Citations

ABSTRACTIntroduction: Mycophenolate mofetil (MMF) is frequently used to treat myasthenia gravis, but there is little information to guide clinicians on the safety of reducing the dose in well‐controlled patients. Methods: This retrospective chart review at 3 institutions identified 92 patients who had undergone MMF taper after achieving either pharmacologic remission or minimal manifestations status. Statistical analysis was performed to assess differences in patient characteristics between patients who had successfully tapered MMF and those who relapsed. Results: Of 92 patients undergoing a taper, 30 relapsed. The relapses were mild, transient, and usually responded to increased MMF dose. MG crisis did not occur. The mean dose at time of relapse was 888 mg/day. Patients with relapses were tapered more quickly (8.4 vs. 62.4 months). Conclusions: Tapering MMF appears safe after years of disease stability. Reducing the dose at a dose of only 500 mg/day every 12 months is recommended. Muscle Nerve 52: 211–215, 2015

The field of gene transfer has developed in an era of expanding biomedical knowledge. The potential for gene transfer to treat cardiovascular disease is great, yet identified and unidentified barriers remain. Gene transfer and its ultimate application, gene therapy, require extensive details of not only the mechanism of disease but the biological implications of the vectors used to deliver the therapeutic genes as well. Many of these details are becoming available via the study of genomics. Genomics, the study of complete genetic sequences, holds the potential for enabling and amplifying the therapeutic hopes for gene transfer. Identification of new therapeutic genes, new regulatory sequences, and establishing the patterns of gene expression from tissues exposed to vectors and transgenes will rapidly advance the application of gene transfer. Finally, there are historical and ongoing lessons learned from the development of gene transfer that may be applicable to the challenging field of genomics and may enable its future success.

Plasma membrane calcium pumps differentially affect the pattern of calcium signals.

SummaryHighly sensitive flow cytometry studies may incidentally identify B cell clones when used to assess plasma cell clonality in bone marrows. Clinical history, which can help differentiate related clones (low grade B cell lymphoma with plasmacytic differentiation/LBCL‐PD) from unrelated ones (plasma cell proliferative disorder (PCPD) with an unrelated B cell clone), is often unavailable in referred specimens. We sought to identify morphologic or phenotypic features that would help predict the significance of these clones in the absence of history. We included only cases with identical light chain B and plasma cell clones, as determined by 6‐color flow cytometry with additional DNA ploidy analysis, in which the relationship between clones could be established by review of medical records. There were 26 cases; 18 were related (14 were Waldenstrom macroglobulinemia) and eight were unrelated (seven multiple myeloma). Features seen exclusively in LBCL‐PD include CD19+/CD45+ clonal plasma cell phenotype (66·7%, P = 0·0022) and morphologic features such as paratrabecular bone marrow involvement, increased mast cells, and plasma cells surrounding B‐cell nodules. Aneuploidy was identified exclusively in PCPD cases (75%, P = 0·000028). We conclude that CD19+/CD45+ clonal plasma cell phenotype and aneuploidy are useful in distinguishing related clones (LBCL‐PD) from unrelated clones (PCPD).

Despite preexisting cytomegalovirus (CMV) immunity, CMV‐seropositive liver transplantation (LT) patients remain at risk of CMV infection. We hypothesized that the pre‐transplant CMV antibody titer correlates with the risk of CMV reactivation. We conducted a retrospective study of CMV‐seropositive LT recipients who did not receive anti‐CMV prophylaxis from 2007 to 2013. The pre‐transplant CMV immunoglobulin G (IgG) titer, which was measured with an enzyme‐linked fluorescent immunoassay, was assessed as a risk factor for CMV reactivation with multivariate Cox proportional hazards models. The population consisted of 225 CMV‐seropositive LT patients with a median age of 57 years (interquartile range, 47‐62 years). The CMV titer distributions were as follows: <60 (40%) and ≥60 AU/mL (60%). The Kaplan‐Meier estimates for CMV infection were 17% at 3 months, 18% at 6 months, and 19% at 12 months after transplantation. In a univariate analysis, a marginally significant increased risk of CMV infection was seen in LT recipients with a pre‐transplant CMV IgG titer < 60 AU/mL versus ≥ 60 AU/mL [hazard ratio (HR), 1.79; 95% confidence interval (CI), 0.98‐3.28 (P =0.06)]. This risk was statistically significant in the subgroup of recipients who received allografts from CMV‐seropositive donors [HR, 2.21; 95% CI, 1.15‐4.26 (P =0.02)]. In a multivariate analysis, a pre‐transplant CMV IgG titer < 60 AU/mL was significantly associated with CMV infection [HR, 3.11; 95% CI, 1.60‐6.03 (P < 0.001)]. The other risk factors were high body mass index, donor CMV seropositivity, prolonged cold ischemic time, use of an interleukin‐2 receptor antagonist for induction therapy, and high numbers of post‐transplant infections. A lower pre‐transplant CMV antibody titer is significantly associated with CMV infection after LT. Quantitative measurement of CMV‐specific humoral immunity may have a potential role in improving the CMV prevention strategy in CMV‐seropositive LT recipients.Liver Transpl 21:539–546, 2015. © 2015 AASLD.

A 67-year-old male presented to the emergency department with concern for accidental aspiration of an aluminum beverage can pull tab. Neck and chest radiographs did not reveal an aspirated foreign body. Despite ongoing complaint of dysgeusia and adamancy of aspiration by the patient, he was discharged to home without recommendation for further follow-up. Seven months later, a computed tomography (CT) scan of the chest performed as part of an unrelated lung cancer work up confirmed the presence of a left mainstem bronchus metallic foreign body compatible with a pull tab. This case report illustrates the poor negative predictive value of radiographs for a suspected aluminum foreign body and demonstrates the superiority of CT for this purpose. In such presentations it is imperative to have a low threshold for performing further diagnostic evaluation with CT due to the relatively high radiolucency of aluminum.

Purpose To determine the optimal dose and schedule of anthracycline and taxane administration as adjuvant therapy for early-stage breast cancer. Patients and Methods A 2 × 2 factorial design was used to test two hypotheses: (1) that a novel continuous schedule of doxorubicin-cyclophosphamide was superior to six cycles of doxorubicin-cyclophosphamide once every 2 weeks and (2) that paclitaxel once per week was superior to six cycles of paclitaxel once every 2 weeks in patients with node-positive or high-risk node-negative early-stage breast cancer. With 3,250 patients, a disease-free survival (DFS) hazard ratio of 0.82 for each randomization could be detected with 90% power with two-sided α = .05. Overall survival (OS) was a secondary outcome. Results Interim analyses crossed the futility boundaries for demonstrating superiority of both once-per-week regimens and once-every-2-weeks regimens. After a median follow-up of 6 years, a significant interaction developed between the two randomization factors (DFS P = .024; OS P = .010) in the 2,716 patients randomly assigned in the original design, which precluded interpretation of the two factors separately. Comparing all four arms showed a significant difference in OS (P = .040) but not in DFS (P = .11), with all treatments given once every 2 weeks associated with the highest OS. This difference in OS seemed confined to patients with hormone receptor–negative/human epidermal growth factor receptor 2 (HER2) –negative tumors (P = .067), with no differences seen with hormone receptor–positive/HER2-negative (P = .90) or HER2-positive tumors (P = .40). Conclusion Patients achieved a similar DFS with any of these regimens. Subset analysis suggests the hypothesis that once-every-2-weeks dosing may be best for patients with hormone receptor–negative/HER2-negative tumors.

AbstractObjectivesApproximately 15% of patients with multiple myeloma (MM) exhibit a t(4;14) translocation, which often results in constitutive activation of the receptor tyrosine kinase (RTK) fibroblast growth factor receptor 3 (FGFR3). This study evaluated the efficacy and safety of dovitinib, an RTK inhibitor with in vitro inhibitory activity against FGFR, in patients with relapsed or refractory MM with or without t(4;14) translocation.MethodsAdult patients with relapsed or refractory MM who had received ≥2 prior regimens were enrolled in this multicenter, 2‐stage, phase 2 trial. Patients were grouped based on their t(4;14) status. Dovitinib (500 mg/day orally) was administered on a 5‐days‐on/2‐days‐off schedule. The primary endpoint was overall response rate by local investigator review (per International Myeloma Working Group criteria). In non‐responding patients, treatment could continue with the addition of low‐dose dexamethasone.ResultsIn total, 43 patients (median age, 63 years) were enrolled (13 t(4;14) positive, 26 t(4;14) negative, and 4 t(4;14) status non‐interpretable). Patients had received a median of 5 prior regimens. Median duration of treatment was 8.7 weeks in the t(4;14)‐positive group and 3.7 weeks in the t(4;14)‐negative group. None of the patients on dovitinib had objective responses. The stable disease rate was 61.5% in the t(4;14)‐positive group and 34.6% in the t(4;14)‐negative group. Overall, 39 patients (90.7%) had adverse events suspected to be related to study drug, most commonly diarrhea (60.5%), nausea (58.1%), vomiting (46.5%), and fatigue (32.6%).ConclusionDovitinib showed no single‐agent activity in relapsed or refractory MM but may stabilize disease in some t(4;14)‐positive patients.