Drug-drug Interactions of Statins Potentially Leading to Muscle-Related Side Effects in Hospitalized Patients

Introduction. The associations of drugs that may interact with the statins resulting in elevated serum concentration of the statins are an important risk factor for statin induced muscle disorders. We aimed to determine the prevalence of these associations in all hospitalized patients that had been prescribed statins before/during hospitalization and to find out how often they are associated with muscle-related side effects. Methods. This prospective, non-interventional study performed in two internal medicine departments included patients with statin therapy before/during hospitalization. Data on each patient demographic characteristics, co-morbidities and treatment was collected from medical charts and interviews. We evaluated patients’ therapy for the targeted associations using Thomson Micromedex Drug Interactions checker and we ranked the identified drug-drug interactions (DDIs) accordingly. Each patient with statin treatment before admission was additionally interviewed in order to identify muscular symptoms. Results. In 109 patients on statin treatment we found 35 potential (p) DDIs of statins in 30 (27.5%) patients, most of which were in the therapy before admission (27 pDDIs). The pDDIs were moderate (20 pDDIs) and major (15 pDDIs). Of the total number of pDDIs, 24 were targeting the muscular system. The drugs most frequently involved in the statins’ pDDIs were amiodarone and fenofibrate. Two of the patients with pDDIs reported muscle pain, both having additional risk factors for statin induced muscular effects. Conclusion. The prevalence of statins’ pDDIs was high in our study, mostly in the therapy before admission, with only a small number of pDDIs resulting in clinical outcome.

Multiple Intracerebral Hemorrhages in an Old Patient with Rheumatoid Arthritis

A 78-year-old Caucasian man was admitted in the Department of Neurology for visual disturbances, started two days before. The next day the patient experienced headache, fever and gait disturbances. He had hypertension, diabetes mellitus, an ischemic stroke 13 years ago, longstanding seronegative rheumatoid arthritis (17 years), polynodular goiter, right ischio-pubian fracture and right femoral vein thrombosis a year ago due to a car accident, since he is treated with oral anticoagulants associated to antiaggregant, hypotensors, statin and oral antidiabetics. The neurologic examination had evidenced nuchal rigidity, left homonymous hemianopsia, left central facial palsy, ataxia of the inferior limbs with wide-based gait, achilean reflexes abolished bilaterally, bilaterally abolished plantar reflexes, ideomotor apraxia, dysarthria, hypoprosexia, and preserved consciousness patient. A non-contrast cerebral CT scan had shown right temporal and parieto-occipital intraparenchymatous hemorrhages, a right frontal sequelar lesion, multiple old lacunar infarcts, cortical atrophy. Laboratory findings included an inflammatory syndrome, absence of rheumatoid arthritis positive serology, normal coagulogram, an elevated proteinuria. The cerebral IRM performed on the seventh day of hospitalisation was suggestive for subacute right parietal hemorrhage, old cerebral infarction in the right anterior cerebral artery area, old lacunar infarcts and cerebral atrophy. The anticoagulant and antiaggregant treatment was stopped after a generalized tonic-clonic seizure occurred. Antiedematous, hypotensor, anticonvulsivant, beta-blocker, and symptomatic treatment was started, while the antidiabetic treatment was continued. All symptoms remitted. Arguments for amyloid angiopathy in our patient are previous non-cardioembolic ischemic stroke and a chronic inflammatory disease-rheumatoid arthritis in his personal medical history.

P Wave Signal-Averaged Electrocardiography in Patients with Chronic Obstructive Pulmonary Disease

Introduction. Chronic obstructive pulmonary disease (COPD) is associated with higher incidence of supraventricular arrhythmias. Atrial late potentials (ALP) detected by P-wave signal-averaged electrocardiography (SAECG) could be useful in detecting the patients at risk for supraventricular arrhythmias. Our objective was to assess the role of P-wave SAECG and ALP detection for arrhythmic risk evaluation of the patients with exacerbated COPD. Methods. We prospectively included 45 patients with exacerbation of COPD and 58 age-matched patients with no history of pulmonary disease in a control group. We performed pulmonary function tests, arterial blood gases, echocardiography, 24-hour Holter monitoring and P-wave SAECG. We measured filtered P-wave duration (FPD), the root mean square (RMS) voltages in the last 40, 30 and 20 ms of the filtered P-wave (RMS 40, RMS 30 and RMS 20), the root mean square voltage of the filtered P-wave potentials (RMS-p), and the integral of the potentials during the filtered P-wave (Integral-p). ALP was defined as FPD > 132 ms and RMS 20 < 2.3 µV. Results. Isolated atrial premature beats (APB) and supraventricular tachycardias (SVT) were more frequent in the COPD group. There were no significant differences between groups regarding the P wave SAECG parameters. In the COPD group none of the supraventricular arrhythmias was correlated with ALP or any P-wave SAECG parameters. Conclusions. The patients with acute exacerbation of COPD but no apparent cardiac disease have a higher incidence of supraventricular arrhythmias. P-wave SAECG analysis and ALP detection have little value in the arrhythmic risk evaluation of these patients.

Homocysteine, trace elements and oxidant/antioxidant status in mild cognitively impaired elderly persons: a cross-sectional study

Introduction. Mild cognitive impairment (MCI) is the prodromal stage of Alzheimer’s disease (AD), so identification of the related risk factors can be helpful. There are controversial data regarding the serum oxidant/antioxidant status, trace elements and homocysteine (Hcy) as effective parameters in this disease, therefore the status of these factors was determined in this study. Methods. One hundred-twenty elderly persons with cognitive impairment and 120 elderly healthy persons who were differentiated using Mini-mental state examination (MMSE) participated in this study. The patients were divided into mild and moderate-to-severe cognitive impairment group. Serum antioxidant/oxidant, copper (Cu), manganese (Mn), zinc (Zn) and Hcy concentrations were measured using routine methods. Results. Oxidant and antioxidant levels increased and decreased based on the severity of the disease and were higher and lower in patients than in control group, respectively (p<0.001). With adjusting for age, gender and education, significant difference in Hcy levels was not observed. There was no significant difference in trace elements levels among groups. Conclusions. Results confirmed the association between oxidative damage with increasing the severity of cognitive impairment. These factors may be involved in the etiology of cognitive impairment and AD. Identification of such biomarkers is important to select appropriate treatment goals before the onset of irreversible clinical signs.

Dermatoscopy of Verrucous Pigmented Lesions is Essential for Choosing the Appropriate Treatment

Dermatoscopy, as a noninvasive rapid method, which allows the viewing of melanin in the epidermis and papillary dermis, has an important role in diagnosis of the pigmented lesions localized on skin, mucous membrane, scalp and nails. The term of verrucous pigmented lesions includes a series of non-melanocytic and melanocytic, benign and malignant lesions. Among these, the most frequent is the seborrheic keratosis, a common epidermal tumor, affecting the sun exposed areas of adult. At the other end of the spectrum regarding the frequency is the seborrheic keratosis-like melanoma, whose underdiagnosis has a serious impact on the patient’s life. In this work we present the clinical and dermoscopical aspects of three cases of verrucous pigmented lesions (two seborrheic keratoses and one seborrheic keratosis-like melanoma) that determined the diagnostic algorithm as well as the therapeutic approach. The above-presented cases underline the importance of dermatoscopy to determine the malignant potential of the pigmented lesions, the final appropriate treatment being possible after the histopathologic confirmation.

Liver Fibrosis: Causes and Methods of Assessment, A Review

Hepatic fibrogenesis is the final result of injury to the liver. Fibrosis could lead to hepatic dysfunction, important in the pathogenesis of other chronic problems. Therefore, understanding the mechanism, accurate diagnosis and staging of it in early stages accelerates the treatment and reduces the prevalence of chirrosis. Treatment strategies of liver problems and detction methods depend on the amount and progression of liver fibrosis and the rate of cirrhosis development. Traditionally the invasive method, liver biopsy, is reference standard to follow progression and stage of fibrosis. However, during the past decade, progressive development of novel non-invasive methodologies has challenged the invasive method. Non-invasive methods have been initially introduced for chronic hepatitis C with increasing use in other chronic liver diseases. The need for liver biopsy has nowadays decreased significantly as a result of these methodologies. Most of the new non-invasive methods depend on either ‘biological’ or ‘physical’ approaches.In this review, starting from the mechanism of fibrogenesis, the current knowledge about diagnosis, treatment strategies and different methods for its evaluation is discussed. This is followed by a conclusion on what is expected to be known in this field during the future research.

Acute Atherothrombotic Disease and Severe Bleeding: A Difficult Clinical Presentation in Medical Practice

Management of antithrombotic therapy in elderly patients with unstable atherothrombotic disease and increased risk of bleeding is a major clinical challenge. We report the case of a 79 year-old diabetic man with rheumatoid arthritis on both oral corticosteroids and NSAID therapy with mild renal dysfunction, who presented to our hospital because of disabling claudication. Prior to admission he had several episodes of TIA. He also had recurrent small rectal bleeding and mild anemia attributed to his long-standing hemorrhoid disease. Angiography showed a sub-occlusive left internal carotid artery stenosis associated with a significant LAD stenosis and complex peripheral artery disease. Cataclysmic bleeding and hemorrhagic shock occurred in the third day post admission. Withdrawal of all antithrombotic treatment, blood transfusion and emergency sigmoidectomy were performed for bleeding colonic diverticulosis. Subsequently antiplatelet therapy was reinitiated and the patient successfully underwent left carotid artery endarterectomy and LAD stenting. He was discharged from hospital on the 21st day post admission and is doing well at 24 months follow-up.

Caspases, Cell Death and Diabetic Nephropathy

Diabetic Nephropathy. In 2014 (according to data published by the World Health Organization) 9% of the global population was affected by Diabetes which was considered to be directly responsible for 1.5 million deaths just two years prior (in 2012). From the entire number of patients suffering from diabetes, approximately a quarter of them develop renal affection. Diabetic nephropathy has similar physiopathology mechanisms and ultrastructural changes in cell injury characteristics in both Type 1 and Type 2 diabetes. Cell Death. Cell Death was less studied in the renal diabetic disease, although it could represent an important pathogenic mechanism in the appearance and progression of nephropathy. At renal level the cellular loss can be explained by several mechanisms; different stimuli with cellular lesion potential can trigger apoptosis signaling with appearance of regulatory proteins having a double role (they participate in the initiation of the apoptosis path and cell death or in the ending of this process). The types of Cell Death and their relative proportion between themselves in the renal tissue have not been completely elucidated. Caspases. Discovered in the middle of the 1990’s, Caspases are a part of the cysteine proteases family and play a role in numerous aspects of physiology (having a role in development, aging and apoptosis), but also in aspects of physiopathology of several degenerative affections, autoimmune diseases, oncologic diseases – having an important part in apoptosis, necrosis and also inflammation.

Eosinophilia and Hypereosinophilic Disorders – Update on Etiopathogeny, Classification and Clinical Approach

Eosinophils are innate immune leukocytes recruited in large numbers to sites of allergic inflammation and parasitic infections. Recent studies show additional pleiotropic effects of recruited eosinophils impacting immunomodulation, tissue homeostasis and repair. Pathologic conditions accompanied by blood eosinophilia are quite frequent in medical practice and may raise serious differential diagnosis problems in severe cases, that require a multidisciplinary approach. Hypereosinophilia may be reactive to other diseases or primary, representing hypereosinophilic syndromes, that are diagnosed based on clinical and laboratory criteria, according to actual international guidelines. The etiopathogenic diagnosis is difficult and delayed in many cases and clinical evolution may be severe, with multiorgan involvement and poor prognosis. Some cases remain idiopathic, despite exhaustive investigation. This paper aims to review the most recent data in the literature referring to the role of eosinophils in human pathology, diagnostic criteria and treatment strategies of hypereosinophilic syndromes, actual classification and to draw some useful recommendations in clinical practice.

The Effect of Arterial PaCO2 in COPD Exacerbations with and without Peripheral Edema

Introduction. Studies often suggest hypoxemia is an important factor for sodium retention in chronic obstructive pulmonary disease (COPD), although hypercapnia is also associated with sodium retention in these patients. Hence, we have presented the major role of PaCO2 in edema due to COPD.Method. COPD patients who were hospitalized due to exacerbation were enrolled in the study and divided into two groups: with and without edema. Exclusion criteria included primary hepatic diseases, nephrotic syndrome and other renal diseases, left heart failure, or using drugs that would interfere with these organs or endocrine function. Data were coded and analyzed by SPSS software. Arterial blood gas variables including bicarbonate, pH, and PaO2, PaCO2 and O2 saturation, and FEV1, FVC, FEV1/FVC were measured and compared between the groups.Results. No significant difference was found between the averages of bicarbonate, pH, PaO2, O2 saturation, FEV1, FVC and FEV1/FVC in COPD in the two groups. PaCO2 levels were significantly higher in patients with edema, compared to those without edema (p = 0.05). A reverse and significant correlation between PaCo2 and FEV1 levels (p = 0.03) (r = −0.501) was observed in patients with edema.Conclusion. This study suggests that hypercapnia is a major factor in causing edema in COPD patients compared to hypoxemia.