Comparison of a transfusion preparation of newly formed red cells and standard washed red cell transfusions in patients with homozygous beta- thalassemia

BACKGROUND: Previous studies of transfusions of newly formed red cells (neocytes) demonstrated modest extensions of transfusion interval in patients with homozygous beta-thalassemia. STUDY DESIGN AND METHODS: The clinical benefits of a new system of neocyte preparation (Neocel, Cutter Biological, Berkeley, CA), reported to combine ease of preparation with reduction in the transfusion requirements of thalassemia patients, were evaluated. Sixteen thalassemic patients who had undergone splenectomy received eight consecutive, standard, automated, washed red cell transfusions (standard transfusions), followed by eight transfusions with the neocyte preparation (neocyte transfusions). In each arm of the study, mean pretransfusion hemoglobin and mean red cell mass transfused were carefully controlled and were similar. RESULTS: A significant (p < 0.0001) extension of transfusion interval was observed in patients receiving neocyte transfusions (mean +/− SD; 38.7 +/− 34 days; range, 35.0-44.5), over that in those receiving standard transfusions (32.9 +/− 2.5 days; range, 29.6-38.5). The mean prolongation of transfusion interval by neocyte transfusion corresponded to a mean reduction of 25 mL in packed red cells transfused per kg of body weight per patient per year and a mean reduction in transfused iron of 15 percent per year per patient. During neocyte transfusions, blood preparation costs were considerably increased and donor exposure was significantly (p < 0.0005) higher than during the standard transfusion period. CONCLUSION: These data demonstrate that extension of the transfusion interval, and reduction in transfused iron, may be achieved in thalassemic patients by use of the Neocel system. These benefits are achieved, however, with substantial increases in donor exposure and in component preparation costs.     

Rehabilitation following hand transplantation

Background

Hand allotransplantation can restore motor, sensory and cosmetic functions to upper extremity amputees. Over 70 hand transplant operations have been performed worldwide, but there is little published regarding post-hand transplant rehabilitation.

Methods

The Brigham and Women's Hospital (BWH) Hand Transplantation Team's post-hand transplant rehabilitation protocol is presented here. The protocol must be modified to address each transplant recipient's unique needs. It builds on universally used modalities of hand rehabilitation such as splinting, edema and scar management, range of motion exercises, activities of daily living training, electrical stimulation, cognitive training and strengthening.

Results

The BWH hand transplant rehabilitation protocol consists of four phases with distinct goals, frequency, and modalities. (1) Pre-operative: functional assessments are completed and goals and expectations of transplantation are established. (2) Initial post-operative (post-operative weeks 1–2): hand protection, minimization of swelling, education, and discharge. (3) Intermediate (post-operative weeks 2–8): therapy aims to prevent and/or decrease scar adhesion, increase tensile strength, flexibility and function, and prevent joint contractures. (4) Late (from 8 weeks forward): maximization of function and strength, and transition to routine activities. The frequency of rehabilitation therapy decreases gradually from the initial to late phases.

Conclusions

Rehabilitation therapy after hand transplantation follows a progressive increase in activity in parallel with wound healing and nerve regeneration. Careful documentation of progress and outcomes is essential to demonstrate the utility of interventions and to optimize therapy protocols.     

Randomized controlled trial of interpersonal psychotherapy versus enhanced treatment as usual for women with co-occurring depression and pelvic pain

Objective

Our study assessed the effectiveness of Interpersonal Psychotherapy (IPT) tailored for biomedical patients with depression and pain. IPT was compared to enhanced treatment as usual (E-TAU) among women with co-occurring depression and chronic pain presenting for care at a women's health or family medicine practice. We hypothesized that women presenting to urban medical practices with depression and chronic pain would benefit from IPT tailored to address their needs to a greater degree than from E-TAU.

Methods

We conducted a randomized controlled psychotherapy trial of 61 women from 2 urban medical practices who met criteria for major depressive disorder and chronic pelvic pain. Participants were assigned to receive either 8 sessions of IPT or a facilitated psychotherapy referral to a community mental health center, and assessed for depression, social interactions, and pain at 0-, 12-, 24-, and 36-weeks, with score on the Hamilton Rating Scale for Depression as the primary outcome. Both intent-to-treat (ITT) and causal modeling analyses correcting for treatment attendance were conducted.

Results

ITT analyses were not significant. In causal modeling analyses, participants assigned to IPT showed significantly more improvement for depression and social interactions, but not for pain.

Conclusion

IPT may be a viable option as part of a comprehensive treatment program for women in medical practices with depression and chronic pain.Clinical Trials Registration: Clinical Trials.gov, www.clinicaltrials.gov, NCT00895999.     

Daratumumab,bortezomib and dexamethasone at first relapse for patients with multiple myeloma: A real-world multicentre UK retrospective analysis

Daratumumab, bortezomib and dexamethasone (DVd) is approved for patients with relapsed multiple myeloma following the CASTOR phase 3 clinical trial. This retrospective multicentre analysis assesses the overall response rate (ORR) and progression-free survival (PFS) in routine clinical practice for patients at first relapse treated with DVd incorporating weekly bortezomib. Data were collected from 296 sequential patients treated across 15 UK centres. After a median follow-up of 21 months, the ORR was 82% (26% partial response, 56% very good partial response or better) and the median PFS was 16 months [95% confidence interval (CI) 12–20 months]. Results were similar regardless of prior lenalidomide exposure. The median time to next treatment was 20 months (95% CI 15–25 months) and the estimated overall survival at two years was 74%. Patients with high-risk features (by cytogenetics, International Staging System or extramedullary disease) and those treated within 18 months of initiation of progression-free treatment, or within 12 months of autologous stem cell transplant, had significantly inferior outcomes. The grade 2 and 3 peripheral neuropathy rate was 7%. DVd with weekly bortezomib was effective in a heterogenous real-world population at first relapse with a low rate of peripheral neuropathy. However, high-risk patients had inferior outcomes and should be considered for alternative treatments.     

Schwann cell spectrins modulate peripheral nerve myelination

During peripheral nerve development, Schwann cells ensheathe axons and form myelin to enable rapid and efficient action potential propagation. Although myelination requires profound changes in Schwann cell shape, how neuron-glia interactions converge on the Schwann cell cytoskeleton to induce these changes is unknown. Here, we demonstrate that the submembranous cytoskeletal proteins αII and βII spectrin are polarized in Schwann cells and colocalize with signaling molecules known to modulate myelination in vitro. Silencing expression of these spectrins inhibited myelination in vitro, and remyelination in vivo. Furthermore, myelination was disrupted in motor nerves of zebrafish lacking αII spectrin. Finally, we demonstrate that loss of spectrin significantly reduces both F-actin in the Schwann cell cytoskeleton and the Nectin-like protein, Necl4, at the contact site between Schwann cells and axons. Therefore, we propose αII and βII spectrin in Schwann cells integrate the neuron-glia interactions mediated by membrane proteins into the actin-dependent cytoskeletal rearrangements necessary for myelination.     

Dysbindin-1 mutant mice implicate reduced fast-phasic inhibition as a final common disease mechanism in schizophrenia

DTNBP1 (dystrobrevin binding protein 1) is a leading candidate susceptibility gene in schizophrenia and is associated with working memory capacity in normal subjects. In schizophrenia, the encoded protein dystrobrevin-binding protein 1 (dysbindin-1) is often reduced in excitatory cortical limbic synapses. We found that reduced dysbindin-1 in mice yielded deficits in auditory-evoked response adaptation, prepulse inhibition of startle, and evoked γ-activity, similar to patterns in schizophrenia. In contrast to the role of dysbindin-1 in glutamatergic transmission, γ-band abnormalities in schizophrenia are most often attributed to disrupted inhibition and reductions in parvalbumin-positive interneuron (PV cell) activity. To determine the mechanism underlying electrophysiological deficits related to reduced dysbindin-1 and the potential role of PV cells, we examined PV cell immunoreactivity and measured changes in net circuit activity using voltage-sensitive dye imaging. The dominant circuit impact of reduced dysbindin-1 was impaired inhibition, and PV cell immunoreactivity was reduced. Thus, this model provides a link between a validated candidate gene and an auditory endophenotypes. Furthermore, these data implicate reduced fast-phasic inhibition as a common underlying mechanism of schizophrenia-associated intermediate phenotypes.