. The topics dealt with include age-induced loss of skeletal muscle (sarcopenia), the aging immune system (immunosenescence) and neurodegenerative disorders (Alzheimer's and Parkinson's disease).

Vitamin D status and physical function in nursing home residents: a 1-year observational study.

OBJECTIVE: Low vitamin D blood levels are highly prevalent in elderly people, particularly in nursing home residents (NHR). A relation between vitamin D levels and physical function (PF) is described in several studies in older adults; however, data on NHR are scarce and there is presently no information on the time course of vitamin D levels and PF in this population. The aim of the present study was to describe the 25-hydroxyvitamin D [25(OH)D] status of NHR at baseline (t1) and after 1 year (t2) to examine whether 25(OH)D blood levels are related to PF at t1 and at t2, and whether changes in 25(OH)D levels over 1 year are related to changes in PF. METHODS: All NHR (≥ 65 years) without tube-feeding and severe acute or end-stage disease were asked to participate. At t1 and t2 fasting blood samples were taken for the analysis of 25(OH)D serum levels and PF was estimated by activities of daily living (Barthel ADL) and measured by handgrip strength (HGS) and timed 'up and go' test (TUG). RESULTS: In total, 115 residents, aged 87 (82-93) years (all data in median and 1st-3rd quartile), showed the following values for PF: ADL 50 (20-65) points, HGS 40 (30-50) kPa and TUG 26 (18-31) s. Vitamin D deficiency (< 50 nmol/l) was present in 93.9 % (70.4 % < 25 nmol/l) at t1 and in 71.2 % (57.3 % < 25 nmol/l) at t2. At t1 and at t2 a weak correlation between vitamin D level and PF (Spearman's correlation coefficient t1: ADL r = 0.367, HGS r = 0.313; t2: ADL: r = 0.247; all p < 0.01) was observed. There was no correlation between changes in vitamin D levels over 1 year and changes in PF. CONCLUSIONS: Almost all NHR included in the study showed vitamin D deficiency. 25(OH)D levels were weakly correlated to PF at baseline and at follow-up, and an increase in vitamin D levels was not associated with positive effects on PF in this study.

Polypharmacy in the elderly from the clinical toxicologist perspective.

INTRODUCTION: Polypharmacy is closely associated with multimorbidity in the elderly and can lead to problems and drug interactions. AIM: This study assessed polypharmacy in the elderly, tracking inquiries to the Poison Information Centre Nuremberg (PICN) and patients needing toxicological intensive care therapy. METHODS: From 2006-2009, all PICN inquiries involving individuals > 70 years were tracked, as were cases at the Toxicological Intensive Care Unit (T-ICU) regarding adverse drug reactions (ADRs) and drug poisoning. RESULTS: Of 11,683 PICN calls about pharmaceuticals, 175 (1.5%) were from people > 70 years; 156 (4.8%) of 3,272 T-ICU patients were > 70 years. Calls about psychopharmaceuticals (46.9%) and analgesics (25.7%) were most frequent. Among the T-ICU patients, psychopharmaceuticals like sedatives and hypnotics were frequently involved (20.5%), as were tricyclic antidepressants (17.9%) and analgesics (29.5%). Ethanol was co-ingested by 18.3%. CONCLUSION: Population-specific poison prevention strategies are needed to reduce toxic exposures. Such strategies could include pharmacist intervention, improved prescriber communication and education regarding the geriatric population, and computerized drug databases.

The plant sterol brassicasterol as additional CSF biomarker in Alzheimer's disease.

OBJECTIVE: Plant sterols (sitosterol, campesterol, stigmasterol and brassicasterol) are solely dietary-derivable sterols that are structurally very similar to cholesterol. In contrast to peripheral cholesterol, plant sterols can cross the blood-brain barrier and accumulate within mammalian brain. As an impaired function of the cerebrospinal fluid (CSF)-blood barrier is linked to neurodegenerative disorders, i.e. Alzheimer's disease (AD), we investigated whether this results in altered plant sterol concentrations in CSF. METHOD: Applying gas chromatography/mass spectrometry analysis, plant sterol concentrations were measured in plasma and CSF of patients with AD (n = 67) and controls (n = 29). Age, gender, plasma-to-CSF albumin ratio, CSF Aß(42) , CSF pTau, APOE4 genotype, and serum creatinine were applied as covariates in the statistical analysis for individual plant sterols in order to compare plasma and CSF plant sterol concentrations between patients with AD and controls. RESULTS: Albumin quotient was a consistent predictor in CSF for cholesterol and methyl plant sterols campesterol and brassicasterol. Comparison of lipid parameters per diagnosis based on relevant predictors revealed significantly lower concentrations of brassicasterol (P < 0.001) in CSF of patients with AD. Binary logistic regression analysis revealed that brassicasterol improved the predictive value when added to pTau and Aß42 in a biomarker model. CONCLUSION: Brassicasterol might be a relevant additional biomarker in AD.

Alpha-1-Fetoprotein (AFP): international proficiency study with different test systems.

BACKGROUND: The present proficiency study aimed to elucidate the comparability and reliability of test systems for the determination of AFP concentrations. METHODS: 25 laboratories using 8 different commercial test systems used liquid BIOREF-AFP control serum in their routine internal quality control over a period of one year. For statistical analysis the results were collected centrally. RESULTS: The statistical analysis of the test results revealed considerable variation for the different laboratories. The deviations of the mean values of different laboratories from the overall mean value varied between 0.1 and 26.1%, and for most of the laboratories the deviation was round about 10%. The precision of measured values in the individual laboratories was in most cases acceptable: Nevertheless, the coefficients of variation of the individual laboratories ranged from 13 to 16.1%. CONCLUSIONS: In conclusion, this study indicates that AFP results vary between different laboratories albeit an international standard for AFP is available. Therefore, every laboratory should participate in external ring studies and should use a quality control serum independent of the test kit manufacturer for the internal quality control.

[Diagnostics of acute myocardial infarction in elderly patients]. / Diagnostik des akuten Myokardinfarkts bei älteren Patienten.

The early diagnosis of an acute myocardial infarction (MI) is improved by the introduction of novel high-sensitivity troponin assays. These assays can measure low level myocardial injury not detectable by standard troponin assays. Especially in older patients who appear to have a higher basal troponin level, the results must always be judged in the context of the medical history, physical examination, electrocardiogram (ECG) and any further findings. Even small increases in high-sensitivity troponin indicate increased risk for death or MI during follow-up. In the case of MI an invasive strategy results in better survival rates compared with conservative therapy but at the expense of an increased risk of bleeding in elderly patients. This article provides an overview on the diagnosis of MI in elderly patients.

Procalcitonin: inflammatory biomarker for assessing the severity of community-acquired pneumonia--a clinical observation in geriatric patients.

Community-acquired pneumonia is a common disease of the elderly and involves a high mortality risk. Demographic developments are creating new challenges for acute medical treatment strategies in geriatric patients with their underlying multimorbidity. In addition to the diagnostic parameters recorded on hospital admission, such as white cell count and C-reactive protein, procalcitonin, more than the risk scores CRB- and CURB-65 evaluated to date, appears to be a promising parameter for assessing the severity of pneumonia in elderly patients to allow early detection of severe courses and initiation of suitable treatment. The decisive factor is the dynamic course of the procalcitonin values over 3 consecutive days, as demonstrated in this case series.

Precision and long-term stability of different estradiol immunoassays assessed in a multi-center quality control study.

BACKGROUND: Because of the vast range of physiological relevant estradiol concentrations the requirements to be met by an estradiol assay are high. In the present study the performance of various commercially available estradiol assays was evaluated with regard to imprecision and long-term stability. METHODS: Precision and long-term stability of 7 commercially available estradiol immunoassays were assessed in a multi-centre quality control study based on the repeated measurement of liquid BIOREF estradiol control sera by 18 laboratories during a 14-month study period. RESULTS: The mean estradiol concentrations determined in 594 runs performed for each control level were 71 pg/ml, 349 pg/ml and 676 pg/ml. A high variation was found for the method specific mean values calculated from all results measured with the same method, which ranged between 32 - 90 pg/ml, 187 - 392 pg/ml and 373 - 790 pg/ml, resulting in a similar high inter-laboratory variation with coefficients of variation (CVs) of 25.0%, 16.7% and 17.5%. In contrast, the intra-laboratory variation of estradiol values as well as the variation of values measured with the same method were found to be considerably lower with coefficients of variation < 10% for most laboratories and methods; only the low control level was measured with CV values > 10% by the majority of laboratories and methods. For none of the laboratories a tendency was observed in the results from beginning to end of the 14 month study period indicating a high uniformity in assay production and a good long-term stability of the control material used. CONCLUSIONS: The present data demonstrate that also with the currently available estradiol immunoassays the comparability of results measured with different methods is limited. With most assays very low estradiol concentrations, as observed in postmenopausal women, can be determined only with a precision which is not adequate for clinical assessment.

Cellular determination in the Xenopus retina is independent of lineage and birth date.

Xenopus embryos injected with tritiated thymidine throughout the stages of embryonic retinal neurogenesis showed that more than 95% of the embryonic retinal cells are born within a 25 hr period. While there are shallow central to peripheral, dorsal to ventral, and interlaminar gradients of neurogenesis in these eyes, throughout most of this 25 hr period, postmitotic cells are being added to all sectors and layers. Small clones of differentiated retinal neurons and glia derived from single neuroepithelial cells injected with HRP. These clones were elongated radially. They were also composed of many different combinations of cell types, suggesting a mechanism whereby determination is arbitrarily and independently assigned to postmitotic cells. Such a model, when tested statistically, fits our data very well. We present a scheme for cellular determination in the Xenopus retina in which a coherent group of clonally related cells stretch out radially as lamination begins. This brings different cells into different microenvironments. Local interactions in these microenvironments then lead the cells toward specific fates.

Percutaneous Closure of Left Atrial Appendage significantly affects Lipidome Metabolism.

Patients with non-valvular atrial fibrillation (AF) and a high risk for oral anticoagulation can be treated by percutaneous implantation of left atrial appendage occlusion devices (LAAC) to reduce the risk of cardio-embolic stroke. This study evaluates whether LAAC may influence lipid metabolism, which has never been investigated before. Patients with successful LAAC were included consecutively. Venous peripheral blood samples of patients were collected immediately before (T0, baseline) and 6 months after (T1, mid-term) LAAC. A targeted metabolomics approach based on electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and MS/MS measurements was performed. A total of 34 lipids revealed a significant change from baseline to mid-term follow-up after successful LAAC. Subgroup analysis revealed confounding influence by gender, age, diabetes mellitus type II, body mass index, left ventricular ejection fraction, creatinine and NT-proBNP. After multivariable adjustment within logistic regression models, these 34 lipids were still significantly altered after LAAC. Successful percutaneous LAAC may affect lipid metabolism and thereby may potentially affect pro-atherogenic and cardio-toxic effects.

Nutritional and Functional Status in Geriatric Day Hospital Patients - MNA Short Form Versus Full MNA.

OBJECTIVES: The aims of this study were to determine the prevalence of malnutrition in patients of a geriatric day hospital using the Mini Nutritional Assessment short form (MNA-SF) and the full MNA, to compare both tools, and to examine the relationship between nutritional and functional status. DESIGN: Cross-sectional study. SETTING: Geriatric day hospital. PARTICIPANTS: 190 patients (72.1% female, median 80 years) aged 65 years or older. MEASUREMENTS: In consecutively admitted geriatric day hospital patients nutritional status was assessed by MNA-SF and full MNA, and agreement between both tools calculated by Cohen´s kappa. Basic activities of daily living (ADL), instrumental activities of daily living (IADL) and short physical performance battery (SPPB) were determined and related to MNA categories (Chi2-test, Mann-Whitney-U-test). RESULTS: 36.3 % and 44.7% of the patients were at risk of malnutrition, 8.9 % and 5.8 % were malnourished according to MNA-SF and full MNA, respectively. Agreement between both MNA forms was moderate (κ=0.531). No significant associations between MNA-SF and ADL, IADL and SPPB, and between full MNA and SPPB were observed. According to full MNA, the proportion of patients with limitations in ADL and IADL significantly increased with declining nutritional status (ADL: 2.1 vs. 8.2 vs. 18.2 %, p=0.044; IADL: 25.5 vs. 47.1 vs. 54.5 %, p=0.005) with a simultaneous decrease of the proportion of patients without limitations. Well-nourished patients reached significantly higher ADL scores than patients at risk of malnutrition (95 (90-100) vs. 95 (85-100), p=0.005) and significantly higher IADL scores than patients at risk or malnourished (8 (6-8) vs. 7 (5-8) vs. 6 (4-8), p=0.004). CONCLUSION: The high prevalence of risk of malnutrition and the observed association between functional status and nutritional status according to full MNA call for routine nutritional screening using this tool in geriatric day hospital patients.

[Cardiogenic shock after drug therapy for atrial fibrillation with tachycardia : Case report of an 89-year-old woman]. / Kardiogener Schock nach bradykardisierender Therapie bei tachykardem Vorhofflimmern : Fallvorstellung einer 89-jährigen Patientin.

ß-Blockers and calcium channel blockers are commonly used drugs in the treatment of atrial fibrillation with tachycardia. However, in patients with high myocardial susceptibility and vulnerability, combination therapy with ß-blockers and non-dihydropyridine calcium channel blockers (verapamil or diltiazem) but also individual administration can cause drug-induced cardiogenic shock. Thus, the simultaneous administration of ß-blockers and non-dihydropyridine calcium channel blockers is absolutely contraindicated. In case of acute heart failure, isolated application is also contraindicated. In the treatment of a cardiogenic shock induced by ß-blockers and/or non-dihydropyridine calcium channel blockers, administration of intravenous calcium, glucagon or high-dose insulin is recommended.