Proposal of a New Standardized Freeze-Thawing Technical Protocol for Leucocyte-Poor Platelet-Rich Plasma Preparation and Cryopreservation

A human platelet-rich plasma (PRP) concentrate can be defined as a preparation of autologous human plasma with increased platelet concentration produced by centrifugation of a larger volume of a patient's own blood. Platelets contain a plethora of growth factors in their α-granules that are concentrated through the centrifugation process in order to then be injected in supraphysiologic amounts to an injury site with the final aim of augmenting the natural healing process. Preparations of PRP concentrates can be further classified as leucocyte-rich (LR-PRP), defined as having a leucocyte concentration above baseline, and leucocyte-poor (LP-PRP), defined as having a leucocyte concentration below baseline. Although many preclinical and clinical trials have shown the ability of leucocyte-poor PRP concentrates to significantly improve symptomatic mild to moderate hip and/or knee osteoarthritis, to date there is no consensus on the optimal way of obtaining PRP preparations, specifically with respect to the concentration of blood components. In this technical report, we describe a new standardized freeze-thawing technique for leucocyte-poor PRP preparation and cryopreservation, which has been shown to be superior to currently available techniques based solely on centrifugation. By describing this technical protocol, which we have been using on a daily basis in the setting of a Regenerative Medicine Outpatient Clinic in a European tertiary university hospital center, we aim to contribute to a future consensus on the optimal way of obtaining and preserving leucocyte-poor PRP concentrates.info:eu-repo/semantics/publishedVersio

Is a Combined Programme of Manual Therapy and Exercise More Effective than Usual Care in Patients with Non-Specific Chronic Neck Pain? A Randomized Controlled Trial

Objective: The aim of this study was to compare the effectiveness of a combined intervention of manual therapy and exercise (MET) versus usual care (UC), on disability, pain intensity and global perceived recovery, in patients with non-specific chronic neck pain (CNP). Design: Randomized controlled trial. Setting: Outpatient care units. Subjects: Sixty-four non-specific CNP patients were randomly allocated to MET (n = 32) or UC (n = 32) groups. Interventions: Participants in the MET group received 12 sessions of mobilization and exercise, whereas the UC group received 15 sessions of usual care in physiotherapy. Main measures: The primary outcome was disability (Neck Disability Index). The secondary outcomes were pain intensity (Numeric Pain Rating Scale) and global perceived recovery (Patient Global Impression Change). Patients were assessed at baseline, three weeks, six weeks (end of treatment) and at a three-month follow-up. Results: Fifty-eight participants completed the study. No significant between-group difference was observed on disability and pain intensity at baseline. A significant between-group difference was observed on disability at three-week, six-week and three-month follow-up (median (P25-P75): 6 (3.25-9.81) vs. 15.5 (11.28-20.75); P < 0.001), favouring the MET group. Regarding pain intensity, a significant between-group difference was observed at six-week and three-month follow-up (median (P25-P75): 2 (1-2.51) vs. 5 (3.33-6); P < 0.001), with superiority of effect in MET group. Concerning the global perceived recovery, a significant between-group difference was observed only at the three-month follow-up (P = 0.001), favouring the MET group. Conclusion: This study's findings suggest that a combination of manual therapy and exercise is more effective than usual care on disability, pain intensity and global perceived recovery.info:eu-repo/semantics/publishedVersio

Gold in the Lousal mine, Iberian Pyrite Belt, Portugal

Recent exploration boreholes in the Lousal Mine, located within the Portuguese sector of the Iberian Pyrite Belt (IPB) yielded marked concentrations in gold/electrum in a section of core consisting of banded metasediments with massive pyrite. Preliminary research indicates that the gold is associated with native bismuth and bismuthinite and is clearly late in the paragenetic sequence occurring in fine chalcopyrite (± covellite)-bismuthinite-gold filled veinlets within the dominant and more massive pyrite. The pale yellow gold grains are fine, seldom reaching more than 6 ..m in length and half of that in thickness. EPMA results indicate that silver concentrations in gold grains can be as high as 27 wt.%. The results show similarities with conclusions drawn from the IPB on the Spanish side where gold of Co-Bi geochemical association is found as electrum with abundant to common Co and Bi minerals. These associated with pyrite and/or chalcopyrite are characterized by an abundance of sedimentary facies and show that the gold association formed at high temperature (>300 °C) during the initial phases of massive sulphide formation

Síndrome Dolorosa Regional Complexa do Tipo I - da Prevenção ao Tratamento

A Síndrome Dolorosa Regional Complexa do tipo I é uma entidade clínica que se caracteriza por um quadro de dor neuropática intensa associada a múltiplas alterações sensitivomotoras e autonómicas. Afecta principalmente as extremidades, estando especialmente associada a eventos traumáticos como as fracturas. O seu diagnóstico é clínico e o tratamento não é orientado por guidelines, facto que reflete um conhecimento imperfeito da sua fisiopatologia. O diagnóstico deve ser precoce e a abordagem multidisciplinar, com recurso a tratamento farmacológico, programa de reabilitação e – em caso de falência dos anteriores – técnicas invasivas, com o objectivo de promover a funcionalidade dos segmentos atingidos reduzindo o risco de manutenção ou agravamento do quadro. A mobilização precoce e a administração de vitamina C têm assumido, cada vez mais, um papel de relevo na sua prevenção.info:eu-repo/semantics/publishedVersio

O Que Acontece aos Não Respondedores na Terapia de Ressincronização Cardíaca?

INTRODUCTION AND OBJECTIVES: Left ventricular reverse remodeling (LVRR) is strongly related to the long-term prognosis of patients undergoing cardiac resynchronization therapy (CRT). The aim of this study was to assess the long-term clinical outcome of patients without LVRR at six months after CRT implantation and to determine the prognostic impact of clinical response in this population. METHODS: We analyzed 178 consecutive patients who underwent successful CRT device implantation (age 64±11 years; 69% male; 89% in New York Heart Association [NYHA] functional class III; 35% with ischemic cardiomyopathy). Clinical status and echocardiographic parameters were determined before and six months after CRT implantation. We identified those without criteria for LVRR (≥10% increase in left ventricular ejection fraction with ≥15% reduction in left ventricular end-systolic diameter compared to baseline). Clinical responders were defined by a sustained improvement of at least one NYHA functional class. RESULTS: At six-month assessment after CRT, 109 (61%) patients showed LVRR. During a mean follow-up of 56±21 months, 47 (26%) patients died, with higher mortality in the group without LVRR (36% vs. 20%, p=0.023). Clinical response was greater in patients with LVRR (88% vs. 55%, p<0.001). In patients without LVRR, clinical response to CRT was the strongest independent predictor of survival (hazard ratio: 0.120; 95% confidence interval: 0.039-0.366; p<0.001). CONCLUSION: Although patients without LVRR six months after CRT implantation had a worse prognosis, with higher all-cause mortality, clinical response can be an independent predictor of survival in this population.info:eu-repo/semantics/publishedVersio

Antiarrhythmic Effect of Sacubitril-Valsartan: Cause or Consequence of Clinical Improvement?

Sacubitril/Valsartan (LCZ696) reduced sudden cardiac death in the PARADIGM-HF trial. However, the mechanism by which LCZ696 reduces ventricular arrhythmias remains unclear. The aim of this study was to compare electrocardiographic (ECG) parameters and mechanical dispersion index, assessed by left ventricular (LV) global longitudinal strain (GLS), before and after LCZ696 therapy. We prospectively evaluated chronic Heart Failure (HF) patients with LV ejection fraction ≤40%, despite optimal medical and device therapy, in which LCZ696 therapy was started, while no additional HF treatment was expected to change. ECG and transthoracic echocardiographic data were gathered in the week before starting LCZ696 and at six months of therapy. A semiautomated analysis of LV GLS was performed and mechanical dispersion index was defined as the standard deviation from 16 time intervals corresponding to each LV segment. Of the 42 patients, 35 completed the six month follow-up, since two patients died and five discontinued treatment for adverse events. QTc interval (451.9 vs. 426.0 ms, p < 0.001), QRS duration (125.1 vs. 120.8 ms, p = 0.033) and mechanical dispersion index (88.4 vs. 78.1 ms, p = 0.036) were significantly reduced at six months. LCZ696 therapy is associated with a reduction in QTc interval, QRS duration and mechanical dispersion index as assessed by LV GLS.info:eu-repo/semantics/publishedVersio

Echocardiographic Variables Predictive of Appropriate Therapies for Ventricular Tachyarrhythmia in Patients Undergoing Combined Cardiac Resynchronization Therapy

INTRODUCTION: The significant risk of sudden arrhythmic death in patients with congestive heart failure and electromechanical ventricular dyssynchrony has led to increased use of combined cardiac resynchronization therapy defibrillator (CRT-D) devices. OBJECTIVES: To evaluate the echocardiographic variables in patients undergoing CRT-D that predict the occurrence of appropriate therapies (AT) for ventricular tachyarrhythmia. METHODS: We analyzed 38 consecutive patients (mean age 60 +/- 12 years, 63% male) with echocardiographic evaluation before and 6 months after CRT-D implantation. Patients with AT were identified in a mean follow-up of 471 +/- 323 days. A standard echocardiographic study was performed including tissue Doppler imaging (TDI). Responders were defined as patients with improvement in NYHA class of 25%. RESULTS: The responder rate was 74%, and the reverse remodeling rate was 55%. AT occurred in 21% of patients, who presented with greater left ventricular end-diastolic internal diameter (LVEDD) before implantation (86 +/- 8 vs. 76 +/- 11 mm, p = 0.03) and at 6 months (81 +/- 8 vs. 72 +/- 14 mm, p = 0.08), and increased left ventricular end-systolic internal diameter (66 +/- 14 vs. 56 +/- 14 mm, p = 0.03) and lower ejection fraction (24 +/- 6 vs. 34 +/- 14%, p = 0.08) at 6 months. In the group with AT, the responder rate was lower (38 vs. 83%, p = 0.03), without significant differences in reverse remodeling (38% for the AT group vs. 60%, p = 0.426) or in the other variables. By univariate analysis, predictors of AT were LVEDD before implantation and E' after implantation. Age, gender, ischemic etiology, use of antiarrhythmic drugs, reverse remodeling and the other echocardiographic parameters did not predict AT. In multivariate logistic regression analysis, both LVEDD before implantation (OR 1.24, 95% CI 1.04-1.48, p = 0.019) and postimplantation E' (OR 0.27, 95% CI 0.09-0.76, p = 0.014) remained as independent predictors of AT. CONCLUSIONS: In patients undergoing CRT-D, episodes of ventricular tachyarrhythmia occur with high incidence, independently of echocardiographic response, with LVEDD before implantation and E' after implantation as the only independent predictors of AT in the medium-term. These results highlight the importance of combined devices with defibrillation capability