Brentuximab vedotin in real life, a seven year experience in patients with refractory/relapsed CD30+ T cell lymphoma.

INTRODUCTION: Brentuximab vedotin (Bv) has been approved for the treatment of Refractory/Relapsed (R/R) Anaplastic Large Cell Lymphomas (ALCL) and cutaneous T-Cell Lymphomas, but is also effective in other CD30+ malignancies. We report here the outcomes of patients with various R/R Peripheral T Cell Lymphoma (PTCL) treated with Bv in real life practice. METHOD: This was a retrospective, single-center study based on medical records of patients with R/R PTCL treated either with Bv alone or in combination with chemotherapy. RESULTS: Among 27 patients treated with Bv, neutropenia was the main serious adverse event observed in particular when Bv was used as combination treatment. The complete Response Rates (CRR) was 40.7%; it was significantly improved when Bv was used as combination treatment. The majority of eligible patients (7/10) underwent Stem Cell Transplantation. Median Progression Free Survival (PFS) and Overall Survival (OS) were 5.2 months and 12.5 months respectively. CONCLUSION: Our current study shows that Bv used in combination with chemotherapy provides a high CRR and thereby allows SCT in R/R PTCL. The use of Bv treatments in this setting warrants further investigation.

Population Pharmacokinetic Study of the Suitability of Standard Dosing Regimens of Amikacin in Critically Ill Patients with Open-Abdomen and Negative-Pressure Wound Therapy.

The aim was to assess the appropriateness of recommended regimens for empirical MIC coverage in critically ill patients with open-abdomen and negative-pressure therapy (OA/NPT). Over a 5-year period, every critically ill patient who received amikacin and who underwent therapeutic drug monitoring (TDM) while being treated by OA/NPT was retrospectively included. A population pharmacokinetic (PK) modeling was performed considering the effect of 10 covariates (age, sex, total body weight [TBW], adapted body weight [ABW], body surface area [BSA], modified sepsis-related organ failure assessment [SOFA] score, vasopressor use, creatinine clearance [CLCR], fluid balance, and amount of fluids collected by the NPT over the sampling day) in patients who underwent continuous renal replacement therapy (CRRT) or did not receive CRRT. Monte Carlo simulations were employed to determine the fractional target attainment (FTA) for the PK/pharmacodynamic [PD] targets (maximum concentration of drug [Cmax]/MIC ratio of ≥8 and a ratio of the area under the concentration-time curve from 0 to 24 h [AUC0-24]/MIC of ≥75). Seventy critically ill patients treated by OA/NPT (contributing 179 concentration values) were included. Amikacin PK concentrations were best described by a two-compartment model with linear elimination and proportional residual error, with CLCR and ABW as significant covariates for volume of distribution (V) and CLCR for CL. The reported V) in non-CRRT and CRRT patients was 35.8 and 40.2 liters, respectively. In Monte Carlo simulations, ABW-adjusted doses between 25 and 35 mg/kg were needed to reach an FTA of >85% for various renal functions. Despite an increased V and a wide interindividual variability, desirable PK/PD targets may be achieved using an ABW-based loading dose of 25 to 30 mg/kg. When less susceptible pathogens are targeted, higher dosing regimens are probably needed in patients with augmented renal clearance (ARC). Further studies are needed to assess the effect of OA/NPT on the PK parameters of antimicrobial agents.

First cases of calcium pyrophosphate deposition disease after zoledronic acid therapy.

A number of medications promote the development of calcium pyrophosphate deposition disease (CPDD). We report 2 cases of acute CPDD after intravenous zoledronic acid therapy. Case #1: a 63-year-old female was admitted for vertebroplasty at the site of an osteoporotic fracture. She received an intravenous infusion of zoledronic acid 5mg on the day after the procedure. Acute CPDD developed in her right knee 24hours later. Findings from joint aspiration and standard radiography confirmed the diagnosis. Case #2: this 79-year-old woman had a history of CPDD was on glucocorticoid and hydroxychloroquine therapy for lupus. She was given an intravenous infusion of zoledronic acid 5mg as prophylaxis of glucocorticoid-induced osteoporosis. Joint pain and a fever developed later on the same day. After 5 days, she had arthritis of the right wrist, laboratory evidence of systemic inflammation, and hypocalcemia. Radiographs showed evidence of CPDD. A Medline search identified 6 cases of bisphosphonate-related CPDD, including 2 due to pamidronate, 2 to etidronate, 1 to alendronic acid, and 1 to neridronic acid. The features were similar to those in our patients, with a short time to onset, systemic inflammation in many cases, a tendency toward hypocalcemia, and radiographs that often showed evidence of CPDD. Bisphosphonate-induced CPDD is a rare eventuality that should nevertheless be borne in mind by rheumatologists. Also, in patients with CPDD while taking bisphosphonate therapy, a role for the drug in the symptoms should be considered.

Efficacy and safety of prasugrel in acute coronary syndrome patients.

Ischemic heart disease is the primary cause of death worldwide. The pathophysiological process of cardiovascular diseases is linked to atheromatous plaque formation, while plaque rupture releases thrombogenic elements, which lead to activation of platelets, blood clotting and formation of thrombi. Platelet inhibitors are used to prevent thrombosis. The present systematic review discusses the efficacy of prasugrel in terms of platelet inhibition potential and clinical prevention of cardiovascular outcomes. The balance between reduction of ischemic events as a measure of drug efficacy and the risk of bleeding is reviewed. Other adverse events observed in patients treated with this platelet inhibitor are discussed, including hematological complications, and cutaneous and hepatic idiosyncratic reactions. The complex relationship between prasugrel use and cancer promotion is also described.

Biologic therapies in inflammatory bowel disease.

Inflammatory bowel disease, including its 2 entities ulcerative colitis and Crohn's disease, is a chronic medical condition characterized by the destructive inflammation of the intestinal tract. Biologics represent a class of therapeutics with immune intervention potential. These agents block the proinflammatory cascade that triggers the activation and proliferation of T lymphocytes at the level of the intestine, therefore reestablishing the balance between the pro- and anti-inflammatory messages. All 7 biologics showing clinical benefits in inflammatory bowel disease are monoclonal antibodies. The following systematic review discusses the pharmacokinetics and efficacy of the tumor necrosis factor blockers infliximab, adalimumab, certolizumab pegol, and golimumab. In addition, we describe the α4 integrin inhibitors natalizumab and vedolizumab, which are directed against cell adhesion molecules, as well as the interleukin 12/23 blocker ustekinumab.