Cisplatin-Based Chemotherapy for Pulmonary Metastasized Germ Cell Tumors of the Testis - Be Aware of Acute Respiratory Distress Syndrome

Background: Cisplatin-based combination chemotherapy is regarded as standard of care for patients with advanced germ cell tumors. In patients with lung metastases and a high tumor load, an association between induction chemotherapy and the development of a `tumor-associated' acute respiratory distress syndrome (ARDS) has been hypothesized. Case Report: We report the clinical course of a 19-year-old patient who rapidly developed fatal ARDS during the first cycle of chemotherapy using the PEI regimen (cisplatin, etoposide and ifosfamide) for a metastasized (lung, liver, lymph nodes) germ cell tumor of the testis. Conclusion: Further clinical research in order to better define risk factors for developing ARDS in this patient population as well as novel strategies for the prevention and treatment of ARDS in those patients are necessary

Haben die Konzentrationen von Interleukin 6, Procalcitonin und CRP bei Intensivpatienten während des ersten Fieberanstieges eine prognostische Bedeutung?

Serum levels of interleukin 6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) were measured in 38 critically ill patients immediately after an increase in body temperature above 38.3 degrees C. Ten healthy controls were also included for comparison. The onset of fever was accompanied by elevated circulating levels of all the 3 markers in comparison to healthy control subjects. However, only IL-6 levels were significantly higher (p<0.05) in nonsurvivors compared with survivors. Sensitivity, specificity, positive, and negative predictive values for survival were higher for IL-6 in comparison to levels of PCT and CRP. Areas under receiver characteristic operating curves revealed the highest area under the curve for IL-6 compared to PCT and CRP. These data suggest that IL-6 rather than PCT or CRP may be an early predictor of prognosis and mortality in patients with the onset of fever

Review of extended-release niacin/laropiprant fixed combination in the treatment of mixed dyslipidemia and primary hypercholesterolemia

Although statins reduce cardiovascular morbidity and mortality further risk reduction is needed. In this respect low HDL-cholesterol concentrations and/or elevated triglyceride concentrations may be potential treatment targets. Niacin (nicotinic acid) is an effective drug which increases the plasma concentration of high-density lipoprotein (HDL)-cholesterol and decreases the concentration of low-density lipoprotein (LDL)-cholesterol, triglycerides and lipoprotein(a). Clinical studies indicate that niacin can significantly reduce the risk for cardiovascular events. However, niacin is not very commonly used because of significant side effects (especially flushing). Laropiprant is a potent selective antagonist of PGD2-receptor subtype-1 and can thus reduce niacin-induced flushing. Although the addition of laropiprant will reduce the frequency of flushing, it will not completely eliminate this side effect. Laropiprant does not change the effect of niacin on lipids or other side effects of niacin (ie, gastro-intestinal problems, glucose elevation). The combination of niacin with laropiprant may therefore enable use of niacin at higher doses and therefore exploit the full potential of the drug. Endpoint studies that will be published over the next few years will show whether this treatment modality also translates into clinical effect in patients treated with statins. Until publication of these studies niacin/laropiprant should be used only in high-risk patients not achieving lipid goals on statins

Oral Lipid-Lowering Treatments Beyond Statins: Too Old and Outdated or Still Useful?

PURPOSE OF REVIEW For many years, the lipid-lowering armamentarium consisted of statins and/or ezetimibe and/or bile acid sequestrants and/or fibrates. Now, with the availability of new drugs mostly injectables, the field has changed and the role of oral non-statin drugs (including bempedoic acid) must be reevaluated. RECENT FINDINGS Ezetimibe remains a very important combination partner for statins with continuously increasing treatment numbers. Bempedoic acid is another interesting combination partner for statin/ezetimibe or ezetimibe alone but lacks in contrast to ezetimibe evidence from outcome trials. The role of fibrates is less clear as they have shown disappointing results in outcome trials but may still be used in selected, high-risk patients with combined dyslipidemia. Bile acid sequestrants are now rarely used as there are stronger, better tolerable ways to lower LDL-cholesterol. With the introduction of new injectable lipid-lowering drugs, some oral drugs such as ezetimibe and bempedoic acid still have an important spot in our treatment algorithm others such as fibrates have a less clear role while again others are now rarely used

Mipomersen: evidence-based review of its potential in the treatment of homozygous and severe heterozygous familial hypercholesterolemia

Familial hypercholesterolemia (FH) is an autosomal-dominant inherited disease with a prevalence of one in 500 (heterozygous) to one in 1,000,000 (homozygous). Mutations of the low-density lipoprotein (LDL) receptor gene, the apolipoprotein B100 gene, or the PCSK9 gene may be responsible for the disease. The resulting LDL hypercholesterolemia results in premature atherosclerosis as early as childhood (homozygous FH) or in adulthood (heterozygous FH). Current treatment modalities include lifestyle modification, combination drug therapy (statin-based), and apheresis. Mipomersen is an antisense oligonucleotide which inhibits apolipoprotein B production independent of LDL receptor function and thus works in homozygous FH, heterozygous FH, and other forms of hypercholesterolemia. Mipomersen is given 200 mg/week subcutaneously. Phase III studies indicate that the LDL cholesterol concentration can be reduced by 25%–47%, lipoprotein(a) levels by 20%–40%, and triglyceride concentrations by approximately 10%. In general, mipomersen has no effect on high-density lipoprotein cholesterol concentrations. Although there is considerable interindividual variability, the observed lipid effects are largely independent of age, gender, concomitant statin therapy, and underlying dyslipoproteinemia. The most common side effects are injection site reactions (70%–100%), flu-like symptoms (29%–46%), and elevated transaminases associated with an increased liver fat content (6%–15%). Mipomersen may be an interesting addon drug in patients with heterozygous or homozygous FH not reaching treatment goals, either because baseline values are very high or because high-dose statins are not tolerated

Effect of the angiotensin receptor blocker irbesartan on metabolic parameters in clinical practice: the DO-IT prospective observational study

Aims: A number of intervention studies have shown that therapy with angiotensin receptor blockers, such as irbesartan, can improve metabolic parameters and reduce the incidence of diabetes mellitus. It is unknown whether this observation also holds true in routine clinical settings. Methods: We evaluated the effect of irbesartan (150 mg or 300 mg/d) together with or without hydrochlorothiazide (12.5 mg/d) in 3259 German patients. A total of 750 primary care physicians evaluated up to 5 subsequent patients with metabolic syndrome (58.9% diabetic), in whom irbesartan therapy was newly initiated (87%) or continued (13%). Results: Six months of irbesartan therapy decreased systolic blood pressure by 14% (157.4 +/- 14.7 vs. 135.0 +/- 10.7 mmHg) and diastolic blood pressure by 13% (92.9 +/- 9.2 vs. 80.8 +/- 6.8 mmHg). This was associated with a decrease in body weight (-2.3%), fasting glucose (-9.5%), HbA1c (-4.6%), LDL-cholesterol (-11%), triglycerides (-16%) and gamma-GT (-12%) and an increase in HDL-cholesterol (+5%). These changes were somewhat more pronounced in male than in female patients and in obese than in lean patients. Changes in glucose concentration and HbA1c were much more prominent in diabetic patients. Conclusion: Irbesartan therapy improves metabolic parameters in routine clinical settings. Thus, our study confirms previously published results from large intervention trials and extends the findings to routine clinical practice

Prevalence of Cardiovascular Disease Risk Factors in Migrants Participating in the PEP Family Heart Study, Nuremberg

Objectives: The aim of this study was to assess the prevalence of cardiovascularrisk factors in adults and their children from the 3 majorgroups of migrants participating in the PEP Family Heart Study 11 andto compare the cardio-metabolic risk profiles between migrants andGerman participants.Methods: In this community-based cross-sectional study, anthropometricdata, blood pressure and lipid profiles of migrants (480 children,363 adults) from Turkey (TUR), Eastern Europe (EEU) and Germanimmigrants from the former Soviet Union (GFSU) were comparedwith age- and gender adjusted German (GER) residents (3253 children,2491 adults).Results: The profile of risk factors differed considerably regardingspecificity and frequency. The prevalence of ≥3 risk factors was asfollows: in GFSU men 62%, women 36%, boys 19% and girls 17%; inTUR men 57%, women 30%, 15% boys and 6% girls; in GER men48%, women 19%, boys 4% and girls 6%; for EEU men 38%, women25% and 0% in children. No risk factor was present in GFSU men13%, women 25%, boys 38% and girls 42%; TUR men 13%, women28%, boys 27% and girls 22 %; GER men16%, women 45%, boys 46%and girls 41%; EEU men 17%, women 42 %, boys 29% and girls 27%.About 50% of the adults from Turkey and Eastern Europe were currentsmokers and one third of women and half of men from these twocountries were overweight.Conclusions: The implementation of primary care measures for theprevention of cardiovascular disease in migrants is necessary, and itshould consider the ethnic differences and the heterogeneous risk profile

Mortality of Patients with Hematological Malignancy after Admission to the Intensive Care Unit

Background: The admission of patients with malignancies to an intensive care unit (ICU) still remains a matter of substantial controversy. The identification of factors that potentially influence the patient outcome can help ICU professionals make appropriate decisions. Patients and Methods: 90 adult patients with hematological malignancy (leukemia 47.8%, high-grade lymphoma 50%) admitted to the ICU were analyzed retrospectively in this single-center study considering numerous variables with regard to their influence on ICU and day-100 mortality. Results: The median simplified acute physiology score (SAPS) II at ICU admission was 55 (ICU survivors 47 vs. 60.5 for non-survivors). The overall ICU mortality rate was 45.6%. With multivariate regression analysis, patients admitted with sepsis and acute respiratory failure had a significantly increased ICU mortality (sepsis odds ratio (OR) 9.12, 95% confidence interval (CI) 1.1-99.7, p = 0.04; respiratory failure OR 13.72, 95% CI 1.39-136.15, p = 0.025). Additional factors associated with an increased mortality were: high doses of catecholamines (ICU: OR 7.37, p = 0.005; day 100: hazard ratio (HR) 2.96, p < 0.0001), renal replacement therapy (day 100: HR 1.93, p = 0.026), and high SAPS II (ICU: HR 1.05, p = 0.038; day 100: HR 1.2, p = 0.027). Conclusion: The decision for or against ICU admission of patients with hematological diseases should become increasingly independent of the underlying malignant disease

Differential effects of fenofibrate versus atorvastatin on the concentrations of E-selectin and vascular cellular adhesion molecule-1 in patients with type 2 diabetes mellitus and mixed hyperlipoproteinemia: a randomized cross-over trial

BACKGROUND: Diabetic dyslipoproteinemia is characterized by hypertriglyceridemia, low HDL-cholesterol and often elevated LDL-cholesterol and is a strong risk factor for atherosclerosis. Adhesion molecule levels are elevated both in hyperlipoproteinemia and diabetes mellitus. It is unclear whether fibrate or statin therapy has more beneficial effects on adhesion molecule concentrations. METHODS: Atorvastatin (10 mg/d) was compared to fenofibrate (200 mg/d) each for 6 weeks separated by a 6 week washout period in 11 patients (6 male, 5 female; 61.8 ± 8.2 years; body mass index 29.8 ± 3.1 kg/m(2)) with type 2 diabetes mellitus (HbA(1c )7.3 ± 1.1 %) and mixed hyperlipoproteinemia using a randomized, cross-over design. Fasting blood glucose, HbA(1)c, lipid parameters, E-selectin, ICAM-1, VCAM-1, and fibrinogen concentrations were determined before and after each drug. RESULTS: Glucose and HbA(1)c concentrations remained unchanged during the whole study period. LDL cholesterol was reduced during atorvastatin therapy, triglycerides were lowered more effectively with fenofibrate. Comparison of pre- and postreatment concentrations of E-selectin showed a reduction during atorvastatin (-7 %, p = 0.11) and fenofibrate (-10 %, p < 0.05) therapy. Atorvastatin treatment reduced VCAM-1 levels by 4% (p < 0.05), while VCAM-1 concentrations remained unchanged (+1%, ns) during fenofibate therapy. However, direct comparisons of post-treatment levels during both forms of therapy were not of statistical significance. ICAM-1 levels were not influenced by either form of therapy. CONCLUSIONS: In addition to the different beneficial effects on lipid metabolism, both drugs appear to lower adhesion molecule plasma concentrations in a different manner in patients with type 2 diabetes and mixed hyperlipoproteinemia. Our observations should be confirmed in a larger cohort of such patients