[Hyperglycemia in critically ill]. / Therapie der Hyperglykämie bei erwachsenen, kritisch kranken PatientInnen (Update 2023).

In critical illness hyperglycemia is associated with increased mortality. Based on the currently available evidence, an intravenous insulin therapy should be initiated when blood glucose is above 180 mg/dl. After initiation of insulin therapy blood glucose should be maintained between 140 and 180 mg/dl.

Changes in the prognostic values of modern cardiovascular biomarkers in relation to duration of diabetes mellitus.

BACKGROUND: Based on the complex pathophysiology of type 2 diabetes and atherosclerosis we hypothesized a dynamic change in prognostic value of cardiovascular biomarkers over time. METHODS: In this prospective study 746 patients with type 2 diabetes mellitus, being followed up for 60 months were analysed. The primary endpoint was defined as unplanned hospitalization for cardiovascular disease or death. Beside others, especially the prognostic performance of the biomarkers of interest (GDF-15, NT-proBNP, hs-TnT) was evaluated in relation to quartiles of diabetes duration. RESULTS: In patients having a diabetes duration below 7 years lnGDF-15 (HR 2.84; p < 0.01) and lnhs-TnT (HR 2.96; p < 0.01) were significant predictors of the primary endpoint. LnAge (HR 40.01; p < 0.01) and lnNT-proBNP (HR 1.56; p = 0.03) were significant predictors in patients with a diabetes duration between 7 and 12 years. In the third quartile (diabetes duration 12-22 years) lnurinary albumin to creatinine ratio (HR 1.25; p = 0.005) and lnNT-proBNP (HR 2.13, p < 0.001) predicted the endpoint. In patients with a diabetes duration above 22 years, lnAge (HR 75.35; p = 0.001) and lnNT-proBNP (HR 2.0; p < 0.01) were the only significant predictors of the endpoint. CONCLUSION: Prognostic power of cardiovascular biomarkers changes dynamically in relation to duration of type 2 diabetes mellitus. In patients with shorter duration of the disease markers of subclinical cardiovascular dysfunction and inflammation perform better than markers of systemic advanced organ dysfunction and cardiovascular disease.

Targeted multiple biomarker approach in predicting cardiovascular events in patients with diabetes.

OBJECTIVE: We hypothesised that biomarkers representing different pathophysiological pathways of atherosclerosis namely growth differentiation factor 15 (GDF-15), N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitive troponin T (hs-TnT) could enhance cardiovascular risk prediction in patients with type 2 diabetes mellitus. METHODS: This is a prospective study in 746 patients with type 2 diabetes mellitus, who were followed up for 60 months. The primary endpoint was defined as unplanned hospitalisation for cardiovascular disease or death. The prognostic performance of the biomarkers of interest (GDF-15 in comparison with NT-proBNP and hs-TnT) was evaluated in univariate as well as in stepwise Cox regression models. HRs are presented per standard unit increase. RESULTS: The primary endpoint was registered in 171 patients (22.9%). In univariate Cox regression models, GDF-15 as well as hs-TnT provided significant prognostic information. Even after adjusting for established cardiovascular risk factors, GDF-15, hs-TnT and NT-proBNP remained strong independent predictors of the endpoint (logGDF-15: HR 1.37, p<0.01, CI 1.12 to 1.68; loghs-TnT: HR 1.43, p<0.01, CI 1.13 to 1.1.82; logNT-proBNP: HR 1.45, p<0.01, CI 1.26 to 1.66). The number of elevated markers showed a strong complementarity to predict future long-term risk. Adding hs-TnT and GDF-15 to a zero model already including NT-proBNP led to a net reclassification improvement (NRI) of 33.6% (CI 16.0% to 50.8%, NRI for patients with event: 11.1% CI -4.7% to 26.6%, for patients without event: 22.5% CI 13.6% to 30.5%). CONCLUSIONS: GDF-15 and hs-TnT are strong independent cardiovascular biomarkers augmenting the predictive value of NT-proBNP in patients with diabetes.

Effects of B-type natriuretic peptide on cardiovascular biomarkers in healthy volunteers.

Cardiovascular biomarkers provide independent prognostic information in the assessment of mortality and cardiovascular complications. However, little is known about possible interactions between these biomarkers. In the present study, we evaluated the influence of B-type natriuretic peptide (BNP) on midregional-proadrenomedullin (MR-proADM), C-terminal-proendothelin-1 (CT-proET-1), growth differentiation factor-15 (GDF-15), midregional-proatrial natriuretic peptide (MR-proANP), copeptin, and procalcitonin in healthy volunteers. Ten healthy male subjects (mean age 24 yr) participating in a randomized, placebo-controlled, single-blinded crossover study received placebo or 3.0 pmol·kg(-1)·min(-1) human BNP 32 during a continuous infusion lasting for 4 h. Effects of BNP on other cardiovascular biomarkers were assessed. BNP did not change concentrations of MR-proADM, copeptin, CT-proET1, GDF-15, or procalcitonin. In contrast, MR-proANP was significantly decreased during BNP infusion. BNP as an established cardiovascular biomarker did not affect plasma concentrations of other cardiovascular biomarkers in a model of healthy volunteers.

B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men.

AIMS/HYPOTHESIS: B-type natriuretic peptide (BNP) is a hormone released from cardiomyocytes in response to cell stretching and elevated in heart failure. Recent observations indicate a distinct connection between chronic heart failure and diabetes mellitus. This study investigated the role of BNP on glucose metabolism. METHODS: Ten healthy volunteers (25 ± 1 years; BMI 23 ± 1 kg/m(2); fasting glucose 4.6 ± 0.1 mmol/l) were recruited to a participant-blinded investigator-open placebo-controlled cross-over study, performed at a university medical centre. They were randomly assigned (sequentially numbered opaque sealed envelopes) to receive either placebo or 3 pmol kg(-1) min(-1) BNP-32 intravenously during 4 h on study day 1 or 2. One hour after beginning the BNP/placebo infusion, a 3 h intravenous glucose tolerance test (0.33 g/kg glucose + 0.03 U/kg insulin at 20 min) was performed. Plasma glucose, insulin and C-peptide were frequently measured. RESULTS: Ten volunteers per group were analysed. BNP increased the initial glucose distribution volume (13 ± 1% body weight vs 11 ± 1%, p < 0.002), leading to an overall reduction in glucose concentration (p < 0.001), particularly during the initial 20 min of the test (p = 0.001), accompanied by a reduction in the initial C-peptide levels (1.42 ± 0.13 vs 1.62 ± 0.10 nmol/l, p = 0.015). BNP had no impact on beta cell function, insulin clearance or insulin sensitivity and induced no adverse effects. CONCLUSIONS/INTERPRETATION: Intravenous administration of BNP increases glucose initial distribution volume and lowers plasma glucose concentrations following a glucose load, without affecting beta cell function or insulin sensitivity. These data support the theory that BNP has no diabetogenic properties, but improves metabolic status in men, and suggest new questions regarding BNP-induced differences in glucose availability and signalling in various organs/tissues. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01324739 FUNDING: The study was funded by Jubilée Fonds of the Austrian National Bank (OeNB-Fonds).

Serum uric acid is related to cardiovascular events and correlates with N-terminal pro-B-type natriuretic peptide and albuminuria in patients with diabetes mellitus.

BACKGROUND: Hyperuricemia is a risk factor for cardiovascular events and renal insufficiency. It correlates to intima-media thickness and microalbuminuria. In this study we evaluated uric acid as an independent marker for cardiac events in patients with diabetes. METHODS: In a prospective observational study we recruited 494 patients with diabetes. Patients were then followed for 12.8 months (mean follow-up) and hospitalizations as a result of cardiac events (ischaemic heart disease, arrhythmias, heart failure) were recorded. RESULTS: The median duration of diabetes was 11 ± 10.35 years. Patients were in the mean 60 ± 13 years old and mean HbA(1c) was 62 ± 13 mmol/mol (7.8 ± 3.3%). At baseline, mean uric acid was 321.2 ± 101.1 µmol/l (range 101.1-743.5 µmol/l), median N-terminal pro-B-type natriuretic peptide was 92 ± 412 pg/ml and median urinary albumin to creatinine ratio was 8 ± 361 mg/g; Uric acid significantly correlated to N-terminal pro-B-type natriuretic peptide (r = 0.237, P < 0.001) and urinary albumin:creatinine ratio (r = 0.198, P < 0.001). In a Cox regression model, including age, estimated glomerular filtration rate, gender, systolic blood pressure, smoking and alcohol consumption, uric acid was the best predictor of cardiac events (hazard ratio 1.331, confidence interval 1.095-1.616, P = 0.04). However, uric acid lost its prognostic value when the natural logarithm of N-terminal pro-B-type natriuretic peptide was added to the model. CONCLUSION: Serum uric acid is a predictor of cardiac events and correlates to N-terminal pro-B-type natriuretic peptide and albuminuria, underscoring the importance of uric acid as a cardiovascular risk marker in patients with diabetes.

Interactions of glucose metabolism and chronic heart failure.

BACKGROUND: We evaluated insulin sensitivity and beta cell function in patients with chronic heart failure (CHF), and investigated a possible correlation of these metabolic parameters with specific biomarkers of heart failure. Additionally, we investigated the effects of two angiotensin receptor blockers (ARBs), namely telmisartan and candesartan, that were administered over a 5 month treatment period, as additional therapy to standard care. METHODS AND RESULTS: The study group consisted of 94 CHF patients. Insulin sensitivity (OGIS index) and insulin secretion parameters were investigated by frequently sampled oral glucose tolerance tests and consecutive mathematical modelling. In total, 94.6 % of patients had clinically overt diabetes, impaired glucose tolerance or insulin resistance at the time of enrolment HbA1c was found to correlate to NT-proBNP, MR-proADM, CT-proET-1, and MR-proANP, but not to Copeptin. NT-proBNP correlated inversely to OGIS. None of the metabolic parameters were altered significantly after candesartan or telmisartan treatment in either the patient or standard care group. CONCLUSION: Insulin sensitivity and insulin secretion are impaired in CHF and biomarkers of heart failure and atherosclerotic disease correlate to glucose metabolism.

[Long-term results of surgical treatment in lung cancer]. / Dlouhodobé výsledky chirurgické lécby plicní rakoviny.

The surgical treatment of lung cancer has got a long tradition at our department. The aim of this work is to evaluate the group of 3,857 patients from the years 1948-1997. The special analysis has been performed of the group of 1572 patients from the years 1974-1997 undergoing lung resection. Evaluating our operation policy a strong trend from pneumonectomy to less extensive operations can be found. The introduction of bronchoplastic operations and modern diagnostic methods has substantially improved the possibility of surgical treatment. The utilization of TNM system enabled to compare the different groups of patients according to the unified classification. The long term survival was directly related to the stage and histological type of disease. The five years period survived 33% of patients in whom the lung resection was performed during the period 1974-1997. The operative hospital mortality has been substantially reduced to 1.7%. Even though it is our duty to provided the surgical treatment to all the patients if the resection is still possible the best results are to be expected in patients in the first stage of disease. Therefore the early diagnosis followed by adequately sized resection without delay offers the best chance for the patients long term survival.

Proliferative activity in primary ovarian carcinoid tumors.

The proliferative potential of six primary ovarian carcinoids with different clinical outcome and histogenetic origin was examined immunohistochemically. The results showed that two cases with extremely high level of proliferative activity were associated with metastatic spread. In the remaining tumors, the examined factor was found to be at low level comparable with excellent prognosis of typical carcinoids in other locations. The preliminary results showed a possibility of a prognosis prediction according to typing of the ovarian carcinoids into two categories, i.e., tumors of low and intermediate malignancy. Topoisomerase II-alpha and Ki-67 are suitable markers giving valuable information about this phenomenon.

[Plant tissues in biopsies]. / Rostlinné tkáne v bioptické praxi.

A short communication demonstrates examples of plant tissues or their derivates in biopsies. Diagnostic pitfalls are emphasized.

[An AV aneurysm of a branch of the pulmonary artery associated with a pulmonary tumorlet]. / A-V aneuryzma vetve plicní tepny s plicním tumorletem.

The authors present a rare case of a relatively large A-V aneurysm of the branch of the pulmonary artery in the right upper pulmonary lobe. Successful and technically easy surgical treatment was preceded by a serious dilemma whether to select in a high risk patient another (less invasive) therapeutic method or even conservative treatment. The surgical finding and smooth postoperative course confirmed that the indication of surgery was correct. As a further pathological finding in the resected portion a pulmonary tumourlet was detected. The combination of the two rare findings is an extreme rarity.

[Pulmonary changes in rheumatoid arthritis]. / Plicní zmeny pri revmatoidní artritide.

A 78-year-old smoker with a medical history of rheumatoid arthritis (RA) diagnosed 23 years before death and treated for 10 years by sulfasalazine followed by 7 years of therapy by purine antimetabolite (AZAMUN, Leiras Co.). Two years before his death chemotherapy was added to treat a low grade malignant lymphoma. Pulmonary changes revealed during autopsy consisted of diffuse interstitial fibrosis, diffuse alveolar damage in its acute to subacute phase, and massive multiple bilateral ossifications. The possible side effect of RA treatment on pulmonary tissue is discussed. Post mortem low-voltage X-ray examination appears as a method which may contribute to the accurate distribution and correct diagnosis of multiple pulmonary ossification.

DNA topoisomerase II-alpha in pulmonary carcinoid tumors.

Fifty-four pulmonary carcinoid tumors of surgically treated patients were diagnosed according to modified Arrigoni histological criteria (WHO 1999). Forty-seven typical (TC) and seven atypical carcinoids (AC) formed the basic groups. Four subgroups were selected from the TCs and consisted of cases with higher tumor size (T2) or those associated with nodal involvement (N1), tumor satellites, and tumorlets. Subgroup tumors were regarded as affections with possible increased proliferation potential. The proliferate activity was examined immunohistochemically by topoisomerase II-alpha (clone SWT3D1) on paraffin material and calculated by the number of positive nuclei per 10 HPF. The topoisomerase expression was found to be statistically different in both principal groups made up of typical and atypical carcinoids with a mean value of 49 and 135 positive nuclei per 10 high power field in TC and AC, respectively. The remaining subgroups of the TCs associated with examined characteristics (larger tumor diameter, metastases, satellites, tumorlets) were not found to be statistically different. The topoisomerase II-alpha is a marker giving valuable information about the diagnosis of pulmonary typical and atypical carcinoids.

[Surgical treatment of lung cancer]. / Chirurgická lécba plicní rakoviny.

The surgical treatment of lung cancer has got a long tradition at our department. The aim of this work is to evaluate the group of 3,727 patients from the years 1948-1995. The special analysis has been performed of the group of 1,456 patients from the years 1974-1995 undergoing lung resection. Evaluating our operation policy a strong trend from pneumonectomy to less extensive operations can be found. The introduction of bronchoplastic operations and modern diagnostic methods has substantially improved the possibility of surgical treatment. The utilization of TNM system enabled to compare the different groups of patients according to the unified classification. The long term survival was directly related to the stage and histological type of disease. The five years period survived 32% of patients in whom the lung resection was performed during the period 1974-1995. The operative hospital mortality has been substantially reduced to 2%. Even though it is our duty to provide the surgical treatment to all the patients if the resection is still possible the best results are to be expected in patients in the first stage of disease. Therefore the early diagnosis followed by adequately sized resection without delay offers the best chance for the patients long term survival.

[Pulmonary "tumorlet" as a neoplastic condition?]. / Plicní tumorlet jako neoplastická afekce?

A 66-year-old woman, non-smoker, with a diffuse bilateral pulmonary interstitial involvement caused by multiple carcinoid tumorlets associated with a diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). The process has developed during the last two years of the patient's life. There were no pathologic changes in the remnant pulmonary parenchyma. Moreover, the minute typical carcinoid (5.2 mm) was encountered after extensive pulmonary tissue examination. The spectrum of DIPNECH, multiple tumorlets, and typical carcinoid tumor demonstrates a possible neoplastic character of the pulmonary tumorlet.

[A localized form of metastatic pulmonary calcification in a patient after renal transplantation]. / Lokalizovaná forma metastatického plicního zvápenení u pacienta po renální transplantaci.

A 51-year-old woman with a 20-year history of renal transplantation during the end-stage of chronic renal failure caused by tubulointerstitial nephritis. She died of chronic graft rejection. An interstitial calcification limited to 1. and 2. left segments was encountered as an incidental autoptic finding. There were two unusual microscopic findings, i.e., no involvement of arterioles and larger vessel inclusive veins, and a foreign-body response to some of the calcified tissue.

[Proliferative activity in pulmonary carcinoids]. / Proliferacní aktivita plicních karcinoidu.

AIM: On the basis of known Ki-67 dependence on tumor malignancy in some lesions, we compared this marker expression quantitatively in pulmonary typical and atypical carcinoid tumors and attempted to predict their biological behavior especially in cases associated with tumorous lymphadenopathy, satellites, and carcinoid tumorlets. METHOD: Using material from surgically treated patients, we examined 54 cases of pulmonary carcinoids divided into five groups. 1. Forty-two typical carcinoids (TC), 2. Twelve atypical carcinoids (AC) diagnosed according to modified Arrigoni's criteria (Travis et al., 1998), 3. Thirty-two TC without metastases, satellites, and tumorlets (M, S, T), 4. Eight AC without M, S, T, and 5. Fourteen TC and AC associated with M, S, T. Groups 3, 4, and 5 were formed of cases selected from group 1 and 2. The proliferate activity was evaluated by Ki-67 (MIB-1, Immunotech France, 1:25). Its nuclear labeling was counted in more than 50 HPF and calculated as a number of positive nuclei in 10 HPF. The Fisher exact test was used for statistical analysis. RESULTS: The Ki-67 nuclear expression was found in 19 (45%) out of 42 TC and in 9 (75%) out of 12 AC. In the set of TC without metastases (M, S, T), the Ki-67 positive labeling was found in 14 (44%) out of 32 cases (group III) and in six (75%) out of eight AC (group IV). In all TC and AC tumors with M, S, T (group V), the Ki-67 expression was encountered in 8 (57%) out of 14 cases. The Fisher exact test showed no significant difference between all examined groups. CONCLUSION: No statistically significant difference was found in Ki-67 expression in pulmonary typical and atypical carcinoids. It appears to be a factor which can not be used for tumor prognosis prediction or adjuvant therapy indication in surgically treated patients.

Endometrial polyps. A clinical study of 245 cases.

OBJECTIVES: Endometrial polyps (EPs) are among the common cases of abnormal uterine bleeding. Hormonal factors may be involved in the pathogenesis as indicated by endometrial abnormalities in patients treated with tamoxifen. This study was designed to analyse the patient characteristics which may be associated with polyp occurrence and assess the diagnostic and therapeutic difficulties. Group of 245 patients was formed to 152 postmenopausal and 93 premenopausal women with EP diagnosed hysteroscopically and confirmed histologically. Evaluated factors were as follows: 1) patient characteristics: age, body mass, systemic hypertension, diabetes mellitus, nulliparity, late menopause, estrogen replacement therapy, and tamoxifen treatment; 2) clinical features of EPs, and 3) the number of curettage's (D & C) and hysteroscopies. RESULTS: Hypertension associated with obesity appears to be an important factor in combination which may play role in the pathogenesis of EPs like the late menopause which was noted in 30% of examined postmenopausal women. An association between EPs and tamoxifen was found in 8% patients with breast cancer. 2. Postmenopausal uterine bleeding and menstrual disorders were prominent clinical symptoms in 44% post- and in 82% of premenopausal women. The other 56% post- and 18% premenopausal patients were asymptomatic. 3. The multiple EPs were present in 26% of postmenopausal and in 15% premenopausal women. 4. Transvaginal ultrasonography supplemented by sonohysterography in cases with abnormal ultrasonographic findings should be the main diagnostic method. 5 Hysteroscopical polypectomy is regarded as the optimal therapy and the removal of the endometrial basalis in the EP origin area prevents persistence or recurrence of EP.

Sustentacular cells in pulmonary neuroendocrine tumours.

AIMS: To determine the prevalence of sustentacular cells across the range of pulmonary neuroendocrine tumours: typical and atypical carcinoid tumours and large cell and small cell neuroendocrine carcinomas. METHODS AND RESULTS: Sustentacular cells were sought in 80 pulmonary neuroendocrine tumours by immunolabelling for S100 protein, nerve growth factor receptor and glial fibrillary acidic protein. Intratumoural macrophages and Langerhans cells were identified with the KP 1 (CD68) and CD1A antibodies. S100-positive sustentacular cells were present in 25 of 30 typical carcinoids, 200 of 25 atypical tumours, six of 10 large cell carcinomas and six of 15 small cell lesions. They were most numerous in the typical carcinoids but very few in the small cell carcinomas, their prevalance being clearly related to grade of differentiation and, in particular, to the degree of architectural organization. CONCLUSIONS: Sustentacular cells are often found in pulmonary neuroendocrine tumours, especially better-differentiated lesions with a well-developed architecture. their prevalence clearly reflecting the degree of structural organization. Whether their prevalence is a useful prognostic indicator within a particular group of such tumours, such as the atypical carcinoids or the large cell carcinomas, as appears to be the case with paragangliomas, is unclear.

Surgery for bullous emphysema.

The present indications for surgery are mainly large or increasing bullae that result in compression of apparently good lung tissue, and the complications of bullous diseases such as pneumothorax. The results of local resection of localized giant bullae are dramatic. The resection of small bullae generally has little effect on lung function. Lobectomy should not be done until bullae have been removed locally and the remaining lung has been tested by positive ventilation. The indications for the resection of large bullae in the presence of diffuse emphysema require very careful individual study. Pulmonary function tests are mandatory but computed tomography is the single most useful method of assessing the extent of the bullous disease and the underlying lung disease. If the underlying lung is diffusely cystic then any surgical treatment is palliative only.