Citations

AbstractBackgroundSome cardiac transplant programs may upgrade listed patients to United Network for Organ Sharing (UNOS) 1A‐status during the holidays. Whether more transplants actually occur during holidays is unknown.MethodsWe assessed rates of single‐organ heart transplantation from 2001 to 2010 for recipients age ≥18 yr using the UNOS database. Patients were stratified by transplantation during holiday (±3 d, n = 2375) and non‐holiday periods (n = 16 112). Holidays included Easter/Spring break, Memorial Day, July 4th, Labor Day, Thanksgiving, and Christmas/New Years (winter holidays). Secondary analysis assessing transplant rates across seasons was also completed.ResultsDonor and recipient characteristics were similar between groups. Compared with non‐holidays, July 4th had higher transplant rates (5.69 vs. 5.09 transplants/d, p = 0.03) while the winter holiday had lower transplant rates (4.50 vs. 5.09 transplants/d, p < 0.01). There was a trend toward lower transplant rates for all holidays compared with non‐holidays (p = 0.06). Transplant rates were significantly different across seasons with greater rates in spring and summer (p < 0.01).ConclusionHeart transplant rates were higher during the July 4th and lower during the winter holidays. Although there was a higher likelihood of transplantation during the spring and summer seasons, upgrading patients to 1A status during most holidays may not improve their chances for transplantation.

BACKGROUNDFine‐needle aspiration of the thyroid is a common procedure, with an established role in reducing unnecessary thyroid surgery and identifying neoplasms and malignancies.METHODSThe study evaluated 1558 responses in the American Society for Clinical Pathology (ASCP) Non‐GYN Assessment program of aspirates of thyroid neoplasms and malignancies and placed them into the following groups: group A (target or correct interpretation), group B (incorrect interpretation as a benign thyroid nodule), group C (incorrect interpretation malignant aspirate as thyroid neoplasm), and group D (malignant diagnosis with incorrect interpretation). In clinical practice, responses in groups A, C, and D would lead to surgical excision, whereas responses in group B would not.RESULTSOf a total of 1558 responses, 78.5% of the responses were in group A, 8.5% in group B, 3.75% in group C, and 9.25% in group D. By individual diagnosis, the group rates were 86.5%, 0%, 11%, and 2.5% for anaplastic thyroid carcinoma; 83%, 5.5%, 4.25%, and 7.25% for papillary thyroid carcinoma; 79%, 7%, 6%, and 8% for medullary thyroid carcinoma; 83.5% 6.75%, 0%, and 9.75% for Hürthle cell neoplasm; and 61%, 22%, 0%, and 17% for follicular neoplasm in groups A, B, C, and D respectively.CONCLUSIONSFine‐needle aspiration was effective in diagnosing thyroid neoplasms and malignancies and in separating thyroid nodules into surgical and nonsurgical categories. Data from a large group of cytology professionals showed good performance; however, there is room for improvement, especially in making specific diagnoses. In particular, follicular neoplasm and follicular variant of papillary thyroid carcinoma were challenging diagnoses for participants. Cancer (Cancer Cytopathol) 2014;122:745–750. © 2014 The Authors. Cancer Cytopathology published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Human adipose‐derived mesenchymal stromal cells (AMSCs) grown in platelet lysate are promising agents for therapeutic tissue regeneration. Here, we investigated whether manipulation of epigenetic events by the clinically relevant histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) alters differentiation of AMSCs. The multipotency of AMSCs was validated by their ability to differentiate into osteogenic, chondrogenic, and adipogenic lineages. High‐throughput RNA sequencing and RT‐qPCR established that human histone deacetylases (HDAC1 to HDAC11, and SIRT1 to SIRT7) are differentially expressed in AMSCs. SAHA induces hyper‐acetylation of histone H3 and H4, stimulates protein expression of the HDAC‐responsive gene SLC9A3R1/NHERF1 and modulates the AKT/FOXO1 pathway. Biologically, SAHA interferes with osteogenic, chondrogenic and adipogenic lineage commitment of multipotent AMSCs. Mechanistically, SAHA‐induced loss of differentiation potential of uncommitted AMSCs correlates with multiple changes in the expression of principal transcription factors that control mesenchymal or pluripotent states. We propose that SAHA destabilizes the multi‐potent epigenetic state of uncommitted human AMSCs by hyper‐acetylation and perturbation of key transcription factor pathways. Furthermore, AMSCs grown in platelet lysate may provide a useful biological model for screening of new HDAC inhibitors that control the biological fate of human mesenchymal stromal cells. J. Cell. Physiol. 230: 52–62, 2015. © 2014 Wiley Periodicals, Inc.

AbstractImproving the effectiveness of adipose‐tissue derived human mesenchymal stromal/stem cells (AMSCs) for skeletal therapies requires a detailed characterization of mechanisms supporting cell proliferation and multi‐potency. We investigated the molecular phenotype of AMSCs that were either actively proliferating in platelet lysate or in a basal non‐proliferative state. Flow cytometry combined with high‐throughput RNA sequencing (RNASeq) and RT‐qPCR analyses validate that AMSCs express classic mesenchymal cell surface markers (e.g., CD44, CD73/NT5E, CD90/THY1, and CD105/ENG). Expression of CD90 is selectively elevated at confluence. Self‐renewing AMSCs express a standard cell cycle program that successively mediates DNA replication, chromatin packaging, cyto‐architectural enlargement, and mitotic division. Confluent AMSCs preferentially express genes involved in extracellular matrix (ECM) formation and cellular communication. For example, cell cycle‐related biomarkers (e.g., cyclins E2 and B2, transcription factor E2F1) and histone‐related genes (e.g., H4, HINFP, NPAT) are elevated in proliferating AMSCs, while ECM genes are strongly upregulated (>10‐fold) in quiescent AMSCs. AMSCs also express pluripotency genes (e.g., POU5F1, NANOG, KLF4) and early mesenchymal markers (e.g., NES, ACTA2) consistent with their multipotent phenotype. Strikingly, AMSCs modulate expression of WNT signaling components and switch production of WNT ligands (from WNT5A/WNT5B/WNT7B to WNT2/WNT2B), while upregulating WNT‐related genes (WISP2, SFRP2, and SFRP4). Furthermore, post‐proliferative AMSCs spontaneously express fibroblastic, osteogenic, chondrogenic, and adipogenic biomarkers when maintained in confluent cultures. Our findings validate the biological properties of self‐renewing and multi‐potent AMSCs by providing high‐resolution quality control data that support their clinical versatility. J. Cell. Biochem. 115: 1816–1828, 2014. © 2014 Wiley Periodicals, Inc.

ObjectiveThe purpose of this study was to determine if institutions with inpatient cardiovascular credentialed pharmacists exhibit improved quality measures for acute myocardial infarction (AMI) and heart failure (HF) care compared with institutions without inpatient cardiovascular credentialed pharmacists.MethodsWe conducted a multicenter, retrospective, cross‐sectional, matched case‐control study. Hospitals with at least one Added Qualification in Cardiology (AQCV) inpatient pharmacist were included in the case group. Each case group hospital was matched to hospitals without an AQCV pharmacist by region, number of cardiovascular discharges, and teaching hospital designation in a 1:3 ratio (case:control). The 34 AQCV hospitals were matched to 102 non‐AQCV hospitals. The proportions of discharges meeting HF and AMI process of care measures and 30‐day outcomes (readmission and mortality) for each hospital were determined from public data and compared between the case and control groups.ResultsHospitals with AQCV pharmacists performed better on process of care measures than hospitals without AQCV pharmacists (odds ratio 1.41, 95% confidence interval 1.25–1.58, p<0.0001, p<0.001 for heterogeneity), which was mainly driven by the aspirin on discharge for AMI and angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker on discharge for HF measures. No differences were observed between the groups for either readmission or mortality at 30 days.ConclusionsHospitals that used inpatient AQCV pharmacists performed better on process of care measures than hospitals that do not use inpatient AQCV pharmacists. However, improvements in process of care performance measures observed in AQCV hospitals did not translate into improved 30‐day clinical outcomes.

Curricular changes continue at United States medical schools and directors of gross anatomy, microscopic anatomy, neuroscience/neuroanatomy, and embryology courses continue to adjust and modify their offerings. Developing and supplying data related to current trends in anatomical sciences education is important if informed decisions are going to be made in a time of curricular and course revision. Thus, a survey was sent to course directors during the 2012–2013 academic years to gather information on total course hours, lecture and laboratory hours, the type of laboratory experiences, testing and competency evaluation, and the type of curricular approach used at their institution. The data gathered were compared to information obtained from previous surveys and conclusions reached were that only small or no change was observed in total course, lecture and laboratory hours in all four courses; more gross anatomy courses were part of an integrated curriculum since the previous survey; virtual microscopy with and without microscopes was the primary laboratory activity in microscopic anatomy courses; and neuroscience/neuroanatomy and embryology courses were unchanged. Anat Sci Educ 7: 321–325. © 2014 American Association of Anatomists.

Key Points Methylation analysis at ZAP-70 CpG+223 in CLL provides superior prognostic information vs IGHV status or CD38 or ZAP-70 expression. A pyrosequencing method for the feasible assessment of CpG+223 methylation in CLL samples is provided.

ABSTRACT Here we describe the first reported case of Nocardia beijingensis infection in the United States, made rarer by its presence in an immunocompetent patient.

Ewing sarcoma is an aggressive pediatric small round cell tumor that predominantly occurs in bone. Approximately 85% of Ewing sarcomas harbor the EWS/FLI fusion protein, which arises from a chromosomal translocation, t(11:22)(q24:q12). EWS/FLI interacts with numerous lineage‐essential transcription factors to maintain mesenchymal progenitors in an undifferentiated state. We previously showed that EWS/FLI binds the osteogenic transcription factor RUNX2 and prevents osteoblast differentiation. In this study, we investigated the role of another Runt‐domain protein, RUNX3, in Ewing sarcoma. RUNX3 participates in mesenchymal‐derived bone formation and is a context dependent tumor suppressor and oncogene. RUNX3 was detected in all Ewing sarcoma cells examined, whereas RUNX2 was detected in only 73% of specimens. Like RUNX2, RUNX3 binds to EWS/FLI via its Runt domain. EWS/FLI prevented RUNX3 from activating the transcription of a RUNX‐responsive reporter, p6OSE2. Stable suppression of RUNX3 expression in the Ewing sarcoma cell line A673 delayed colony growth in anchorage independent soft agar assays and reversed expression of EWS/FLI‐responsive genes. These results demonstrate an important role for RUNX3 in Ewing sarcoma. J. Cell. Physiol. 229: 2049–2056, 2014. © 2014 Wiley Periodicals, Inc.