Standard (8 weeks) vs long (12 weeks) timing to minimally-invasive surgery after NeoAdjuvant Chemoradiotherapy for rectal cancer: A multicenter randomized controlled parallel group trial (TiMiSNAR)

Background: The optimal timing of surgery in relation to chemoradiation is still controversial. Retrospective analysis has demonstrated in the recent decades that the regression of adenocarcinoma can be slow and not complete until after several months. More recently, increasing pathologic Complete Response rates have been demonstrated to be correlated with longer time interval. The purpose of the trial is to demonstrate if delayed timing of surgery after neoadjuvant chemoradiotherapy actually affects pathologic Complete Response and reflects on disease-free survival and overall survival rather than standard timing. Methods: The trial is a multicenter, prospective, randomized controlled, unblinded, parallel-group trial comparing standard and delayed surgery after neoadjuvant chemoradiotherapy for the curative treatment of rectal cancer. Three-hundred and forty patients will be randomized on an equal basis to either robotic-assisted/standard laparoscopic rectal cancer surgery after 8 weeks or robotic-assisted/standard laparoscopic rectal cancer surgery after 12 weeks. Discussion: To date, it is well-know that pathologic Complete Response is associated with excellent prognosis and an overall survival of 90%. In the Lyon trial the rate of pCR or near pathologic Complete Response increased from 10.3 to 26% and in retrospective studies the increase rate was about 23-30%. These results may be explained on the relationship between radiation therapy and tumor regression: DNA damage occurs during irradiation, but cellular lysis occurs within the next weeks. Study results, whether confirmed that performing surgery after 12 weeks from neoadjuvant treatment is advantageous from a technical and oncological point of view, may change the current pathway of the treatment in those patient suffering from rectal cancer. Trial registration: ClinicalTrials.gov NCT3465982

Standard (8 weeks) vs long (12 weeks) timing to minimally-invasive surgery after NeoAdjuvant Chemoradiotherapy for rectal cancer: a multicenter randomized controlled parallel group trial (TiMiSNAR)

BACKGROUND: The optimal timing of surgery in relation to chemoradiation is still controversial. Retrospective analysis has demonstrated in the recent decades that the regression of adenocarcinoma can be slow and not complete until after several months. More recently, increasing pathologic Complete Response rates have been demonstrated to be correlated with longer time interval. The purpose of the trial is to demonstrate if delayed timing of surgery after neoadjuvant chemoradiotherapy actually affects pathologic Complete Response and reflects on disease-free survival and overall survival rather than standard timing. METHODS: The trial is a multicenter, prospective, randomized controlled, unblinded, parallel-group trial comparing standard and delayed surgery after neoadjuvant chemoradiotherapy for the curative treatment of rectal cancer. Three-hundred and forty patients will be randomized on an equal basis to either robotic-assisted/standard laparoscopic rectal cancer surgery after 8\u2009weeks or robotic-assisted/standard laparoscopic rectal cancer surgery after 12\u2009weeks. DISCUSSION: To date, it is well-know that pathologic Complete Response is associated with excellent prognosis and an overall survival of 90%. In the Lyon trial the rate of pCR or near pathologic Complete Response increased from 10.3 to 26% and in retrospective studies the increase rate was about 23-30%. These results may be explained on the relationship between radiation therapy and tumor regression: DNA damage occurs during irradiation, but cellular lysis occurs within the next weeks. Study results, whether confirmed that performing surgery after 12\u2009weeks from neoadjuvant treatment is advantageous from a technical and oncological point of view, may change the current pathway of the treatment in those patient suffering from rectal cancer

Efficacy and Drug Survival after Switching from Etanercept to the Biosimilar SB4: A Real-Life Long-Term Study

We evaluated the 3-year drug survival and efficacy of the biosimilar SB4/Benepali in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients, pre-viously treated with etanercept (ETA). Drug survival rate was calculated using the Kaplan\u2013Meier method and Cox proportional hazard models were developed to examine predictors of SB4 discontin-uation. 236 patients (120 RA, 80 PsA and 36 AS), aged 60.7 \ub1 13.8 years and with an ETA duration of 4.1 \ub1 3.4 years were included. The 3-year retention rate for SB4 was 94.4%, 88% and 86% in AS, RA and PsA patients, respectively, with no difference between groups. Patients without comorbid disease had higher retention rates vs. patients with comorbid disease (90% vs. 60%, p < 0.0001). Disease activity, as measured by DAS28, DAPSA and BASDAI remained stable over the 3 years. Comorbid disease (hazard ratio; HR: 4.06, p < 0.0001) and HAQ at baseline (HR: 2.42, p = 0.0024) significantly increased the risk of SB4 discontinuation, while previous ETA duration was negatively associated with SB4 discontinuation (HR: 0.97, p = 0.0064). Forty-one (17.4%) patients left the study due to the interruption of the SB4 treatment, 31 (75.6%) discontinued due to inefficacy and 10 (24.4%) due to adverse events. This real-life study confirms the similar efficacy profile of ETA with long-term retention and a good safety profile in inflammatory arthritis patients

Platelet function tests: a comparative review

Rita Paniccia,1,2 Raffaella Priora,1,2 Agatina Alessandrello Liotta,2 Rosanna Abbate1,2 1Department of Experimental and Clinical Medicine, Thrombosis Center, University of Florence, Florence, Italy; 2Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy Abstract: In physiological hemostasis a prompt recruitment of platelets on the vessel damage prevents the bleeding by the rapid formation of a platelet plug. Qualitative and/or quantitative platelet defects promote bleeding, whereas the high residual reactivity of platelets in patients on antiplatelet therapies moves forward thromboembolic complications. The biochemical mechanisms of the different phases of platelet activation – adhesion, shape change, release reaction, and aggregation – have been well delineated, whereas their complete translation into laboratory assays has not been so fulfilled. Laboratory tests of platelet function, such as bleeding time, light transmission platelet aggregation, lumiaggregometry, impedance aggregometry on whole blood, and platelet activation investigated by flow cytometry, are traditionally utilized for diagnosing hemostatic disorders and managing patients with platelet and hemostatic defects, but their use is still limited to specialized laboratories. To date, a point-of-care testing (POCT) dedicated to platelet function, using pertinent devices much simpler to use, has now become available (ie, PFA-100, VerifyNow System, Multiplate Electrode Aggregometry [MEA]). POCT includes new methodologies which may be used in critical clinical settings and also in general laboratories because they are rapid and easy to use, employing whole blood without the necessity of sample processing. Actually, these different platelet methodologies for the evaluation of inherited and acquired bleeding disorders and/or for monitoring antiplatelet therapies are spreading and the study of platelet function is strengthening. In this review, well-tried and innovative platelet function tests and their methodological features and clinical applications are considered. Keywords: platelets, method, point-of-care testing, laboratory assessment, bleeding, thrombosi

Measurement of mixed disulfides including glutathionylated proteins

Mixed disulfides between protein cysteines and low-molecular-weight thiol cysteine or glutathione lead to the formation of cysteinylated proteins or glutathionylated proteins. These types of posttranslational modification are of great importance in the so-called redox regulation, by which changes in the redox state of the cell regulate a number of biochemical processes. We describe the methods for quantitatively measuring the various redox states of cellular thiols including protein cysteines and these mixed disulfides. These include spectrophotometric methods, which do not distinguish between protein-cysteine and protein-glutathione disulfides, and HPLC methods that make such distinction. Finally, we report a method for labeling proteins susceptible to glutathionylation with biotin, to allow their visualization by Western blot after electrophoretic separation, which is used to identify proteins undergoing this posttranslational modification. © 2010 Elsevier Inc

The clinical presentation in adulthood of juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is a chronic systemic inflammatory disease, which affects children and adolescents, characterized by significant differences when compared to inflammatory rheumatisms in adulthood. Today, in a panorama enriched in the last decades with great improvements in the diagnostic and therapeutic field, a far from negligible portion and an increasing number of patients with JIA require the continuation of treatments in adulthood. This specific population of patients, given the high incidence of extra-articular manifestations, residual irreversible disabilities, comorbidities related to an inflammatory process and extended immunosuppressive treatments during the age of development, requires precise attentions in the follow-up and a multidisciplinary approach characterized by different clinical, psychological and social aspects

Ultrasound-guided intra-articular injection: Efficacy of hyaluronic acid compared to glucocorticoid in the treatment of knee osteoarthritis

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease which causes pain and functional impairment in adults over 50 years old with consequent important disability. Unfortunately, there is no definitive cure for OA, thus the approach is characterized by multiple treatments that can manage its symptoms. Even though data from randomized controlled trials and meta-analyses indicate that intra-articular hyaluronic acid (IAHA) offers the best benefit/risk balance among the various pharmacologic treatments to improve OA-related knee pain, there is a lack of agreement among national and international guidelines about such uses of IAHA for the medical management of symptomatic knee OA. To minimize confounding factors and biases, the aim of our study was to evaluate the efficacy of the different weight and concentration of IAHA treatment in patients suffering from knee OA comparing to glucocorticoids (GC) joint injections. Furthermore, to make the procedure more accurate and assessment more objective, we use ultrasonography (US) with power Doppler (PWD) to help us differentiate between active and inactive inflammation within joints and periarticular soft tissues. METHODS: We performed a retrospective evaluation of a cohort of patients with knee OA, diagnosed according to the ACR criteria, treated by US-guided joint injection of HA and GC. The patients were catalogued according to the type of treatment they underwent: group A, patients treated with HA (1.5%) >1500 kDa (three US-guided knee injections one week apart); group B, patients treated with HA (2%) 800-1200 kDa (three US-guided knee injections one week apart); group C, patients treated with glucocorticoids (three US-guided knee injections of triamcinolone acetate 40 mg one week apart). All patients were monitored for 6 months, evaluating: subjective pain using a 10-cm Visual Analogue Scale; pain, stiffness, and functionality using the Western Ontario and McMaster Universities Arthritis Index (WOMAC); the concomitant intake of anti-inflammatory and/or analgesic drugs through a questionnaire; and US results by grey scale and PWD. RESULTS: A total of 171 patients affected by knee OA were evaluated (women 72.3%) with a mean age of 69.3\ub14.1 years. All the subjects analyzed showed a pain reduction at 6 months after treatment (group A: -39.5; group B: -36.9; group C: -30.8). The difference between the three groups was statistically significant (Kruskall-Wallis P=0.001) and in particular between group A and group C (P=0.000) and between group B and group C (P=0.005), but not between A and B (P=0.258). WOMAC was statistically significantly improved from baseline in all groups examined (group A: -11.9; group B: -14.9; group C: -11.2). The PWD score showed a statistically significant improvement in group B (-0.64) even after 6 months (P=0.004). All patients in the different groups showed a statistically significant reduction of concomitant therapy compared to baseline with respect to paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs)/COX2 therapy, while only group B showed a statistically significant reduction for opioids. CONCLUSIONS: This study demonstrated the efficacy of OA treatment with medium molecular weight HA in favor of the higher concentration of HA that may affect the reduction of pro-inflammatory mediators. Furthermore, US monitoring allowed to evaluate aspects related to synovial involvement, which cannot be appreciated with standard imaging