Hospitalization patterns in severe acute asthma in children

We set out to determine associations between hospitalization and disease severity before and 2 hours after initiation of asthma therapy in the Emergency Department, and to describe the outcome of patients admitted and discharged. This is a retrospective review of data and charts from a randomized, double blind, placebo-controlled trial (R.C.T.) of 120 asthmatics 5–17 years of age with baseline forced expiratory volume in 1 second (FEV₁) <50% predicted, treated with 3 or 1 or 0 doses of nebulized ipratropium added to three albuterol nebulizations administered over 1 hour. None of the clinical parameters measured at baseline were associated with hospitalization. However, by 2 hours after initiation of therapy, both the FEV₁ percent of predicted values (% pred.) and the total asthma score were associated with likelihood of hospital admission. Baseline O₂ saturation <92% indicated a longer hospital stay (75.3 ± 51 hours vs. 43.0 ± 24.4 hours, P = 0.015) and a later onset of infrequent nebulizations (46.7 ± 35.1 vs. 26.6 ± 17.4 hours, P = 0.006). By 2 hours, those with a post-treatment FEV₁ % pred ≤30% and an asthma score ≥6 of 9 had a high likelihood of hospitalization (86 and 80%, respectively, combined probability 100%), whereas FEV₁ % pred ≥60% and total asthma score <3 were associated with successful discharge (probability of 92 and 83%, respectively). We conclude that pre-treatment assessments were not associated with hospitalization, while patients with post-treatment FEV₁ % pred ≤30% and a score ≥6 had high likelihood of hospitalization. Pediatr. Pulmonol. 1997; 23:184–192 © 1997 Wiley-Liss, Inc.     

Hodgkin lymphoma arising in patients with chronic lymphocytic leukemia: outcomes from a large multi-center collaboration

Chronic lymphocytic leukemia (CLL) patients who develop Hodgkin lymphoma (HL) have limited survival. No current therapeutic standard of care exists. We conducted a multi-center retrospective study of patients with Hodgkin transformation (HT) of CLL. Clinicobiologic characteristics, treatment type, and survival outcomes were analyzed and compared with historic case series. Ninety-four patients were identified. Median age at HT was 67 years (range, 38-85). Median time from CLL diagnosis to HT was 5.5 years (range, 0-20.2). Prior to HT, patients received a median of two therapies for CLL (range, 0-12). As initial therapy for HT, 61% (n=62) received ABVD-based regimens (adriamycin, bleomycin, vinblastine, and dacarbazine). Seven (7%) patients received hematopoietic cell transplantation (HCT) while in first complete remission (CR1). The median number of treatments for HT per patient was one (range, 0-5) with 59 (61%) patients only receiving one line of therapy. After HT, patients had a median follow-up of 1.6 years (range, 0-15.1). Two-year overall survival (OS) after HT diagnosis was 72% (95% Confidence Interval: 62-83). The patients who received standard ABVD-based therapy had a median OS of 13.2 years. Although limited by small sample size, the patients who underwent HCT for HT in CR1 had a similar 2-year OS (n=7; 67%) compared to patients who did not undergo HCT for HT in CR1 (n=87; 72%; P=0.46). In this multi-center study, HT patients treated with ABVD-based regimens had prolonged survival supporting the use of these regimens as standard of care for these patients.     

Identification and characterization of a B-cell determinant within the amphipathic domain (residues 178–238) of the myelin proteolipid protein

Pooled polyclonal rabbit anti-rat myelin and mouse anti-human proteolipid protein (PLP) antisera were screened against a panel of PLP synthetic peptides spanning residues 178–238 of the protein. Cross-reactivity against one determinant defined by PLP_200–219 was particularly prominent in both the anti-myelin and anti-PLP antisera and was chosen for further study. Competitive inhibition studies, utilizing a panel of overlapping synthetic peptides, demonstrated that the C-terminal portion of PLP_200–219, specifically residues comprising PLP_209–217, was important for antibody recognition of this region. Immunohistochemical analyses with an affinity-purified rabbit anti-PLP_200–219 antiserum demonstrated antibody cross-reactivity with PLP in both paraffin- and gelatin-embedded brain sections and immunocytochemical staining of mouse oligodendrocyte-enriched cultures demonstrated antibody binding with native PLP in situ. Staining of living non-permeabilized cells localized binding to the extracellular face of the myelin membrane. Collectively, these data argue for the presence of an immunodominant B-cell determinant defined by PLP residues 200–219. Furthermore, the structural conformation of this determinant in native PLP can be mimicked by the synthetic peptide, resulting in the generation of an antibody reagent that has considerable utility for immunohistochemical and immunocytochemical investigations of PLP expression and localization within the central nervous system myelin membrane. © 1996 Wiley-Liss, Inc.     

全科住院医师培训的全方位评估体系

全科医生的能力决定了我国基层医疗服务的水平,但形式单一的考核方法无法有效地评估全科住院医师的能力水平,因此需要建立系统、全面的评估体系,对住院医师进行多方面的考核。本文在分析西方国家全科住院医师评估体系、Miller金字塔4个学习阶段及评估方法的基础上,建立了全科住院医师培训的全方位评估体系。该评估体系包括笔试、计算机模拟考试、客观结构化临床考试（OSCE）、临床日志、基于工作场所的评估、导师报告、病例分析、个人档案8个方面,可以多方面、全方位地了解全科住院医师的能力水平。     

Editorial Commentary: SCR: Substantial Confusion Remains

Superior capsular reconstruction is gaining acceptance as a procedure to treat massive and irreparable superior and posterosuperior rotator cuff tears. With a paucity of clinical and no long-term data, early results suggest that superior capsular reconstruction may offer improvements in pain, range of motion, function, and validated outcome measurements.     

Comprehensive genomic profiling of malignant phyllodes tumors of the breast

Purpose

Malignant phyllodes tumors (MPT) are exceptionally rare, and the genomic drivers of these tumors are still being elucidated. We performed comprehensive genomic profiling (CGP) of MPT to identify genomic alterations that will inform approaches to targeted therapy for patients with MPT, including relapsed, refractory, and metastatic disease.

Methods

DNA was extracted from formalin-fixed, paraffin-embedded samples from 24 consecutive patient cases of MPT. CGP was performed using a hybrid capture, adaptor ligation-based next generation sequencing assay to a high, uniform coverage (mean, 582×). Tumor mutational burden (TMB) was calculated from a minimum of 1.14 Mb of sequenced DNA as previously described and reported as mutations/Mb. The results were analyzed for all classes of genomic alterations, including short variants (SV; base substitutions, small insertions, and deletions), rearrangements, and copy number changes, including amplifications and homozygous deletions.

Results

The 24 cases of MPT included 15 patients with localized and 9 with metastatic disease. The median TMB was 2.7 mut/Mb, and no cases had a TMB > 10 mut/Mb. 20 out of 24 cases were evaluable for microsatellite status, and all were microsatellite stable. The most commonly mutated genes were TP53 (58.3%), TERT-promoter (57.9%), NF1 (45.8%), MED12 (45.8%), CDKN2A/B (33.3%), and MLL2 (33.3%). Targetable kinase fusions including KIAA1549-BRAF or FGFR3-TACC3 were identified in 2/24 (8.3%) tumors.

Conclusions

This study identifies clinically relevant genomic alterations that suggest novel targeted therapy approaches for patients with MPT.