Autologous stem cell transplant in 716 patients with multiple myeloma: low treatment-related mortality, feasibility of outpatient transplant, and effect of a multidisciplinary quality initiative

We report on the feasibility of outpatient transplant in 716 patients undergoing autologous stem cell transplant for multiple myeloma at Mayo Clinic's site in Rochester, MN, from January 1, 2000, through October 31, 2007. We also report on the development and effect of a multidisciplinary quality initiative implemented by the Mayo Clinic Blood and Marrow Transplant Program involving physicians, nurses, pharmacists, dietitians, and financial specialists for outpatient management of patients undergoing stem cell transplant. This approach uses an electronic ordering system for diagnostic tests and chemotherapy to minimize medical errors. Analysis of hospitalization trends since inception of the program showed that 278 (39%) of the 716 patients treated completed the transplant procedure as outpatients. The median duration of hospitalization for all patients was 4 days; age and serum creatinine levels were predictive of the need for and duration of hospitalization. We also assessed recent treatment-related mortality rates during a 33-month period after implementation of the program (between January 1, 2005, and October 1, 2007). The 100-day survival rate was 99.5% for patients with low-risk myeloma (transplant during first plateau; n=201) and 97.2% for patients with high-risk myeloma (refractory, relapsing or second or greater plateau; n=71). The overall 100-day survival rate was 98.9%. Our experience shows that outpatient transplant is feasible for all patients with multiple myeloma and results in shorter hospital stays and low treatment-related mortality rates.     

The A3 adenosine receptor: an enigmatic player in cell biology

Adenosine is a primordial signaling molecule present in every cell of the human body that mediates its physiological functions by interacting with 4 subtypes of G-protein-coupled receptors, termed A1, A2A, A2B and A3. The A3 subtype is perhaps the most enigmatic among adenosine receptors since, although several studies have been performed in the years to elucidate its physiological function, it still presents in several cases a double nature in different pathophysiological conditions. The 2 personalities of A3 often come into direct conflict, e.g., in ischemia, inflammation and cancer, rendering this receptor as a single entity behaving in 2 different ways. This review focuses on the most relevant aspects of A3 adenosine subtype activation and summarizes the pharmacological evidence as the basis of the dichotomy of this receptor in different therapeutic fields. Although much is still to be learned about the function of the A3 receptor and in spite of its duality, at the present time it can be speculated that A3 receptor selective ligands might show utility in the treatment of ischemic conditions, glaucoma, asthma, arthritis, cancer and other disorders in which inflammation is a feature. The biggest and most intriguing challenge for the future is therefore to understand whether and where selective A3 agonists or antagonists are the best choice.     

Serial casting versus positioning for the treatment of elbow contractures in adults with traumatic brain injury: a randomized controlled trial

OBJECTIVE: To compare the effects of serial casting with positioning for 1 hour per day for the treatment of elbow flexion contracture in adults with traumatic brain injury. DESIGN: Pragmatic randomized controlled trial with concealed allocation and assessor blinding. SETTING: Four brain injury rehabilitation units. SUBJECTS: Twenty-six adults with elbow flexion contracture after traumatic brain injury participating in multidisciplinary inpatient rehabilitation. INTERVENTIONS: Subjects were randomized to receive either serial casting or positioning for two weeks. In the subsequent four weeks subjects could be positioned for up to 1 hour/day. MAIN MEASURES: Torque-controlled passive elbow extension was measured at baseline, post-intervention (two weeks), post-intervention plus one day, and at follow-up (four weeks post-intervention). RESULTS: All 26 subjects completed the study. Post-intervention, serial casting reduced contracture by an average of 22 degrees (95% confidence interval (CI) 13 to 31; P <0.001) compared with the positioning group. One day later this effect had decreased to 11 degrees (95% CI 0 to 21 degrees; P= 0.052). The effect had almost completely disappeared at the four-week follow-up (mean 2 degrees, 95% CI -13 to 17; P= 0.782). CONCLUSIONS: Serial casting induces transient increases in range of motion. These effects are not maintained.     

Pediatric liver transplantation in Hong Kong—a domain with scarce deceased donors

Aim

The study aimed to assess the outcome of live-donor liver transplantation for pediatric patients in a region with limited access to deceased donors.

Patients and Methods

From September 1993 to September 2008, 78 pediatric patients aged between 73 days and 17 years (mean, 40 months) received 83 liver transplants. Sixty-two were living-related liver transplantations (LRLTs), and 21 were deceased-donor liver transplantations (DDLTs). The mean follow-up period was 6.5 years. The prospectively collected data of these patients were analyzed retrospectively.

Results

The 1-, 2-, and 5-year survival rates of patients and grafts were 91%, 90%, 88% and 87%, 86%, 83%, respectively. The survival rates of LRLT patients and DDLT patients were 89%, 89%, 87%, and 90%, 86%, 86%, respectively (P = .58). The survival rates of patients aged 12 months or younger and patients older than 12 months were 95%, 92%, 90% and 90%, 90%, 87%, respectively (P = .65). One live donor developed temporary peroneal palsy, and another developed lung collapse (3%, 2/62). All live donors resumed their normal activities with no difficulty.

Conclusion

With meticulous surgical techniques and postoperative care, it is justifiable to accept donated livers from voluntary live donors for transplantation to save pediatric patients in a place with scarce deceased donors.     

Measuring vocabulary by free expression and recognition tasks: Implications for assessing children, adolescents, and young adults

Vocabulary tests are commonly used for assessing verbal ability. Most vocabulary tests employ the free expressive format that taps both verbal knowledge and expressive ability. The recognition format, which requires less expressive ability, has been suggested to be more sensitive in assessing the fund of verbal knowledge. We assessed vocabulary performance of 285 normal individuals (aged 6 to 23 years) using both free expressive and recognition tasks. Results showed that participants aged 6 to 15 performed significantly better on the recognition than on the free expressive task. While the recognition task significantly correlated with the Test of Nonverbal Intelligence-Third Edition (TONI-III) IQ for individuals aged 9 and above, the free expressive task correlated with TONI-III IQ only for young adults. Shortened 18-item versions yielded high reliability and correlation with the full version and reliable association with TONI-III IQ. These results highlight the utility of recognition tasks in measuring the fund of knowledge and suggest the possibility of developing shorter vocabulary tests for more cost-effective assessment.     

Sorl1 as an Alzheimer's disease predisposition gene?

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressively disabling impairments in memory, cognition, and non-cognitive behavioural symptoms. Sporadic AD is multifactorial and genetically complex. While several monogenic mutations cause early-onset AD and gene alleles have been suggested as AD susceptibility factors, the only extensively validated susceptibility gene for late-onset AD is the apolipoprotein E (APOE) epsilon4 allele. Alleles of the APOE gene do not account for all of the genetic load calculated to be responsible for AD predisposition. Recently, polymorphisms across the neuronal sortilin-related receptor (SORL1) gene were shown to be significantly associated with AD in several cohorts. Here we present the results of our large case-control whole-genome scan at over 500,000 polymorphisms which presents weak evidence for association and potentially narrows the association interval.     

Arthroscopic hemitrapeziectomy with tendon interposition for arthritis at the first carpometacarpal joint

The first carpometacarpal (CMC) joint, also referred to as trapeziometacarpal joint, is the area of the hand most commonly symptomatic of osteoarthritis. Although there are a variety of surgical techniques that treat this condition, this article focuses on the technical aspects of arthroscopic hemitrapeziectomy with tendon interposition. Furthermore, this study evaluated the use of arthroscopy to treat CMC arthritis, with the expectation that an arthroscopic procedure would lead to low morbidity, quick recovery of function, rapid resolution of pain, and satisfactory results in patients' strength, range of motion, and pain relief. Early outcomes data indicate that all patients experienced statistically significant improvement in their pain scale rating at a mean of 11 months after the operation. All patients were satisfied with the outcome of their surgery. All patients would choose to have this surgery again. This study supports arthroscopic hemitrapeziectomy with tendon interposition as a safe and effective treatment for CMC arthritis.     

The use of enteric-coated mycophenolate sodium in the treatment of relapsing and steroid-dependent minimal change disease

We report on the successful treatment of 5 consecutive adult patients with steroid-dependent or frequently relapsing minimal change disease (MCD), using a regimen of enteric-coated mycophenolate sodium (E-MPS) and prednisolone. E-MPS was used for induction therapy in 3 patients, and maintenance therapy in 2, all in conjunction with steroid treatment in tapering doses. Eventually 4 patients managed to discontinue steroid treatment, and 2 of them were also withdrawn from E-MPS. This combination therapy resulted in sustained remission and was well tolerated by our patients, with no signs of gastrointestinal upset, marrow suppression or increased incidence of infections. Our preliminary experience suggests that E-MPS is a promising new alternative in the management of steroid-dependent and relapsing MCD with a possibility of improving gastrointestinal tolerance.