N-Acetylcistein for thrombotic thrombocytopenic purpura: an observational case series study.

Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder. N-Acetylcysteine (NAC) rapidly degrades ultra-large von Willebrand factor multimers by disrupting the disulfide bonds. We report a series of twelve consecutive patients diagnosed with acquired TTP successfully treated with high-dose NAC (150 mg/kg/day) in combination with plasma exchange and steroids. Eight patients also received rituximab. Two patients presented refractory TTP. All patients achieved a quick clinical response in a median time of 5.5 days after starting NAC and are alive after a median follow-up of 29 months. The treatment was feasible and well tolerated. These data provide further evidence of the potential benefit and safety of adding NAC to the standard of care.

Intervertebral Disc Repair by Allogeneic Mesenchymal Bone Marrow Cells: A Randomized Controlled Trial.

BACKGROUND: Degenerative disc disease often causes severe low-back pain, a public health problem with huge economic and life quality impact. Chronic cases often require surgery, which may lead to biomechanical problems and accelerated degeneration of the adjacent segments. Autologous mesenchymal stromal cells (MSC) treatments have shown feasibility, safety and strong indications of clinical efficacy. We present here a randomized, controlled trial using allogeneic MSC, which are logistically more convenient than autologous cells. METHODS: We randomized 24 patients with chronic back pain diagnosed with lumbar disk degeneration and unresponsive to conservative treatments into 2 groups. The test group received allogeneic bone marrow MSCs by intradiscal injection of 25 × 10 cells per segment under local anesthesia. The control group received a sham infiltration of paravertebral musculature with the anesthetic. Clinical outcomes were followed up for 1 year and included evaluation of pain, disability, and quality of life. Disc quality was followed up by magnetic resonance imaging. RESULTS: Feasibility and safety were confirmed and indications of clinical efficacy were identified. MSC-treated patients displayed a quick and significant improvement in algofunctional indices versus the controls. This improvement seemed restricted to a group of responders that included 40% of the cohort. Degeneration, quantified by Pfirrmann grading, improved in the MSC-treated patients and worsened in the controls. CONCLUSIONS: Allogeneic MSC therapy may be a valid alternative for the treatment of degenerative disc disease that is more logistically convenient than the autologous MSC treatment. The intervention is simple, does not require surgery, provides pain relief, and significantly improves disc quality.

An automatic wash method for dimethyl sulfoxide removal in autologous hematopoietic stem cell transplantation decreases the adverse effects related to infusion.

BACKGROUND: Products cryopreserved with dimethyl sulfoxide (DMSO) in stem cell transplant (SCT) often cause many adverse effects during their infusion (major cardiovascular events, dyspnea … even death). These are especially frequent in pediatric patients. We tested if a fully automated and closed wash procedure (Sepax S-100, Biosafe) allowed us to maintain the absolute CD34+ cell number, cell viability, and engraftment potential, decreasing the untoward reactions. STUDY DESIGN AND METHODS: Forty-six washes of DMSO cryopreserved peripheral blood hematopoietic progenitor (HP) apheresis were studied. Blood aliquots were taken both after thawing and after washing to assess the total nucleated and CD34+ cell counts, as well as cell viability. The washed products were infused in 26 autologous SCTs (ASCTs). Results were compared with the 53 previous SCTs performed without DMSO removal. RESULTS: After washing there were no significant differences between the pre- and postwashing CD34+ cell counts (p=0.08) or viability (p=0.68). No significant differences were observed between washed and nonwashed infusions in relation to the day of the neutrophil (p=0.46) and platelet (p=0.26) engraftment. One adverse event, abdominal pain, occurred during the washed cells infusions. When compared with the 14 untoward reactions that took place during the nonwashed HP infusions, significance was reached (p=0.00043). CONCLUSIONS: The automatic method described is effective in terms of CD34+ cell recovery and viability in ASCT. Moreover, Sepax decreased significantly the untoward reactions during the infusion.

A systematic review of the antifungal effectiveness and tolerability of amphotericin B formulations.

OBJECTIVE: A systematic review was performed to compare the effectiveness and tolerability of lipid-based amphotericin B (AmB) formulations and conventional AmB in the treatment of systemic fungal infections. METHODS: The literature and unpublished studies were searched using MEDLINE, EMBASE, Biological Abstracts, AIDSLINE, CANCERLIT, CRD database, Cochrane Controlled Trials Register, and other databases. Search terms included: amphotericin, liposom*, lipid*, colloid*, antifungal agents, and mycoses. Studies were selected according to predetermined criteria. The outcome measures reviewed were efficacy, mortality, renal toxicity, and infusion-related reactions. Meta-analyses and number-needed-to-treat (NNT) analyses were performed. RESULTS: Seven studies (8 publications) met the entry criteria. Meta-analysis showed that lipid-based formulations significantly reduced all-cause mortality risk by an estimated 28% compared with conventional AmB (odds ratio [OR], 0.72; 95% CI, 0.54 to 0.97). There was no significant difference in efficacy between the lipid-based formulations and conventional AmB (OR, 1.21; 95% CI, 0.98 to 1.49). AmB lipid complex (ABLC) and liposomal AmB (L-AmB) significantly reduced the risk of doubling serum creatinine by an estimated 58% (OR, 0.42; 95% CI, 0.33 to 0.54). There was no significant reduction in risk of infusion-related reactions with lipid-based formulations, although this was difficult to interpret given the lack of consistent control of confounding factors. Comparing the lipid-based formulations with conventional AmB, the overall NNT to prevent 1 death was 31. The NNT to prevent a doubling of serum creatinine for both ABLC and L-AmB compared with conventional AmB was 6. CONCLUSIONS: This study demonstrates advantages with lipid-based formulations over conventional AmB in terms of reduced risk of mortality and renal toxicity. Future trials in patients with proven fungal infection should control for factors such as premedication, infusion rates, fluid preloading, sodium/potassium supplementation, and concomitant medication.