Increased risk of bone loss without fracture risk in long-term survivors after allogeneic stem cell transplantation.

We studied bone mineral density (BMD) in 79 long-term survivors of allogeneic stem cell transplantation (SCT) (median follow-up: 78 months; range: 38-160). Seventy patients received a total body irradiation (TBI)-based myeloablative SCT and 9 patients received a non-TBI, reduced-intensity SCT. Fourteen (18%) patients were receiving immunosuppressive therapy (IST) for chronic graft-versus-host disease (cGVHD) beyond 3 years from SCT. Fifty-eight (73.4%) of patients had bone loss (BL): 33 (41.8%) with osteopenia and 25 (31.6%) with osteoporosis. Factors associated with a significantly increased risk of osteoporosis were age and prolonged IST and for overall BL prolonged IST. However, BL was not associated with an increased fracture risk, despite the fact that most patients had not received prophylactic biphosphonates. Our data shows that BL is a long-term posttransplant complication, and emphasize the importance of serial BMD scans, and the treatment of BL with biphosphonates reserved for worsening BL or additional risk factors.     

Fluorescent Amplified-Fragment Length Polymorphism Analysis of an Outbreak of Group A Streptococcal Invasive Disease

Fluorescent amplified-fragment length polymorphism (FAFLP) analysis was carried out for an outbreak of group A streptococcal (GAS) invasive disease. Streptococcal genomic DNAs were digested with endonucleases EcoRI and MseI, site-specific adaptors were ligated, and PCR amplification was carried out with an EcoRI adaptor-specific primer labelled with fluorescent dye. Amplified fragments of up to 600 bp in size were separated on a polyacrylamide sequencing gel which contained internal size markers in each lane. These data were automatically scanned and analyzed, fragments were precisely sized (±1 bp), and electropherograms were generated for each genome with GeneScan 2.1 software. All isolates were compared in this way. Among 27 GAS isolates examined, we found 18 FAFLP profiles, compared with 12 macrorestriction profiles by pulsed-field gel electrophoresis. FAFLP readily distinguished genotypes for two clones of GAS serotype M77 which were responsible for outbreaks of invasive disease in a care-of-the-elderly system. It provided an automated analysis of the whole genome of bacterial isolates. It was reproducible, more discriminatory, and capable of higher throughput than other molecular typing methods. Given agreed conditions, FAFLP would be reproducible between laboratories for rapid characterization of outbreak strains.     

Augmentation of cisplatin cytotoxicity using cytokines on cervical carcinoma cell lines

We investigated whether the biological response modifiers like IFN-alpha, IFN-gamma and TNF-alpha could enhance the cytotoxic action of cisplatin on cervical carcinoma cell lines in vitro. The sensitivity of three cell lines SiHa, ME 180 and C33A to these agents was tested using colorimetric MTT assay as well as tritiated thymidine uptake. All the three cell lines demonstrated range of sensitivity to cisplatin and cytokines. Interferons and TNF when used in combination with lower dose of cisplatin showed a significant enhancement of cytotoxic action of the drug in all the cell lines. Thus these data indicate that cytokines in concert with the drug may have a potential to improve the 'in vivo' therapy in these patients.     

A randomized, double-blinded comparison of Thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients

BACKGROUND: The aim of this study was to compare the efficacy and safety of Thymoglobulin (a rabbit-derived polyclonal antibody) to Atgam (a horse-derived polyclonal antibody) for induction in adult renal transplant recipients. METHODS: Transplant recipients (n=72) were randomized 2:1 in a double-blinded fashion to receive Thymoglobulin (n=48) at 1.5 mg/kg intravenously or Atgam (n=24) at 15 mg/kg intravenously, intraoperatively, then daily for at least 6 days. Recipients were observed for at least 1 year of follow-up. RESULTS: By 1 year after transplantation, 4% of Thymoglobulin-treated patients experienced acute rejection compared with 25% of Atgam-treated patients (P=0.014). The rate of acute rejection was lower with Thymoglobulin than Atgam (relative risk=0.09; P=0.009). Rejection was less severe with Thymoglobulin than Atgam (P=0.02). No recurrent rejection occurred with Thymoglobulin compared with 33% with Atgam (P=NS). Patient survival was not different, but the composite end point of freedom from death, graft loss, or rejection, the "event-free survival," was superior with Thymoglobulin (94%) compared with Atgam (63%; P=0.0005). Fewer adverse events occurred with Thymoglobulin (P=0.013). Leukopenia was more common with Thymoglobulin than Atgam (56% vs. 4%; P<0.0001) during induction. The mean absolute lymphocyte count remained below baseline with Thymoglobulin throughout the study (P<0.007), but with Atgam, significant lymphocyte reductions occurred only at day 7. The incidence of cytomegalovirus disease was less with Thymoglobulin than Atgam at 6 months (10% vs. 33%; P=0.025). CONCLUSIONS: Brief (7-day) induction with Thymoglobulin resulted in less frequent and less severe rejection, a better event-free survival, less cytomegalovirus disease, fewer serious adverse events, but more frequent early leukopenia than induction with Atgam. These results may in fact be explained by a more profound and durable beneficial lymphopenia.     

The Case for Enrolling High-Cost Patients in an ACO

Though accountable care organizations (ACOs) are increasingly important to American healthcare, ethical inquiry into ACOs remains in its nascent stages. Several articles have raised the concern that ACOs have an incentive to avoid enrolling high-cost patients and, thereby, have an incentive to deny care to those who need it the most. This concern is borne out by the reports of consultants working with newly formed ACOs. This paper argues that, contra initial appearances, there is no financial incentive for ACOs to avoid enrolling high-cost patients.     

ST segment depression in acute anterior myocardial infarction

We initiated a retrospective study to determine whether ST segment depression seen in inferior leads (II, III, and aVF) during acute anterior myocardial infarction (MI) is a reciprocal change or an independent sign of ischemia of additional myocardium. We selected 20 patients with anterior MI and attempted to compare findings of subsequent cardiac catheterization and the clinical course of 14 patients with ST segment depression (group A) and six without ST segment depression (group B). Patients in group A had a higher prevalence of right coronary artery disease (13 vs 0, P less than .01), multivessel disease (14 vs two, P less than .01), inferior wall motion abnormalities (seven vs 0, P less than .01), and ejection fraction of less than .50 (ten vs two, P greater than .05) than those in group B. A greater number of patients in group A had serious in-hospital and follow-up complications (12 vs two, P less than .05). We conclude that ST depression in leads II, III and aVF during acute anterior MI is not "reciprocal change" but a high-risk indicator.