Anemia and stroke: Where do we stand?

Anemia seems to have a clear relationship with cerebrovascular events (CVEs), as there is a direct connection between central nervous system, blood supply, and tissue oxygen delivery. Anemia is considered a hyperkinetic state which disturbs endothelial adhesion molecule genes that may lead to thrombus formation. Furthermore, blood flow augmentation and turbulence may result in the migration of this thrombus, thus producing artery-to-artery embolism. It is for this reason that anemia is characterized as "the fifth cardiovascular risk factor." Anemia is consistently present in patients with acute stroke, ranging from 15% to 29%, while the mortality rate was significantly higher in patients suffering from anemia at the time of admission. Different types of anemia (sickle cell disease, beta thalassemia, iron deficiency anemia [IDA]) have been associated with increased cardiovascular and CVE risk. The relation between hemoglobin level and stroke would require further investigation. Unfortunately, treatment of anemia in cardiovascular and cerebrovascular disease still lacks clear targets and specific therapy has not developed. However, packed red blood cell transfusion is generally reserved for therapy in patients with CVEs. What is more, treatment of IDA prevents thrombosis and the occurrence of stroke; although iron levels should be checked, chronic administration favors thrombosis. Regarding erythropoietin (EPO), as there is lack of studies in anemic stroke patients, it would be desirable to utilize both neuroprotective and hematopoietic properties of EPO in anemic stroke patients. This review aims to clarify the poorly investigated and defined issues concerning the relation of anemia and CVEs.

Is management of hyperglycaemia in acute phase stroke still a dilemma?

INTRODUCTION: Close monitoring of blood glucose levels during the immediate post-acute stroke phase is of great clinical value, as there is evidence that the risk of neurological deterioration is associated with both hyper- and hypoglycaemia. The aim of this review paper is to summarise the evidence on post-stroke blood glucose management and its impact on clinical outcomes, during the early post-acute stage. FINDINGS: Post-stroke hyperglycaemia has been associated with increased cerebral oedema, haemorrhagic transformation, lower likelihood of recanalisation and deteriorating neurological state. Thus, hyperglycaemia during an acute stroke may result in poorer clinical outcomes, infarct progression, poor functional recovery and increased mortality rates. Although hypoglycaemia may also lead to poorer outcomes via further brain injury, it can be readily reversed by glucose administration. In most patients, the goal of regular treatment is euglycaemia and for acute-stroke patients, a reasonable approach is to target control of glucose level at 100-150 mg/dL. CONCLUSION: Both hypoglycaemia and hyperglycaemia may lead to further brain injury and clinical deterioration; that is the reason these conditions should be avoided after stroke. Yet, when correcting hyperglycaemia, great care should be taken not to switch the patient into hypoglycaemia, and subsequently aggressive insulin administration treatment should be avoided. Early identification and prompt management of hyperglycaemia, especially in acute ischaemic stroke, is recommended. Although the appropriate level of blood glucose during acute stroke is still debated, a reasonable approach is to keep the patient in a mildly hyperglycaemic state, rather than risking hypoglycaemia, using continuous glucose monitoring.

Hypercalcemia and multiple osteolytic lesions in an adult patient with relapsed pre-B acute lymphoblastic leukemia: a case report.

BACKGROUND: Hypercalcemia and severe osteolytic lesions are rare complications of acute lymphoblastic leukemia (ALL) in childhood, and those cases share similar clinical features. Similarly, hypercalcemia is a rare feature in adult ALL. Here, we report an uncommon case of an adult patient with relapsed precursor B ALL (pre-B ALL) who developed multiple osteolytic lesions and hypercalcemia. CASE DESCRIPTION: A 24-year-old male patient, diagnosed with pre-B ALL, was admitted in our hospital due to severe lumbar pain. After reviewing laboratory, radiological and clinical findings, the patient was diagnosed as having relapse of a mixed phenotype acute leukemia, according to bone marrow aspiration (9% blasts) and cytogenetic analysis, with multiple osteolytic lesions in all lumbar vertebrae, sacrum and ilium and severe hypercalcemia (13.3 mg/dL). Thus, FLAG-IDA rescue therapy and hydration plus furosemide, corticoids and bisphosphonates were administered. Despite initial amelioration, his hematological condition deteriorated and he died due to severe sepsis as a result of severe immunosuppression. CONCLUSION: Two possible mechanisms have been suggested for hypercalcemia in hematological malignancy, either the leukemic infiltration or the paraneoplastic production of a variety of humoral factors and proinflammatory cytokines. However, hypercalcemia and severe osteolytic lesions are rare features in ALL adult patients and their combination may be indicator of poor prognosis. Hippokratia 2015, 19 (1): 78-81.

Simultaneous manifestation of pleural effusion and acute renal failure associated with dasatinib: a case report.

WHAT IS KNOWN AND OBJECTIVE: Dasatinib is a novel second-generation inhibitor of multiple tyrosine kinases, indicated for the treatment for Philadelphia chromosome-positive (Ph+) chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL) and lymphoid blast CML with resistance or intolerance to prior therapy. Although dasatinib is a potent, efficacious and generally well-tolerated drug, patients are also subject to various adverse effects. The most common pulmonary-related side effect is pleural effusion (PE). Renal failure has been reported rarely as a side effect of dasatinib treatment. We report the first case of a patient with imatinib-resistant CML who developed PE and acute renal failure (ARF) simultaneously, after being placed on dasatinib therapy. CASE SUMMARY: We report a 58-year-old female dasatinib-treated patient with Ph+ chronic phase CML who was admitted to our hospital due to persisted dyspnoea and fever. After reviewing the laboratory and clinical findings, we determined our patient as having simultaneously ARF and PE related to dasatinib therapy. Dasatinib was discontinued, and after 10 days of treatment with ampicillin-sulbactam, allopurinol, amlodipine, furosemide and methylprednisolone, she was discharged home effusion free and with ameliorated renal function. WHAT IS NEW AND CONCLUSION: PE is the most common extra-haematological toxicity observed during dasatinib treatment whose pathogenesis is still unclear. A possible role of cytokines, such as platelet-derived growth factor receptor (PDGFR)-ß and vascular endothelial growth factor (VEGF), in causing endothelial permeability has been suggested. The aetiology of renal failure is also unclear in these patients, but two different possible mechanisms have been suggested such as tumour lysis syndrome and toxic tubular damage. In conclusion, here we describe the first case of simultaneous manifestation of PE and ARF associated with dasatinib. Thus, in patients treated with tyrosine kinase inhibitors, especially those with predisposing nephrological or haematological factors, serum creatinine levels should be monitored routinely.

Hypovitaminosis D and peripheral arterial disease: emerging link beyond cardiovascular risk factors.

Vitamin D has received increasing interest for its beneficial effect on health. Beyond its conventional role in bone metabolism, emerging evidence suggests a possible link between low vitamin D levels and cardiovascular disease (CVD), including peripheral arterial disease (PAD), and cardiovascular risk factors. Vitamin D interacts either directly with the vascular tree or indirectly through its association with cardiovascular risk factors, but the exact mechanism remains controversial. This review outlines the association between hypovitaminosis D and PAD. Both entities are quite prevalent in the general population and, therefore, their potential association might have important clinical implications. Whether vitamin D deficiency represents a novel risk factor for PAD/CVD, and whether vitamin D supplementation would reduce the burden of CVD still remains to be answered. Until then, vitamin D intake is not recommended for PAD/CVD prevention. Outdoor physical activity, coupled with adequate but safe sun exposure, is a healthy lifestyle practice suggested for the prevention of both PAD and hypovitaminosis D.

Effects of buflomedil on skin blood flow in patients with type 2 diabetes mellitus without overt micro- or macroangiopathy.

AIM: The aim of this study was to assess the effects of buflomedil on the peripheral microcirculation in patients with type 2 diabetes mellitus (T2DM) without overt micro- or macroangiopathy. METHODS: Twenty-three patients with T2DM were randomly assigned to receive buflomedil 600 mg/day for six months (N.=12) or no medication (N.=11). Skin blood flow in the lower limbs was assessed at baseline and after 3 and 6 months using Laser Doppler. We measured the following laser Doppler parameters: volume, flow and velocity. RESULTS: In patients treated with buflomedil, there was a significant increase in volume (P=0.039) and a trend for an increase in both flow and velocity (P=0.097 for both parameters). In contrast, significant decreases in volume and flow were observed in the control group (P=0.045 and P=0.027, respectively) whereas velocity did not change (P=0.150). CONCLUSION: In conclusion, buflomedil appears to have a beneficial effect on the peripheral microcirculation in patients with T2DM.

Role of phytosterols in lipid-lowering: current perspectives.

The cholesterol-lowering effect of plant sterols was first discovered in the early 1950s. However, it is only recently that plant sterols have become clinically important, when advances in food-technology have made it possible to combine sterols with a variety of food products including margarines, yogurts, fruit juices and cereal bars. We review the clinical trial evidence of lipid-lowering efficacy of plant sterols and discuss their implications in routine clinical practice. To generate the evidence we searched the Pubmed database for English language literature, using relevant keywords and medical subject heading (MeSH) terms, and extracted the findings from recently published studies and meta-analyses on this topic. Our findings suggest that the short-term use of food supplements rich in plant sterols is a safe and effective strategy; to maximize the benefits of dietary and lifestyle therapy, either with or without statin therapy, among majority of dyslipidemic patients with need for additional lipid-lowering.

Breastfeeding and diabetes.

The present review outlines the role of breastfeeding in diabetes. In the mother, breastfeeding has been suggested to reduce the incidence of type 2 diabetes mellitus, the metabolic syndrome and cardiovascular disease. Moreover, it appears to reduce the risk of premenopausal breast cancer and ovarian cancer. In the neonate and infant, among other benefits, lactation confers protection from future both type 1 and type 2 diabetes. Whether lactation protects women with gestational diabetes mellitus and their offspring from future T2DM remains to be answered. Importantly, for diabetic mothers, antidiabetic treatment itself may affect breastfeeding. There is not enough data to allow the use of oral hypoglycaemic agents. Therefore, insulin currently remains the optimal antidiabetic treatment during lactation. In conclusion, breastfeeding could be considered a modifiable risk factor for the development of diabetes and even a potential protective lifestyle measure from future cardio-metabolic and malignant diseases. Therefore, health care professionals should encourage both women with and without diabetes to breastfeed their children.

Standardized arrangement for a guideline-driven treatment of the metabolic syndrome: the SAGE-METS study.

AIM: To substantially increase awareness, treatment and effective control of the metabolic syndrome (MetS) and its components. SUBJECTS AND METHODS: This is a pilot best practice implementation enhancement programme to reduce the estimated cardiovascular disease (CVD) risk in 628 MetS patients with or without diabetes or CVD by improving quality of care. A baseline visit was followed by action to improve adherence to lifestyle advice and drug treatment for CVD risk factors by physicians specifically trained to implement guidelines. Finally, after 6 months, a single-page form was completed, showing if patients were at CVD risk factor target. If not, there was an analysis of the reason why. RESULTS: The programme was effective in improving utilization of evidence-based treatment in 628 MetS patients. There was a substantially greater patient perception of MetS, an enhancement in compliance with lifestyle advice and increased prescription of evidence-based medication, leading to a 48% (p < 0.0001) improvement in estimated CVD risk. There was a substantial increase in the number of subjects on target for specific CVD risk factors. CONCLUSIONS: This is the first study to increase adherence to multiple interventions for all MetS components on an outpatient basis, in both primary care and teaching hospital settings. Physician and patient education, distribution of printed guidelines and brochures, and completion of a single-page form motivated both physicians and patients to achieve multiple CVD risk factor guideline goals. The absence of a control group is a limitation of this study. Further work is also needed to establish if the improvements observed are sustained on a long-term basis.

Implementation of strategy for the management of overt dyslipidemia: the IMPROVE-dyslipidemia study.

BACKGROUND: To assess the efficacy of a strategy aimed at improving vascular risk management in patients with dyslipidemia with or without cardiovascular disease (CVD). METHODS: This is a pilot implementation enhancement program that was evaluated in 1127 patients with dyslipidemia. There was a baseline visit, followed by a concerted effort from previously trained physicians to improve adherence to lifestyle advice and optimize drug treatment for all vascular risk factors. After 6 months the patients were re-evaluated. The PROspective-Cardiovascular-Munster (PROCAM) and Framingham trials risk engines were used to estimate CVD risk in primary prevention patients (n=609). RESULTS: This strategy induced a better compliance to lifestyle measures and use of evidence-based medication, focusing on statins. This resulted in a 45% (Framingham) to 63% (PROCAM) reduction in estimated CVD risk in primary prevention (both p<0.0001). There was also a substantial increase in the proportion of secondary prevention patients (n=518) achieving CVD risk factor targets (from 29% at baseline to 76% at 6 months, p<0.0001). CONCLUSIONS: This is the first study to increase the adherence to multiple interventions in patients with dyslipidemia, and other CVD risk factors, in both primary care and teaching hospital settings. Simple measures, such as educating physicians and patients, distributing printed guidelines and brochures, and completing a 1-page form, motivated physicians and patients to achieve multiple CVD risk factor goals.

Buflomedil: potential new indications for an old agent.

Our understanding of vascular pathophysiology has significantly improved during the past two decades. Patients with type 2 diabetes mellitus have an increased vascular risk and a series of modifiable risk factors play a crucial role in the atherosclerotic process. The microvascular dysfunction in diabetes results in increased vascular permeability and impaired regulation of blood flow and vascular tone. These changes culminate in nephropathy, retinopathy and neuropathy and probably contribute to the increase vascular morbidity and mortality in this population. Moreover, studies in the skin microvasculature suggest that this microvascular dysfunction contributes significantly to the pathogenesis of diabetic foot. Several studies showed a beneficial effect of vasoactive drugs, including buflomedil, in non-diabetic patients. However, it remains to be established whether these drugs could also be beneficial in the diabetic population, especially in the early stages of diabetes.

The neuroprotective role of erythropoietin in the management of acute ischaemic stroke: from bench to bedside.

Recombinant human erythropoietin was produced soon after the discovery of the erythropoietin gene in 1985 and since then, it is used in various clinical conditions such as chronic renal failure. Moreover, experimental studies have shown that erythropoietin exerts neuroprotective action as well. Recently, a clinical trial yielded promising results concerning the use of erythropoietin in stroke management. In this review, we summarize the main data which suggest that recombinant human erythropoietin and its analogues may indeed have a role in stroke treatment.

Association of phosphodiesterase 4D gene G0 haplotype and ischaemic stroke in a Greek population.

We have examined the association of phosphodiesterase 4D (PDE4D) single nucleotide polymorphism (SNP45) and microsatellite marker AC008818-1 with ischaemic stroke, in an independent cohort of Greek patients and control individuals with no clinical manifestations of vascular disease. Significantly different distributions were observed with respect to the AC008818-1 alleles, with allele 148 associating with an increased risk of stroke incidence, and allele 144 with a protective effect. In addition, the haplotype defined by allele 148 and G allele of SNP45 was found to be significantly increased in patients even though no statistically significant differences emerged with respect to SNP45 alone. The previously established association of a PDE4D gene haplotype with ischaemic stroke in a population from Iceland was independently confirmed in our Greek population, suggesting that PDE4D may be involved in the aetiology and pathogenesis of stroke.

Primary pancreatic anaplastic large cell lymphoma, ALK negative: a case report.

We present the fourth case of a primary pancreatic anaplastic large cell lymphoma (ALCL), ALK-. An 80-year-old man was admitted to our clinic for further investigation of a fever of unknown origin. He noted anorexia, weight loss and fatigue. His laboratory tests showed anemia and a great elevation of ESR, LDH, and beta (2) microglobulin. In CT and MRI scan, a soft tissue mass in the pancreas was observed. A repeated endoscopy after his admission revealed an ulcerated mass-like deformity of the duodenal bulb. Explorative laparotomy confirmed a diffuse spread of an unresectable malignant pancreatic mass extending to the adjacent organs. Duodenal and surgical biopsies identified an ALCL of T-cell lineage, ALK-. The patient died in the Intensive Care Unit due to hemodynamic instability. Our case is the first one indicating that primary pancreatic lymphoma should be suspected in a patient with pancreatic mass and elevated serum LDH and beta(2) microglobulin.

Epidemiologic characteristics of hypertension in the civilians of Kosovo after the war.

34th Greek regimen, which was part of the NATO forces, provided medical services to the civilians of Kosovo. We studied epidemiologic data in the population of Kosovo regarding hypertension in order to determine the prevalence and characteristics of hypertension. 830 patients (281 - 33.86% male, 62 +/- 26 yrs and 549 - 66.14% female, 49 +/- 28 yrs) were examined for different diseases. We identified 254 (30.6%) patients with hypertension (188 female and 66 male). According to the international criteria used for the classification of the severity of hypertension, more than half of the patients (51.2%) had severe hypertension, 31.5% modest and 17.3% mild. Statistically significant relation between the severity of hypertension and age or sex was not found out. Increased BMI as well as the presence of proteinuria and rheumatic diseases were significantly related to the severity of the hypertension while the coexistent heart disease, diabetes mellitus and chronic obstructive pulmonary disease (COPD) wasn't. The use of non-steroid anti-inflammatory agents (NSAIDs) was related to the severity of hypertension with a borderline significance. 31.4% of the patients were on treatment with NSAIDs and/or cortisone because of rheumatic disease or obstructive pulmonary disease. Overfunction of the sympathetic system was present in 62.99%. The mean heart rate was greater in women (84/min) than in men (72/min). 28.35% of the patients had secondary hypertension, including the patients on a drug that can elevate the blood pressure and patients with increased activity of the sympathetic nervous system. So, 8.6% of the patients had usual causes of secondary hypertension and 19.6% hypertension secondary related to the use of NSAIDs or cortisone, or due to the increased activity of the sympathetic nervous system. Antihypertensive treatment was started in 248 patients, i.e. in all of them except the ones already on treatment having their blood pressure well controlled. For antihypertensive treatment beta-blockers or central adrenergic inhibitors either as monotherapy or in combination with other agents were used most frequently combined with diuretics and Ca antagonists and ACE inhibitors. In conclusion the diagnosis and treatment of hypertension in the population of Kosovo during the post war period had certain particularities.

Parasuicidal poisoning treated in a Greek medical ward: epidemiology and clinical experience.

OBJECTIVE: To study the epidemiology of acute poisoning patients presenting to an acute medical service ward in a Greek hospital between January 1998 and December 2000. DESIGN: Prospective case series. RESULTS: A total of 273 patients with self-poisoning were included in the study. This represented 3.8% of the overall admissions to the unit. The mean age of patients was 33, the most frequent age group being that aged 20-30 years (36.2% of total) with a male-to-female ratio of 1:1.97. Sixty per cent of patients was admitted within 4 h. Those from urban areas comprised 76.2% and 23.8% from rural areas. The most frequently ingested agents were psychopharmaceuticals (37.4%) and analgesics/anti-rheumatics (32.6%). Pesticides (7.7% of total) were most frequently used by patients coming from rural areas (32.3% of patients from rural areas). Alcohol was included in the overdose in 8.4%. Of the patients, 16.2% had a previous history of overdose. In this case series, psychiatric assessment suggested that 52% of the patients had a formal psychotic diagnosis, 21% had personality disorder and 27% had taken an overdose in response to stress. The most frequently documented precipitating factors were family problems and disputes (37%). Unusually, the seasonal distribution in these patients suggested a peak in summer (37.5% of presentations) with lower numbers in spring (30.2%), autumn (17.7%) and winter (14.6%). Of the patients, 23.7% presented in July. A total of 73.5% of patients was conscious, 16.4% was somnolent, 4.5% was in precoma and 5.6% was in coma (GCS <8). Patients who received antidotal therapy comprised 17.9%. Evidence of hepatic dysfunction was observed in 8.9% of patients and renal dysfunction in 3.6%. Extracorporeal techniques for drug removal (hemodialysis and hemoperfusion) were used in 2.2% of patients. Intensive care therapy was required in 11.4% of patients. The mean overall hospitalization time was 3.3 days. The mortality rate was 2.9%. CONCLUSIONS: This study shows that the epidemiology of self-harm by overdose in Greece is significantly different in terms of the seasonal presentation from other parts of Europe. The agents ingested and other features are similar to northern Europe. Psychiatric diagnoses are more common in our group than in those reported from northern Europe.