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Objective: The efficacy and safety of memantine in patients with moderate-to-severe Alzheimer's disease (AD) receiving stable doses of donepezil were recently demonstrated in a phase III trial. The cost-effectiveness of such therapy is unknown.Research Design and Methods: A microsimulation model was developed to depict AD progression over time and associated clinical and economic outcomes. AD progression was measured in terms of decline in cognitive function, as assessed by the Severe Impairment Battery (SIB). At model entry, patients were assumed to have moderate-to-severe AD, to be on stable doses of donepezil, and to begin combination therapy with memantine, or continue to receive donepezil alone; duration of therapy was assumed to be 1 year. Drug efficacy was based on data from a phase III trial. Key assumptions of the model included: (1) efficacy of study drugs would extend to 1 year; (2) measures of cognitive function could be mapped to one another, as well as to global measures of disease severity; and (3) following therapy discontinuation, cognitive function would revert immediately to natural history levels. Cost-effectiveness was assessed in terms of cost (2005 US$) per quality-adjusted life-year (QALY) gained over a lifetime (3% discount rate).Results: SIB scores were estimated to improve by 3.3 over 1 year from therapy with memantine plus donepezil (vs. donepezil alone). While pharmacotherapy costs were estimated to increase by $1250 during the year of memantine treatment, costs of formal and informal services were estimated to decrease by $1240 over this period and by $1493 (discounted present value) over a lifetime. Findings were sensitive to the assumed SIB score at therapy initiation; cost-effectiveness was better for patients with higher initial SIB scores (i.e., less severe disease).Conclusion: In patients with moderate-to-severe AD already receiving donepezil, treatment with memantine results in improved clinical outcomes and reduced total costs of care. [ABSTRACT FROM AUTHOR]

Using data from the 2000-2004 US Healthcare Cost and Utilization Project National Inpatient Sample, we found that total hospital admissions for skin and soft tissue infections increased by 29% during 2000-2004; admissions for pneumonia were largely unchanged. These results are consistent with recent reported increases in community-associated methicillin-resistant Staphylococcus aureus infections. [ABSTRACT FROM AUTHOR]

Purpose: Defects in the gene encoding selenocysteine insertion sequence binding protein 2, SECISBP2, result in global impaired selenoprotein synthesis manifesting a complex syndrome with characteristic serum thyroid function tests due to impaired thyroid hormone metabolism. Knowledge about this multisystemic defect remains limited., Methods: Genetic and laboratory investigations were performed in affected members from six families presenting with short stature, failure to thrive., Results: Four probands presented a complex neurodevelopmental profile, including absent speech, autistic features, and seizures. Pediatric neurological evaluation prompted genetic investigations leading to the identification of SECISBP2 variants before knowing the characteristic thyroid tests in two cases. Thyroid hormone treatment improved motor development, while speech and intellectual impairments persisted. This defect poses great diagnostic and treatment challenges for clinicians, as illustrated by a case that escaped detection for 20years, as SECISBP2 was not included in the neurodevelopmental genetic panel, and his complex thyroid status prompted anti-thyroid treatment instead., Conclusion: This syndrome uncovers the role of selenoproteins in humans. The severe neurodevelopmental disabilities manifested in four patients with SECISBP2 deficiency highlight an additional phenotype in this multisystem disorder. Early diagnosis and treatment are required, and long-term evaluation will determine the full spectrum of manifestations and the impact of therapy., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

CsPbBr 3 exhibits outstanding optoelectronic properties and thermal stability, making it a coveted material for detectors, light-emitting diodes, and solar cells. Despite observations of ferroelectricity in CsPbBr 3 quantum dots, synthesizing bulk ferroelectric CsPbBr 3 crystals has remained elusive, hindering its potential in next-generation optoelectronic devices like optical switches and ferroelectric photovoltaics. Here, a breakthrough is reported: a novel solvothermal technique enabling the growth of ferroelectric CsPbBr 3 nanoplatelets with lateral dimensions in the tens of micrometers. This represents a significant step toward achieving large-area ferroelectric CsPbBr 3 crystals. Unlike traditional methods, this approach allows for growth and crystallization of CsPbBr 3 in alcohol solutions by enhancing precursor solubility. This study confirms the ferroelectric nature of these nanoplatelets using second harmonic generation, electrical characterizations, and piezoresponse force microscopy. This work paves the way for utilizing ferroelectric CsPbBr 3 in novel optoelectronic devices, significantly expanding the potential of this material and opening doors for further exploration in this exciting field., (© 2024 Wiley‐VCH GmbH.)

Initial systematic reviews demonstrated the reduction of surgical site infection (SSI) following perioperative oxygen supplementation. SSI among colorectal surgeries was reduced by more than 50% with high-flow oxygen. However, recent randomized trials are coming up with conflicting results. The objective of this review was to comprehend whether the application of perioperative supplemental oxygen decreased the hazard of SSI following cesarean delivery. The initial search identified 95 studies. After screening title and abstracts 59 studies were included, and 33 studies were found to be relevant after checking eligibility. After a careful analysis, five articles were found fit for this systematic review. Extracted information included study design and methodology, the cumulative incidence of post-cesarean SSI following supplemental oxygen, the odds ratio, and associated variability for all factors considered in univariate and/or multivariate analysis. The cumulative incidence of the standard care group and supplemental oxygen group were comparable in all five studies with statistically significant differences. The secondary outcomes such as hospital readmission, wound separation, and intravenous antibiotics were similar in both groups as stated in the two studies. The rate of SSI in diabetics was 6.9% and 14.4% in the standard care group and supplemental oxygen group, respectively, as analyzed in a study. An increase in intra-operative blood loss was found to be the major risk factor leading to SSI. In one of the studies, Caucasian race, increased basal metabolic index, and prolonged surgery were associated with increased risk of SSI. There was no difference in neonatal umbilical artery pH resulting from supplemental oxygen during cesarean. The available literature is quite sufficient to prove that supplemental oxygen offers no added benefit in reducing post-cesarean SSI. Hence, we do not recommend its use for this purpose., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sarkar et al.)

The reduced dielectric screening in atomically thin two-dimensional materials makes them very sensitive to the surrounding environment, which can be modulated to tune their optoelectronic properties. In this study, we significantly improved the optoelectronic properties of monolayer MoS 2 by varying the surrounding environment using different liquid dielectrics, each with a specific dielectric constant ranging from 1.89 to 18. Liquid mediums offer the possibility of environment tunability on the same device. For a back-gated field effect transistor, the field effect mobility exhibited more than two-order enhancement when exposed to a high dielectric constant medium. Further investigation into the effect of the dielectric environment on the optoelectronic properties demonstrated a variation in photoresponse relaxation time with the dielectric medium. The rise and decay times were observed to increase and decrease, respectively, with an increase in the dielectric constant of the medium. These results can be attributed to the dielectric screening provided by the surrounding medium, which strongly modifies the charged impurity scattering, the band gap, and defect levels of monolayer MoS 2 . These findings have important implications for the design of biological and chemical sensors, particularly those operating in a liquid environment. By leveraging the tunability of the dielectric medium, we can optimize the performance of such sensors and enhance their detection capabilities., (© 2023 IOP Publishing Ltd.)

Background: Molecular testing is increasingly used to refine the probability of cancer and assess recurrence risk in thyroid nodules with Bethesda III/IV fine needle aspiration (FNA) cytology. However, limited data exist for Bethesda V (suspicious for malignancy [SFM]) samples. This study evaluated the performance of ThyroSeq v3 (TSv3) in thyroid nodules with SFM cytology. Methods: In this single-institution retrospective cohort study, consecutive thyroid FNA samples diagnosed as SFM with TSv3 testing and known surgical outcome were identified. Clinical, pathology, and molecular findings were reviewed. The TSv3 Cancer Risk Classifier was used to determine molecular risk groups (MRGs). For test-negative cases diagnosed as cancer/noninvasive follicular thyroid neoplasm with papillary-like nuclear features, TSv3 was performed on the resected tumors. Results: Among 128 SFM samples studied, 100 (78.1%) were TSv3 positive, and 28 (21.9%) were negative. The cancer prevalence on surgery was 82.8%. Among test-positive samples, 95% were malignant and 5% benign. Among test-negative samples, 17 (60.7%) were benign and 11 (39.3%) malignant. Overall, TSv3 had a sensitivity of 89.6% (confidence interval; CI 82.4-94.1) and a specificity of 77.3% (CI 56.6-89.9). For a cancer prevalence of 50-75% expected in SFM cytology by the Bethesda system, the negative predictive value was expected to range from 71.2% to 88.1% and the positive predictive value from 79.8% to 92.2%. Among test-positive nodules, 20% were MRG-Low (mostly RAS-like alterations), 66% MRG-Intermediate (mostly BRAF-like alterations), and 14% MRG-High. Among patients with cancer, 65 (61.3%) were American Thyroid Association low risk, 25 (23.6%) intermediate risk, and 6 (5.7%) high risk. During the mean follow-up of 51.2 months (range: <1 to 470 months), 12 (13.0%) patients had disease recurrence, which was more common in MRG-High (54.6%) compared with MRG-Intermediate (9.5%) and MRG-Low (0%) cancers ( p  < 0.001). Upon reexamining tumors with false-negative results, half of evaluable cases had alterations likely missed due to limiting FNA sampling, and the remainder represented low-risk tumors. Potentially targetable alterations were identified in 10 samples. Conclusions: In this large series of SFM thyroid nodules, TSv3 further improved cancer prediction and detected RAS-like, BRAF-like, high-risk, and potentially targetable alterations, all of which may inform more optimal patient management. MRGs were associated with recurrence-free survival, offering potential preoperative cancer risk stratification.

Background: Noninvasive encapsulated follicular variant papillary thyroid carcinoma (EFVPTC) was reclassified as "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) in 2016. Most existing studies that examined outcomes included patients managed as EFVPTC and only retrospectively reclassified as NIFTP. This is the first study to evaluate the clinicopathologic, molecular, and surveillance characteristics of patients diagnosed with NIFTP at the time of surgery and managed based on this diagnosis. Methods: We performed a retrospective cohort study of consecutive cases diagnosed as NIFTP from June 2016 to October 2021 identified from electronic medical records at a large tertiary care institution. Patients with coexisting low-risk thyroid cancers ≥1.0 cm in size or any size aggressive histology were excluded, and review of demographic, clinical, imaging, cytologic, and molecular genetic data was performed. Initial care was delivered according to existing clinical guidelines, with a consensus institutional plan for five-year follow-up after surgery. Results: Among 79 patients with 84 nodules diagnosed as NIFTP after surgery, 83.5% (66/79) were women and the mean age was 51 years (range, 21-84). Mean NIFTP size was 2.4 cm (range 0.15-8.0). On ultrasound, the majority of nodules were categorized as thyroid imaging, reporting and data system TI-RADS 3 (55.3%, 42/76), and TI-RADS 4 (36.8%, 28/76). On cytology, they were typically diagnosed as Bethesda III (69.1%, 47/68) or Bethesda IV (23.5%, 16/68). Molecular testing was performed on 62 nodules, and molecular alterations were found in 93.5% (58/62). The most common alterations identified in NIFTP were RAS mutation (75.4%, 43/57), THADA fusion (12.3%, 7/57), and BRAF K601E mutation (7.0%, 4/57). Fifty-two (65.8%) patients underwent lobectomy and 27 (34.2%) total thyroidectomy, and no patient received completion thyroidectomy. Twenty-one patients (26.5%) had coexisting papillary or follicular microcarcinoma. None of the patients received radioiodine ablation. On a mean follow-up of 28.5 months (range, 6-69 months), no structural or biochemical recurrences were observed. Conclusions: In this large cohort of patients with NIFTP diagnosed at the time of surgery and managed typically by lobectomy with no radioiodine ablation, no evidence of tumor recurrence was identified on a limited follow-up. This finding supports indolent clinical course of NIFTP.

Renal cell carcinoma (RCC) is the most common type of cancer found to metastasize to the thyroid gland. These tumors may represent a diagnostic challenge in cytology. However, most RCC tumors carry VHL alterations, which are rare in primary thyroid tumors. The aim of this study was to evaluate the utility of molecular testing in detecting metastatic RCC in thyroid fine-needle aspiration (FNA) samples. From November 2017 until March 2022, thyroid FNA samples with ThyroSeq v3 results showing both VHL alterations and low/absent expression of thyroid cell markers were analyzed. Eighteen samples from 15 patients met the inclusion criteria. On molecular analysis, deleterious VHL mutations were found in nine (50%) nodules, VHL copy number alteration (CNA) in two (11%), and both mutations and CNA in seven (39%). None of the cases showed mutations commonly found in thyroid tumors. The mean age of these patients was 68 (range, 49-89) years with a male to female ratio of 2:1. Eight (53%) patients had multiple thyroid nodules on ultrasound. On cytology, 14 (78%) nodules were diagnosed as Bethesda III, 2 (11%) as Bethesda IV, and 2 (11%) as Bethesda V. At the time of cytology review, the history of RCC, sometimes remote, was available for ten patients. Of the 14 patients with medical history or surgical follow-up available, all had history of RCC or renal mass or revealed metastatic RCC on thyroidectomy. This study demonstrates that molecular testing can reliably identify metastatic RCC in thyroid nodules with indeterminate cytology, which could improve patient management.

This report describes a case of pituitary apoplexy with rapidly evolving hemorrhage in a 74-year-old female with coronavirus disease 2019 (COVID-19) disease. The patient presented with severe headache and mild respiratory symptoms, with laboratories concerning for pituitary hypofunction. Brain imaging demonstrated a sellar mass concerning for a pituitary adenoma with ischemic apoplexy. She subsequently developed visual deficits within 24 hours of presentation, and repeat imaging demonstrated evolving hemorrhage and new mass effect on the optic chiasm. She was successfully managed with urgent endoscopic endonasal surgery despite her COVID-19 positive status by taking special intraoperative precautions to mitigate SARS-CoV2 transmission risk. Only a handful of cases of pituitary apoplexy have been reported in association with COVID-19 disease, and even fewer reports exist of endonasal procedures in such cases. We discuss the potential implication of COVID-19 in the occurrence of pituitary apoplexy, in addition to the safety and success of endonasal surgery in this population., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Today, research in biomedicine often requires the knowledge and technologies in diverse fields. Therefore, there is an increasing need for collaborative team science that crosses traditional disciplines. Here, we discuss our own lessons from both interdisciplinary and transdisciplinary teams, which ultimately ushered us to expand our research realm beyond bone biology., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

We report that two widely-used drugs for erectile dysfunction, tadalafil and vardenafil, trigger bone gain in mice through a combination of anabolic and antiresorptive actions on the skeleton. Both drugs were found to enhance osteoblastic bone formation in vivo using a unique gene footprint and to inhibit osteoclast formation. The target enzyme, phosphodiesterase 5A (PDE5A), was found to be expressed in mouse and human bone as well as in specific brain regions, namely the locus coeruleus, raphe pallidus, and paraventricular nucleus of the hypothalamus. Localization of PDE5A in sympathetic neurons was confirmed by coimmunolabeling with dopamine β-hydroxylase, as well as by retrograde bone-brain tracing using a sympathetic nerve-specific pseudorabies virus, PRV152. Both drugs elicited an antianabolic sympathetic imprint in osteoblasts, but with net bone gain. Unlike in humans, in whom vardenafil is more potent than tadalafil, the relative potencies were reversed with respect to their osteoprotective actions in mice. Structural modeling revealed a higher binding energy of tadalafil to mouse PDE5A compared with vardenafil, due to steric clashes of vardenafil with a single methionine residue at position 806 in mouse PDE5A. Collectively, our findings suggest that a balance between peripheral and central actions of PDE5A inhibitors on bone formation together with their antiresorptive actions specify the osteoprotective action of PDE5A blockade., Competing Interests: The authors declare no competing interest.

The primitive neurohypophyseal nonapeptide oxytocin (OXT) has established functions in parturition, lactation, appetite, and social behavior. We have shown that OXT has direct actions on the mammalian skeleton, stimulating bone formation by osteoblasts and modulating the genesis and function of bone-resorbing osteoclasts. We deleted OXT receptors (OXTRs) selectively in osteoblasts and osteoclasts using Col2.3Cre and Acp5Cre mice, respectively. Both male and female Col2.3Cre + : Oxtr fl/fl mice recapitulate the low-bone mass phenotype of Oxtr +/- mice, suggesting that OXT has a prominent osteoblastic action in vivo. Furthermore, abolishment of the anabolic effect of estrogen in Col2.3Cre + : Oxtr fl/fl mice suggests that osteoblastic OXTRs are necessary for estrogen action. In addition, the high bone mass in Acp5Cre + : Oxtr fl/fl mice indicates a prominent action of OXT in stimulating osteoclastogenesis. In contrast, we found that in pregnant and lactating Col2.3Cre + : Oxtr fl/fl mice, elevated OXT inhibits bone resorption and rescues the bone loss otherwise noted during pregnancy and lactation. However, OXT does not contribute to ovariectomy-induced bone loss. Finally, we show that OXT acts directly on OXTRs on adipocytes to suppress the white-to-beige transition gene program. Despite this direct antibeiging action, injected OXT reduces total body fat, likely through an action on OXT-ergic neurons. Consistent with an antiobesity action of OXT, Oxt -/- and Oxtr -/- mice display increased total body fat. Overall, the actions of OXT on bone mass and body composition provide the framework for future therapies for osteoporosis and obesity.

Background: A diagnosis of breast cancer (BC) can result in multifactorial stress. If not addressed, distress can have a negative impact on outcomes. The experience of patients with newly diagnosed BC has not been sufficiently investigated. This study characterizes distress among new patients in a multidisciplinary care (MDC) clinic. The study aimed to determine the degree of distress at presentation, to characterize the sources, and to evaluate the impact of an MDC visit., Methods: A retrospective review was performed from January 2015 to November 2017. Charts were accessed for demographics, tumor characteristics, and treatment data. Distress scores (DS) and problems as captured using the National Comprehensive Cancer Network (NCCN) Distress Thermometer were completed before evaluation and in a subgroup after an MDC visit. Predictors of severe distress (DS ≥4) were investigated using multivariable logistic regression. The paired t test was used to determine the impact of an MDC visit., Results: The mean initial DS (n = 474) was 4.98. The top four sources of distress were worry, anxiety, fears, and sadness. Age younger than 65 years was significantly associated with a higher DS at presentation (p < 0.003). Among the patients queried before and after MDC (n = 137), a significant reduction in distress was identified (5.58-2.94; p < 0.0005)., Conclusions: Severe distress was found in 66 % of the patients with a recent diagnosis of BC, with younger age related to higher distress scores at presentation. Emotional stressors were the predominant factors accounting for distress. A same-day MDC visit was associated with a significant reduction in DS. These data indicate the importance and feasibility of proactively screening patients. Our research lends support to the value of multidisciplinary evaluation in this setting.

FSH has a primary function in procreation, wherein it induces estrogen production in females and regulates spermatogenesis in males. However, in line with our discoveries over the past decade of non-unitary functions of pituitary hormones, we and others have described hitherto uncharacterized functions of FSH. Through high-affinity receptors, some of which are variants of the ovarian FSH receptor (FSHR), FSH regulates bone mass, adipose tissue function, energy metabolism, and cholesterol production in both sexes. These newly described actions of FSH may indeed be relevant to the pathogenesis of bone loss, dysregulated energy homeostasis, and disordered lipid metabolism that accompany the menopause in females and aging in both genders. We are therefore excited about the possibility of modulating circulating FSH levels toward a therapeutic benefit for a host of age-associated diseases, including osteoporosis, obesity and dyslipidemia, among other future possibilities.

The traditional view of follicle - stimulating hormone (FSH) as a reproductive hormone is changing. It has been shown that FSH receptors (FSHRs) are expressed in various extra-gonadal tissues and mediate the biological effects of FSH at those sites. Molecular, animal, epidemiologic, and clinical data suggest that elevated serum FSH may play a significant role in the evolution of bone loss and obesity, as well as contributing to cardiovascular and cancer risk. This review summarizes recent data on FSH action beyond reproduction.

The lysosomal enzyme glucocerebrosidase-1 (GCase) catalyzes the cleavage of a major glycolipid glucosylceramide into glucose and ceramide. The absence of fully functional GCase leads to the accumulation of its lipid substrates in lysosomes, causing Gaucher disease, an autosomal recessive disorder that displays profound genotype-phenotype nonconcordance. More than 250 disease-causing mutations in GBA1 , the gene encoding GCase, have been discovered, although only one of these, N370S, causes 70% of disease. Here, we have used a knowledge-based docking protocol that considers experimental data of protein-protein binding to generate a complex between GCase and its known facilitator protein saposin C (SAPC). Multiscale molecular-dynamics simulations were used to study lipid self-assembly, membrane insertion, and the dynamics of the interactions between different components of the complex. Deep learning was applied to propose a model that explains the mechanism of GCase activation, which requires SAPC. Notably, we find that conformational changes in the loops at the entrance of the substrate-binding site are stabilized by direct interactions with SAPC and that the loss of such interactions induced by N370S and another common mutation, L444P, result in destabilization of the complex and reduced GCase activation. Our findings provide an atomistic-level explanation for GCase activation and the precise mechanism through which N370S and L444P cause Gaucher disease., Competing Interests: The authors declare no conflict of interest.

Purpose: The purpose of this study was to examine the incidence and economic burden of peristomal skin complications (PSCs) following ostomy surgery., Design: Retrospective cohort study based on electronic health records and administrative data stores at a large US integrated healthcare system., Subjects and Settings: The sample comprised 168 patients who underwent colostomy (ICD-9-CM 46.1X) (n = 108), ileostomy (46.2X) (n = 40), cutaneous ureteroileostomy (56.5X), or other external urinary diversion (56.6X) (n = 20) between January 1, 2012, and December 31, 2014. The study setting was an integrated health services organization that serves more than 2 million persons in the northeastern United States., Methods: We scanned electronic health records of all study subjects to identify those with evidence of PSCs within 90 days of ostomy surgery and then examined healthcare utilization and costs over 120 days, beginning with date of surgery, among patients with and without evidence of PSCs. Testing for differences in continuous measures between the 3 ostomy groups was based on one-way analysis of variance; testing for differences in such measures between the PSC and non-PSC groups was based on a t statistic, and the χ statistic was used to test for differences in categorical measures., Results: Sixty-one subjects (36.3%) had evidence of PSCs within 90 days of ostomy surgery (ileostomy, 47.5%; colostomy, 36.1%; urinary diversion, 15.0%; P < .05 for differences between groups). Among patients with evidence of PSCs, the mean (SD) time from surgery to first notation of this complication was 26.4 (19.0) days; it was 24.1 (13.2) days for ileostomy, 27.2 (21.1) days for colostomy, and 31.7 (25.7) days for urinary diversion (P = .752). Patients with PSCs were more likely to be readmitted to hospital by day 120 (55.7% vs 35.5% for those without PSCs; P = .011). The mean length of stay for patients readmitted to hospital was 11.0 days for those with PSCs and 6.8 days for those without PSCs (P = .111). The mean total healthcare cost over 120 days was $58,329 for patients with evidence of PSCs and $50,298 for those without evidence of PSCs (P = .251)., Conclusions: Approximately one-third of ostomy patients developed PSCs within 90 days of their surgery. Peristomal skin complications are associated with a greater likelihood of hospital readmission. Our findings corroborate results of earlier studies.

Purpose: BioZorb ® (Focal Therapeutics, Aliso Viejo, CA) is an implantable 3-dimensional bioabsorbable marker used for tumor bed volume (TBV) identification during postoperative radiation therapy (RT) planning. We aimed to calculate and compare RT TBVs between two cohorts managed with and without the device., Methods and Materials: Data from patients with breast cancer who were treated at Rhode Island Hosptial, Providence RI between May 1, 2015 and April 30, 2016 were retrospectively reviewed and grouped based on 3-dimensional bioabsorbable marker placement. Pathology reports were used to calculate tumor excision volume (TEV) after breast conservation. Specifically, the three dimensions provided were multiplied to generate a cubic volume, defined as TEV. TBV was calculated using treatment volumes generated with Philips Pinnacle3 treatment planning software (Andover, MA). Linear regression analyses assessed the relationship between excised TEV and TBV. T tests compared the slopes of the best fit lines for plots of TEV versus TBV., Results: In this retrospective case-control study, 116 patients undergoing breast RT were identified; of whom 42 received a 3-dimensional bioabsorbable marker and 74 did not. The mean TEVs were 102.7 cm 3 with the device and 103.2 cm 3 without the device, and the mean TBVs for the same groups were 27.5 cm 3 and 40.1 cm 3 , respectively. The TBV standard errors for patients who did and did not receive 3-dimensional bioabsorbable markers were 23.739 and 38.685, respectively. The t tests found the slopes of the lines of best fit for these cohorts to be statistically significantly different (P = .001), with smaller TBVs achieved with 3-dimensional bioabsorbable marker placement., Conclusions: When comparing TBVs between patients contemporaneously treated with or without a 3-dimensional bioabsorbable marker, device placement was associated with statistically significantly smaller TBVs in the setting of similar TEVs., (Copyright © 2018 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

A critical component for accelerating the clinical uptake of research data in the area of pediatric concussion or mild traumatic brain injury (MTBI) pertains to the establishment and utilization of common databases. The objective of the first phase of our CanPedCDE initiative was to agree upon pediatric common data elements (CDEs) that could best characterize children with MTBI over their recovery period. The selection of CDEs for our framework aimed to balance factors such as the comprehensiveness of outcomes collected, their applicability to diverse settings, as well as the costs associated with their use. Selection began by identifying relevant domains of functioning (e.g., post-concussion symptoms, attention, and balance). Two sources were used to make this process more efficient: 1) the World Health Organization International Classification of Functioning (ICF) Traumatic Brain Injury Core Set, and the U.S. National Institute of Neurological Disorders and Stroke Traumatic Brain Injury Common Data Elements, both of which had already suggested relevant domains to include in TBI research. The process was completed in two phases: 1) using an online survey of experts and 2) through an in-person consensus meeting. Measurement tools were also proposed that were best felt to capture these domains. Forty experts in MTBI in children from multiple health-related perspectives (e.g., emergency medicine, pediatrics, neurosurgery, nursing, physiotherapy, and neuroscience), as well as knowledge users, participated in the selection process. The final list of CDEs included 77 distinct areas of functioning, covering all categories of the ICF model. Outcome measures were attached to each element, when applicable. The CanPedCDE initiative addresses a significant limitation in MTBI research to date and may help both researchers and clinicians to organize and standardize their assessment of children and youth post-MTBI in order to move the field in promising directions.

Purpose: The purpose of this study was to estimate the risk and economic burden of peristomal skin complications (PSCs) in a large integrated healthcare system in the Midwestern United States., Design: Retrospective cohort study., Subjects and Setting: The sample comprised 128 patients; 40% (n = 51) underwent colostomy, 50% (n = 64) underwent ileostomy, and 10% (n = 13) underwent urostomy. Their average age was 60.6 ± 15.6 years at the time of ostomy surgery., Methods: Using administrative data, we retrospectively identified all patients who underwent colostomy, ileostomy, or urostomy between January 1, 2008, and November 30, 2012. Trained medical abstractors then reviewed the clinical records of these persons to identify those with evidence of PSC within 90 days of ostomy surgery. We then examined levels of healthcare utilization and costs over a 120-day period, beginning with date of surgery, for patients with and without PSC, respectively. Our analyses were principally descriptive in nature., Results: The study cohort comprised 128 patients who underwent ostomy surgery (colostomy, n = 51 [40%]; ileostomy, n = 64 [50%]; urostomy, n = 13 [10%]). Approximately one-third (36.7%) had evidence of a PSC in the 90-day period following surgery (urinary diversion, 7.7%; colostomy, 35.3%; ileostomy, 43.8%). The average time from surgery to PSC was 23.7 ± 20.5 days (mean ± SD). Patients with PSC had index admissions that averaged 21.5 days versus 13.9 days for those without these complications. Corresponding rates of hospital readmission within the 120-day period following surgery were 47% versus 33%, respectively. Total healthcare costs over 120 days were almost $80,000 higher for patients with PSCs., Conclusions: Approximately one-third of ostomy patients over a 5-year study period had evidence of PSCs within 90 days of surgery. Costs of care were substantially higher for patients with these complications.

Mild traumatic brain injury (mTBI) is a common health problem. There is tremendous variability and heterogeneity in human mTBI, including mechanisms of injury, biomechanical forces, injury severity, spatial and temporal pathophysiology, genetic factors, pre-injury vulnerability and resilience factors, and clinical outcomes. Animal models greatly reduce this variability and heterogeneity, and provide a means to study mTBI in a rigorous, controlled, and efficient manner. Rodent models, in particular, are time- and cost-efficient, and they allow researchers to measure morphological, cellular, molecular, and behavioral variables in a single study. However, inter-species differences in anatomy, morphology, metabolism, neurobiology, and lifespan create translational challenges. Although the term "mild" TBI is used often in the pre-clinical literature, clearly defined criteria for mild, moderate, and severe TBI in animal models have not been agreed upon. In this review, we introduce current issues facing the mTBI field, summarize the available research methodologies and previous studies in mTBI animal models, and discuss how a translational research approach may be useful in advancing our understanding and management of mTBI., (Copyright © 2016 Elsevier Ltd. All rights reserved.)