Partial trisomy 14q24 leads to qter.

A newborn male with partial trisomy for the distal part of the long arm of chromosome 14 (14q24 leads to qter) is described. The anomaly arose as an adjacent 1 meiotic segregation product from a balanced translocation t(11;14) (q25;q24) in the mother (figure). To our knowledge only one previous case involving the same segment has been reported. The karyotype was confirmed as 46,XY,der(11),t(11;14)(q25;q24) mat.     

Diffuse “encephalitic” cerebral toxoplasmosis in AIDS

Summary Four patients with AIDS presented with a rapidly fatal global neurologicl illness. CT did not show any focal lesion and gross post mortem examination of the brain was normal in three of the four cases. Microscopic examination revealed numerous widespread microglial nodules in the brain parenchyma, most containing central toxoplama cysts or free tachyzoites. Such diffuse, non-necrotic, encephalitic forms of cerebral toxoplasmosis appear unique to ADIS and, to our knowledge, have not been documented previously. They represent a treatable, often misdiagnosed cause of diffuse neurological involvement in AIDS patients.     

A Randomized Encouragement Trial to Increase Mail Order Pharmacy Use and Medication Adherence in Patients with Diabetes

BackgroundMail order pharmacy (MOP) use has been linked to improved medication adherence and health outcomes among patients with diabetes. However, no large-scale intervention studies have assessed the effect of encouraging MOP use on medication adherence.ObjectiveTo assess an intervention to encourage MOP services to increase its use and medication adherence.DesignRandomized encouragement trial.Patients63,012 diabetes patients from three health care systems: Kaiser Permanente Northern California (KPNC), Kaiser Permanente Hawaii (KPHI), and Harvard Pilgrim Health Care (HPHC) who were poorly adherent to at least one class of cardiometabolic medications and had not used MOP in the prior 12 months.InterventionPatients were randomized to receive either usual care (control arm) or outreach encouraging MOP use consisting of a mailed letter, secure email message, and automated telephone call outlining the potential benefits of MOP use (intervention arm). HPHC intervention patients received the letter only.MeasurementsWe compared the percentages of patients that began using MOP and that became adherent to cardiometabolic medication classes during a 12-month follow-up period. We also conducted a race/ethnicity-stratified analysis.ResultsDuring follow-up, 10.6% of intervention patients began using MOP vs. 9.3% of controls (p < 0.01); the percent of cardiometabolic medication delivered via mail was 42.1% vs. 39.8% (p < 0.01). Metformin adherence improved in the intervention arm relative to control at the two KP sites (52% vs. 49%, p < 0.01). Stratified analyses suggested a significant positive effect of the intervention in White (RR: 1.12, 95% CI: 1.03, 1.22) and Asian (RR: 1.30, 95% CI: 1.17, 1.45) patients.ConclusionThis pragmatic trial showed that simple outreach to encourage MOP modestly increased its use and improved adherence measured by refills to a key class of diabetes medications in some settings. Given its minimal cost, clinicians and health systems should consider outreach interventions to actively promote MOP use among diabetes patients.Trial RegistrationClinicalTrials.gov registration number: {"type":"clinical-trial","attrs":{"text":"NCT02621476","term_id":"NCT02621476"}}NCT02621476KEY WORDS: diabetes, mail order pharmacy, medication adherence, encouragement trial     

Immediate versus delayed angioplasty in infarct-related arteries with TIMI III flow and ST segment recovery: a matched comparison in acute myocardial infarction patients

Background  Early management of patients with patent infarct-related artery (IRA) and optimal ST resolution in ST elevation myocardial infarction (STEMI) has never been assessed. We compared immediate vs delayed PCI in these patients. Methods  Matched comparison of immediate vs delayed (24 h) PCI in STEMI patients presenting with patent IRA, thrombus-containing lesion and ST resolution ≥70%. Patients were matched for duration of symptoms, intervention type, angiographic data, diabetes. Patients in immediate PCI group received standard therapy in the cathlab. Patients in delayed PCI group received dual antiplatelet therapy, antithrombins, and GPIIb-IIIa inhibitors until PCI. Primary endpoint was procedural success. Secondary endpoints were enzyme release and in-hospital adverse events. Results  Seventy-eight patients were included: 39 per group. Average age 62 years, 75% males. There was a significantly higher procedural success rate in the delayed PCI group (95% success, Vs. 77% in the immediate group, P = 0.008). Initial thrombus burden score did not differ between immediate and delayed PCI groups, but improved significantly in the delayed group between baseline angiography and time of PCI (P = 0.039). There was no difference in major adverse events or bleeding complications between groups. Peak CK levels were significantly higher in the immediate versus delayed PCI group (P = 0.02), although there was no difference between groups in peak CK-MB, peak troponin, or peak CK-MB ratio. Conclusion  Our data suggest that in STEMI patients with patent IRA, optimal ST-segment resolution, and thrombus-containing lesion, deferred PCI when patients are given dual antiplatelet therapy, antithrombin agents, and GPIIb-IIIa inhibitors results in a higher procedural success rate, without an increased risk of MACE.     

S-phase fraction and DNA ploidy in 633 T1T2 breast cancers: a standardized flow cytometric study.

The lack of a standardized methodology for quantifying DNA ploidy and S-phase fraction (SPF) by flow cytometry is hindering routine use of these markers in breast cancer management. In a retrospective clinical multicenter study, we validated a standardized flow cytometry protocol. We tested 633 frozen T(1)T(2), N(0)N(1), M(0) breast tumors obtained in four institutions. Cell preparation was standardized, and precise rules for data interpretation were followed. Three SPF classes were defined on the basis of tertiles after adjustment for ploidy. DNA aneuploidy was observed in 61.0% of cases. No significant difference was observed among centers. Aneuploidy and high SPF were associated with large tumor size, node involvement, high histological grade, and hormone receptor negativity. In the overall population (median follow-up, 69 months), patients with medium and high SPF values had shorter disease-free survival (DFS) than those with low SPF values (P < 0.0001). Ploidy had no significant influence. By Cox analysis, SPF, pN, and estrogen receptor status were independent predictors of DFS (P = 0.0002, P = 0.001, and P = 0.05). In node-negative patients, SPF was the only predictor of DFS (P = 0.01), whereas in node-positive patients, the risk of relapse increased with both high SPF (P = 0.003) and estrogen receptor negativity (P = 0.004). Low SPF values distinguished grade II tumors with a particularly good outcome. Our results strongly support the use of SPF in multicenter studies and clinical trials and suggest that node-negative patients with slowly proliferating tumors do not require systemic adjuvant therapy.     

Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10-producing suppressive CD4+ T cells

Dendritic cells (DCs) can initiate and shape host immune responses toward either immunity or tolerance by their effects on antigen-specific CD4(+) T cells. DC-asialoglycoprotein receptor (DC-ASGPR), a lectinlike receptor, is a known scavenger receptor. Here, we report that targeting antigens to human DCs via DC-ASGPR, but not lectin-like oxidized-LDL receptor, Dectin-1, or DC-specific ICAM-3-grabbing nonintegrin favors the generation of antigen-specific suppressive CD4(+) T cells that produce interleukin 10 (IL-10). These findings apply to both self- and foreign antigens, as well as memory and naive CD4(+) T cells. The generation of such IL-10-producing CD4(+) T cells requires p38/extracellular signal-regulated kinase phosphorylation and IL-10 induction in DCs. We further demonstrate that immunization of nonhuman primates with antigens fused to anti-DC-ASGPR monoclonal antibody generates antigen-specific CD4(+) T cells that produce IL-10 in vivo. This study provides a new strategy for the establishment of antigen-specific IL-10-producing suppressive T cells in vivo by targeting whole protein antigens to DCs via DC-ASGPR.