Non-Compartment and compartmental pharmacokinetics, efficacy, and safety of Kedrion FIX concentrate.

BACKGROUND: An open-label phase II, multicenter clinical trial was conducted at 11  Haemophilia Centres in  Italy, Romania, and Turkey, to evaluate the pharmacokinetics (PK), efficacy, and safety of high purity, plasma-derived, double virus inactivated and double nano-filtered factor IX (pd-FIX) concentrate (Kedrion FIX), EudraCT Number: 2005-006186-14. MATERIAL AND METHODS: 16 previously treated patients (PTPs) with severe or moderately severe haemophilia B were enrolled in the study. At enrolment, 14 underwent the first PK assessment (PK I), and the second PK (PK II) assessment was performed after six months of treatment (5 on-demand and nine prophylaxis) at the end of the study. PK parameters were evaluated by Non-Compartmental Analysis (NCA), One-Compartment model (OCM), and Two-Compartment Model (TCM). Efficacy of Kedrion FIX in all 16 patients was evaluated by the number of bleeding events, and clinical response following the infusions. Periodic FIX inhibitor assays and thrombogenicity tests were scheduled throughout the study to assess the safety of the drug. RESULTS: As compared to the published data on PK of pdFIX, Kedrion FIX displayed a longer half-life (22.37-55.73 hrs), reduced clearance, and regular volume of distribution at PK I by both NCA and OCM. The comparison of outcomes of PK II with those of PK I by OCM,  also showed significant changes, particularly in patients on prophylaxis, who showed some improved parameters of PK. Due to two outlier values at the end of the trial, the NCA parameters of PK I were not compared to those of PK II. Breakthrough bleeds were successfully treated with 1 or 2 infusions. No significant adverse events were observed during the study. DISCUSSION: During the six-month clinical study period, the use of Kedrion FIX resulted in a safe and effective pd-FIX concentrate with excellent PK characteristics.

Hepatotoxicity of paracetamol and related fatalities.

Paracetamol, also known as acetaminophen, is the most commonly used antipyretic and pain reliever and since 1955 it is available over-the-counter as a single formulation or in combination with other substances and, as indicated by the World Health Organization, it can be used in all the three steps of pain intensity. Paracetamol toxicity is one of the most common causes of poisoning worldwide. While paracetamol is described as relatively nontoxic when administered in therapeutic doses, it is known to cause toxicity when taken in a single or repeated high dose, or after chronic ingestion. Repeated supratherapeutic misuse, non-intentional misuse, and intentional ingestion may all result in hepatic toxicity, the main cause of acute liver failure (ALF) in the United States and Europe. Since paracetamol is responsible for nearly half of the cases in the US of acute liver failure and remains the leading cause of liver transplantation, continued awareness promotion, education and research should be constantly undertaken. We herein review the literature on paracetamol toxicity with particular attention to aspects of liver damage and related fatalities.

Setup of a rapid method to distinguish among dead, alive, and viable but not cultivable cells of Pseudomonas spp. in mozzarella cheese.

Pseudomonas spp. is the main psychrotrophic genus involved in the spoilage of raw milk and more in general of dairy products, such as mozzarella cheese. The members of this bacterial species are able to produce heat-resistant proteolytic enzymes, determining the casein hydrolysis, and as a consequence, a reduction of the shelf life and sensory quality of the products. Therefore, the spoilage activity could be attributed not only to viable, but also to viable but noncultivable (VBNC) cells. For this reason, the setup of a non-culture-based method is useful for a rapid detection of cells that are still alive, but no longer cultivable, such as VBNC cells. Here we propose a method based on DNA or RNA content (or both) to reveal the presence of dead, alive, and VBNC cells belonging to the genus Pseudomonas. The obtained results clearly indicate the limits of the classical plating count overcome by molecular detection of Pseudomonas spp. through DNA and RNA analysis, enabling us to establish the presence of different states of the cells.

Ultrasound in Rheumatologic Interstitial Lung Disease: A Case Report of Nonspecific Interstitial Pneumonia in Rheumatoid Arthritis.

According to the American Thoracic Society (ATS)/European Respiratory Society consensus classification, idiopathic interstitial pneumonias (IIPs) include several clinic-radiologic-pathologic entities: idiopathic pulmonary fibrosis (IPF), usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis-associated ILD, desquamative interstitial pneumonia, and lymphoid interstitial pneumonia. Ultrasound Lung Comets (ULCs) are an echographic chest-sonography hallmark of pulmonary interstitial fibrosis. We describe the ultrasound (US) findings in the follow-up of a NSIP's case in rheumatoid arthritis (RA).

Effects of hyaluronic acid (HA) viscosupplementation on peripheral Th cells in knee and hip osteoarthritis.

OBJECTIVE: Determine Th lymphocytes concentration in patients with knee or hip osteoarthritis (OA). Evaluate their change after HA viscosupplementation. METHODS: Patients with early primary knee or hip OA (ACR Criteria) were recruited in two groups: group A was only observed longitudinally, group B was treated with a course of three weekly intra-articular injections of HA. A healthy control group gender and age matched was enrolled too. All subjects were followed for 3 months. Flow cytometry was performed from blood samples to assess T cells subpopulations (CD3, CD4, CD8, CCR6, CD38, CxCR3, HLA DR) at baseline and at 3-months visit. RESULTS: 86 patients were recruited with OA: 49 in Group A (35 knee OA, 14 hip OA), 37 in Group B (24 knee OA, 13 hip OA). 23 in Control Group. Activated CD4 T cells (CD4(+)CD38(+)DR(+), CD4(+)CD38(-)DR(+)), Th2 (CD4(+)CXCR3(-)CCR6(-)),Th1 (CD4(+)CXCR3(+)CCR6(-)) were higher at baseline in group A and B than in control group. After the HA course activated T cells were lower in group B than in group A (P = 0.01). Th17 (CD4(+)CXCR3(-)CCR6(+)) at baseline were higher in groups A and B than in control group and decreased levels in Group B after the HA course were observed (P = 0.03). CONCLUSION: The presence of activated T cells in patients with OA confirm that OA is a disease with an immunological/inflammatory involvement. Our preliminary results seems to show that HA injections could lower the levels of activated T cells, and so regulate the articular milieu.

Drug-induced angioedema: experience of Italian emergency departments.

Acute angioedema represents a cause of admission to the emergency department requiring rapid diagnosis and appropriate management to prevent airway obstruction. Several drugs, including angiotensin-converting enzyme inhibitors (ACE-I), nonsteroidal anti-inflammatory drugs (NSAIDs) and oral antidiabetics, have been reported to induce angioedema. The aim of this prospective observational study conducted in a setting of routine emergency care was to evaluate the incidence and extent of drug-induced non-histaminergic angioedema in this specific clinical setting, and to identify the class of drugs possibly associated with angioedema. Patients admitted to seven different emergency departments (EDs) in Rome with the diagnosis of angioedema and urticaria were enrolled during a 6-month period. Of the 120,000 patients admitted at the EDs, 447 (0.37 %) were coded as having angioedema and 655 (0.5 %) as having urticaria. After accurate clinical review, 62 cases were defined as drug-induced, non-histaminergic angioedema. NSAIDs were the most frequent drugs (taken by 22 out of 62 patients) associated with the angioedema attack. Of the remaining patients, 15 received antibiotic treatment and 10 antihypertensive treatment. In addition, we observed in our series some cases of angioedema associated with drugs (such as antiasthmatics, antidiarrheal and antiepileptics) of which there are few descriptions in the literature. The present data, which add much needed information to the existing limited literature on drug-induced angioedema in the clinical emergency department setting, will provide more appropriate diagnosis and management of this potentially life-threatening adverse event.

Italian Society for Rheumatology recommendations for the management of hand osteoarthritis.

Hand osteoarthritis (OA) is a common and potentially disabling disease, with different features from hip and knee OA so that a specific therapeutic approach is required. Evidence based recommendations for the management of hand OA were developed by the European League Against Rheumatism (EULAR) in 2006. The Italian Society for Rheumatology (SIR) aimed to update, adapt to national contest and disseminate the EULAR recommendations for the management of hand OA. The multidisciplinary group of experts included specialists involved in the management of patients with hand OA. In order to maintain consistency with EULAR recommendations, a similar methodology was utilized by the Italian group. The original propositions were reformulated in terms of a search query and for every recommendation a systematic search was conducted updating EULAR recommendations' review. The propositions were translated in Italian and reformulated basing on collected evidences and expert opinion. The strength of recommendation was measured for each proposition with the EULAR ordinal and visual analogue scales. The original 11 propositions of EULAR recommendations were translated and adapted to Italian context. Further evidences were collected about non-pharmacological therapies, local treatments, intra-articular injection with SYSADOA and corticosteroids, and surgery. The SIR has developed updated recommendations for the management of hand OA adapted to the Italian healthcare system. Their implementation in clinical practice is expected to improve the management of patients with hand OA.

[Statistical evaluation of potential mistakes and malpractice in a Chest Pain Unit]. / Valutazione statististica riguardante i possibili errori dimalpractice in una unità del dolore toracico.

AIMS: The Chest Pain Unit (CPU) of Policlinico Umberto I, established in 2008, is charged with the management of patients with non-traumatic chest pain transferred from the Emergency Department and aims at: a) an early recognition of patients at high risk of acute coronary syndrome (ACS), in order to perform a primary PCI within 90 minutes; b) an early diagnosis of patients at low risk of ACS in order to discharge them in a short time, and c) the diagnostic performance of clinical tests in patients at intermediate risk of ACS in order to identify those who require either a new PCI or a coronary artery bypass graft (CABG). The purpose is to avoid malpractice which could even imply the risk of legal conflicts. MATERIALS AND METHODS: We evaluated the total number of admissions to the Emergency Department of Policlinico Umberto I in the period 2010-2011 and selected the patients with non-traumatic chest pain and acute coronary syndrome. In the Chest Pain Unit, patients with non-traumatic chest pain or ACS were recruited through a) the use of the Chest Pain Score to define the typicality or atypicality of chest pain; b) the stratification of the risk of ACS using the modified Braunwald Score; and c) the stratification of patients at intermediate or high risk of ACS using the GRACE ACS Model in order to perform a PCI. RESULTS: In the period 2010-2011, 603 patients were admitted to the CPU with non-traumatic chest pain. Of them, 15.75% (95) were diagnosed with atypical chest pain; 27.03% (163) with chronic stable angina pectoris; 9.3% (56) received a diagnosis of chronic heart failure and 47.92% (289) suffered from non ischemic cardiovascular disease. Other 124 subjects were admitted to the CPU with a diagnosis of ACS, but only in 91.93% of the cases such diagnosis was confirmed, whereas for the remaining 8.06% was discarded. On the whole, 54.2% (394) of the 727 patients admitted to the CPU with non-traumatic chest pain and acute coronary syndrome showed a low cardiovascular risk; 30.12% (219) were at intermediate risk and 15.68% (144) at high risk. DISCUSSION: The aim of the CPU is to accomplish a selection of the subjects at high risk of ACS, to drastically reduce the time of diagnosis and treatment to 24-36 hours and to avoid possible mistakes or adverse events by using both unsophisticated diagnostic tests and a personalized management of diagnosis and treatment.

[An unusual cause of chest pain in]. / Una causa insolita di dolore toracico in Chest Pain Unit: un caso di miocardite.

Myocarditis seems to be mostly caused by a viral infection or more rarely by a pharmacological hypersensitivity or by radiations exposure. Nevertheless, it is not so easy to know the ethiopathogenesis of the myocarditis, because mostly it is impossible to determine the infectious agent that causes the pathology even if it is isolated. The diagnosis could often remain uncertain, so a suspect of myocarditis has to be opportunely confirmed by specific serological and diagnostic investigations, in order to avoid the appearance of a dilated cardiomyopathy which is one of its principal sequences.

[The syncope in Emergency Department: usual management vs guidelines]. / La sincope nel Dipartimento di Emergenza: tra applicazionedelle linee guida e impatto con la realtà dell'urgenza.

INTRODUCTION: The syncope is a common cause of admission to Emergency Departments, representing around 1-3% of all admissions to the service. However, elderly age and important comorbidities often hinder a definite etiologic diagnosis, with increasing requests for diagnostic tests and longer periods of hospitalization. MATERIALS AND METHODS: We analyzed the management of 1,204 patients admitted to our Emergency Department for transient loss of consciousness in the period between 1 June 2009 and 1 June 2010, evaluating the following parameters: average age, gender, triage color code at admittance, performed diagnostic tests, diagnosis at discharge from ED and destination ward. We also studied a subgroup of 93 patients admitted to emergency medicine units evaluating their OESIL score at admittance, comorbidities, performed diagnostic tests and diagnosis at discharge from the ward. RESULTS: In the Emergency Department, 45% of patients were discharged with a diagnosis of syncope of unknown origin; in 21% of patients syncope was excluded; 19% of patients received a diagnosis of cardiogenic syncope; 11% were diagnosed with a presyncope; 3% with orthostatic hypotension and 1% with vasovagal syncope. In emergency medicine units, 51% of patients were discharged with a diagnosis of cardiogenic syncope, 11% were diagnosed with vasovagal syncope, 11% with presyncope, 11% with TIA, 8% with loss of consciousness non-syncope and 8% with syncope of unknown origin. CONCLUSIONS: Management of patients with syncope, elderly people with important comorbidities in particular, is still a serious problem for the emergency physician. The creation of specialized units for the management of syncope, the so-called syncope units, through the implementation of a shared diagnostic and therapeutic protocol, aims at reducing inappropriate hospitalization and average length of stay.

[High digoxin serum levels in an elderly patient for the endogenous digoxin-like immunoreactive substances. A case report]. / Elevati livelli di digossinemia in una paziente anziana per ifattori endogeni immunoreattivi digossino-simili. Caso clinico.

UNLABELLED: Digoxin is typically prescribed in the treatment of heart failure. Its limited therapeutic range requires systematic monitoring of plasmatic concentration through immunoreactive tests. Laboratory results, however, can be altered by the presence of digoxin-like immunoreactive factors (DLIF) which are released in all clinical conditions involving volemic expansion. CASE REPORT: An 86-year-old woman arrived in emergency with severe dyspnoea, atrial flutter and a medical history of ischemic cardiopathy. The patient was treated with ACE inhibitor, furosemide, spironolactone and digoxin. The first lab test for digoxin showed levels of digoxin of 7.05 ng/ml. Although the patient did not show any clinical evidence of digital intoxication nor was she treated with drugs which might interfere with digoxin kinetics and even if she had markers of renal function within clinical limits, digoxin was suspended and a treatment was initiated with 0.9% NaCl solution and furosemide. The second lab test showed levels of digoxin of 8.38 ng/ml. A possible interference of DLIF with immunoreactive tests was therefore assumed. MATERIALS AND METHODS: The patient's serum was ultrafiltered and centrifugated to remove possible DLIF; subsequently, the measurement of digoxin levels was repeated. As a result, the digoxin level decreased to 0.25 ng/ml. CONCLUSIONS: DLIF increase in several diseases, including heart failure, end-stage renal disease, pre-eclampsy and acromegaly. High digoxin levels in a patient who does not show any symptoms of digital intoxication should lead to suspect the presence of these factors and to preventively determine DLIF in serum so as not to incur the risk of suspending an important treatment like digoxin in heart failure.

[The use of cardiac markers bed test in acute coronary syndrome in emergency department]. / Utilizzo dei biomarcatori cardiaci bed-test nella sindrome coronarica acuta nel Dipartimento di Emergenza.

AIMS: The evaluation of the patient with chest pain in the emergency department is one of the most common situations that the doctor has to face. The diagnostic procedure supposes an observation period of at least 6-12 hours, a well organized medical facilities and the identification of all SCA cases to reduce inappropriate admission. MATERIALS AND METHODS: In our study we have estimated the utility of the marker assay that is associated to the use of risk scores (TIMI and GRACE risk score) to obtain indication about the most appropriate assistance level. In particular, we used the assay of necrosis markers to highlight the damage along with the assay of natriuretic peptides for their role in the diagnosis and in the monitoring of the patients with cardiac damage. RESULTS: Also PCR has an important role such as marker of plaque stability and of inflammation. These markers associated to the necrosis markers could give important clinical information of independent nature. DISCUSSION: The sensibility of laboratory markers, without important necrosis, is low and it is not possible to exclude in a few time a SCA There is now an alternative strategy: a precocious risk stratification. Using clinical criteria it is possible to do a first evaluation of the probability of SCA and the complications.

Comparison of the Recent-Onset Arthritis Disability questionnaire with the Health Assessment Questionnaire disability index in patients with rheumatoid arthritis.

BACKGROUND: Physical disability in patients with rheumatoid arthritis (RA) is often assessed by questionnaires. We compared the Recent-Onset Arthritis Disability (ROAD) questionnaire with the Health Assessment Questionnaire (HAQ) disability index (DI) in a cohort of RA patients. The aim of this study was to obtain information on several aspects of construct validity of these measures. METHODS: A cross-sectional multicentre study was carried out among patients with RA who were attending hospital outpatient clinics. The patient group included 196 patients partially or not responding to disease modifying anti-rheumatic drugs. For the evaluation of the psychometric properties of the ROAD in comparison with HAQ-DI this population has been compared to another cohort of 247 outpatients with RA who were participating in a long-term observational study. All patients completed the ROAD and HAQ-DI. Additional comparator composite indices of disease activity were analysed. The ROAD structural validity was first assessed using exploratory factor analysis. Concurrent validity was analysed by Spearman's correlations and cross-tabulations. Discriminant validity to distinguish patients with active and non-active disease was assessed with receiver operating characteristic (ROC) curve analysis. For agreement analysis Bland and Altman plots were calculated. RESULTS: Factor analysis yielded a two-factor ROAD score that accounted for 68.74% of the explained variance in the questionnaire. The first factor, namely upper extremity function/activity daily living and work (ROAD-upper) accounted for 55.6% of the explained variance. The second factor, namely lower extremity function (ROAD-lower) accounted for 13.1% of the explained variance. Significant correlations were found between the scores of the ROAD and the other clinical variables with a high ability to measure pain and disease activity, supporting the concept of convergent construct validity. The discriminatory power of both questionnaires to assess inactive and active RA patients was good, without significant difference. CONCLUSIONS: ROAD is a good alternative to the HAQ-DI for the assessment of physical disability in RA. Use of the ROAD makes it easier and less costly to collect data and reduces the burden on RA patients and should be applied in both clinical trials and routine clinical care settings.

[Management model of chest pain in Medical Emergency Room and Chest Pain Unit of Policlinico Umberto I of Rome]. / Modello di gestione del dolore toracico in Pronto Soccorso Medico e nella Chest Pain Unit dell'Azienda Policlinico Umberto I di Roma.

In Italy one of the most common cause of access to the Emergency Departments is not traumatic chest pain, representing from the 6% to 10% of all the diagnoses. Admissions to the Emergency Department (DEA) of Policlinico Umberto I of Rome for non-traumatic chest pain, occurred between 2000 and 2008, were analyzed in this study. Out of 26,8910 admissions to the medical emergency room (PS), 21,088 (7.84%) were due to non-traumatic or precordial chest pain. Of these, 2881 (14%) patients had a diagnosis of myocardial infarction STEMI, NSTEMI and IA and 18,207 (86%) had a diagnosis of atypical chest pain, representing respectively 1.07% and 6.77% of all admissions to PS. About 27.62% of patients with atypical chest pain were discharged from the PS, 33.27% were hospitalized, 36.73% refused hospitalization, 1.68% were transferred elsewhere, and 0.7% did not uptake the visit. 85% of patients with myocardial infarction STEMI, NSTEMI and IA were hospitalized, 3.75% refused hospitalization, 8.82% were transferred elsewhere, and 1.71% died in the PS. Hospitalizations resulted often in unjustified and protracted length of hospital stays for clinical investigations, with negative repercussions for patients and costs. In the last years, the number of inappropriate hospitalizations progressively increased, partly as consequence of recourse to the court aiming at defining legal responsibility of the health board.Since avoiding inappropriate hospital admissions is an essential requirement for containing healthcare costs and improving the health service, Chest Pain Unit has been established. Its responsibility is to recognize and promptly treat patients with chest pain and acute coronary syndrome. As well, it is responsible to quickly discharge patients with chest pain at low and intermediate risk of acute coronary insufficiency, after careful clinical assessment lasting 24-36 hours.

Phenotypic and genotypic characterization of lactic acid bacteria isolated from Artisanal Italian goat cheese.

The lactic acid bacteria community in traditional goat cheese produced in three dairies in Valsesia (Piemonte, Italy) was studied at different steps of the manufacturing process. These cheeses were produced from raw milk without starter bacteria, and no protocol was followed during the manufacturing process. Three hundred thirty-two isolates were characterized and grouped by results of both morphophysiological tests and random amplification of polymorphic DNA plus PCR analysis. Bacteria were identified by partial sequencing of the 16S rRNA gene. Lactococci were the dominant lactic acid bacteria in raw milk. Their initial numbers ranged from 5 to 7 log CFU ml(-1). Their levels increased during manufacturing and decreased during ripening. The growth trend for enterococci was comparable to that of lactococci, although enterococci counts were lower. Lactococcus lactis subsp. cremoris, Lactococcus garviae, and Enterococcus faecalis were the most frequently isolated species during goat cheese manufacturing, whereas the highest numbers of Enterococcus (E. faecium, E. durans, E. gilvus, and E. casseliflavus) were isolated with the greatest frequency from ripened cheese samples. Occasionally, Leuconostoc mesenteroides, Leuconostoc lactis, and Lactobacillus paraplantarum also were isolated.

[The role of D-dimer in aortic dissection]. / Il D-dimero nella dissezione aortica.

OBJECTIVES: The aim of this retrospective study is to indicate the correlation between the grade of the extent of the aortic pathology, the presence of complications, the evolution of the pathology value of the D-dimer in all the patients with aortic dissection in order to know a prognostic role a short-long time of this test. MATERIALS AND METHODS: Only in 40 patients were possible to determine the value of D-dimer priol of these patients were not received invasive cares. The patients are divided into 4 classes in accordance with the extent of the aortic pathology valued TAC images and after we have taken in observation the presence of clinical complications shown and the positive history for chronic aortic dissection. RESULTS: The elevation of D-dimer is strictly associated with the extent of the aortic dissection. The value of D-dimer is more elevated during the progress of the pathology and in the presence of clinical complications than during chronic aortic dissection. CONCLUSIONS: The D-dimer is considered a diagnostic marker by the clinicians during the acute setting of the aortic dissection. A lot of points of view should be valued and cleared, its possible to attribute a prognostic role at the D-dimer during the acute aortic dissection.

Psychometric properties of an index of three patient reported outcome (PRO) measures, termed the CLinical ARthritis Activity (PRO-CLARA) in patients with rheumatoid arthritis. The NEW INDICES study.

OBJECTIVES: To evaluate the psychometric properties of an index based on 3 patient reported outcomes measures, termed PRO-CLinical ARthritis Activity (PRO-CLARA), in order to facilitate rapid and easy rheumatoid arthritis (RA) activity assessment in daily routine. METHODS: 196 patients partially or not responding to disease modifying anti-rheumatic drugs (DMARDs), consented to participate in a multicentre cross-sectional study. For the evaluation of the psychometric properties of the PRO-CLARA, this population has been compared to another cohort of 247 outpatients with RA who were participating in a long-term observational study and who satisfying minimal disease activity and remission definitions. All patients completed the PRO-CLARA, combining patient's physical function, self-administered tender joint count and perception of global health status into a single measure of disease activity. Additional comparator composite indices were analysed. Internal consistency was assessed with Cronbach's alpha coefficient. A confirmatory factor analysis was carried out to test factor structure. Concurrent validity was analyzed using Spearman's correlations and cross-tabulations. Discriminant validity to distinguish patients with active and non-active disease was assessed with receiver operating characteristic (ROC) curve analysis. For agreement analysis, kappa statistics were calculated. RESULTS: In testing for internal consistency, we found that Cronbach's alpha for the PRO-CLARA was 0.893, indicating high reliability. PRO-CLARA proved to be significantly correlated to established RA activity assessment tools. The area under ROC curve of the PRO-CLARA gives identical results to those provided by other comparator indices. CONCLUSIONS: The study showed satisfactory psychometric properties of the PRO-CLARA.

Relationship between NK Cell Activation and Clinical Response in Rheumatoid Arthritis Treated with Rituximab.

INTRODUCTION: We investigated the relationship between the anti CD20 therapy and the NK cell phenotype in patients with Rheumatoid Arthritis (RA). METHODS: patients with seropositive RA according to the ACR criteria that was refractory to conventional and anti TNF alpha agents were studied. All patients were treated with Rituximab (1.0 g at days 1 and 15). At baseline and day 30 were collected: absolute counts of B cells (CD19+), total T cells (CD3+), helper (CD3+CD4+), cytotoxic (CD3+CD8+) and NK (CD16+CD56+). As NK activation marker was used CD54bright expression. Disease activity was primarily assessed using the the Clinical Disease Activity Index (CDAI); in addition, we calculated the Disease Activity Score 28-joint assessment (DAS28). RESULTS: 18 patients were enrolled (mean age ± SD 58.6 ± 2.8 years old). After the rituximab course, as expected CD19+ cells were not detectable, the cytotoxic lymphocytes and CD56+CD16+ cells downregulated (283 ± 34 and 85 ± 15 respectively), instead an up regulation of CD56+CD16+CD54bright was observed (187 ± 43). The dynamic of NK cells activation was significantly associated with clinical variables (r=0.811, p<0.001). CONCLUSIONS: our data suggest a role of rituximab therapy in varying NK phenotype in patients with RA and show that NK cells activation correlates with clinical response.

Biomarkers, type II collagen, glucosamine and chondroitin sulfate in osteoarthritis follow-up: the "Magenta osteoarthritis study".

BACKGROUND: The purpose of the present study was to determine relationship between disease activity, systemic markers of cartilage degradation, urinary C-terminal cross-linking telopeptides of type II collagen (uCTX-II), and bone degradation, urinary C-terminal cross-linking telopeptides of type I collagen (uCTX-I), structural progression of osteoarthritis (OA) and potential therapeutic efficacy of type II collagen (COLLII) in combination with glucosamine and chondroitin sulfate (GC). MATERIALS AND METHODS: An observational retrospective study, 1-year follow-up, on 104 patients with OA (nodular osteoarthritis of the hand, erosive osteoarthritis of the hand, EOA, osteoarthritis of the knee or hip) who were treated with GC or glucosamine, chondroitin sulfate and collagen type II (GCC). The following information was collected at entry: demographics, BMI, characteristics of OA, patient global assessment (VAS), C-terminal cross-linking telopeptides of collagen types I (uCTX-I) and II (uCTX-II) and radiographs. After 6 months: VAS, uCTX-I and uCTX-II. After 1 year: VAS, uCTX-I, uCTX-II and radiographs. RESULTS: After 6 months and 1 year of treatment VAS, uCTX-I and uCTX-II mean values were significantly lower than the baseline. 57 were treated with GCC and 47 with GC. The group that received GCC showed a similar VAS mean value after 6 months and 1 year when compared with the group treated with GC. uCTX-I and uCTX-II mean level was lower in the group treated with GCC (P < 0.05). Radiological score (Kellgren and Lawrence summarized score for hands) after 1 year showed a reduced progression compared to the baseline in the hand osteoarthritis group, especially after GCC treatment (P < 0.05). Finally, uCTX-I has better correlation with radiological score and with GC in the EOA subgroup (Pearson index: R = 0.44). CONCLUSIONS: (a) uCTX-I and uCTX-II proved to be useful biomarkers in OA monitoring; (b) uCTX-I is better correlated with hand EOA and could represent a potential further marker to assess the evolution of EOA bone damage; (c) GC slow down OA progression; (d) finally COLLII could represent a further protective factor in OA cartilage.

[Therapy optimization of heart failure through the evaluation of the plasma concentration variation of B-type natriuretic peptide]. / Ottimizzazione della terapia dello scompenso cardiaco attraverso il monitoraggio delle variazioni delle concentrazioni plasmatiche del peptide natriuretico di tipo B.

AIM: Our research was based over the critical evaluation of the plasmatic concentration variation of B-type Natriuretic Peptide in emergency in patients with heart failure during therapy with diuretics, anti-aldosterone, ACE-inhibitors, beta-blockers and nitroderivates. MATERIALS AND METHOD: We selected 108 patients: 30 control subjects (average 58.40 +/- SD13.32 for 20 M, and 65 +/- SD 14.74 for 10 W), and 78 subjects (average 75.90 +/- SD 9.60 for 41 M, and 77.89 +/- SD 8.62 for 37 W) arrived to the emergency and reception department for dyspnea and/or precordialgia and/or palpitations with heart failure diagnosis according to NYHA Classification. The variation of BNP concentration was evaluated in these subjects at the admission, after 1 week, and 1 month from the beginning of the therapy. RESULTS: Patients with heart failure had a BNP concentration high during all measurements. The values were high during admission, but after 1 week and after 1 month, they reduced reaching the balance. CONCLUSIONS: BNP evaluation is a good indicator for the diagnosis of heart failure and for improving the therapy. The main limit of BNP diagnostic role is the need of knowing in advance the specific values for each patient.