Pecam-1 expression in patients with relapsing-remitting multiple sclerosis

PECAM-1 is an adhesion molecule - a member of the immunoglobulin superfamily - involved in the transendothelial migration of leukocytes. PECAM-1 is expressed on lymphocytes, monocytes and granulocytes. It is also found on endothelial cells and platelets. We present data showing that the cell-bound form of PECAM-1 expression on monocytes is increased in MS patients, compared to controls. We also show that PECAM-1 is significantly over-expressed on lymphocytes in patients with active MRI lesions, when compared to those without gadolinium-enhancing lesions. Our results suggest that the cell-bound form of PECAM-1 can be regarded as a marker of MS activity

Effect of cladribine treatment on ß-2 microglobulin and soluble intercellular adhesion molecule 1 (ICAM-1) in patients with multiple sclerosis

β-2 Microglobulin ( β2M) is a low molecular weight protein located extracellularly and associated with class 1 antigens of the major histocompatibility complex and is considered a marker for disease activity in immune disorders. Cladribine (2-chloro-2-deoxyadenosine, 2-CDA) is a potent lymphocytotoxic agent under investigation in the treatment in MS patients. As β2M levels may indicate inflammatory events in CNS we determined CSF- β2M and serum β2M levels in patients with relapsing-remitting MS before and after cladribine treatment as well as in a control group. There was a significant β2M decrease in sera but not in CSF in MS patients after the cladribine treatment, associated with a slight but significant clinical improvement measured by Kurtzke's Expanded Disability Status Scale. We also found a significant decrease in sICAM-1 level in CSF but not in sera in MS patients. The data support a role of cladribine in MS therapy and deliver new information on cladribine immunological effects in MS patients

Obwodowa neuropatia indukowana chemioterapią — epidemiologia i patogeneza

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most important neurologic complications experienced by patients receiving chemotherapy. The neuropathy often interferes with daily activities and exercise leading to severe impairment of the patient’s quality of life (QoL). The evolution of most CIPNs is characterized by a gradual onset of signs/symptoms, beginning in the lower limbs and advancing proximally into a bilateral stocking and glove distribution. Patients often complain of numbness, tingling and pain in the affected areas. The symptoms become aggravated with repeated cycles of chemotherapy. When the offending agent is withheld, the symptoms generally abate, but relief is not guaranteed. The consequences of delay or discontinuation of treatment may affect overall patient survival.Obwodowa neuropatia indukowana chemioterapią jest jednym z najważniejszych powikłań neurologicznych u pacjentek jej podanych, często zakłócając codzienne aktywności i upośledzając jakość życia a jej objawy pogarszają się przy powtarzanych cyklach chemioterapii. Omówiono stopnie nasilenia neuropatii (Tabela I), jej epidemiologię (szacuje się że doświadcza jej 30% do 55% pacjentów otrzymujących chemioterapię). Jej nasilenie i jakość zależy od czynników osobistego ryzyka (wcześniej istniejące neuropatie, choroby towarzyszące i operacje) i od stosowanego leku (jego typu, sposobu podawania, dawki itp). Omówiono efekty podawania rożnych czynnikowa chemioterapii (docetakselu, winkrystyny, iksabepilonu, oksaliplatyny, cisplatyny, talodomidu, lenalidomidu, bortezomibu), różnice wrażliwości na neuropatię wynikające z polimorfizmu genowego, wieku pacjenta

An evaluation of the reproducibility of the measurement of the intima-media thickness of carotid arteries

The intima-media thickness (IMT) of carotid arteries was demonstrated to be a reliable measure for early stages of atherosclerosis. B-mode ultrasound may be used to measure carotid IMT. The measurements of the IMT of the carotid artery (CA) conducted by different investigators can be comparable and enable the implementation of clinical trial successfully while maintaining a high reproducibility value. The objective of the study was to evaluate the reproducibility of the measurements made by the same investigator on two separate occasions (intraobserver variability) and the reproducibility of the off-line measurements between four sonographers in our laboratory (interobserver variability). The IMT of CA in 25 subjects (15 post stroke and 10 healthy persons) was investigated with the use of high-resolution ultrasonography. The CA subdivided into the common, bulbs and internal segments were scanned twice with a 3-week interval. Additionally three other readers with different levels of experience and skills in ultrasonography were asked to perform the same measurements in duplicate with at least a 3-week interval between. A high concurrence for intraobserver variability was detected with a correlation coefficient ranging from 0.92 to 0.95; p < 0.0001, and maximal bias 0.019 mm. Interobserver variability for all four readers also demonstrated a high correlation coefficient ranging from 0.72 to 0.83; p < 0.0001, and the maximal bias of measurements did not exceed 0.08 mm. The analogue measurements performed by the team demonstrate a reliable reproducibility in terms of the results of morphologic measurements. The differences obtained in the study were less than the error of the method (i.e. 0.1 mm) and should not influence clinical decision-making. Additionally, this study demonstrated that interobserver concurrence increases with the increasing experience of the investigators

Prevalence of electrocardiographic left ventricular hypertrophy among patients with coronary artery disease and diabetes mellitus

Introduction. Electrocardiography (ECG) is a widely used non-invasive diagnostic method for assessment of patients with cardiovascular diseases. Numerous different electrocardiographic criteria exist for detection of left ventricular hypertrophy (LVH). LVH is an important risk factor in patients with coronary artery disease (CAD) or diabetes mellitus and its presence is associated with increased cardiovascular morbidity and mortality. The aim of this study was to evaluate the prevalence of the most frequently used electrocardiographic left ventricular hypertrophy (ECG-LVH) criteria among patients with CAD and diabetes. Methods. A cross-sectional, multicenter study was conducted in outpatient clinics across Poland. Family physicians performed physical examinations and collected relevant information about: onset of CAD and diabetes, presence and onset of hypertension, dyslipidemia, heart failure, diabetic complications, history of acute coronary syndrome and pharmacotherapy. In order to detect LVH, we used seven ECG criteria: 1) the Sokolow-Lyon voltage, 2) the Gubner voltage, 3) the criterion of the R wave amplitude on the leads V5–V6 and 4) aVL, 5) the gender specific Cornell voltage and 6) product, and 7) the Romhilt-Estes point score. Centralized manual assessment of the obtained ECG tracings were performed. Results. We enrolled 1001 patients (48.5% women, 51.5% men, mean age 65 ± 11 years) into the study. At least one ECG-LVH criterion was met in 20.0% (n = 200) of the study participants. The ECG-LVH diagnosis was the most common when using the Romhilt-Estes point score (n = 138; 13.8%). The corresponding prevalence rates for the Cornell voltage, the Cornell product, the R wave amplitude on the lead aVL, the Sokolow-Lyon voltage, the Gubner voltage and the R wave amplitude on the leads V5-V6 criteria were 5.5% (n = 55), 5.2% (n = 52), 3.2% (n = 32), 2.2% (n = 22), 1.9% (n = 19) and 1.3% (n = 13) respectively. Subsequently, the prevalence of the three most frequently used in clinical practice electrocardiographic criteria for LVH (the Sokolow-Lyon voltage, the Cornell voltage and the Romhilt-Estes point score) was analyzed. At least one of them was fulfilled in 185 ECGs. All three criteria at the same time were met only in 5 ECGs (2.7% of 185). Two and only one out of three criteria were fulfilled in 20 (10.8%) and 160 (86.5%) ECGs respectively. Conclusions. The co-occurrence of all assessed ECG-LVH criteria, including the three most frequently applied in clinical practice, is very low in diabetic CAD patients. The Romhilt-Estes point score identifies the highest number of ECG-LVH cases in this setting. However, it seems reasonable to use routinely several ECG criteria for detection of LVH. Further studies are needed to compare diagnostic values of ECG-LVH criteria with imaging methods and to assess prognostic values of various ECG-LVH criteria

Chemotherapy-induced peripheral neuropathy — diagnosis, evolution and treatment

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent neurologic complications experienced by patients receiving antineoplastic drugs. Involvement of the peripheral nerves may have an important impact on daily activi­ties and lead to severe impairment of the patient’s quality of life (QoL). It seems to be of crucial importance to make a correct and early diagnosis of polyneuropathy and, if possible, spare the patient unnecessary suffering or loss of function. In the preceding article we have presented epidemiology, grading and pathogenesis of the toxic CIPN. The purpose of this article is to review current knowledge of diagnostic techniques, prevention and management strategies in the context of CIPN.

Pathological Q waves as an indicator of prior myocardial infarction in patients with coronary artery disease and diabetes mellitus: a comparison of the prevalence and diagnostic accuracy according to present and former criteria

Introduction. Electrocardiography (ECG) is a widely used diagnostic method for identification of patients with previous myocardial infarction (MI). The ECG manifestation of prior MI is the presence of the pathological Q waves. Patients with coronary artery disease (CAD) and diabetes are at high risk of MI. The aim of this study was to compare the prevalence and diagnostic accuracy of the pathological Q waves as an indicator of prior MI in patients with CAD and diabetes according to the present and former criteria. Methods. A cross-sectional, multi-centre study was conducted in outpatient clinics across Poland. Family physicians performed physical examinations, registered ECGs, and collected relevant information about onset of CAD and diabetes, presence and onset of hypertension, dyslipidaemia, heart failure, diabetic complications, history of MI, and pharmacotherapy. Centralised manual assessment of the obtained ECG tracings was performed. Two definitions of the pathological Q-waves were used — a present one according to the Universal Definition of MI and a former one based on the definition of MI developed by the World Health Organization. Results. We enrolled 796 patients (48.1% women, mean age 67.5 ± 10.2 years, and 51.9% men, mean age 64.3 ± 10.3 years) into the study. There were 158 patients (19.8%) — 102 men (24.7%) and 56 women (14.6%), who met the present definition of the pathological Q waves and 106 patients (13.3%) — 74 men (17.9%) and 32 women (8.4%), who met the former definition of the pathological Q waves. The prevalence of the pathological Q waves varied due to the certain group of leads. It was highest in the inferior leads — 104 and 75 according to the present and former definitions, respectively. Of note, the rate of the pathological Q waves increased up to 2.6 times in the lateral leads after the introduction of the less restrictive present definition. Sensitivity of prior MI detection by means of the present and former criteria was 26.8% and 19.8%, and specificity was 87.0% and 92.8%, respectively. The application of the present and former definitions detected prior MI with 65.6% and 71.6% positive predictive value, and with 56.3% and 55.6% negative predictive value, respectively. Conclusions. In the era of reperfusion therapy, ECG appears to be a poor diagnostic tool for detection of previous MI due to its low sensitivity. However, it may identify individuals without previous MI with rather high specificity. In diabetics with CAD, the present definition of the pathological Q waves increases sensitivity of prior MI detection by 7%, with a decrease in specificity by 6% as compared with the former definition

CAR-T cell therapy – toxicity and its management

Chimeric antigen receptor T-cell (CAR-T) therapy is an effective new treatment for hematologic malignancies. Two anti-CD19 CAR-T products, namely axicabtagene ciloleucel and tisagenlecleucel, have been approved for the management of relapsed/refractory large B-cell lymphoma after two lines of systemic therapy. Additionally, tisagenlecleucel is indicated for refractory acute lymphoblastic leukemia in pediatric patients and young adults up to 25 years of age. CAR-T cells are undoubtedly a major breakthrough therapy in hematooncology resulting in up to 90% response rate with durable remissions in population with refractory high-risk disease. However, there are serious side effects resulting from CAR-T therapy, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Manifestations of CRS mostly include fever, hypotension, hypoxia, and end organ dysfunction. Neurologic toxicities are diverse and include encephalopathy, cognitive defects, dysphasia, seizures, and cerebral edema. Since the symptoms are potentially severe, practitioners need to familiarize themselves with the unique toxicities associated with these therapies. In this article, we present a practical guideline for diagnosis, grading and management of CRS and CAR-T neurotoxicity. In addition, infectious complications and late toxicities including prolonged cytopenias and hypogammaglobulinemia are discussed

Oral NAloxone to overcome the moRphine effect in acute COronary syndrome patients treated with TICagrelor — NARCOTIC trial

Background: Numerous worldwide clinical trials have proven the indisputably negative influence of morphine on the pharmacokinetics and pharmacodynamics of P2Y12 receptor inhibitors in patients presenting with acute coronary syndromes. The aim of this trial was to evaluate whether oral co-administration of an anti-opioid agent, naloxone, can be considered a successful approach to overcome ‘the morphine effect’. Methods: Consecutive unstable angina patients receiving ticagrelor and morphine with or without orally administered naloxone underwent assessment of platelet reactivity using Multiplate analyzer as well as evaluation of the pharmacokinetic profile of ticagrelor and its active metabolite, AR-C124910XX, at nine pre-defined time points within the first 6 hours following oral intake of the ticagrelor loading dose. Results: The trial shows no significant differences regarding the pharmacokinetics of ticagrelor between both study arms throughout the study period. AR-C124910XX plasma concentration was significantly higher 120 min after the ticagrelor loading dose administration (p = 0.0417). However, the evaluation of pharmacodynamics did not show any statistically significant differences between the study arms. Conclusions: To conclude, this trial shows that naloxone co-administration in ticagrelor-treated acute coronary syndrome patients on concomitant treatment with morphine shows no definite superiority in terms of ticagrelor pharmacokinetic and pharmacodynamic profile