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Introduction Physician burnout has severe consequences on clinician well-being. Residents face numerous work-stressors that can contribute to burnout; however, given specialty variation in work-stress, it is difficult to identify systemic stressors and implement effective burnout interventions on an institutional level. Assessing resident preferences by specialty for common wellness interventions could also contribute to improved efficacy. Methods This cross-sectional study used best–worst scaling (BWS), a type of discrete choice modelling, to explore how 267 residents across nine specialties (anaesthesiology, emergency medicine, internal medicine, neurology, obstetrics and gynaecology, pathology, psychiatry, radiology and surgery) prioritised 16 work-stressors and 4 wellness interventions at a large academic medical centre during the COVID-19 pandemic (December 2020). Results Top-ranked stressors were work-life integration and electronic health record documentation. Therapy (63%, selected as ‘would realistically consider intervention’) and coaching (58%) were the most preferred wellness supports in comparison to group-based peer support (20%) and individual peer support (22%). Pathology, psychiatry and OBGYN specialties were most willing to consider all intervention options, with emergency medicine and internal medicine specialties least willing to consider intervention options. Conclusion BWS can identify relative differences in surveyed stressors, allowing for the generation of specialty-specific stressor rankings and preferences for specific wellness interventions that can be used to drive institution-wide changes to improve clinician wellness. BWS surveys are a potential methodology for clinician wellness programmes to gather specific information on preferences to determine best practices for resident wellness.

The improvement of effective multidrug agents has allowed more patients to undergo resection for pancreatic cancer (PC). In the conversion cases of initially unresectable PC after induction chemotherapy, pancreatic surgeons often encounter challenging vein resections cases such as those of long-segment portal vein (PV)/superior mesenteric vein (SMV) encasement or occlusion of the distal (caudal) SMV. Given the lack of consensus for the optimal approach for major vein resections and reconstructions in these situations, this review summarizes the literature on this topic and provides the best currently available approaches for challenging vein reconstruction cases. For long-segment PV/SMV encasement, tips for direct end-to-end anastomosis without grafts and the splenic vein (SpV) reconstruction to prevent left-side portal hypertension will be introduced. For distal SMV encasement, several bypass techniques to deal with collateralizations will be introduced. Even though some high-volume PC centers are obtaining favorable outcomes for challenging vein resection cases, existing evidence on this topic is limited. It is essential to organize the well-designed international multicenter studies for the small population of challenging vein resection cases. With the emergence of effective chemotherapies, the number of PC patients who can undergo curative resection is increasing. Achieving more successful vessel resection and reconstruction in the treatment of PC is a common goal that pancreatic surgeons should focus on together.

To explore the effect of 23.4% hypertonic saline for management of elevated intracranial pressure in children admitted to our institution for severe traumatic brain injury.Single-center, retrospective medical chart analysis.A PICU at a level 1 pediatric trauma center in the United States.Children admitted for severe traumatic brain injury from 2006 to 2016 who received 23.4% hypertonic saline and whose intracranial pressures were measured within 5 hours of receiving 23.4% hypertonic saline.None.Over the 10-year period, 1,587 children were admitted for traumatic brain injury, 155 of whom were deemed severe per this study's criteria. Forty of these children received at least one dose of hypertonic saline, but 14 were excluded for insufficient intracranial pressure data. Among the remaining 26 children, one hundred one 23.4% hypertonic saline boluses were used in the analysis. Use of 23.4% hypertonic saline was associated with a decrease in intracranial pressure of approximately 7 mm Hg at both within 1 hour after the bolus (p0.01) and 4 hours after the bolus (p0.01) when compared with the intracranial pressure measured within 1 hour before the hypertonic saline bolus. These effects remained significant after adjusting for Functional Status Scale score and CT Marshall scores. There was no statistically significant association between adjunctive therapies, such as antiepileptics and analgesics, and changes in intracranial pressure. There was no laboratory evidence of hyperkalemia or renal injury after use of 23.4% hypertonic saline. Across all hospitalizations, 65% of the study population demonstrated an abnormally elevated creatinine at least once, but only three episodes of acute kidney injury occurred in total, all before hypertonic saline administration. Eight of the 26 children in this analysis died during their hospitalization. The Functional Status Scale scores ranged from 6 to 26 with a mean of 12.2 and SD of 5.7.Use of 23.4% hypertonic saline with children admitted for severe traumatic brain injury is associated with a statistically significant decrease in intracranial pressure within 1 hour of use.

Vein resection and reconstruction have become a common approach for the treatment of pancreatic ductal adenocarcinoma (PDAC) and are listed in multiple major guidelines. However, the need of performing large artery resection and reconstruction in treating PDAC is still a debatable topic. Due to the development of modern chemotherapeutic regimens, several reports from specialized centers have shown pancreatectomy with arterial resection is associated with favorable long-term survival results. This chapter gives an overview on the historical notes, technical aspects, management after artery resection, and current outcomes of arterial resection for PDAC. We also gave recommendations for developing a training program that focus on surgical treatment for locally advanced PDAC and forming of a multidisciplinary team. Even if there are few studies that indicate the need of pancreatectomy with artery resection should become a routine, we still need to prepare ourselves to perform these surgeries since more patient will need to undergo artery resections with the emergence of more effective systemic treatment for PDAC. The management of these patients should be standardized and surgeons should receive a dedicated training.

With the introduction of artificial intelligence (AI) and machine learning (ML) in healthcare and the development of an increasing number of commercial products based on software as medical device (SaMD), regulatory processes need to evolve in parallel. This book chapter aims to provide a high-level overview of the history of SaMD and reviews some of the various regulatory aspects associated with this group of medical devices. Although we aim to cover the regulations globally, the main focus is on markets dependent on the Food and Drug Administration (FDA) based review process mostly due to the early stages of regulations in other geographies.

Pancreatic cancer (PC) is likely to become the second leading cause of malignancy-associated mortality within the next 10 years and surgery remains the best hope for cure. The introduction of effective neoadjuvant treatment (NAT) has increased the resection rate of PC in the era of contemporary pancreatology. This review summarizes the surgical selection criteria for locally advanced PC (LAPC), by focusing on the commonly used predictors for resectability and better overall survival outcome. Based on the currently available evidence, the role of change in carbohydrate antigen 19-9 (CA 19-9) and patient's tumor response to NAT are critical in surgical candidacy selection. Although, consensus on surgical candidacy selection for LAPC still needs to be made, several data have shown that surgery provides the most optimistic chance of cure for PC. Surgery is, therefore, recommended whenever the benefits of pancreatectomy outweigh surgical complications, and the chance of local or distant metastases in the postoperative setting is low. This review also provided our insight for and experience in selecting surgical candidates by focusing on optimizing the overall survival of LAPC patients. Nevertheless, a collaborative approach to formulating standardized criteria for surgical candidate selection and treatment guidelines for LAPC is a common goal that pancreatologists worldwide should focus on.

Background/objectives Pancreatic cystic neoplasms (PCNs) are common, among which 13%–23% are serous cystic neoplasms (SCNs). However, diffuse and multifocal variants of SCNs are extremely rare. The differential diagnosis of SCNs from other PCNs is important as the former entities are benign and do not become invasive. Objective This study analyzes the clinical characteristics of multifocal/diffuse SCN through a systematic review of the literature and a case report. Methods A comprehensive literature search was executed in the Ovid MEDLINE, Embase, and Google Scholar databases. The search strategy was designed to capture the concept of multifocal/diffuse SCN cases with sufficient clinical information for detailed analysis. Using the final included articles, we analyzed tumor characteristics, diagnostic modalities used, initial management and indications, and patient outcomes. Results A review of 262 articles yielded 19 publications with 22 cases that had detailed clinical information. We presented an additional case from our institution database. The systematic review of 23 cases revealed that the diffuse variant is more common than the multifocal variant (15 vs 8 cases, respectively). Patients were managed with surgical intervention, conservative treatment, or conservative treatment followed by surgical intervention. Indications for surgery following conservative management mainly included new onset or worsening of symptoms. Only one case reported significant tumor growth after attempting an observational approach. No articles reported recurrence of SCN after pancreatectomy, and no articles reported mortality related to multifocal/diffuse SCNs. Conclusion Despite their expansive-growing and space-occupying characteristics, multifocal/diffuse SCNs should be treated similarly to their more common unifocal counterpart.

Continuous positive airway pressure (CPAP) is a method of respiratory support used around the world to treat children with lower respiratory tract infections (LRTI) (WHO, 2016, Oxygen Therapy for Children, World Health Organization, Geneva, Switzerland, Report). Bubble continuous positive airway pressure (bCPAP) is an effective form of CPAP that is currently used in both high- and low-resource countries. Low-cost, modified bCPAP devices have been designed as an ideal form of CPAP in low-resource areas (Bjorklund, A. R., Mpora, B. O., Steiner, M. E., Fischer, G., Davey, C. S., and Slusher, T. M., 2018, “Use of a Modified Bubble Continuous Positive Airway Pressure (bCPAP) Device for Children in Respiratory Distress in Low- and Middle-Income Countries: A Safety Study,” Paediatr. Int. Child Health, 39(3), pp. 1–8). However, patients in low-resource settings undergoing bCPAP treatment are often given pure oxygen, which has been linked to retinopathy of prematurity, cardiovascular complications, and patient mortality (Rodgers, J. L., Iyer, D., Rodgers, L. E., Vanthenapalli, S., and Panguluri, S. K., 2019, “Impact of Hyperoxia on Cardiac Pathophysiology,” J. Cell. Physiol., 234(8), pp. 1–9; Ramgopal, S., Dezfulian, C., Hickey, R. W., Au, A. K., Venkataraman, S., Clark, R. S. B., and Horvat, C. M., 2019, “Association of Severe Hyperoxemia Events and Mortality Among Patients Admitted to a Pediatric Intensive Care Unit,” JAMA Network Open, 2(8), p. e199812). This problem is typically avoided by using commercial oxygen blenders, which can titrate down the concentration of oxygen delivered to the minimum needed; however, these blenders can cost nearly 1000 USD and are almost always unavailable in low-resource settings. The lack of available low-cost oxygen blenders compatible with modified bCPAP circuits creates a barrier for low-resource hospitals to be able to provide blended oxygen to patients. There is a need for a low-cost oxygen blender for use in low-resource settings. We propose a passive oxygen blender that operates via entrainment of atmospheric air. The device can easily be assembled in low-resource areas using a 22 gauge hypodermic needle, two 3 cc syringes, tape or super glue, and the materials required for bCPAP—for approximately 1.40 USD per device. The blender has not been clinically tested yet, but can achieve oxygen concentrations as low as 60% with bCPAP levels of 5 cm H2O (490 Pa) when used in a standard bCPAP circuit without a patient.

Green technology has increasingly penetrated our daily lives over the past decade. Electric vehicles (EVs) have been widely accepted by both corporate users and individual customers. Recently, the Chinese government has been firmly driving forward its macro-economic policy, “Made in China 2025,” in manufacturing and industry. At the same time, Chinese citizens are demanding a cleaner, healthier natural environment for their urban lives. Promotion of EV has turned out to be one attractive solution for a large number of stakeholders from various sectors. This chapter begins with a review of cutting-edge EV technology development internationally. It covers smart control and driving technology, new batteries, and energy storage devices. It is followed by a comparative analysis of a range of policy incentives currently effective in the Greater Bay Area (GBA) of China. These policies from different authorities and departments need subtle cooperation in order to be fully executed. This chapter discusses multiple incentives from three aspects: technology, economics, and policy direction. The author believes that both EV manufactory and consumption in the GBA will experience steady growth in the coming years. We conclude that an upward trend of EV penetration in the GBA will positively contribute toward energy sustainability as well as the green finance of projects in the future.

PURPOSE To compare the outcomes of children with orbital cellulitis treated with intravenous (IV) dexamethasone and antibiotics on admission to patients treated with antibiotics alone. METHODS Prospective comparative interventional study. Forty-three children admitted to a tertiary institution with orbital cellulitis were enrolled. On admission, all patients were started on broad spectrum IV antibiotics and parents were offered IV dexamethasone (0.3 mg/kg/d every 6 hours for 3 days). Patients whose parents refused steroid treatment served as the control group. RESULTS Twenty-eight (65%) patients received IV steroids and antibiotics on admission while 15 (35%) received IV antibiotics alone. Children who received IV steroids had significantly shorter hospital stays than those who did not receive steroids (3.8 ± 0.2 days vs. 6.7 ± 0.3 days; p < 0.001). This was true both for children who underwent surgery (5/28 with steroids, 3/15 without; 5.0 ± 0.7 days vs. 7.3 ± 1.2 days; p = 0.011) and for those who did not require surgical intervention (23/28 with steroids, 12/15 without; 3.6 ± 0.6 and 6.5 ± 1.0 days; p < 0.001). Side effects of steroid treatment were mild and did not require termination of therapy. During follow up, all study patients had returned to their baseline health without any cases of decreased vision or disease recurrence. CONCLUSIONS The results of the current study give additional evidence to the relative safety and efficacy of systemic steroid use concurrently with IV antibiotics in children with orbital cellulitis. This is the first study to recommend IV steroids on hospital admission and a standardized dosing regimen. Children who received steroids had a shorter hospital stay than those who did not.

Aim Fibrosis is the most common complication from chronic diseases, and yet no therapy capable of mitigating its effects is available. Our goal is to unveil specific signaling regulating the fibrogenic process and to identify potential small molecule candidates that block fibrogenic differentiation of fibro/adipogenic progenitors. Method We performed a large-scale drug screen using muscle-resident fibro/adipogenic progenitors from a mouse model expressing EGFP under the Collagen1a1 promotor. We first confirmed that the EGFP was expressed in response to TGFβ1 stimulation in vitro. Then we treated cells with TGFβ1 alone or with drugs from two libraries of known compounds. The drugs ability to block the fibrogenic differentiation was quantified by imaging and flow cytometry. From a two-rounds screening, positive hits were tested in vivo in the mice model for the Duchenne Muscular Dystrophy (mdx mice). The histopathology of the muscles was assessed with picrosirius red (fibrosis) and laminin staining (myofiber size). Key findings From the in vitro drug screening, we identified 21 drugs and tested 3 in vivo on the mdx mice. None of the three drugs significantly improved muscle histopathology. Significance The in vitro drug screen identified various efficient compounds, none of them strongly inhibited fibrosis in skeletal muscle of mdx mice. To explain these observations, we hypothesize that in Duchenne Muscular Dystrophy, in which fibrosis is a secondary event due to chronic degeneration and inflammation, the drugs tested could have adverse effect on regeneration or inflammation, balancing off any positive effects and leading to the absence of significant results.

Background: Eczema coxsackium (EC) can manifest in patients with underlying atopic dermatitis (AD) as a diffuse vesicular rash in a febrile child. The presentation overlaps clinically with the feared diagnosis of eczema herpeticum (EH), which makes differentiating between the conditions very important. Case presentation: A 6-month-old girl with known AD presented with fever and rapidly spreading vesicular rash. The patient had multiple exposures including a new antibiotic prescription, introduction of new foods, 6-month vaccinations and a sick contact. She was treated empirically with acyclovir for EH until herpes simplex virus (HSV) polymerase chain reaction (PCR) returned negative and enterovirus PCR returned positive. Once the diagnosis of EC was confirmed, antiviral therapy was discontinued and she was treated successfully with supportive measures without sequelae. Conclusions: Differentiating EC from EH is important clinically as EC is self-limiting and resolves spontaneously whereas EH may cause severe complications if not treated early. While morphology alone cannot reliably distinguish between the conditions, clinical suspicion based on history can prompt proper testing and improve patient outcomes.

Background/Purpose Calcium silicate (CS) cements have excellent bioactivity and can induce the bone-like apatite formation. They are good biomaterials for bone tissue engineering and bone regenerative medicine. However, they have degradability and the dissolved CS can cause the inflammatory response at the early post-implantation stage. The purpose of this study was to design and prepare the curcumin-loaded mesoporous CS (MesoCS/curcumin) cements as a strategy to reduce the inflammatory reaction after implantation. Methods The MesoCS/curcumin cements were designed and prepared. The characteristics of MesoCS/curcumin specimens were examined by transmission electron microscopy (TEM), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Their physical properties, biocompatibility, and anti-inflammatory ability were also evaluated. Results The MesoCS/curcumin cements displayed excellent biocompatibility and physical properties. Their crystalline characterizations were very similar with MesoCS cements. After soaking in simulated body fluid, the bone-like apatite layer of the MesoCS/curcumin cements could be formed. In addition, it could inhibit the expression of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) after inflammation reaction induced by lipopolysaccharides and had good anti-inflammatory ability. Conclusion Adding curcumin in MesoCS cements can reduce the inflammatory reaction, but does not affect the original biological activity and properties of MesoCS cements. It can provide a good strategy to inhibit the inflammatory reaction after implantation for bone tissue engineering and bone regenerative medicine.

Objectives To assess whether lactate levels are associated with clinical outcomes in adult congenital heart disease patients who undergo cardiac surgery. Design Retrospective study. Setting Single quaternary academic referral center. Participants Adult congenital heart disease patients (≥18 y old) with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass. Interventions Participants were classified into 3 groups according to their peak arterial lactate level within the first 48 hours of surgery. Measurements and Main Results In-hospital 30-day mortality, hospital and intensive care unit length of stay, duration of mechanical ventilation after surgery, acute kidney injury defined by Acute Kidney Injury Network criteria, and intensive care unit and hospital readmission within 30 days of surgery were examined. There was no significant difference among different lactate level groups in acute kidney injury, hospital length of stay, intensive care unit length of stay, hours of mechanical ventilation, need for redo surgery, or rates of hospital or intensive care unit readmission. In multivariable analysis, which included cardiopulmonary bypass time, redo surgery, nonelective case, and the adult congenital heart disease complexity score, lactate levels were not a significant predictor of either acute kidney injury or hospital length of stay. Conclusions The appeal of using lactate levels to risk stratify-patients or to develop a model to predict mortality and morbidity has potential merit, but currently there is insufficient evidence to use lactate levels as a predictor of outcomes in adult patients with congenital heart disease undergoing cardiac surgery.

Developing effective methods for the automated detection of IDC remains a challenging problem for breast cancer diagnosis. Recently, Cruz and his coworkers proposed a machine learning approach for detection of invasive ductal carcinoma (IDC) from whole image slides containing breast cancer cells. Their method, based on a Convolutional Neural Network (CNN), does not need to handcraft features from images. Their work has the potential of revolutionizing cancer detection, promoting further research and development in this exciting direction. Inspired by Cruz's work, our team investigated various CNN architectures for automated detection of breast cancer. We first implemented a baseline CNN similar to Cruz'ss, and then extended it to four different architectures. All architectures were trained over a large dataset of approximately 275,000, 50x50 RGB image patches. Measurement of quantitative results were done through a global average of 10-Fold Cross Validation tests. Each methodology used the performance measures, F-Measure (F1), and Balanced Accuracy (BAC). One of the fine-tuned CNN architectures yielded the best results in F1, BAC and accuracy (92%, 87%, and 89%, respectively). We also discovered through this study that data augmentation was not effective in automatic detection of breast cancers with the given dataset.

Simple Summary Intraductal papillary mucinous neoplasms (IPMN) are common but difficult to manage since accurate tools for diagnosing malignancy are unavailable. This study evaluates the diagnostic value of main pancreatic duct (MPD) diameter for detecting IPMN malignancy, using a meta-analysis of published data. The result suggests that malignancy is highly prevalent in IPMN with ductal dilatation of >5 mm. Abstract Intraductal papillary mucinous neoplasms (IPMN) are common but difficult to manage since accurate tools for diagnosing malignancy are unavailable. This study tests the diagnostic value of the main pancreatic duct (MPD) diameter for detecting IPMN malignancy using a meta-analysis of published data of resected IPMNs. Collected from a comprehensive literature search, the articles included in this analysis must report malignancy cases (high-grade dysplasia (HGD) and invasive carcinoma (IC)) and MPD diameter so that two MPD cut-offs could be created. The sensitivity, specificity, and odds ratios of the two cutoffs for predicting malignancy were calculated. A review of 1493 articles yielded 20 retrospective studies with 3982 resected cases. A cutoff of ≥5 mm is more sensitive than the ≥10 mm cutoff and has pooled sensitivity of 72.20% and 75.60% for classification of HGD and IC, respectively. Both MPD cutoffs of ≥5 mm and ≥10 mm were associated with malignancy (OR = 4.36 (95% CI: 2.82, 6.75) vs. OR = 3.18 (95% CI: 2.25, 4.49), respectively). The odds of HGD and IC for patients with MPD ≥5 mm were 5.66 (95% CI: 3.02, 10.62) and 7.40 (95% CI: 4.95, 11.06), respectively. OR of HGD and IC for MPD ≥10 mm cutoff were 4.36 (95% CI: 3.20, 5.93) and 4.75 (95% CI: 2.39, 9.45), respectively. IPMN with MPD of >5 mm could very likely be malignant. In selected IPMN patients, pancreatectomy should be considered when MPD is >5 mm.

The Chinese government has introduced policy measures and financial incentives to promote electric vehicles (EVs) in alignment with its advanced industrial development and environmental sustainability. In order to stimulate market adoption and technological innovation, a dual-credits policy regime with strictly guided subsidies was first announced in 2017 and then tightened up in 2019 by relevant authorities of the central government. This study focuses on examining the latest development of EV policy in the Chinese mainland. It reviews the pertinent national-level policy measures and financial incentives for sustainable development of the EV industry in a macro scope over the past decade. Further, we develop a mathematical model to quantify the impact of the most update policy – the dual-credits policy regime. Our simulation results reveal a significant gap between the recent EV sales and the estimated future EV production needed under the new policy regime. Such significant gap implies remarkable policy pressure and inevitable execution challenges of the recently tightened dual-credits regime. In conclusion, we articulate strategic implications for EV market participants in China. Upcoming challenges including gradual phasing out of financial support and impending market competition are discussed.

Introduction: Otology relies on clinical examination to teach anatomy of the ear. The purpose of this report is to introduce the Buckingham Virtual Tympanum iPhone app as an adjuvant educational tool to teach the anatomical details of the tympanic membrane (TM). Materials and Methods: This app, available free at the Apple Store, was constructed using archival photographs of normal and abnormal TMs, stratified by difficulty. Each image has 4 labeled structures, linked to questions to encourage active learning. Third-year medical students then used the app to familiarize themselves with the TM. Results: The free app was readily accessible and functioned without technical issues. By being interactive, it forced the user into the role of active learner. This pilot study found that students who used the app understood images of the TM better than those who did not use it. Discussion: We introduce an interactive, iPhone-based smartphone application that we found to be a useful adjunct for teaching TM anatomy.

Background Severe dysphagia may occur in the immune mediated necrotizing myopathies (IMNM). Neck swelling and severe dysphagia as the initial symptoms upon presentation has not been previously described. Case presentation A 55-year-old male with a 4 week history of neck swelling, fatigue, dysphagia, myalgias, night sweats, and cough was admitted for an elevated CK. He underwent extensive infectious and inflammatory evaluation including neck imaging and muscle biopsy. Neck CT and MRI showed inflammation throughout his strap muscles, retropharyngeal soft tissues and deltoids. Infectious work up was negative. Deltoid muscle biopsy demonstrated evidence of IMNM. Lab tests revealed anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies confirming the diagnosis of HMGCR IMNM. Conclusions HMGCR IMNM is a rare and incompletely understood disease process. Awareness of HMGCR IMNM could potentially lead to earlier diagnosis, treatment and improved clinical outcomes as disease progression can be rapid and severe.

Kidney cancer is one of the deadliest diseases and its diagnosis and subtype classification are crucial for patients&rsquo, survival. Thus, developing automated tools that can accurately determine kidney cancer subtypes is an urgent challenge. It has been confirmed by researchers in the biomedical field that miRNA dysregulation can cause cancer. In this paper, we propose a machine learning approach for the classification of kidney cancer subtypes using miRNA genome data. Through empirical studies we found 35 miRNAs that possess distinct key features that aid in kidney cancer subtype diagnosis. In the proposed method, Neighbourhood Component Analysis (NCA) is employed to extract discriminative features from miRNAs and Long Short Term Memory (LSTM), a type of Recurrent Neural Network, is adopted to classify a given miRNA sample into kidney cancer subtypes. In the literature, only a couple of kidney subtypes have been considered for classification. In the experimental study, we used the miRNA quantitative read counts data, which was provided by The Cancer Genome Atlas data repository (TCGA). The NCA procedure selected 35 of the most discriminative miRNAs. With this subset of miRNAs, the LSTM algorithm was able to group kidney cancer miRNAs into five subtypes with average accuracy around 95% and Matthews Correlation Coefficient value around 0.92 under 10 runs of randomly grouped 5-fold cross-validation, which were very close to the average performance of using all miRNAs for classification.

Orbital floor fractures (OFF) with entrapment require prompt clinical and radiographic recognition for timely surgical correction. Correct CT radiographic interpretation of entrapped fractures can be subtle and thus missed. We reviewed the clinical, radiographic and intraoperative findings of 45 cases of entrapped OFF to correlate pre- and intraoperative findings with radiography. Retrospective review and statistical analysis of 45 patients with OFF using the chi squared and Kruskal-Wallis tests. Main outcome measures included patient demographics, clinical features, radiologic interpretation, intraoperative findings, and treatment outcomes. Twenty-one cases (47%) had radiologic evaluations of orbital CT scans that included commentary on possible entrapment. Intraoperatively, 16 (76%) of these patients had the inferior rectus muscle incarcerated in the fracture, while 5 (24%) patients had incarceration of the orbital fat. Possibility of entrapment was not commented on in the radiology reports of the remaining 24 (53%) cases. Intraoperatively, 13 (54%) of these patients had the inferior rectus muscle incarcerated in the fracture, while 11 (46%) patients had incarceration of the orbital fat. It is vital to assess the possibility of entrapment, especially in young patients, in the setting of OFF as a delay in diagnosis may lead to persistent diplopia, disfigurement, or bradycardia. Most radiology reports did not mention the possibility of entrapment in this cohort. A key concept is that entrapment occurs when any orbital tissue (muscle or fat) is trapped in the fracture site.

ObjectivesWe aimed to study the prevalence of CTCs in breast cancer (BC) patients undergoing neoadjuvant or palliative therapy with a label-free microfluidic platform (ClearCell FX), and its prognostic relevance in metastatic BC (mBC).Materials and methodsPeripheral blood samples were collected from 108 BC patients before starting a new line of treatment ("baseline"), majority of whom had mBC (76/108; 70.4%). CTCs were retrieved by dean flow fractionation that enriched for larger cells, and enumerated using immunofluorescence-based staining. Progression-free survival (PFS) in mBC patients was analysed using Kaplan-Meier method; cox proportional hazard models were used for univariable and multivariable analyses.ResultsThe detection rate of CTCs before starting a new line of treatment was 75.9% (n = 108; median: 8 CTCs/7.5 ml blood) at a cut off of ≥2 CTCs. PFS was inferior for mBC patients with baseline CTC count ≥5 CTCs/7.5 ml blood vs. those with < 5 CTCs/7.5 ml blood (median PFS: 4.3 vs. 7.0 months; p-value: 0.037). The prognostic relevance of CTCs was most significant in patients with HER2- mBC (median PFS: 4.1 vs. 8.3 months; p-value: 0.032), luminal (HR+HER2-) subtype (median PFS: 4.2 vs. 8.3 months; p-value: 0.048), and patients who had one or more prior treatments (median PFS: 4.2 vs. 7.0 months; p-value: 0.02). On multivariable analysis, baseline CTC level (hazard ratio (HR): 1.84, p-value: 0.02) and pre-treatment status (HR: 1.87, p-value: 0.05) were independent predictors of PFS.ConclusionsThis work demonstrates the prognostic significance of CTCs in mBC detected using a label-free size-based enrichment platform.

Since 2012, a number of case reports have described the occurrence of thrombotic microangiopathy (TMA) following IV abuse of extended-release oxymorphone hydrochloride (Opana ER), an oral opioid for long-term treatment of chronic pain. Here, we present unique clinical features of 3 patients and investigate IV exposure to the tablet’s inert ingredients as a possible causal mechanism. Guinea pigs were used as an animal model to understand the hematopathologic and nephrotoxic potential of the inert ingredient mixture (termed here as PEO+) which primarily contains high-molecular-weight polyethylene oxide (HMW PEO). Microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury were found in a group of 3 patients following recent injection of adulterated extended-release oxymorphone tablets. Varying degrees of cardiac involvement and retinal ischemia occurred, with TMA evident on kidney biopsy. A TMA-like state also developed in guinea pigs IV administered PEO+. Acute tubular and glomerular renal injury was accompanied by nonheme iron deposition and hypoxia-inducible factor-1α upregulation in the renal cortex. Similar outcomes were observed following dosing with HMW PEO alone. IV exposure to the inert ingredients in reformulated extended-release oxymorphone can elicit TMA. Although prescription opioid abuse shows geographic variation, all physicians should be highly inquisitive of IV drug abuse when presented with cases of TMA.

Renal sympathetic hyperactivity is associated with hypertension, a leading cause of mortality worldwide. Renal sympathetic denervation via the Symplicity Catheter System has been shown to decrease blood pressure by 33/11 mmHg by 6 months, with no radiofrequency (RF)-related adverse sequelae visible by CT/MR angiography or renal duplex ultrasound 6 months after the procedure. Here, we present preclinical work predating those clinical results. We performed therapeutic renal sympathetic denervation in a swine animal model to characterize the vascular safety and healing response 6 months after renal denervation therapy.In December 2007, seven domestic swine received a total of 32 radiofrequency ablations via the Symplicity Catheter System and were euthanatized 6 months later. Renal angiography was done before, immediately after, and 6 months after procedure. The renal vessels were examined histologically with HE and Movat pentachrome stains to identify evidence of vascular and neural injury. The kidneys and urinary system were also examined for evidence of gross and microscopic abnormalities.Renal nerve injury involved primarily nerve fibrosis, replacement of nerve fascicles with fibrous connective tissue, and thickening of the epineurium and perineurium. Renal arterial findings included fibrosis of 10-25% of the total media and underlying adventitia, with mild disruption of the external elastic lamina. No significant smooth muscle hyperplasia or inflammatory components were observed. There was no renal arterial stenosis or thrombosis observed by angiography or histology. No gross or microscopic device-related abnormalities were noted in the kidney, surrounding stroma, or urinary bladder.In a swine model, renal denervation via the Symplicity Catheter System resulted in no clinically significant adverse renal artery or renal findings 6 months after the procedure. This is corroborated by the vascular safety profile demonstrated in subsequent human clinical studies.

Die „narbenlose“ Chirurgie ist ein wunschenswertes Ziel in der Welt der Laparoskopie und interventionellen Endoskopie. Eine Moglichkeit, dieses Ziel zu erreichen, ist der abdominelle Zugang durch eine naturliche Korperoffnung („natural orifice translumenal endoscopic surgery”, NOTES); diesem Verfahren fehlt jedoch noch eine geeignete Plattform und die Anwendung ist bisher limitiert. Weitere Moglichkeiten sind Reduced-Port-Techniken oder die „single port access surgery“, die nur minimale fasziale Defekte hinterlassen. Die Entwicklungs- und Wachstumsmoglichkeiten auf diesem Gebiet umfassen eine weites Spektrum. Allerdings muss vor einer breiten Anwendung der Verfahren gewahrleistet sein, dass diese Techniken auf sichere Art und Weise sowie wirtschaftlich und okologisch sinnvoll umgesetzt werden konnen. Der Beitrag gibt einen Uberblick uber die Verfahrensentwicklung, die Erlernbarkeit und den Einsatz der neuen Verfahren.

Intensity-modulated radiation therapy (IMRT) has been applied for treatments of primary head with neck nodes, lung with supraclavicular nodes, and high-risk prostate cancer with pelvis wall nodes, all of which require large fields. However, the design of the Varian multileaf collimator requires fields >14 cm in width to be split into 2 or more carriage movements. With the split-field technique, both the number of monitor units (MUs) and total treatment time are significantly increased. Although many different approaches have been investigated to reduce the MU, including introducing new leaf segmentation algorithms, none have resulted in widespread success. In addition, for most clinics, writing such algorithms is not a feasible solution, particularly with commercial treatment planning systems. We introduce a new approach that can minimize the number of split fields and reduce the total MUs, thereby reducing treatment time. The technique is demonstrated on the Eclipse planning system V7.3, but could be generalized to any other system.

Because of the dose limit for critical structures such as brainstem and spinal cord, administering a dose of 60 Gy to patients with recurrent head and neck cancer is challenging for those who received a previous dose of 60-70 Gy. Specifically, previously irradiated head and neck patients may have received doses close to the tolerance limit to their brainstem and spinal cord. In this study, a reproducible intensity-modulated radiation therapy (IMRT) treatment design is presented to spare the doses to brainstem and spinal cord, with no compromise of prescribed dose delivery. Between July and November 2008, 7 patients with previously irradiated, recurrent head and neck cancers were treated with IMRT. The jaws of each field were set fixed with the goal of shielding the brainstem and spinal cord at the sacrifice of partial coverage of the planning target volume (PTV) from any particular beam orientation. Beam geometry was arranged to have sufficient coverage of the PTV and ensure that the constraints of spinal cord

Cold atmospheric pressure plasmas have emerged as a promising new tool for medical applications. Compared to conventional thermal plasma, such as arc coagulators and desiccators, cold plasma can be more selective in its application and may be used for effective sterilization of skin and wound tissue, wound healing and tissue regeneration, cancer treatment and blood coagulation. One of the key questions that has to be answered before these plasma technologies are introduced in medical practice is the safety of plasma treatment of living tissues, i.e. toxic dose levels of plasma exposure should be determined. It is well established that porcine (pig) skin closely resembles human skin; hence we evaluated the potential toxic effects of plasma treatment on intact and wounded skin in a Yorkshire pig model. Varying doses of Floating Electrode Dielectric Barrier Discharge (FE-DBD) and microsecond Pin-to-Hole Spark Discharge (PHD) plasmas were applied to determine a dosage regime where tissue damage occurs.

A plenary session at the annual meeting of the International Association of Medical Science Educators introduced the challenges and successes experienced with two models of interprofessional education (IPE). Representatives from the Vanderbilt Program in Interprofessional Learning (VPIL) and a five-university IPE consortium, the Southeastern Conference (SEC) for IPE, answered moderated questions from the audience including methods for integrating basic science learning with interprofessional students, in the clinical and digital environment. Online modules for delivering IPE with both asynchronous and synchronous connectivity were introduced. Additional areas of discussion included integration and relevance of IPE integration with basic science, the impact of IPE models on student behavior and career choice, concerns associated with documenting IPE activities for promotion and tenure, and managing difficulties associated with integrating IPE across multiple curricula.

Most deformation algorithms use a single-value smoother during optimization. We investigate multi-scale regularizations (smoothers) during the multi-resolution iteration of two non-parametric deformable registrations (demons and diffeomorphic algorithms) and compare them to a conventional single-value smoother. Our results show that as smoothers increase, their convergence rate decreases; however, smaller smoothers also have a large negative value of the Jacobian determinant suggesting that the one-to-one mapping has been lost; i.e., image morphology is not preserved. A better one-to-one mapping of the multi-scale scheme has also been established by the residual vector field measures. In the demons method, the multi-scale smoother calculates faster than the large single-value smoother (Gaussian kernel width larger than 0.5) and is equivalent to the smallest single-value smoother (Gaussian kernel width equals to 0.5 in this study). For the diffeomorphic algorithm, since our multi-scale smoothers were implemented at the deformation field and the update field, calculation times are longer. For the deformed images in this study, the similarity measured by mean square error, normal correlation, and visual comparisons show that the multi-scale implementation has better results than large single-value smoothers, and better or equivalent for smallest single-value smoother. Between the two deformable registrations, diffeormophic method constructs better coherence space of the deformation field while the deformation is large between images.

Laparoscopic ventral hernia repair has been demonstrated to be an acceptable and successful technique. Aside from similar, albeit fewer, complications compared to open hernia repair, the laparoscopic technique has the additional complication of port site hernia to its follow-up criteria. Our initial experience with reduced port surgery in hernias was described as a two-port one-stitch repair technique in 2002. We initially applied our Single Port Access (SPA™) technique to ventral hernia repairs and reported it at the American Hernia Society meeting in 2008. Now we present the first 30 cases, some with 6–24-month follow-up. The charts of 30 patients undergoing surgery for primary and recurrent ventral hernias employing the SPA technique were reviewed. The SPA technique was applied through a 1.0–1.6-cm incision remote from and lateral to the hernia location in the abdominal wall. Polypropylene-based coated mesh and non-fascial fixation were used in all cases. All procedures were completed via the SPA technique. Operative time, length of stay, and estimated blood loss were acceptable. The size of mesh placed ranged from 81 to 500 cm2. Postoperative seromas were observed and all resolved spontaneously. There have been no wound infections or port site hernias during the 6–24-month follow-up period. There have been no recurrent hernias at the primary site. We have successfully demonstrated the applicability of Single Port Access surgery for ventral hernia repair. In our initial series we performed this procedure on smaller hernias but have now begun applying it to larger repairs.

The interplay between a mobile target and a dynamic multileaf collimator can compromise the accuracy of intensity-modulated radiation therapy(IMRT). Our goal in this study is to investigate the dosimetric effects caused by the respiratory motion during IMRT. A moving phantom was built to simulate the typical breathing motion. Different sizes of the gating windows were selected for gated deliveries. The residual motions during the beam-on period ranged from 0.5 to 3 cm. An IMRT plan with five treatment fields from different gantry angles were delivered to the moving phantom for three irradiation conditions: Stationary condition, moving with the use of gating system, and moving without the use of gating system. When the residual motion was 3 cm, the results showed significant differences in dose distributions between the stationary condition and the moving phantom without gating beam control. The overdosed or underdosed areas enclosed about 33% of the treatment area. In contrast, the dose distribution on the moving phantom with gating window set to 0.5 cm showed no significant differences from the stationary phantom. With the appropriate setting of the gating window, the deviation of dose from the respiratory motion can be minimized. It appeals that limiting the residual motion to less than 0.5 cm is critical for the treatments of mobile structures.

An effective fluence concept was employed to make forward dose calculations to investigate the effects of a distorted fluence map on dose plans. Fluence changes caused by organ motion were calculated using Chui's algorithm (2003 Med. Phys. 30 1736). In two test cases with various fluence maps, the effects of motion were simulated using a maximal displacement from 5 mm to 25 mm; 108 fluence maps that were calculated from 16 IMRT plans for eight liver cancer patients were analyzed and compared with and without gating. Fluoroscopic measurements were made of a moving diaphragm in this study. Fluence changes associated with superior-inferior organ motion, perpendicular to the moving MLC, were also examined. The effects of motion on the fluence maps were evaluated from both the fluence differences between static and motion and the chi function. The maximum displacements of the organs in all of these cases were analyzed and correlated with the change in fluence generated from the liver IMRT plans. The dosimetric effects on the target coverage were evaluated for each plan. The results indicate that, for the same fluence map, the mean fluence intensity error or the percentage of the fluence points that have an unacceptable error is linearly related to the extent of motion. For different fluence maps, the degree to which the fluence is distorted by motion is strongly related to the product of the motion extent and the fluence gradient in the direction of diaphragm motion. For eight liver patients and 16 IMRT plans in this work (with gated technique, motion extent from 0.5 cm to 1.0 cm; without gated technique, motion extent from 0.9 cm to 1.8 cm), the fluence modulations are mild, such that the respiratory motion of each patient did not strongly affect the CTV coverage. The mean dose error is 1.5% for free motion (0.9-1.8 cm) and is around 1% for gated motion (0.5-1 cm).

This study assesses the feasibility and implementation of respiratory-gated whole-abdominal intensity-modulated radiation therapy (RG-WAIMRT). Three patients were treated with RG-WAIMRT. The planning target volume (PTV1) included the entire peritoneal cavity and a pelvic boost field was created (PTV2). The dose prescribed was 30 Gy to PTV1 and 14.4 Gy to PTV2. For comparison, a conventional three-dimensional (3D) plan was generated for each patient. In the WAIMRT plan, an average of 90% of PTV1 received 30 Gy compared to 70% for the conventional 3D plan. The percent volume receiving 30 Gy (V30) for liver averaged 54% (WAIMRT) vs 43% (3D). The percent volume receiving 20 Gy (V20) for kidneys averaged 19% vs 0%, and the mean V20 for bone marrow was 74% vs 83%, respectively. Major acute toxicities were anemia (grade 2: 1/3), leukopenia (grade 3: 2/3 patients), and thrombocytopenia (grade 2: 1/3 patients, grade 3: 1/3 patients). One patient could not complete the whole-abdomen field after 19.5 Gy because of persistent nausea. No major subacute toxicity has been reported. WAIMRT demonstrated superior target coverage and reduced dose to bone marrow, with a slightly increased dose to liver and kidneys. WAIMRT is a novel and feasible technique for ovarian cancer treatment.

An association between the serotonin 2A receptor (5-HT2A receptor) gene and suicidal behavior has been reported in many studies. However, no consistent conclusion has been reached. One potential reason for this is heterogeneity in the studies analyzed, which may have been caused by the selection of different types of cases and controls. In the present study, we pooled data from the previous published papers to clarify the association between HTR2A 102T/C and attempted suicide. All case-control studies written in English and published up until 20 November 2013 were selected. The history of suicide attempts and other relevant data were extracted. According to the findings of previous studies, the recessive model was used to evaluate the role of genotype in attempted suicide. We divided the patients into three groups on the basis of the history of suicide attempts and mental disorder. Genotype distribution of the suicide attempters was compared with normal controls and patients with mental disorder, respectively. There were no significant differences in 5-HT2A receptor 102T/C genotype distributions between those who attempted suicide and the normal controls, and the results were similar for the comparisons with mental disorder patient controls. When subgroup analysis of the types of mental disorder was carried out, all heterogeneity disappeared and effect sizes increased. A significant association was observed for the schizophrenia disorder subgroup (odds ratio=1.73; 95% confidence interval: 1.11-2.69). Our meta-analysis does not support the previously suggested association between HTR2A 102T/C and attempted suicide in the general population. However, in patients with schizophrenia, the C/C genotype of 5-HT2A receptor 102T/C may increase the risk of attempted suicide. The heterogeneity in relevant studies may have been caused by the characteristic variety of mixed mental disorders. Language: en

Introduction The disease burden and risk factors for respiratory syncytial virus (RSV) and human metapneumovirus (MPV) infections among children living in remote, rural areas remain unclear. Materials and Methods We conducted a prospective, household-based cohort study of children aged

This paper introduces the functionality of a new type of Autodriller software system, which can acquire downhole weight on bit (DWOB) based on surface rig measurement. Field tests are performed, including DWOB measured by downhole measuring tools and the hookload below the top drive using a TTS (Torque and Tension Sub). Three sets of drilling data from three horizontal wells in Western Canada were utilized to verify the models of this new Autodriller system. DWOB comparisons between the model and the measuring tools were carried out. The comparisons indicate a good agreement between the downhole measured DWOB and the new Autodriller predicted values. The difference between the new Autodriller prediction and downhole measured DWOB can be quantified using rooted mean square error (RMSE) or relative error (RE). This paper also analyzes the differences in some sections, and some measures are suggested to potentially reduce these differences. The new Autodriller is a closed loop control system which can automatically in real-time adjust surface weight on bit (SWOB) so that the DWOB is accurate, which will directly improve the performance of drill bits, and decrease the cost of drilling, especially in directional well drilling applications.Copyright © 2015 by ASME

Introduction Suicide is a major public health concern and a leading cause of death around the world. How religion influences the risk of completed suicide in different settings across the world requires clarification in order to best inform suicide prevention strategies. Methods A meta-analysis using search results from Pubmed and Web of Science databases was conducted following PRISMA protocol and using the keywords “religion” or “religious” or “religiosity” or “spiritual” or “spirituality” plus “suicide” or “suicidality” or “suicide attempt”. Random and fixed effects models were used to generate pooled ORs and I2 values. Sub-analyses were conducted among the following categories: young age (

Purpose: To measure respiration-induced abdominal organ motion using four-dimensional computed tomography (4D CT) scanning and to examine the organ paths. Methods and Materials: During 4D CT scanning, consecutive CT images are acquired of the patient at each couch position. Simultaneously, the patient’s respiratory pattern is recorded using an external marker block taped to the patient’s abdomen. This pattern is used to retrospectively organize the CT images into multiple three-dimensional images, each representing one breathing phase. These images are analyzed to measure organ motion between each phase. The displacement from end expiration is compared to a displacement limit that represents acceptable dosimetric results (5 mm). Results: The organs measured in 13 patients were the liver, spleen, and left and right kidneys. Their average superior to inferior absolute displacements were 1.3 cm for the liver, 1.3 cm for the spleen, 1.1 cm for the left kidney, and 1.3 cm for the right kidney. Although the organ paths varied among patients, 5 mm of superior to inferior displacement from end expiration resulted in less than 5 mm of displacement in the other directions for 41 of 43 organs measured. Conclusions: Four-dimensional CT scanning can accurately measure abdominal organ motion throughout respiration. This information may result in greater organ sparing and planning target volume coverage.

To evaluate the relationship between the primary breast volume and dose received by the ipsilateral lung, heart (for left-breast cancers), and contralateral breast during primary breast irradiation using intensity-modulated radiation therapy (IMRT).Sixty-five patients with breast carcinoma were treated using 6-MV photons with IMRT technique using the Eclipse Planning System following breast conserving surgery. All patients had a treatment planning CT scan. The primary breast, ipsilateral lung, and heart were contoured on the axial CT slices. The primary breast volume was calculated using the Eclipse Planning System. The mean ipsilateral lung and heart doses were obtained from the dose-volume histogram. The contralateral breast dose was measured using paired thermoluminescent dosimeters (TLDs) placed on the patient's contralateral breast, 4 cm from the center of the medial border of the primary breast irradiation field.The mean dose delivered with photons to the primary breast for all patients was 49.97 Gy. The mean volume of the primary irradiated breast was 1167.9 cc. As a percentage, the mean ipsilateral lung, heart, and contralateral breast doses were 11.2%, 6.1%, and 7.2%, respectively. The primary breast volume positively correlated with the contralateral breast dose (P0.0005). There was no significant correlation between the breast volume and the ipsilateral lung or heart dose (P = 0.463 and 0.943, respectively).This study suggests that the primary breast size significantly affects the scatter dose to the contralateral breast but not the ipsilateral lung or heart dose when using IMRT for breast irradiation.

Purpose: To test whether or not the commonly prescribed daily dose of 2 Gy (whole fraction), when delivered as various partial fraction (PF) dose sequences simulating clinical treatment fields, produces equal biologic effects. Methods and Materials: Eleven actively proliferating cell lines derived from human and animal tissues were used in this study. 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and clonogenic assays were used to determine the radiation effects on cell proliferation and survival, respectively. The 2 Gy dose was divided into 2 or more PFs for delivery to simulate the delivery of clinical treatment fields. Most irradiation sequences contained two parts consisting of at least 1 small PF, denoted by S which was 0.5 Gy or less, and a large PF, denoted by L which was 1 Gy or more. Irradiation schemes were designed to include the following conditions: (a) the 2 Gy dose divided into combinations of an L-dose and one or more S-doses; (b) the L-dose given either before or after the S-doses; and (c) delivery of all partial fractions within a fixed total time. Results: Significant differences in biologic effect were observed between sequences in which the L-dose was given before or after the S-doses in both the MTT and clonogenic assays. Nearly all the latter schemes, that is S-L, produced greater cytotoxic effects than the L-S schemes. Conclusions: These data demonstrate that the biologic effects of 2 Gy may differ in different clinical settings depending on the size and sequence of the partial fractions. The variation between cytotoxic effects is likely a result of the combination of low-dose hyper-radiosensitivity (HRS) and higher-dose increased radioresistance (IRR) effects established recently. We suggest that to ensure the optimal biologic effect of a prescribed dose of 2 Gy clinically, it is critical to consider the sequence in which the treatment fields are delivered when partial fractions of different sizes are used.

Polypoid melanoma represents a distinct variant of melanoma characterized by an ulcerated exophytic nodule. Although this melanocytic tumor is usually restricted to the papillary dermis, it presents with a thick Breslow level and aggressive course. Its rapidly growing vertical phase and its amelanotic nature frequently simulate benign or non-aggressive entities; leading to a delay in biopsy and resulting in an increased risk of metastasis at the time of the diagnosis.

The use of self-gripping mesh during laparoscopic TEP inguinal hernia repairs may eliminate the need for any additional fixation, and thus reduce post-operative pain without the added concern for mesh migration. Long-term outcomes are not yet prospectively studied in a controlled fashion.Under IRB approval, from January 2011-April 2013, 91 hernias were repaired laparoscopically with self-gripping mesh without additional fixation. Patients were followed for at least 1 year. Demographics and intraoperative data (defect location, size, and mesh deployment time) are recorded. VAS is used in the recovery room (RR) to score pain, and the Carolinas Comfort Scale ™ (CCS), a validated 0-5 pain/quality of life (QoL) score where a mean score of1.0 means symptomatic pain, is employed at 2 weeks and at 1 year. Morbidities, narcotic usage, days to full activity and return to work, and CCS scores are reported.Sixty two patients, with 91 hernias repaired with self-gripping mesh, completed follow-up at a mean time period of 14.8 months. Seventeen hernias were direct defects (average size 3.0 cm). Mesh deployment time was 193.7 s. RR pain was 1.1/10 using a VAS. Total average oxycodone/acetaminophen (5 mg/325 mg) usage = 5.0 tablets, days to full activity was 1.6, and return to work was 4.2 days. Thirteen small asymptomatic seromas were palpated without any recurrences or groin tenderness, and all seromas resolved by the 6 month visit. Transient testis discomfort was reported in five patients. Urinary retention was 3.2%. Mean CCS™ scores at the first visit for groin pain laying, bending, sitting, walking, and step-climbing were 0.2, 0.5, 0.4, 0.3, and 0.3, respectively. At the first post op visit, 4.8% had symptomatic pain (CCS1). At 14.8 months, no patients reported symptomatic pain with CCS scores for all 62 patients averaging 0.02, (range 0-0.43). There are no recurrences thus far.Self-gripping mesh can be safely used during laparoscopic TEP inguinal hernia repairs; our cohort had a rapid recovery, and at the 1-year follow-up visit, there were no recurrences and no patients reported any chronic pain as defined by a CCS™1.

Purpose: Analysis of urinary morbidity within the first 12 months following a modified peripheral loading technique for permanent transperineal transrectal ultrasound (TRUS) guided 125 I prostate implantation and comparison of urinary morbidity with various clinical and implant parameters. Materials and Methods: Between October 1, 1996, and March 11, 1998, 87 patients with favorable, early stage prostate cancer were treated with permanent transperineal TRUS guided 125 I prostate implantation. A peripheral loading technique was utilized for source placement with 75–80% source distribution in the periphery and 20–25% source distribution centrally. A mean total activity of 38 mCi of 125 I was implanted (range, 19–66 mCi). The mean source activity was 0.43 mCi/source (range, 0.26–0.61 mCi/source) and the mean number of sources implanted was 88 (range, 56–134). The minimum prescribed dose to the prostate was 145 Gy. The median D 90 , V 100 , and V 150 were 152 Gy (range, 104–211 Gy), 92% (range, 71–99%), and 61% (range, 11–89%), respectively. The median follow-up time was 19 months (range, 12–29 months). Urinary morbidity was scored at 3 weeks and then at 3-month intervals for the first 2 years using a modified Radiation Therapy Oncology Group (RTOG) grading system (scale 0–5). Results: Most patients developed at least minor urinary symptoms with frequency or nocturia being the most common. Overall, 79% (69/87) of patients experienced urinary morbidity with 21% (18/87) reporting no symptoms. The incidence of overall Grade 1 urinary morbidity was 37% (32/87); Grade 2 morbidity was 37% (32/87); and Grade 3 morbidity was 6% (5/87). There was no Grade 4 or 5 morbidity. The incidence of Grade 0 frequency/nocturia was 36% (31/87); Grade 1 was 33% (29/87); Grade 2 was 30% (26/87); and Grade 3 was 1% (1/87). Grade 0 dysuria was seen in 56% (49/87) of patients; 32% (28/87) had Grade 1; 10% (9/87) Grade 2; and 1% (1/87) Grade 3 dysuria. Most urinary symptoms started a few weeks after implantation and began to subside by 6 months. At 12 months, 22% (19/87) of patients had persistent urinary symptoms (78% Grade 0, 15% Grade 1, 3% Grade 2, and 3% Grade 3). The mean urethral point dose was 174 Gy (range, 99–315 Gy). The mean number of sources implanted correlated significantly with the likelihood of developing acute urinary morbidity ( p = 0.03). The total activity implanted also correlated with the morbidity outcome dysuria ( p = 0.01) with a threshold seen at 37 mCi. Urethral point dose, source activity, intraoperative TRUS prostate volume, D 90 , V 100 , V 150 , patient age, pretreatment PSA, Gleason score, and T stage did not correlate with morbidity. Conclusions: Permanent transperineal TRUS guided 125 I prostate implantation using a modified peripheral loading technique is associated with mild urinary morbidity that resolves in 78% of patients by 12 months. Grade 3 urinary morbidity was encountered in only 6% (5/87) of patients. Urinary morbidity may be related to the total number of sources implanted and/or the total activity implanted. Overall urinary morbidity was not correlated with urethral point dose, source activity, intraoperative TRUS prostate volume, D 90 , V 100 , V 150 , patient age, pretreatment PSA, Gleason score, and T stage. The low incidence of urinary morbidity may be a consequence of our modified peripheral loading technique and/or the selection of patients with good-to-excellent preimplant urological parameters. Longer follow-up is necessary to assess biochemical control rates and long-term morbidity.

There is now considerable evidence to suggest that technical innovations, 3D image-based planning, template guidance, computerized dosimetry analysis and improved quality assurance practice have converged in synergy in modern prostate brachytherapy, which promise to lead to increased tumor control and decreased toxicity. A substantial part of the medical physicist's contribution to this multi-disciplinary modality has a direct impact on the factors that may singly or jointly determine the treatment outcome. It is therefore of paramount importance for the medical physics community to establish a uniform standard of practice for prostate brachytherapy physics, so that the therapeutic potential of the modality can be maximally and consistently realized in the wider healthcare community. A recent survey in the U.S. for prostate brachytherapy revealed alarming variance in the pattern of practice in physics and dosimetry, particularly in regard to dose calculation, seed assay and time/method of postimplant imaging. Because of the large number of start-up programs at this time, it is essential that the roles and responsibilities of the medical physicist be clearly defined, consistent with the pivotal nature of the clinical physics component in assuring the ultimate success of prostate brachytherapy. It was against this background that the Radiation Therapy Committee of the American Association of Physicists in Medicine formed Task Group No. 64, which was charged (1) to review the current techniques in prostate seed implant brachytherapy, (2) to summarize the present knowledge in treatment planning, dose specification and reporting, (3) to recommend practical guidelines for the clinical medical physicist, and (4) to identify issues for future investigation.

This special issue concerns acupuncture effects related with meridians. Out of the 34 submitted papers, 15 papers were accepted to be published (acceptance rate of 44.1%). Of the 15 papers, five papers focused on the clinical effects related to meridians. In a study by J.-H. Jeong et al., a simple acupoint flowchart based after meridian theory was used to direct the acupuncture treatment on 102 dogs with various diseases, and good curative effects were achieved in their study that was entitled “Simple acupoints prescription flowchart based on meridian theory: a retrospective study in 102 dogs.” Two papers reported on meridian-sinew therapy for knee osteoarthritis. S. Wei et al. observed better results in 90 cases using meridian-sinew release, as compared to normal acupuncture and drug treatments, in their study that was entitled “Evaluating meridian-sinew release therapy for the treatment of knee osteoarthritis.” In an RCT study, Y.-S. Liu et al. compared 97 patients treated with long-round needle therapy to 95 control patients treated with drugs and found a better effect from long-round needle treatment both immediately after the treatment and at the 3-month followup. The effect mechanism was analyzed according to the relationship between the meridian sinew and the fluid meridian channels in their study that was entitled “Observation on pain release by long-round needle therapy in knee osteoarthritis related with meridian-sinews theory.” S.-H. Lee et al. performed a network analysis of the acupuncture points used in treating low back pain in which modified mutual information value was calculated to illustrate the technique of acupoint combination in acupuncture treatment in their study that was entitled “Network analysis of acupuncture points used in the treatment of low back pain.” I.-S. Lee et al. summarized 37 clinical studies on the treatment of low back pain and found that the most frequently used acupoints were BL23 (51%), BL25 (43%), BL24 (32%), BL40 (32%), BL60 (32%), GB30 (32%), BL26 (28%), BL32 (28%), and GB34 (21%). A visualized meridian chart was drawn based on the data to understand the origin of meridians in their study that was entitled “Visualization of the meridian system based on biomedical information about acupuncture treatment”. All of five papers confirmed the importance of meridian theory in clinical acupuncture. The second group of papers focused on various effects of acupuncture when stimulating acupoints and meridians. W.-B. Zhang et al. found an increase of blood perfusion when needling a point on a meridian but not on an acupoint, as compared to needling a point off meridian but at an acupoint level, which proved the ancient theory that missing a point is less important than missing a meridian in their study that was entitled “Comparison of acupuncture effect on blood perfusion between needling nonacupoint on meridian and needling nonacupoint off meridian.” Gerhard Litscher et al. found that, when acupressing Xiyangguan (GB33), the regional oxygen saturation at the deeper knee tissue increased significantly while no considerable change occurred in the opposite control area, implying a meridian-related effect in their study that was entitled “Acupressure at the meridian acupoint xiyangguan (GB33) influences near-infrared spectroscopic parameters (regional oxygen saturation) in deeper tissue of the knee in healthy volunteers.” Four papers focused on the mechanism of acupuncture. W.-B. Zhang et al. studied the mechanism of acupuncture in channel dredging. A channel blockage model was made by injecting gel into a low hydraulic resistance channel (LHRC) in minipigs resulting in hyperalgesia. Acupuncture was applied to reduce the hydraulic resistance in the LHRC, which verified the ancient meridian theory that acupuncture can dredge a channel to relieve pain in their study that was entitled “Induction of hyperalgesia in pigs through blocking low hydraulic resistance channels and reduction of the resistance through acupuncture: a mechanism of action of acupuncture.” Z.-D. Cheng et al. observed the impact of acupuncture along meridians on the protein expression of chloride channels in myocardial ischemia rats in their study that was entitled “The impacts of along-channel acupuncture on the protein expressions of the chloride channel of the rats with myocardial ischemia.” J. Lu et al. reported that acupuncturing Baihui (Du20) and Neiguan (PC6) can increase the ratio of p-ERK1/2 to ERK1/2 and the ratio of p-CREB to CREB at the hippocampus and prefrontal cortex in rats with chronic unpredictable mild stress in their study that was entitled “Acupuncture activates ERK-CREB pathway in rats exposed to chronic unpredictable mild stress.” Both studies imply that acupuncture may also influence protein expression. M.-F. Luo et al. observed that recruitment and migration of mast cells along blood vessels and nerves to form a compound structure at acupoint sites after electroacupuncture (EA) were applied, implying that a dynamic compound structure may play an important role in the effect of acupuncture in their study that was entitled “Study on the dynamic compound structure composed of mast cells, blood vessels, and nerves in rat acupoint.” The relationship between meridians and internal organs was addressed in four papers. W.-T. Zhou et al. developed a channel stasis model in minipigs by injecting gel into LHRC of the stomach meridian and found a distension of stomach and intestine after one or two months while no change was observed in control pigs that were injected with saline in their study that was entitled “Pathological changes in Internal organs after blocking low hydraulic resistance channels along the stomach meridian in pigs.” S. Hu et al. developed an intestinal barrier injury by ischemic reperfusion. EA was applied at ST36 and nonmeridian points in various conditions. EA at ST36 attenuated the systemic inflammatory response and remote organ injury by protection of the intestinal barrier under the condition of an intact vagus nerve and cholinergic system significantly better than acupuncturing at nonmeridian points in their study that was entitled “Electroacupuncture at zusanli (ST36) prevents intestinal barrier and remote organ dysfunction following gut ischemia through activating the cholinergic anti-inflammatory-dependent mechanism.” X. Shi et al. also studied the impact of acupuncture at ST36 and nonmeridian points on rats after a fatal hemorrhagic shock. They found that EA at ST36 significantly improved the blood pressure and increased the early survival rate, as compared to EA at nonmeridian points. EA can impact internal organs at specific meridian/acupoint sites in their study that was entitled “The influence of zusanli and nonmeridian acupuncture points on the survival rate and intestinal tissue features after fatal hemorrhagic shock in rats.” K.-M. Shin et al. studied the effect of acupuncturing Siguan (bilateral LI4 and LR3) on gastrointestinal motility in healthy people after administering mosapride citrate. They found that acupuncturing Siguan can significantly reduce increased gastrointestinal motility, as compared to sham acupuncture in their study that was entitled “Effect of siguan acupuncture on gastrointestinal motility: a randomized, sham-controlled, crossover trial.” In this special issue, we have provided an overview of the majority of studies related to the effects and mechanisms of acupuncture based on principal meridians. Wei-Bo Zhang Andrew Wu Gerhard Litscher Younbyoung Chae

The efficacy of transmission block technique with contiguous photon irradiation of inguinal as well as pelvic and perineal structures has been reported in literature. In this paper, a simple and accurate method for the proper fabrication of transmission block has been described and also demonstrated to be effective and useful. The procedures for a precise geometrical alignment and dose verification are also detailed.

Background: HER2-positive tumors are often associated with poor prognosis, chemo-resistances and some patients eventually develop refractory disease during HER2 targeted therapy. While different mechanisms of trastuzumab resistance are being identified in recent years, contribution of confounding factors such as inherent genomic heterogeneity, equivocal HER2 amplifications and presence of chromosome 17 polysomy has been less understood thus far. In this pilot study, we aim to examine HER2 heterogeneity in CTCs obtained from breast cancer patients in the Asian population setting. Methods: CTCs were enriched from blood samples using a label-free spiral microfluidics-based ClearCell® FX system. A total of 26 samples were collected from patients diagnosed with HER2 positive (17/26) and HER2 negative (9/26) breast cancer. The enriched CTCs were analyzed using conventional diagnostic modalities (fluorescence in-situ hybridisation (FISH) and immunocytochemistry) to examine HER2 status. Concordance rate between CTCs and matched primary tumor was evaluated. Results: HER2-positive CTCs were successfully identified in 14 out of 17 HER2+ patients (82.4%); HER2 gene amplification and chromosome 17 polysomy were observed in 10(58.8%) and 13(76.5%) patients respectively. HER2+ CTC counts ranged from 2 to 30 cells from 7.5ml blood (median: 4 HER2+ CTCs/7.5ml). HER2 amplification was not observed in any of the 9 patients with HER2-negative tumors, though 5 out of 9 patients (55.6%) were identified with CTCs harbouring gain in chromosome 17 (median: 2 HER2+ CTCs/7.5ml). A “false positive” cut-off of more than 2 cells/7.5ml blood were established using receiver operating characteristic (ROC) curve analysis and a concordance rate of approximately 70% between paired tumor tissue and CTC among the 26 patients. Immunofluorescence labelling of CTCs with cytokeratin, CD45 and HER2 antibodies further revealed heterogeneity in HER2 expression on CTCs. Conclusion: CTCs capture the heterogeneity of breast cancer, and could potentially overcome limitations of tissue biopsy which are site specific. HER2- patients, as confirmed by tissue biopsy, with HER2+ CTCs pose interesting questions while determining treatment regime. Citation Format: Man Chun Leong, Tse Hui Lim, Chye Ling Tan, Yong Wei Chua, Elaine Hsuen Lim, Kiley Wei Jen Loh, Guek Eng Lee, Rebecca Dent, Raymond Chee Hui Ng, Andrew Wu, Wan-Teck Lim, Alvin Soon-Tiong Lim, Yoon-Sim Yap. Elucidating HER2 molecular heterogeneity of circulating tumor cells among breast cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5008.