Citations

We examined the Institutional Review Board (IRB) process at 9 academic institutions in the electronic Medical Records and Genomics (eMERGE) Network, for proposed electronic health record-based genomic medicine studies, to identify common questions and concerns. Sequencing of 109 disease related genes and genotyping of 14 actionable variants is being performed in ~28,100 participants from the 9 sites. Pathogenic/likely pathogenic variants in actionable genes are being returned to study participants. We examined each site’s research protocols, informed-consent materials, and interactions with IRB staff. Research staff at each site completed questionnaires regarding their IRB interactions. The time to prepare protocols for IRB submission, number of revisions and time to approval ranged from 10–261 days, 0–11, and 11–90 days, respectively. IRB recommendations related to the readability of informed consent materials, specifying the full range of potential risks, providing options for receiving limited results or withdrawal, sharing of information with family members, and establishing the mechanisms to answer participant questions. IRBs reviewing studies that involve the return of results from genomic sequencing have a diverse array of concerns, and anticipating these concerns can help investigators to more effectively engage IRBs.

The effects of alterations in serum calcium levels on the volume of distribution of a calcium tracer in bone and on bone blood flow were investigated in dogs by manipulation of parathyroid status. The volume of distribution increases with increasing serum calcium. This implies that there is a concentration-dependent binding mechanism in the extravascular space of bone, which is not saturated at the levels of serum calcium achieved in these experiments. The skeletal exchangeable calcium was increased in hypercalcemic dogs and decreased in hypocalcemic dogs. Cancellous bone contains proportionately more exchangeable calcium than cortical bone. Bone blood flow was decreased by 50% 15 min after injection of a bolus of parathyroid hormone (PTH) but returned to control values by 240 min. Fifty-two hours after the induction of hypercalcemia with repeated doses of PTH, there was no difference in blood flow over control animals.

Objective Distal femoral varus osteotomy (DFVO) is an effective treatment for unloading valgus knee malalignment; however, there is limited evidence on the ability for patients to return to athletics following this procedure. The purpose of this study is to report the functional outcomes and rate of return to sport for athletes that underwent DFVO. Design A consecutive series of athletes that had undergone DFVO were retrospectively reviewed. Radiographs were assessed to determine preoperative and postoperative alignment. Institutional registries were used to collect preoperative and postoperative Marx Activity Scale, International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form scores, and return to sport. Results Thirteen patients (8 males, 5 females) with a mean age of 24 years (range 17-35 years) and a mean follow-up of 43 months (range 24-74 months) were included in the study. Six patients underwent medial closing wedge DFVO versus 7 patients who underwent lateral opening wedge DFVO. Nine of 13 had concomitant chondral, meniscal, or ligamentous procedures performed. The mean alignment correction was 8° (range 5°-13°). All patients were able to successfully return to sport at a mean of 11 months (range 9-13 months). Furthermore, all 13 patients demonstrated an improvement in both Marx Activity Scale (4-11; P < 0.01) and IKDC scores (53-89; P < 0.01) after surgery. Conclusions Correction of valgus knee malalignment through DFVO—either medial closing wedge or lateral opening wedge—can reliably result in improvement in function and return to sport. Concomitant chondral, meniscal, and ligamentous pathology should be addressed.

BACKGROUND It is possible that the relative lack of progress in treatment outcomes among adolescent and young adult (AYA) patients with cancer is caused by a difference in disease biology compared with the corresponding diseases in younger and older individuals. There is evidence that colon cancer is more aggressive and has a poorer prognosis in AYA patients than in older adult patients. METHODS To further understand the molecular basis for this difference, whole‐exome sequencing was conducted on a cohort of 30 adult, 30 AYA, and 2 pediatric colon cancers. RESULTS A statistically significant difference in mutational frequency was observed between AYA and adult samples in 43 genes, including ROBO1 , MYC binding protein 2 ( MYCBP2 ), breast cancer 2 (early onset) ( BRCA2 ), MAP3K3, MCPH1, RASGRP3, PTCH1, RAD9B, CTNND1, ATM, NF1 ; KIT, PTEN , and FBXW7 . Many of these mutations were nonsynonymous, missense, stop‐gain, or frameshift mutations that were damaging. Next, RNA sequencing was performed on a subset of the samples to confirm the mutations identified by exome sequencing. This confirmation study verified the presence of a significantly greater frequency of damaging mutations in AYA compared with adult colon cancers for 5 of the 43 genes ( MYCBP2, BRCA2, PHLPP1, TOPORS , and ATR ). CONCLUSIONS The current results provide the rationale for a more comprehensive study with a larger sample set and experimental validation of the functional impact of the identified variants along with their contribution to the biologic and clinical characteristics of AYA colon cancer. Cancer 2018;124:1070‐82. © 2017 American Cancer Society .

Increasing rates of burnout—with accompanying stress and lack of engagement—among faculty, residents, students, and practicing physicians have caused alarm in academic medicine. Central to the debate among academic medicine’s stakeholders are oft-competing issues of social accountability; cost containment; effectiveness of academic medicine’s institutions; faculty recruitment, retention, and satisfaction; increasing expectations for faculty; and mission-based productivity. The authors propose that understanding and fostering what contributes to faculty and institutional vitality is central to preventing burnout during times of change. They first look at faculty vitality and how it is threatened by burnout, to provide a framework for a greater understanding of faculty well-being. Then they draw on higher education literature to determine how vitality is defined in academic settings and what factors affect faculty vitality within the context of academic medicine. Next, they propose a model to explain and examine faculty vitality in academic medicine, followed by a discussion of the need for a greater understanding of faculty vitality. Finally, the authors offer conclusions and propose future directions to promote faculty vitality. The authors encourage institutional decision makers and other stakeholders to focus particular attention on the evolving expectations for faculty, the risk of extensive faculty burnout, and the opportunity to reduce burnout by improving the vitality and resilience of these talented and crucial contributors. Faculty vitality, as defined by the institution, has a critical role in ensuring future institutional successes and the capacity for faculty to thrive in a complex health care economy.

OBJECTIVE Intensive treatment (INT) of type 1 diabetes reduces the incidence of cardiovascular disease (CVD) events compared with conventional treatment (CONV), but it also results in more weight gain. Our objective was to examine whether excessive weight gain from INT of type 1 diabetes is independently associated with subsequent CVD events. RESEARCH DESIGN AND METHODS Quartiles (Q) of weight gain in 1,213 participants aged 18 years and older at enrollment in the Diabetes Control and Complications Trial (DCCT) were determined within randomized treatment groups (INT vs. CONV) using change in BMI from baseline to the closeout DCCT visits. Effects of this weight gain on CVD risk factors and outcomes during an additional 20 years of observational follow-up were then determined. RESULTS The Q4 INT group experienced greater proportional weight gain (median change in BMI, 6.08 kg/m2), increases in CVD risk factors, and need for medications for hypertension and lipids compared with the Q1–3 INT and comparable CONV groups. Over a mean of 26 years of follow-up, the numbers of major and total CVD events were not statistically different in Q4 compared with Q1–3 of either the INT or CONV group. By year 14, however, the incident CVD event curve became significantly higher in the Q4 INT group than in the Q1–3 INT groups (P = 0.024) and was similar to that for the CONV group. CONCLUSIONS For the first 13 years after DCCT, INT for type 1 diabetes reduced macrovascular events compared with CONV, even when excessive weight gain occurred. After this, total CVD events significantly increased in the Q4 INT group, becoming equivalent to those in the CONV group. Longer follow-up is needed to determine whether this trend continues and results in more major CVD events.