Citations

ObjectiveHuman adipose‐derived mesenchymal stem cells (ADSCs) were used to rehabilitate bone damaged by osteoradionecrosis (ORN) in an established animal model.Study DesignProspective animal study.SettingAcademic department laboratory.Subjects and MethodsAfter institutional review board and Institutional Animal Care and Use Committee approval, 24 athymic nude rats were divided into 5 groups: 4 groups irradiated (20 Gy) by brachytherapy catheter placed at the left hemimandible and 1 mock irradiation control (n = 4). For all groups, ORN was initiated by extraction of the central molar 1 week later. After 28 days, animals (n = 5/group) received injection at the extraction site with saline (SAL), ADSCs, platelet‐rich plasma and collagen (PRP/COL), or ADSCs + PRP/COL. Rats were sacrificed 28 days later and their mandibles harvested for histopathology analysis (osteoblasts, osteoclasts, and fibrosis) and bone volume measurement using 3‐dimensional micro–computed tomography.ResultsAll but 1 rat survived the experiment period (23/24). Radiographic and histological analysis revealed 60% bone loss in the SAL group compared with the nonirradiated control. Injection of ADSCs increased jaw region bone volume by up to 36% (P <. 01). All experimental groups (ADSC, PRP/COL, and ADSC + PRP/COL) showed dramatically decreased osteoclast counts (P <. 001) while injection of PRP/COL with or without ADSCs increased osteoblasts. Increased fibrosis was observed after ADSC injection (P <. 05).ConclusionThe application of human ADSCs to an induced mandibular osteoradionecrosis model in athymic rats results in increased deposition or preservation of bone, demonstrated both histologically and radiographically. This offers an encouraging possible treatment option for translational research in this difficult disease.

ABSTRACTPurpose of the studyTo reduce the number of unnecessary laboratory tests ordered through a measurement of effects of education and cost awareness on laboratory ordering behaviour by internal medicine residents for common tests, including complete blood cell count (CBC) and renal profile (RP), and to evaluate effects of cost awareness on hospitalisation, 30-day readmission rate and mortality rate.Study design567 patients admitted during February, March and April 2014 were reviewed as the control group. Total CBC, CBC with differential and RP tests were counted, along with readmission and mortality rates. Interventions were education and visual cost reminders. The same tests were reassessed for 629 patients treated during 12 months after intervention in 2015.ResultsData showed a significant increase in CBCs ordered after the intervention (mean number per hospitalisation changed from 1.7 to 2.3 (p&lt;0.001)), a decrease in CBCs with differential (mean number changed from 1.7 to 1.2 (p&lt;0.001)) and no change in RPs ordered (mean number, 3.7 both before and after intervention (p=0.23)). No change was found in mortality rate, but the decrease in the readmission rate was significant (p=0.008).ConclusionsEducation in the form of cost reminders did not significantly reduce the overall ordering of the most common daily laboratory testing in our academic teaching service. We believe further research is needed to fully evaluate the effectiveness of other education forms on the redundant ordering of tests in the hospital setting.

ABSTRACTBackgroundThis study aimed to determine the frequency of transactive response DNA binding protein 43 kDa pathology in PSP, the clinical features of patients with this pathology, and genetic risk factors for it.MethodsHippocampal sections were screened with immunohistochemistry for transactive response DNA binding protein 43 kDa in 945 PSP cases. A subset of 261 cases that were negative in hippocampus was screened in the amygdala. The density and disruption of this pathology, as well as regional tau burden, and clinical and genetic characteristics were analyzed.ResultsWe observed transactive response DNA binding protein 43 kDa pathology in 47 cases in the hippocampus and an additional 9 cases that only affected the amygdala. Hippocampal sclerosis was the strongest risk factor, followed by Alzheimer's disease pathology, argyrophilic grain disease, and older age at death. Five stages of transactive response DNA binding protein 43 kDa pathology were identified in PSP: Stage A had pathology only in the amygdala (16%); stage I had pathology confined to the hippocampus and entorhinal cortex (9%); stage II included both regions of stage A and I (38%); stage III spread further to medial occipitotemporal gyrus (20%); and stage IV had pathology in the dorsolateral frontal lobe (18%). Anatomical areas vulnerable to PSP pathology had varying degrees of this pathology in stage II and later. PSP with transactive response DNA binding protein 43 kDa pathology were older at disease onset and had lower median MMSE scores; however, the latter was driven by concurrent pathologies.ConclusionsDistribution and clinical characteristics of transactive response DNA binding protein 43 kDa pathology in PSP were influenced by concurrent pathologies. This is the first study to observe that PSP‐vulnerable regions are also susceptible to this non‐tau pathology. © 2016 International Parkinson and Movement Disorder Society.

Objectives/HypothesisTo evaluate outcomes for patients with pathological N3 (pN3) neck disease from human papillomavirus (HPV)–related oropharyngeal squamous cell carcinoma (OPSCC) and determine variables predictive of survival.Study DesignRetrospective case series with chart review.MethodsThis study was conducted between 1998 and 2013 and included patients with HPV‐related OPSCC treated with surgery with or without adjuvant therapy and who had pN3 nodal disease. The primary outcome was disease‐specific survival (DSS). Secondary outcomes included overall survival (OS), disease‐free survival (DFS), adverse events, and gastrostomy tube rates.ResultsThirty‐nine patients were included, of whom 36 (90%) underwent adjuvant therapy. Median follow‐up was 39 months (range, 2–147 months). Mean age was 56 years, and 87% were male. Seventeen patients (44%) underwent selective neck dissection, whereas six (15%) underwent radical (n = 2) or extended radical (n = 4) neck dissection. Ninety‐two percent had extracapsular extension. Five‐year Kaplan‐Meier estimated DSS, OS, and DFS were 89% (95% confidence interval [CI]: 79%–99%), 87% (95% CI: 75%–99%), and 84% (95% CI: 72%–96%), respectively. The disease recurrence rate was 10% (5% regional, 5% distant metastasis). Patients with less than 5 pathologically positive lymph nodes (P = .041) had improved DFS.ConclusionsPatients with HPV‐related OPSCC and pN3 nodal disease treated with surgery and adjuvant therapy have very favorable long‐term survival and regional control. Patients with five or more pathologically positive lymph nodes may be at higher risk for recurrence.Level of Evidence4. Laryngoscope, 127:2033–2037, 2017

A novel protein complex facilitates lipid droplet autophagy.

Objective: We evaluated whether single-layer renorrhaphy (SLR) without collecting system (CS) closure is sufficient following robot-assisted partial nephrectomy (RAPN). Patients and Methods: One hundred fifty consecutive patients underwent RAPN by a single surgeon and were prospectively labeled with regard to CS entry during surgery. Patients with CS entry were subdivided into two groups: those with classical renorrhaphy (CR) (i.e., two-layer repair) and those with SLR (i.e., without CS repair). Perioperative variables and outcomes were compared between CR and SLR groups. Results: Ninety patients had CS entry during RAPN. Of these 90 patients, 64 had CR, and 26 had SLR, with mean ages of 62 and 59 years ( p = 0.22), tumor sizes of 3.4 and 3.3 cm ( p = 0.61), Mayo Adhesive Probability scores of 1.8 and 1.8 ( p = 0.95), and radius, exophytic/endophytic, nearness to CS, and laterality scores of 8.5 and 8.0 ( p = 0.16), respectively. Mean warm ischemia times (WITs) were 19.6 and 17.3 minutes ( p = 0.04), hospital stays of 3.0 and 2.8 days ( p = 0.62), and drain times of 2.9 and 2.7 days ( p = 0.65), for the CR and SLR groups, respectively. Using the Clavien-Dindo classification, there were a total of six grade III or higher complications, with no difference between the CR and SLR subgroups ( p = 1.0). Renal function using creatinine or glomerular filtration rate as surrogates showed no difference between groups preoperatively or up until 2 years postoperatively. Conclusions: Omitting CS repair during RAPN with SLR decreases WIT without altering complications, hospital stay, or drain time. Long-term renal function was not associated with CS repair.

Adolescents with postural orthostatic tachycardia syndrome (POTS) often have pain and functional impairment. This study evaluated how parental attributions of children’s symptoms relate to child functional impairment. Adolescents with chronic pain and clinical symptoms suggestive of autonomic dysfunction (fatigue, dizziness, nausea) that attended a multidisciplinary chronic pain clinic completed measures of depression, anxiety, and functioning (n = 141). Parents of 114 of these patients completed the Parent Pain Attribution Questionnaire (PPAQ), a measure indicating the extent they believe physical and psychosocial factors account for their child’s health condition. Patients were retrospectively grouped as to whether or not they had significant POTS on tilt table testing (n = 37). Greater parental attribution to physical causes was associated with increased levels of functional disability whether patients had POTS ( r = 0.45, P = .006) or not ( r = 0.25, P = .03). These results suggest that providers should advocate a more comprehensive family-oriented rehabilitative approach to treatment.

Chromosomal instability (CIN), the persistent inability of a cell to faithfully segregate its genome, is a feature of many cancer cells. It stands to reason that CIN enables the acquisition of multiple cancer hallmarks; however, there is a growing body of evidence suggesting that CIN impairs cellular fitness and prevents neoplastic transformation. Here, we suggest a new perspective to reconcile this apparent paradox and share an unexpected link between aneuploidy and aging that was discovered through attempts to investigate the CIN-cancer relationship. Additionally, we provide a comprehensive overview of the function and regulation of the anaphase-promoting complex, an E3 ubiquitin ligase that mediates high-fidelity chromosome segregation, and describe the mechanisms that lead to whole-chromosome gain or loss. With this review, we aim to expand our understanding of the role of CIN in cancer and aging with the long-term objective of harnessing this information for the advancement of patient care.