Dijabetesna ketoacidoza kod bolesnika sa cerebrovaskularnim insultom - uzroci, mehanizmi, dijagnostika i naše smernice za terapiju

Although cerebrovascular disease may be a well recognised trigger for diabetic ketoacidosis (DKA), literature data on the precise mechanisms, characteristics, or treatment guidelines are rare. The risk of developing an ischemic stroke is doubled in adults with diabetes compared to people with normal glucose metabolism. It is important to point out that even children with DKA have a significantly increased risk of cerebrovascular insult and that they can have a stroke with a frequency of about 10%. Given the significant overlap of symptoms between these two diseases, it can be assumed that attributing DKA symptoms as a manifestation of stroke is not uncommon, especially in elderly and less communicative patients. In addition, pH, bicarbonate concentration, and anion gap are not routinely measured in all diabetics suffering from stroke, at least not in secondary health institutions.Children who develop cerebrovascular stroke during DKA often at the beginning have a preserved consciousness or only mild confusion or lethargy. After a few hours, with the institution of therapy, however, loss of consciousness may occur accompanied by signs of increased intracranial pressure. It was previously thought that the cause was too fast fluid replacement. Recent data suggest that reperfusion injury may be a more likely mechanism. Although most of these studies relate to younger individuals with ketoacidosis, it is clear that at least some of them may be operative in adult DKA. Literature therapeutic guidelines for adult diabetics with stroke-related diabetic ketoacidosis are almost lacking, although it is clear that they could not be the same as those utilised in population with normal glucose metabolism. In this paper, we have tried to define our treatment guidelines for these particular patients.

Increased blood BACE1 activity as a potential common pathogenic factor of vascular dementia and late onset Alzheimer's disease

Late onset Alzheimer disease (LOAD) is traditionally considered as a separate disease from vascular dementia (VAD). However, growing evidence suggests that β-amyloid (Aβ) accumulation, that initiates LOAD-related neurodegeneration, is preceded by vascular events. Previous in vitro studies showed that β-secretase 1 (BACE1), the key-enzyme of amyloidogenesis, is upregulated by cerebrovascular insult; moreover, its activity is increased both in brain and serum of LOAD patients. We aimed to investigate whether BACE1 serum activity is altered also in dementias related, or not, to cerebrovascular disease. Thus, we evaluated serum BACE1 activity in a sample of individuals, including patients with LOAD (n. 175), VAD (n. 40), MIXED (LOAD/VAD) dementia (n. 123), other types of dementia (n. 56), and healthy Controls (n. 204). We found that BACE1 was significantly higher not only in LOAD (+ 30%), but also in VAD (+ 35%) and MIXED dementia (+ 22%) (p < 0.001 for all), but not in the other types of dementia (+ 10%). Diagnostic accuracy was 77% for LOAD, 83% for VAD, and 77% for MIXED dementia. In conclusion, we showed for the first time that the increase in peripheral BACE1 activity is a common feature of LOAD and VAD, thus underlying a further pathogenic link between these two forms of dementia.

The Silence Speaks, but We Do Not Listen: Synonymous c.1824C>T Gene Variant in the Last Exon of the Prothrombin Gene as a New Prothrombotic Risk Factor

Background Thrombosis is a major global disease burden with almost 60% of cases related to underlying heredity and most cases still idiopathic. Synonymous single nucleotide polymorphisms (sSNPs) are considered silent and phenotypically neutral. Our previous study revealed a novel synonymous FII c.1824C&gt;T variant as a potential risk factor for pregnancy loss, but it has not yet been associated with thrombotic diseases. Methods To determine the frequency of the FII c.1824C&gt;T variant we have sequenced patients’ DNA. Prothrombin RNA expression was measured by quantitative PCR. Functional analyses included routine hemostasis tests, western blotting and ELISA to determine prothrombin levels in plasma, and global hemostasis assays for thrombin and fibrin generation in carriers of the FII c.1824C&gt;T variant. Scanning electron microscopy was used to examine the structure of fibrin clots. Results Frequency of the FII c.1824C&gt;T variant was significantly increased in patients with venous thromboembolism and cerebrovascular insult. Examination in vitro demonstrated increased expression of prothrombin mRNA in FII c.1824T transfected cells. Our ex vivo study of FII c.1824C&gt;T carriers showed that the presence of this variant was associated with hyperprothrombinemia, hypofibrinolysis, and formation of densely packed fibrin clots resistant to fibrinolysis. Conclusion Our data indicate that FII c.1824C&gt;T, although a synonymous variant, leads to the development of a prothrombotic phenotype and could represent a new prothrombotic risk factor. As a silent variant, FII c.1824C&gt;T would probably be overlooked during genetic screening, and our results show that it could not be detected in routine laboratory tests.

Does Co-occurred Cerebral Palsy Change the Prognosis of West Syndrome?

Aim We aimed to examine the occurrence of cerebral palsy (CP) in children with West syndrome (WS), to estimate the possible causative factors by analyzing the neuroimaging examinations of patients, to evaluate their cognitive/motor function and epileptic status and to compare the prognosis of children with double pathology of WS and CP and of those without CP. Methods The clinical and magnetic resonance imaging (MRI) data of 62 patients with West syndrome were evaluated. A total of 39 of 62 patients (63%) suffered from CP (CP group). The non-CP group included 23 patients. Results Abnormal MRI was found in 55/62 (89%) patients. Main anomalies were: brain malformation (21), hypoxic-ischemic encephalopathy (13), cerebrovascular insult (8), infection (7), and other anomalies (6). In the CP group, the most common MRI abnormalities included pre/perinatal hypoxia/ischemia, brain malformation, cerebrovascular insult, and infection. In the non-CP group, brain malformations were the most frequent. Significantly more negative MRIs were found in the non-CP group. More than 60% of the patients were severely cognitively impaired, almost 90% of them had CP. Not only the occurrence of intellectual disability was lower in the non-CP group, but its severity was milder as well. A total of 78% of the children with CP had a very severe motor disability. Fifty-four percent in the CP and 67% in the non-CP group had therapy-resistant epilepsy. Conclusion WS has an especially unfavorable prognosis: cerebral anomaly was confirmed in 89% of our patients. CP was present in almost two-thirds of the children with WS, most of them had severe cognitive and motor deficits.

Predictive factors for exacerbation and reexacerbation in chronic obstructive pulmonary disease: an extension of the Cox model to analyze data from the Swiss COPD cohort

Background: The Swiss COPD cohort was established in 2006 to collect data in a primary care setting. The objective of this study was to evaluate possible predictive factors for exacerbation and re-exacerbation. Methods: In order to predict exacerbation until the next visit based on the knowledge of exacerbation since the last visit, a multistate model described by Therneau and Grambsch was performed. Results: Data of 1,247 patients (60.4% males, 46.6% current smokers) were analyzed, 268 (21.5%) did not fulfill spirometric diagnostic criteria for COPD. Data of 748 patients (63% males, 44.1% current smokers) were available for model analysis. In order to predict exacerbation an extended Cox Model was performed. Mean FEV1/FVC-ratio was 53.1% (±11.5), with a majority of patients in COPD GOLD classes 2 or 3. Hospitalization for any reason (HR1.7; P = 0.04) and pronounced dyspnea (HR for mMRC grade four 3.0; P < 0.001) at most recent visit as well as prescription of short-acting bronchodilators (HR1.7; P < 0.001), inhaled (HR1.2; P = 0.005) or systemic corticosteroids (HR1.8; P = 0.015) were significantly associated with exacerbation when having had no exacerbation at most recent visit. Higher FEV1/FVC (HR0.9; P = 0.008) and higher FEV1 values (HR0.9; P = 0.001) were protective. When already having had an exacerbation at the most recent visit, pronounced dyspnea (HR for mMRC grade 4 1.9; P = 0.026) and cerebrovascular insult (HR2.1; P = 0.003) were significantly associated with re-exacerbation. Physical activity (HR0.6; P = 0.031) and treatment with long-acting anticholinergics (HR0.7; P = 0.044) seemed to play a significant protective role. In a best subset model for exacerbation, higher FEV1 significantly reduced and occurrence of sputum increased the probability of exacerbation. In the same model for re-exacerbation, coronary heart disease increased and hospitalization at most recent visit seemed to reduce the risk for re-exacerbation. Conclusion: Our data confirmed well-established risk factors for exacerbations whilst analyzing their predictive association with exacerbation and re-exacerbation. This study confirmed the importance of spirometry in primary care, not only for diagnosis but also as a risk evaluation for possible future exacerbations. Trial registration: Our study got approval by local ethical committee in 2006 (EK Nr. 170/06) and was registered retrospectively on ClinicalTrials.gov (NCT02065921, 19th of February 2014).

Predictors of health related quality of life three years after myocardial infarction with ST segment elevation

Background/Aim. Health-related quality of life (HRQoL) is an important indicator of patient condition following myocardial infarction. It may serve as a predictor of mortality and new hospitalization. The aim of this study was to evaluate the association of selected sociodemographic and clinical characteristics with HRQoL in the Serbian cohort of patients with myocardial infarction with ST segment elevation (STEMI) that were treated with primary percutaneous coronary intervention (pPCI). Methods. Patients were recruited from the population of patients with STEMI who were hospitalized in the Clinical Center of Serbia in Belgrade, between 1st December, 2009 and 30th June, 2010. The study was conducted among 507 STEMI patients treated with pPCI. The HRQoL was assessed using the Questionnaire Short Form Health Survey (SF-36). Multivariate logistic regression models were used for each components score in order to determine independent predictors of HRQoL. Results. The patients with the lowest tertiles of Physical component score (PCS) and the Mental component summary score (MCS) were older, likely to be females, unpartnered, with a poor economic status, with diabetes, with prior myocardial infarction and with more extensive coronary artery disease. There were more employed and the individuals with smoking history in the group of patients with the higher scores. The characteristics of patients with lower PCS score were: the higher presence of hypertension, prior cerebrovascular insult and left anterior descending artery as infarct artery. This study demonstrated that HRQoL was significantly associated with patient?s age, gender, diabetes mellitus, a poor way of living and loneliness. Furthermore, the presence of previous cerebrovascular insult seems to affect the physical component score. Conclusion. Knowledge of predictors of HRQoL in the STEMI patients may provide indications for optimal treatment and anticipate their impact on the treatment outcome.