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Background: Endovascular interventions are performed routinely with minimal risk in younger populations. The safety and efficacy of endovascular interventions in nonagenarians is under examined. We sought to examine the following (1) mortality and limb salvage rates in the nonagenarian population and (2) whether frailty was associated with outcomes following lower extremity (LE) interventions for both acute limb ischemia (ALI) and chronic limb threatening ischemia (CLTI)., Methods: A retrospective review of patients ≥90 years who underwent a LE angiogram for ALI or CLTI over a 12-year period at a single institution was performed. Primary outcomes were 30-day and 12-month limb salvage and mortality rates. Patient demographics, 30-day complications, and 12-month target vessel reintervention (TVR) were reviewed. Frailty scores were calculated using the 11-factor modified frailty index (MFI-11)., Results: From 2009 to 2021, 76 patients (36% male) with a mean age of 93 (range: 90-102) underwent endovascular procedures for ALI (n = 13) and CLTI (n = 63). 30-day amputation and mortality rates were 6% and 8%, respectively. Patient demographics, preoperative functional status, and TVR rates were not different between patients who had early amputation (≤30 days) and those who achieved limb salvage. Seventy-two patients (94%) had follow-up data at 30 days. There was an 8% mortality rate at 30 days. Of those alive at 30 days, 94% of patients had successful limb salvage. Fifty-eight patients had complete follow-up data at 12 months. Of the patients alive at 12-month follow-up (75%), the limb salvage rate was 98%. Patients with amputation at 30 days had a significantly higher mortality rate at 12 months compared to those who did not (83% vs. 19%; P < 0.01). Based on MFI-11 scoring, 35% of the population was considered frail (≥0.27). Frail patients did not have significantly different 30-day outcomes (limb salvage: 94% vs. 88%; mortality 8% vs. 9%, P = 0.41 and 0.94, respectively) or 12-month outcomes (limb salvage: 82% vs. 94%; mortality: 32% vs. 22%, P = 0.28 and 0.39, respectively)., Conclusions: Endovascular procedures can be done safely in nonagenarians with low mortality and amputation rates. Patients with early amputation are at significantly higher risk of death at 12 months. Frailty, as measured by a validated index, was not associated with early or late outcomes. When compared to immediate amputation, nonagenarian patients and their families should be counseled as to the benefit from a minimally invasive endovascular procedure., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: We aimed to assess the relationship between diet quality and risk of older-onset Crohn's disease [CD] and ulcerative colitis [UC]., Methods: We conducted a prospective cohort study of 83 147 participants from the Swedish Mammography Cohort and the Cohort of Swedish Men. We used food frequency questionnaires to calculate adherence scores to multiple derived healthy diet patterns: Alternate Healthy Eating Index [AHEI], Healthy Eating Index-2015 [HEI-2015], Healthful Plant-Based Diet Index [HPDI], and modified Mediterranean Diet Score [mMED] at baseline in 1997 in both cohorts. Diagnoses of CD and UC were retrieved from the Swedish Patient Register. We used Cox proportional hazards modelling to estimate the adjusted hazard ratios [HRs] and 95% confidence intervals [CIs]., Results: Through December of 2017, we confirmed 164 incident cases of CD and 395 incident cases of UC. Comparing the highest with the lowest quartiles, the adjusted HRs of CD were 0.73 [95% CI, 0.48, 1.12, ptrend = 0.123] for AHEI; 0.90 [0.57, 1.41, ptrend = 0.736] for HEI 2015; 0.52 [95% CI 0.32, 0.85, ptrend = 0.011] for HPDI; and 0.58 [95% CI 0.32, 1.06, ptrend = 0.044] for mMED. In contrast, we did not observe an association between any diet quality score and risk of UC., Conclusions: We found that several healthy eating patterns were associated with a lower risk of older-onset CD. Our findings provide a rationale for adapting different healthy dietary patterns based on individuals' food preferences and traditions in designing future prevention strategies for IBD., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Recent studies have reported altered methylation levels at disorder-relevant DNA sites in people who are ill with Anorexia Nervosa (AN) compared to findings in people with no eating disorder (ED) or in whom AN has remitted. The preceding implies state-related influences upon gene expression in people with AN. This study further examined this notion., Methods: We measured genome-wide DNA methylation in 145 women with active AN, 49 showing stable one-year remission of AN, and 64 with no ED., Results: Comparisons revealed 205 differentially methylated sites between active and no ED groups, and 162 differentially methylated sites between active and remitted groups ( Q  < 0.01). Probes tended to map onto genes relevant to psychiatric, metabolic and immune functions. Notably, several of the genes identified here as being differentially methylated in people with AN (e.g. SYNJ2, PRKAG2, STAT3 , CSGALNACT1, NEGR1 , NR1H3 ) have figured in previous studies on AN. Effects also associated illness chronicity and lower BMI with more pronounced DNA methylation alterations, and remission of AN with normalisation of DNA methylation., Conclusions: Findings corroborate earlier results suggesting reversible DNA methylation alterations in AN, and point to particular genes at which epigenetic mechanisms may act to shape AN phenomenology.

Introduction: Patients undergoing surgical aortic valve replacement, in isolation or with concomitant coronary artery bypass grafting, have historically been screened for carotid artery disease prior to surgery. Over the past decade, transcatheter aortic valve replacement (TAVR) has incrementally become the predominant technique for the treatment of severe aortic stenosis. The relationship between internal carotid artery stenosis (ICAS) and risk of periprocedural stroke in the TAVR population is uncertain. We sought to evaluate our institution's outcomes with the TAVR procedure and the association with preoperative carotid duplex scan (CDS) results., Methods: A retrospective review of a single institution TAVR registry over a 5-year period was performed. All patients with pre-operative carotid imaging were included. Outcomes included in-hospital, 30-day, and 1-year stroke and all-cause mortality rates. The diagnosis of post-operative stroke was based on neurological exam and confirmed by radiologic imaging. Standard statistical analysis was performed., Results: A total of 436 patients met inclusion criteria. The prevalence of ICAS >50% was 18.3% and 70-99% stenosis was 4.8%. The in-hospital stroke and mortality rates were 2.3% and 1.2%, respectively. The cumulative 30-day and 1- year stroke rates were 3.7% and 6%, respectively. All were ischemic in nature. Bilateral infarcts were identified in 46.2% of stroke patients and 11.5% had an ipsilateral ICAS >50%. A large majority of stroke patients (23, 88.5%) had an ipsilateral ICAS of <50%. Less than 0.5% of patients had ICAS >70% and subsequently had an ipsilateral stroke within 30 days of procedure., Conclusions: The preoperative CDS identified carotid lesions that met criteria for elective repair in only 4.8% of patients. Of these, 9.5% suffered a stroke in the first 30 days after surgery. Over 90% of patients who had a stroke had less than 70% stenosis present in either carotid artery and there was no correlation between degree of ICAS and risk of stroke during the follow-up period. Routine CDS prior to TAVR does not predict in-hospital or 30-day stroke. As TAVR programs evolve, expand, and proliferate across the country, routine preoperative CDS is unlikely to determine the need for pre-operative carotid revascularization or predict stroke risk., (Copyright © 2022. Published by Elsevier Inc.)

Background: No dietary factors have yet been shown to conclusively impact the incidence of microscopic colitis (MC). Here, we sought to examine the relationship between alcohol intake and the risk of MC., Methods: We conducted a prospective cohort study of 209,902 participants (age range, 28.5-66.7 years) enrolled in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII). Validated data on alcohol consumption were collected at baseline in 1986 in the NHS and 1991 in the NHSII and updated every 4 years. Diagnoses of MC were confirmed via review of histopathology data. We used Cox proportional hazards modeling to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs)., Results: Through 2016 in the NHS and 2017 in the NHSII, we confirmed 352 incident cases of MC over 4,994,324 person-years. Higher alcohol consumption was associated with an increased risk of MC (Ptrend < .001). Compared to non-users, the aHRs of MC were 1.20 (95% CI, 0.86-1.67) for consumers of 0.1-4.9 g/day of alcohol, 1.90 (95% CI, 1.34-2.71) for consumers of 5-14.9 g/day, and 2.31 (95% CI, 1.54-3.46) for consumers of ≥15 g/day. The associations were consistent across the histologic subtypes of collagenous and lymphocytic colitis (Pheterogeneity = .523). When stratified by alcohol type, the risk according to every 2 servings/week appeared to be strongest with consumption of wine (aHR, 1.08; 95% CI, 1.04-1.12) as compared to beer (aHR, 1.01; 95% CI, 0.91-1.12) or liquor (aHR, 1.00; 95% CI, 0.92-1.09)., Conclusions: Alcohol consumption was associated with an increased risk of MC. Further studies are needed to determine the mechanism underlying these associations, as well as the impact of reducing alcohol intake in patients with MC., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Disruption to everyday routine during the COVID-19 pandemic has resulted in considerable implications for global mental health. The inter- and intra-personal mechanisms by which disrupted routine can contribute to elevated depressive symptoms has not been well-explored. The present study aimed to examine how feelings of social (dis)connectedness and rumination, as a maladaptive coping strategy, could explain the association between disrupted well-being activities and depressive symptoms., Methods: Participants (N = 496) ranging in age from 18 to 73 years (M = 28.73, SD = 10.93) completed an online survey within the first 3 months of the COVID-19 pandemic, which included measures of disruption to usual psychological and physical well-being activities, social connectedness, rumination, and depressive symptoms. Social connectedness and rumination were investigated as serial mediators of the association between disrupted well-being activities and depression using Hayes' PROCESS macro., Results: 39.5% of the sample reported clinically significant levels of depression. Disruption to well-being activities predicted higher depressive symptoms, and this was partially explained by feelings of social disconnectedness and subsequent rumination. Rumination, alone, was not a significant mediator between disrupted routine and depressive symptoms., Limitations: The cross-sectional survey design does not preclude the possibility of bidirectional effects., Conclusion: The social distancing public health measures to combat COVID-19 have contributed to widespread disrupted routine, and in turn, elevated symptoms of depression. Social disconnectedness plays a particularly important role in this association. Intervention strategies should consider social factors as a 'social cure' for mass, positive mental health promotion during COVID-19., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: It is unclear whether obesity is associated with the development of inflammatory bowel disease despite compelling data from basic science studies. We therefore examined the association between obesity and risk of Crohn's disease (CD) and ulcerative colitis (UC)., Methods: We conducted pooled analyses of 5 prospective cohorts with validated anthropometric measurements for body mass index (BMI) and waist-hip ratio and other lifestyle factors. Diagnoses of CD and UC were confirmed through medical records or ascertained using validated definitions. We used Cox proportional hazards modeling to calculate pooled multivariable-adjusted HRs (aHRs) and 95% confidence intervals (CIs)., Results: Among 601,009 participants (age range, 18-98 years) with 10,110,018 person-years of follow-up, we confirmed 563 incident cases of CD and 1047 incident cases of UC. Obesity (baseline BMI ≥30 kg/m 2 ) was associated with an increased risk of CD (pooled aHR, 1.34; 95% CI, 1.05-1.71, I 2  = 0%) compared with normal BMI (18.5 to <25 kg/m 2 ). Each 5 kg/m 2 increment in baseline BMI was associated with a 16% increase in risk of CD (pooled aHR, 1.16; 95% CI, 1.05-1.22; I 2  = 0%). Similarly, with each 5 kg/m 2 increment in early adulthood BMI (age, 18-20 years), there was a 22% increase in risk of CD (pooled aHR, 1.22; 95% CI, 1.05-1.40; I 2  = 13.6%). An increase in waist-hip ratio was associated with an increased risk of CD that did not reach statistical significance (pooled aHR across quartiles, 1.08; 95% CI, 0.97-1.19; I 2  = 0%). No associations were observed between measures of obesity and risk of UC., Conclusions: In an adult population, obesity as measured by BMI was associated with an increased risk of older-onset CD but not UC., (Copyright © 2022 by the AGA Institute. Published by Elsevier, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Aims: There are limited data on alcohol dose and types and risk of Crohn's Disease (CD) and Ulcerative Colitis (UC). We therefore sought to comprehensively examine the association between alcohol consumption and risk of CD and UC., Methods: We conducted a prospective cohort study of 237,835 participants from the Nurses' Health Study, Nurses' Health Study II, and Health Professional Follow-Up Study. Alcohol consumption was obtained through questionnaires submitted every four years; additional covariates were obtained at two or four-year intervals. Cases were confirmed independently by two physicians through medical record review. We used Cox proportional hazards regression to estimate age and multivariable-adjusted hazards ratios and 95% confidence intervals., Results: Across 5,170,474 person-years of follow-up, 370 cases of CD and 486 cases of UC were documented. Increased consumption of alcohol intake was not associated with CD (Ptrend = 0.455) or UC (Ptrend = 0.745). Compared to non-users, the MV-adjusted HRs for 15.0 + g/day of alcohol intake group were 0.84 (95% CI 0.56, 1.24) for CD and 1.08 (95% CI 0.77, 1.51) for UC. In analyses of alcohol subtypes, we observed that only moderate consumption of beer (>1-4 servings/week) was marginally associated with reduced risk of CD, while consumption of >4 servings/week of liquor was associated with an increased risk of UC., Conclusion: This prospective study did not identify a relationship between overall alcohol consumption and risk of CD or UC. Our suggestive associations between alcohol types and risk of CD and UC deserve additional investigation., (© 2021 John Wiley & Sons Ltd.)

Introduction: Since 2006, the U.S. Navy has conducted six Pacific Partnership (PP) missions throughout Southeast Asia on board the U.S. Naval Ship Mercy (T-AH 19). This study describes trends in overall and surgical specialty operative volumes to better understand the burden of surgical disease treated during these humanitarian and civic assistance (HCA) operations. This information can assist medical planners and surgical leaders involved in future humanitarian missions., Materials and Methods: Following approval from the Naval Medical Center San Diego Institutional Review Board, a retrospective review of surgical case data was performed for the six PP missions from 2006 to 2018. Data collected included patient demographics, Current Procedural Terminology codes, and surgical specialty. The primary outcome was surgical case volume per specialty. Secondary outcomes included surgical staffing per mission and overall trends in operative volume., Results: A total of 3,826 operative procedures were performed during the study period. Mission years in which case volume for both general surgery and ophthalmology were below their respective medians were associated with the least total surgical services to host nations (HNs). The number of active duty Navy surgeons varied with each mission; however, the staffing for a PP mission generally included at least two general surgeons, one ophthalmologist, one plastic surgeon, one pediatric surgeon, one orthopedic surgeon, one otolaryngologist, one oral surgeon, one urologist, and one obstetrician-gynecologist. Case volume per surgeon was highest in 2006 (50 cases per surgeon) and decreased after 2006, reaching an all-time low during the 2018 PP mission (10 cases per surgeon). Pediatric surgery and plastic surgery had the highest average case volumes per surgeon at 58 and 46 cases per surgeon, respectively, while oromaxillofacial surgery and neurosurgery had the lowest average case volumes per surgeon at 9 and 14 cases per surgeon, respectively., Conclusions: Operative volume on military HCA missions is greatly influenced by the priorities of the HN, the mission focus, the number of individuals from the HN that present for screening, and the availability of personnel and resources available on the hospital ship. Future mission planning should optimize general surgery and ophthalmology staffing and essential equipment, as total mission case volumes were highly dependent upon the productivity of these two specialties. Careful determination of the surgical needs of HNs should serve as a guide for the selection of subspecialists to maximize effectiveness in future military HCA missions., (© The Association of Military Surgeons of the United States 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Previous research has shown that the prenatal environment, commonly indexed by birth weight (BW), is a predictor of morphological brain development. We previously showed in monozygotic (MZ) twins associations between BW and brain morphology that were independent of genetics. In the present study, we employed a longitudinal MZ twin design to investigate whether variations in prenatal environment (as indexed by discordance in BW) are associated with resting-state functional connectivity (rs-FC) and with structural connectivity. We focused on the limbic and default mode networks (DMNs), which are key regions for emotion regulation and internally generated thoughts, respectively. One hundred and six healthy adolescent MZ twins (53 pairs; 42% male pairs) followed longitudinally from birth underwent a magnetic resonance imaging session at age 15. Graph theoretical analysis was applied to rs-FC measures. TrackVis was used to determine track count as an indicator of structural connectivity strength. Lower BW twins had less efficient limbic network connectivity as compared to their higher BW co-twin, driven by differences in the efficiency of the right hippocampus and right amygdala. Lower BW male twins had fewer tracks connecting the right hippocampus and right amygdala as compared to their higher BW male co-twin. There were no associations between BW and the DMN. These findings highlight the possible role of unique prenatal environmental influences in the later development of efficient spontaneous limbic network connections within healthy individuals, irrespective of DNA sequence or shared environment., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: The optimal surgical approach and treatment algorithm for thoracic outlet syndrome (TOS) remain controversial. We sought to examine the outcomes of patients treated at a military medical treatment facility (MTF) for TOS., Methods: A retrospective review was performed on all patients who had a first rib resection (FRR) for TOS over a 9-year period at a single MTF. Patient demographics, perioperative details, and patient outcomes were examined. Active duty (AD) status and return to AD were reviewed., Results: From 2008 to 2016, 33 FRRs were performed in 32 patients. Of these, 30 patients were on AD with a mean age of 27 years (range, 19-44). The 29 male and 4 female patients were treated for symptoms of venous (23), neurogenic (6), or arterial (4) TOS. The mean time from onset of symptoms was 11 months (range, 1 to 120). The FRR was performed via a transaxillary (13), supraclavicular (12), or paraclavicular (8) approach. Of 21 AD patients with venous TOS, 16 (76%) underwent preoperative thrombolysis. A postoperative venogram or ultrasound was performed in 20 patients, documenting vein patency in 18 (90%). Nine patients underwent subsequent venoplasty or stent placement. Most patients (15) were placed on anticoagulation for 1-6 months. Two AD patients had perioperative complications including a lymph leak and brachial plexus palsy. Twenty-four (89%) patients returned to AD status. One recruit never returned to AD after successful FRR, and two other patients did not return for medical reasons unrelated to the FRR., Conclusions: Despite a variety of surgical approaches and often delayed presentation, we identified a high percentage of postoperative vein patency and return to AD status in our population. The debate over surgical approach remains; however, a multimodal approach individualized to the patient's presentation and meticulous surgical technique led to successful outcomes in our healthy military population., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Approximately 600,000 persons are released from prison annually in the United States. Relatively few receive sufficient re-entry services and are at risk for unemployment, homelessness, poverty, substance abuse relapse and recidivism. Persons leaving prison who have a mental illness and/or a substance use disorder are particularly challenged. This project aims to create a peer mentor program to extend the reach and effectiveness of reentry services provided by the Department of Veterans' Affairs (VA). We will implement a peer support for reentry veterans sequentially in two states. Our outcome measures are 1) fidelity of the intervention, 2) linkage to VA health care and, 3) continued engagement in health care. The aims for this project are as follows: (1) Conduct contextual analysis to identify VA and community reentry resources, and describe how reentry veterans use them. (2) Implement peer-support, in one state, to link reentry veterans to Veterans' Health Administration (VHA) primary care, mental health, and SUD services. (3) Port the peer-support intervention to another, geographically, and contextually different state., Design: This intervention involves a 2-state sequential implementation study (Massachusetts, followed by Pennsylvania) using a Facilitation Implementation strategy. We will conduct formative and summative analyses, including assessment of fidelity, and a matched comparison group to evaluate the intervention's outcomes of veteran linkage and engagement in VHA health care (using health care utilization measures). The study proceeds in 3 phases., Discussion: We anticipate that a peer support program will be effective at improving the reentry process for veterans, particularly in linking them to health, mental health, and SUD services and helping them to stay engaged in those services. It will fill a gap by providing veterans with access to a trusted individual, who understands their experience as a veteran and who has experienced justice involvement. The outputs from this project, including training materials, peer guidebooks, and implementation strategies can be adapted by other states and regions that wish to enhance services for veterans (or other populations) leaving incarceration. A larger cluster-randomized implementation-effectiveness study is planned., Trial Registration: This protocol is registered with clinicaltrials.gov on November 4, 2016 and was assigned the number NCT02964897 .

Alterations in catecholamine signaling and cortical morphology have both been implicated in the pathophysiology of attention deficit/hyperactivity disorder (ADHD). However, possible links between the two remain unstudied. Here, we report exploratory analyses of cortical thickness and its relation to striatal dopamine transmission in treatment-naïve adults with ADHD and matched healthy controls. All participants had one magnetic resonance imaging (MRI) and two [ 11 C]raclopride positron emission tomography scans. Associations between frontal cortical thickness and the magnitude of d -amphetamine-induced [ 11 C]raclopride binding changes were observed that were divergent in the two groups. In the healthy controls, a thicker cortex was associated with less dopamine release; in the ADHD participants the converse was seen. The same divergence was seen for baseline D2/3 receptor availability. In healthy volunteers, lower D2/3 receptor availability was associated with a thicker cortex, while in the ADHD group lower baseline D2/3 receptor availability was associated with a thinner cortex. Individual differences in cortical thickness in these regions correlated with ADHD symptom severity. Together, these findings add to the evidence of associations between dopamine transmission and cortical morphology, and suggest that these relationships are altered in treatment-naïve adults with ADHD.

Background: Several studies have shown that the in utero environment, which can be indexed by birth weight (BW), is associated with cortical morphology in adolescence and adulthood. Work in monozygotic (MZ) twins suggests that this association is driven by non-shared environmental factors. This correlation could be the result of in utero impacts on DNA methylation. The aim of the present study with MZ twins is to replicate the association between discordance in BW and brain morphology and test whether discordance in DNA methylation mediates this relationship., Methods: One hundred and four adolescent MZ twins (52 pairs, of which 42% were male pairs) who have been followed regularly since birth underwent T1 weighted structural MRI, and epigenome-wide assessment of DNA methylation from saliva at age 15., Results: Co-twins had very similar measures of DNA methylation and cortical morphology. Higher BW members of a twin pair had increased total cortical surface area, and decreased cortical thickness compared to their lower BW sibling. BW Discordance was positively associated with both cortical surface area and cortical volume discordance. Genes involved in neurodevelopment were tentatively identified as mediators of both the BW - cortical volume, and BW- cortical surface area relationships., Conclusions: The association between BW and cortical morphology in adolescence appears to be attributable to in utero environmental effects, and DNA methylation may play a role in mediating this relationship. Hum Brain Mapp 38:2037-2050, 2017. © 2017 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Early creation of arteriovenous fistulas (AVFs) decreases morbidity and mortality in patients with end-stage renal disease and is the standard of care in the United States. However, this procedure is frequently not accessible in low- and middle-income countries (LMICs). We present the first reported case of successful AVF creation as part of a humanitarian assistance mission. The patient was a 51-year-old male with diabetes, hypertension, and end-stage renal disease on hemodialysis via a temporary dialysis catheter. Preoperative assessment and patient selection were coordinated with the host nation (HN) nephrologist and dialysis team. The visiting surgical team provided education on AVF anatomy, complications, and cannulation techniques to the HN dialysis team. A left brachiocephalic AVF was created under regional anesthesia performed by the visiting surgeon and anesthesiologists. There were no postoperative complications, and the AVF was matured and accessed successfully by the HN dialysis team 7 weeks after creation. Performing AVFs as part of humanitarian assistance missions has the potential to significantly reduce morbidity and mortality in LMICs.

Objectives (1) Analyze the relationship between intranasal airflow distribution and subjective nasal patency in healthy and nasal airway obstruction (NAO) cohorts using computational fluid dynamics (CFD). (2) Determine whether intranasal airflow distribution is an important objective measure of airflow sensation that should be considered in future NAO virtual surgery planning. Study Design Cross-sectional. Setting Academic tertiary medical center and academic dental clinic. Subjects and Methods Three-dimensional models of nasal anatomy were created based on computed tomography scans of 15 patients with NAO and 15 healthy subjects and used to run CFD simulations of nasal airflow and mucosal cooling. Subjective nasal patency was quantified with a visual analog scale (VAS) and the Nasal Obstruction Symptom Evaluation (NOSE). Regional distribution of nasal airflow (inferior, middle, and superior) was quantified in coronal cross sections in the narrowest nasal cavity. The Pearson correlation coefficient was used to quantify the correlation between subjective scores and regional airflows. Results Healthy subjects had significantly higher middle airflow than patients with NAO. Subjective nasal patency had no correlation with inferior and superior airflows but a high correlation with middle airflow (| r| = 0.64 and | r| = 0.76 for VAS and NOSE, respectively). Anterior septal deviations tended to shift airflow inferiorly, reducing middle airflow and reducing mucosal cooling in some patients with NAO. Conclusion Reduced middle airflow correlates with the sensation of nasal obstruction, possibly due to a reduction in mucosal cooling in this region. Further research is needed to elucidate the role of intranasal airflow distribution in the sensation of nasal airflow.

Background: Novelty-seeking (NS) and impulsive personality traits have been proposed to reflect an interplay between fronto-cortical and limbic systems, including the limbic striatum (LS). Although neuroimaging studies have provided some evidence for this, most are comprised of small samples and many report surprisingly large effects given the challenges of trying to relate a snapshot of brain function or structure to an entity as complex as personality. The current work tested a priori hypotheses about associations between striatal dopamine (DA) release, cortical thickness (CT), and NS in a large sample of healthy adults., Methods: Fifty-two healthy adults (45M/7F; age: 23.8±4.93) underwent two positron emission tomography scans with [11C]raclopride (specific for striatal DA D2/3 receptors) with or without amphetamine (0.3 mg/kg, p.o.). Structural magnetic resonance image scans were acquired, as were Tridimensional Personality Questionnaire data. Amphetamine-induced changes in [11C]raclopride binding potential values (ΔBPND) were examined in the limbic, sensorimotor (SMS) and associative (AST) striatum. CT measures, adjusted for whole brain volume, were extracted from the dorsolateral sensorimotor and ventromedial/limbic cortices., Results: BPND values were lower in the amphetamine vs. no-drug sessions, with the largest effect in the LS. When comparing low vs. high LS ΔBPND groups (median split), higher NS2 (impulsiveness) scores were found in the high ΔBPND group. Partial correlations (age and gender as covariates) yielded a negative relation between ASTS ΔBPND and sensorimotor CT; trends for inverse associations existed between ΔBPND values in other striatal regions and frontal CT. In other words, the greater the amphetamine-induced striatal DA response, the thinner the frontal cortex., Conclusions: These data expand upon previously reported associations between striatal DA release in the LS and both NS related impulsiveness and CT in the largest sample reported to date. The findings add to the plausibility of these associations while suggesting that the effects are likely weaker than has been previously proposed.

Importance: Historically, otolaryngologists have focused on nasal resistance to airflow and minimum airspace cross-sectional area as objective measures of nasal obstruction using methods such as rhinomanometry and acoustic rhinometry. However, subjective sensation of nasal patency may be more associated with activation of cold receptors by inspired air than with respiratory effort., Objective: To investigate whether subjective nasal patency correlates with nasal mucosal temperature in healthy individuals., Design, Setting, and Participants: Healthy adult volunteers first completed the Nasal Obstruction Symptom Evaluation (NOSE) and a unilateral visual analog scale to quantify subjective nasal patency. A miniaturized thermocouple sensor was then used to record nasal mucosal temperature bilaterally in 2 locations along the nasal septum: at the vestibule and across from the inferior turbinate head., Main Outcomes and Measures: Nasal mucosal temperature and subjective patency scores in healthy individuals., Results: The 22 healthy adult volunteers (12 [55%] male; mean [SD] age, 28.3 [7.0] years) had a mean (SD) NOSE score of 5.9 (8.4) (range, 0-30) and unilateral VAS score of 1.2 (1.4) (range, 0-5). The range of temperature oscillations during the breathing cycle, defined as the difference between end-expiratory and end-inspiratory temperatures, was greater during deep breaths (mean [SD] change in temperature, 6.2°C [2.6°C]) than during resting breathing (mean [SD] change in temperature, 4.2°C [2.3°C]) in both locations (P < .001). Mucosal temperature measured at the right vestibule had a statistically significant correlation with both right-side visual analog scale score (Pearson r = -0.55; 95% CI, -0.79 to -0.17; P = .008) and NOSE score (Pearson r = -0.47; 95% CI, -0.74 to -0.06; P = .03). No other statistically significant correlations were found between mucosal temperature and subjective nasal patency scores. Nasal mucosal temperature was lower (mean of 1.5°C lower) in the first cavity to be measured, which was the right cavity in all participants., Conclusions and Relevance: The greater mucosal temperature oscillations during deep breathing are consistent with the common experience that airflow sensation is enhanced during deep breaths, thus supporting the hypothesis that mucosal cooling plays a central role in nasal airflow sensation. A possible correlation was found between subjective nasal patency scores and nasal mucosal temperature, but our results were inconsistent. The higher temperature in the left cavity suggests that the sensor irritated the nasal mucosa, affecting the correlation between patency scores and mucosal temperature. Future studies should consider noncontact temperature sensors to prevent mucosa irritation., Level of Evidence: NA.

The need for an experienced vascular surgeon in the combat setting is not questioned; however, there is a paucity of literature exploring the utility of vascular surgery during an elective humanitarian mission. We herein present a case of a post-traumatic pseudoaneurysm of the anterior tibial artery treated in the context of a humanitarian mission during Pacific Partnership 2015 aboard the United States Naval Ship Mercy. This case report demonstrates the necessity and unique opportunities for vascular surgeons to participate in humanitarian surgery., (Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.)

Background: Accumulating evidence indicates that drug-related cues can induce dopamine (DA) release in the striatum of substance abusers. Whether these same cues provoke DA release in the human prefrontal cortex remains unknown., Methods: We used high-resolution positron emission tomography with [18F]fallypride to measure cortical and striatal DA D2/3 receptor availability in the presence versus absence of drug-related cues in volunteers with current cocaine dependence., Results: Twelve individuals participated in our study. Among participants reporting a craving response (9 of 12), exposure to the cocaine cues significantly decreased [18F]fallypride binding potential (BPND) values in the medial orbitofrontal cortex and striatum. In all 12 participants, individual differences in the magnitude of craving correlated with BPND changes in the medial orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate, and striatum. Consistent with the presence of autoreceptors on mesostriatal but not mesocortical DA cell bodies, midbrain BPND values were significantly correlated with changes in BPND within the striatum but not the cortex. The lower the midbrain D2 receptor levels, the greater the striatal change in BPND and self-reported craving., Limitations: Limitations of this study include its modest sample size, with only 2 female participants. Newer tracers might have greater sensitivity to cortical DA release., Conclusion: In people with cocaine use disorders, the presentation of drug-related cues induces DA release within cortical and striatal regions. Both effects are associated with craving, but only the latter is regulated by midbrain autoreceptors. Together, the results suggest that cortical and subcortical DA responses might both influence drug-focused incentive motivational states, but with separate regulatory mechanisms.

Background: Pelvic vascular injuries (PVIs) rarely occur in isolation and are often associated with significant morbidity. The purpose of this study was to examine the incidence, trends, and early outcomes of PVIs sustained in combat., Methods: The Department of Defense Trauma Registry was queried to identify all patients treated with PVIs during the first 10 years of Operation Enduring Freedom. Patient demographics, mechanism of injury, type of vascular injury, in-theater complications, and early clinical outcomes were examined., Results: From 2003 to 2012, 143 patients (99% male) sustained a PVI in Afghanistan. During this period, there was a persistent increase in the percentage of patient visits (0.4% in 2003 to 2.0% in 2012). The mean Injury Severity Score (ISS) was 24. Sixty-six percent of patient injuries were secondary to explosions. Improvised explosive devices (IEDs) encountered by dismounted personnel accounted for 47% of all injuries and were associated with a significantly higher ISS (28) compared with all other mechanisms of injury (P < .01). There were 85 (43%) arterial and 112 (57%) venous PVIs. The most frequent arterial injury was the common iliac artery. Injury to the femoral vein was associated with a higher median transfusion requirement. One patient died in combat theater. Injuries from IEDs had higher rates of coagulopathy, acidosis, and hypothermia compared with other mechanisms of injury (P = .03). Forty-two patients (29%) sustained early infectious complications. Injuries from explosions were also associated with a significantly higher rate of infectious complications compared with other mechanisms of injury (P < .01)., Conclusions: PVIs have occurred with increasing frequency during Operation Enduring Freedom. Despite a persistently low mortality, complication and infection rates remain high, particularly when injuries are secondary to explosions. IEDs are associated with higher ISS and complication rates. Future studies must continue to focus on the prevention and treatment of PVIs sustained in combat, particularly those caused by explosions., (Published by Elsevier Inc.)

Background: Successful maturation of arteriovenous fistulas (AVFs) remains a challenge for those managing patients with end-stage renal disease. Time-of-flight magnetic resonance angiography (TOF-MR) can be used to evaluate AVFs without the risk of radiation exposure, intravenous contrast, or reliance on the operator-dependent modality of color Doppler ultrasonography (CDUS). The objective of our study was to assess the utility of TOF-MR in the evaluation of nonmaturing AVFs and to identify the best clinical situations to use this technology., Methods: Consecutive patients with abnormal findings on CDUS or physical examination after AVF creation underwent 3-dimensional (3D) TOF-MR. Imaging was performed at 3 T with a scan acquisition time of approximately 15 min. The technique was similar to head and neck magnetic resonance angiography (MRA), except presaturation bands were not used, thereby allowing simultaneous visualization of both arterial and venous flow. A total of 19 TOF-MR studies were performed., Results: Nineteen patients underwent imaging and were the focus of this study. Seventeen of 19 TOF-MR studies were of diagnostic quality and yielded findings which enabled the vascular surgeon to take corrective measures. Findings included inflow stenosis, anastomotic narrowing, venous outflow stenosis, and hemodynamically significant venous tributaries. Twelve of 17 patients required conventional digital subtraction angiography (DSA). The congruence rate between TOF-MR and DSA was 83.3%. Four patients (21%) avoided DSA and went directly to definitive surgical treatment including branch ligation (3) or new access (1)., Conclusions: This is the first report in the literature of successful implementation of 3D TOF-MR to assist in identifying AVF maturation problems. This unique noninvasive imaging modality provides actionable images without contrast or radiation exposure and can obviate the need for invasive diagnostic procedures or provide an anatomic map for planning corrective intervention., (Published by Elsevier Inc.)

Objective: Evidence associates anorexia nervosa (AN) with epigenetic alterations that could contribute to illness risk or entrenchment. We investigated the extent to which AN is associated with a distinct methylation profile compared to that seen in normal-eater women., Method: Genome-wide methylation profiles, obtained using DNA from whole blood, were determined in 29 women currently ill with AN (10 with AN-restrictive type, 19 with AN-binge/purge type) and 15 normal-weight, normal-eater control women, using 450 K Illumina bead arrays., Results: Regardless of type, AN patients showed higher and less-variable global methylation patterns than controls. False Discovery Rate corrected comparisons identified 14 probes that were hypermethylated in women with AN relative to levels obtained in normal-eater controls, representing genes thought to be associated with histone acetylation, RNA modification, cholesterol storage and lipid transport, and dopamine and glutamate signaling. Age of onset was significantly associated with differential methylation in gene pathways involved in development of the brain and spinal cord, while chronicity of illness was significantly linked to differential methylation in pathways involved with synaptogenesis, neurocognitive deficits, anxiety, altered social functioning, and bowel, kidney, liver and immune function., Discussion: Although pre-existing differences cannot be ruled out, our findings are consistent with the idea of secondary alterations in methylation at genomic regions pertaining to social-emotional impairments and physical sequelae that are commonly seen in AN patients. Further investigation is needed to establish the clinical relevance of the affected genes in AN, and, importantly, reversibility of effects observed with nutritional rehabilitation and treatment., (© 2015 Wiley Periodicals, Inc.)

Background: A pulseless limb is considered a hard sign of an arterial injury after penetrating trauma in the civilian population. However, the reliability of this finding has never been examined in combat trauma. The purpose of this study was to examine the reliability of the pulseless limb in the combat trauma population. Reasons for false positive physical examination findings were also identified., Methods: The Joint Theater Trauma Registry identified all patients who presented to a military treatment facility (MTF) in Kandahar, Afghanistan, with a penetrating extremity injury over a 2-year period. Patients found to have a pulse deficit on initial physical examination were followed, and the results of the subsequent computed tomographic angiogram or arteriogram recorded. Patient demographics, injury patterns, and physiological data were examined. Standard statistical analysis was performed., Results: From 2011 to 2012, 644 patients were treated at a single MTF for lower extremity penetrating injuries. The most common mechanisms of injury were explosions (62%) and gunshot wounds (20%). Of the 577 patients with complete medical records, 448 patients (78%) presented with palpable pulses, 115 patients (20%) presented with a pulseless limb, and 14 (2%) presented with hard signs of vascular injury. Of those with a pulseless limb and abnormal ankle-brachial index (ABI) or no ABI obtained who underwent further radiologic imaging, 38 patients (77%) had no arterial injury identified. Compared with those with a palpable pulse, patients with a pulseless limb without an arterial injury were more likely to have a higher Injury Severity Score (ISS), lower hematocrit, lower pH, greater base deficit, higher heart rate, more frequent use of tranexamic acid, and received greater volumes of packed red blood cells, plasma, and crystalloids., Conclusions: Our results demonstrate that a pulseless limb is a poor predictor of arterial injury and should not be considered a hard sign of vascular injury in the combat population. Variables including a high ISS, anemia, acidosis, and need for resuscitation products, each a surrogate for injury severity, may contribute to the decreased accuracy of the physical examination in our troops. This may translate into unnecessary immediate exploration or other interventions in patients who present with more significant injuries from the battlefield. Future studies must continue to focus on improved algorithms for diagnostic accuracy of extremity vascular injuries in this population., (Published by Elsevier Inc.)

Background: PDA-001 (cenplacel-L), a preparation of placenta-derived mesenchymal-like adherent cells with immunomodulatory effects, previously demonstrated safety and tolerability in an open-label Crohn's disease (CD) study. The current phase 1b/2a study evaluated the safety and efficacy of PDA-001 in subjects with moderate-to-severe CD., Methods: Subjects had active inflammation on colonoscopy or elevated fecal calprotectin and inadequate response to conventional therapy. Concomitant therapy with stable doses of immunomodulators and/or biologics was permitted. Subjects received 8 units of PDA-001 (1.5 × 10 cells per unit) in the phase 1b open-label study. In the phase 2a double-blind study, subjects were randomly assigned placebo, 1 unit, or 4 units of PDA-001 (2 infusions 1 wk apart). The primary endpoint was induction of clinical response (≥100 points and/or 25% decrease in Crohn's Disease Activity Index) at 4 and 6 weeks., Results: Fifty subjects were enrolled (safety analysis, 50 subjects; efficacy analysis, 48 subjects). Four subjects received 8 units of PDA-001 (phase 1b study); 46 subjects were subsequently randomized to 1 or 4 units of PDA-001 or placebo (phase 2a study). The primary endpoint was achieved in 10/28 (36%) of PDA-001 subjects compared with placebo (0%, P = 0.026). Clinical remission was achieved in 4/28 (14%) of PDA-001 subjects compared with placebo (0%, P = 0.3). One treatment-related serious adverse event occurred (systemic hypersensitivity reaction at 8 units). In the phase 2a study, serious adverse events occurred in 9/28 (32%) of PDA-001 subjects and 1/16 (7%) of placebo subjects., Conclusions: A 2-infusion regimen of PDA-001 induced clinical response in subjects with moderate-to-severe CD. Additional studies are warranted.

VMAT is an important tool in the treatment of head and neck cancers, many of which also require treatment to the supraclavicular lymph nodes. However, full VMAT arcs treating this nodal region necessarily cause entrance beam to pass through patients' shoulders. Thus, interfractional variations in shoulder position may cause unwanted dose perturbations. To assess this possibility, six patients undergoing treatment at our institution for head and neck cancers with associated supraclavicular lymph node treatment were imaged with in-room CT-on-rails during the course of their treatments. This allowed for the establishment of a true record of the actual shoulder position during selected treatment fractions. Then, a full VMAT plan and a plan with VMAT arcs superior to the shoulder and a static anteroposterior field inferiorly were copied onto the patients' weekly image sets. The average one-dimensional shoulder motion was generally within 10 mm of the simulated position, with some notable exceptions. The standard deviation in week-to-week shoulder position relative to simulation was 4.3 mm and 4.2 mm in the SI and AP dimensions, respectively. The average nodal target mean dose across all fractions sampled was within 5% of planned for all patients and both plans. Similarly, the average D95 for the nodal target was within 5% of planned across all fractions sampled, with the single exception of the full VMAT plan for one patient. In most cases, the standard deviation in both target mean dose and D95 was smaller with the VMAT+static AP field plan than it was with the full VMAT plan.

Objective: We aimed to determine the safety and efficacy of antiplatelet/anticoagulation regimens after placement of Viabahn stent graft (W. L. Gore & Associates, Flagstaff, Ariz) for the treatment of femoropopliteal occlusive disease., Methods: Clinical, angiographic, and procedural data for patients undergoing endovascular treatment of femoropopliteal occlusive disease using Viabahn covered stent grafts at a single institution between 2006 and 2013 were retrospectively reviewed. Graft patency and freedom from thrombolysis, major adverse limb event, and reintervention were determined by Kaplan-Meier analysis. The influence of relevant variables on clinical outcome was determined through univariate and multivariate Cox proportional hazards analyses., Results: Viabahn stent grafts were placed in a total of 91 limbs in 61 patients (66% men; mean age, 69 ± 12 years) during the study period. Indication for intervention was either claudication (n = 59) or critical limb ischemia (n = 32), with the majority (70%) classified as TransAtlantic Inter-Society Consensus II C (n = 33) or D (n = 31) lesions. Mean follow-up was 38.3 months (range, 1-91 months). Postprocedural pharmacologic regimens included aspirin, clopidogrel, and warfarin (47%); indefinite aspirin and clopidogrel (46%); or aspirin and temporary clopidogrel (7%). Primary and secondary patency rates were 60%, 44%, and 36% and 95%, 82%, and 74% at 1 year, 3 years, and 5 years, respectively. Kaplan-Meier analysis demonstrated more aggressive antiplatelet/anticoagulation regimens to be associated with improved primary patency and freedom from reintervention. Cox proportional hazards analysis demonstrated TransAtlantic Inter-Society Consensus II D lesions, tobacco use, coronary artery disease, and smaller stent diameter to be independent risk factors for stent graft failure. Bleeding events were limited to those in the aspirin, clopidogrel, and warfarin group (11.6% [n = 5]; P = .052), although the majority of these events were not life-threatening, and only two cases required blood transfusion., Conclusions: Increasingly aggressive antithrombotic regimens after Viabahn stent graft placement trended toward improved overall clinical outcomes, although the marginal patency benefit observed with the addition of warfarin to dual antiplatelet therapy was tempered by an observed increased risk of bleeding complications. Longer term follow-up and multicenter studies are needed to further define optimal type and duration of antithrombotic therapy after endovascular peripheral interventions., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Although the incidence of casualties from the Global War on Terror is decreasing, there remains a focus on the long-term sequelae from injuries sustained in the combat. Patients with prior significant limb injuries remain at risk of future complications. This study examines our institution's experience with a multidisciplinary team approach toward this challenging patient population., Methods: A retrospective review was performed on all patients treated in a single institution Limb Preservation Clinic over a 2-year period. Those patients who sustained a combat-related injury in theater were examined. Patient demographics, mechanism of injury, amputation rates, time to amputation, and reasons for failure were examined., Results: Ninety-four patients were evaluated in our multidisciplinary Limb Preservation Clinic over a 2-year period. Twenty patients (21%) were seen for combat-related injuries. Sixteen patients were evaluated and treated for chronic complications at a median of 13 months from their injury. All 16 patients were male with a median age of 24 years (range, 20-35). Ten patients sustained injuries secondary to a dismounted improvised explosive device (IED). All 16 patients had extensive soft tissue injuries and associated fractures. Only 2 patients sustained a vascular injury. The median number of prior surgeries to the affected limb was 8 (range, 3-19). The limb salvage rate of 37% was lower than our noncombat cohort (47%). The most common reasons for delayed amputation included chronic pain, osteomyelitis, and soft tissue infections., Conclusions: The high secondary amputation rates seen in this cohort underscores the need for long-term follow-up. Despite successful initial outcomes, many patients eventually progress to limb loss. Patients who sustain a dismounted IED are at greatest risk for a delayed amputation. Identifying and addressing those factors which lead to delayed amputation should be a priority for returning war veterans and focus of future studies., (Published by Elsevier Inc.)

Background: Combat extremity wounds are complex and frequently require an immediate vascular reconstruction in the operational environment followed by delayed tissue coverage at a stateside medical treatment facility. The purpose of this study was to evaluate limb salvage outcomes after combat-related vascular reconstruction that subsequently required delayed soft tissue coverage during the Global War on Terror., Methods: Patients who incurred a war-related extremity injury necessitating an immediate vascular intervention followed by definitive limb reconstruction requiring flap coverage from combat injuries were reviewed. Patient demographics, types of vascular and extremity injuries, and surgical interventions were examined. Outcomes included limb salvage, primary and secondary graft patency, flap outcomes, and complications. Differences between upper extremities (UEs) and lower extremities (LEs) were compared., Results: From 2003 to 2012, 27 patients were treated for combat-related extremity injuries with an immediate vascular reconstruction followed by delayed tissue coverage. Fifteen LEs and 12 UEs were treated. The mean age was 24 years. An explosion was the cause in 77% of patients, with a mean Injury Severity Score (ISS) of 19. An autogenous vein bypass was the most common reconstruction performed in 20 patients (74%). Other vascular repairs included a primary repair, a patch angioplasty with bovine pericardium, and a bypass with use of a prosthetic graft. Eight patients (30%) had a concomitant venous injury, and 23 (85%) had a bone fracture. Thirty flaps were performed at a mean of 33 days from the original injury. Pedicle flaps were used in 24 limbs and free tissue flaps in six limbs. Muscle, fasciocutaneous, bone, and composite flaps were used for tissue coverage. At a mean follow-up of 16 months, primary patency rates of all arterial reconstructions were 66% in the UE and 53% in the LE (P = .69). Secondary patency rates were 100% in the UE and 86% in the LE (P = .48). The overall limb salvage rate was 81%. Limb salvage rates were 66% in the LE and 100% in the UE (P = .04). Three amputated lower limbs (60%) had inline flow to the foot. The flap success rate was 96%. Reasons for amputation included arterial thrombosis, flap failure, persistent soft tissue infection, osteomyelitis, and debilitating peripheral nerve injuries with associated chronic pain., Conclusions: Immediate vascular repair followed by delayed tissue coverage can be performed with a high (>80%) limb salvage rate after combat trauma. Limb salvage rates were higher in the UE despite equivocally high arterial patency rates. Wounded warriors can expect limb salvage by use of this international algorithm., (Published by Elsevier Inc.)

Prenatal and early postnatal adversities have been shown to be associated with brain development. However, we do not know how much of this association is confounded by genetics, nor whether the postnatal environment can moderate the impact of in utero adversity. This study used a monozygotic (MZ) twin design to assess (1) the association between birth weight (BW) and brain volume in adolescence, (2) the association between within-twin-pair BW discordance and brain volume discordance in adolescence, and (3) whether the association between BW and brain volume in adolescence is mediated or moderated by early negative maternal parenting behaviours. These associations were assessed in a sample of 108 MZ twins followed longitudinally since birth and scanned at age 15. The total grey matter (GM) and white matter (WM) volumes were obtained using the Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) toolbox in the Statistical Parametric Mapping version 8 (SPM8). We found that the BW was significantly associated with the total GM and WM volumes, particularly in the superior frontal gyrus and thalamus. Within-twin-pair discordance in BW was also significantly associated with within-pair discordance in both the GM and the WM volumes, supporting the hypothesis that the specific in utero environment is associated with brain development independently of genetics. Early maternal hostile parenting behaviours and depressive symptoms were associated with total GM volume but not WM volume. Finally, greater early maternal hostility may moderate the association between the BW and GM volume in adolescence, since the positive association between the BW and total GM volume appeared stronger at higher levels of maternal hostility (trend). Together, these findings support the importance of the in utero and early environments for brain development., (© 2015 S. Karger AG, Basel.)

Background: Combat-related extremity injuries frequently require vascular repair within the combat theater before undergoing definitive reconstruction. This study examines the outcomes of early vascular repair with secondary soft-tissue extremity reconstruction over the past decade of war trauma., Methods: War-related extremity injuries necessitating a downrange vascular procedure followed by a definitive limb reconstruction were reviewed. Patient demographics, type and location of vascular injuries, vascular intervention, and soft-tissue reconstruction procedures were examined. Outcomes of vascular repair, tissue transfer, and limb salvage were analyzed., Results: From 2003 to 2012, 79 extremities in 78 patients had a vascular injury requiring in-theater intervention followed by 87 staged flap reconstructions performed distal to the vascular repair. Of the 74 arterial injuries requiring intervention, 27 were proximally located, with 73 percent requiring bypass. The early primary patency rate was 66 percent and the early primary-assisted patency rate was 93 percent for proximal artery repair procedures. The flap complication rate was 31 percent. Overall complications were examined by subtype and were not significantly different compared with flaps performed without a proximal vascular injury in the same limb. The flap success rate (93 percent) and the limb salvage rate (81 percent) were similar to the comparison cohort., Conclusions: This represents one of the largest series of traumatic extremity injuries requiring secondary limb reconstruction with tissue transfer following a vascular intervention. The authors identified no significant difference in outcomes related to flap coverage or limb salvage for patients with or without vascular injuries. Reconstructive options in combat extremity trauma are not limited by proximal vascular injury., Clinical Question/level of Evidence: Therapeutic, III.

DNA methylation patterns are characterized by highly conserved developmental programs, but allow for divergent gene expression resulting from stochastic epigenetic drift or divergent environments. Genome-wide methylation studies in monozygotic (MZ) twins are providing insight into the extent of epigenetic variation that occurs, irrespective of genotype. However, little is known about the variability of DNA methylation patterns in adolescence, a period involving significant and rapid physical, emotional, social, and neurodevelopmental change. Here, we assessed genome-wide DNA methylation using the 450 K Illumina BeadChip in a sample of 37 MZ twin pairs followed longitudinally since birth to investigate: 1) the extent of variation in DNA methylation in identical genetic backgrounds in adolescence and; 2) whether these variations are randomly distributed or enriched in particular functional pathways. We also assessed stability of DNA methylation over 3-6 months to distinguish stable trait-like and variable state-like genes. A pathway analysis found high within-pair variability in genes associated with development, cellular mechanisms, tissue and cell morphology, and various disorders. Test-retest analyses performed in a sub-sample of 8 twin pairs demonstrated enrichment in gene pathways involved in organismal development, cellular growth and proliferation, cell signaling, and particular disorders. The variability found in functional gene pathways may plausibly underlie phenotypic differences in this adolescent MZ twin sample. Furthermore, we assessed stability of methylation over 3-6 months and found that some genes were stable while others were unstable, suggesting that the methylome remains dynamic in adolescence and that dynamic sites tend to be organized in certain gene pathways.

First described in 1924, necrotizing fasciitis (NF) is a rapidly progressing, severe suppurative infection of the superficial fascia, often associated with vascular thrombosis and necrosis of the overlying skin. Despite advances in medical therapy, the mortality remains high, with rates exceeding 25 to 50% in some studies. Early diagnosis and treatment is paramount in the management of this serious infection and should include wide surgical debridement and drainage of all necrotic tissues, coupled with aggressive parenteral antibiotics. This infectious process has been commonly associated with traumatic events in patients with compromised immune systems, diabetes, chronic steroid use, and alcoholism. The common microbacterial organisms associated with necrotizing fasciitis include Streptococcus pyogenes and Staphylococcus aureus and less commonly, facultative and anaerobic microorganisms. Most cases typically present in the extremities, trunk, and/or groin regions. Although this virulent soft tissue infection can occur within the face and neck areas, cases of isolated periorbital NF have been relatively uncommon. However, head and neck cases of NF have had high associated morbidity and mortality rates. In recent publications, the reported mortality rate for isolated periorbital NF was not insignificant, ranging from 8.5 to 12.5%. The prognosis, morbidity, and mortality rates will be greatly increased in those patients who present late in the infectious phase, have a delay in diagnosis and/or treatment, or who demonstrate extension of this virulent infection into the face, cervical, or sternal/mediastinal regions. An aggressive multimodal approach is required in treating periorbital necrotizing infection, with the main tenant remaining wide and adequate surgical debridement of affected tissues. This difficult clinical situation can create a subsequent challenge with respect to achieving good functional and cosmetic outcomes in those patients with periorbital NF. Delayed reconstruction of the eyelids with skin grafts and/or facial flaps is often required to avoid late complications such as cicatricial lid retraction, lid malposition, exposure keratopathy, and potential loss of vision. We describe a patient who presented to a military combat hospital with a virulent periorbital soft tissue infection. We have outlined his treatment course from the initial presentation through definitive reconstruction., (Published by Elsevier Inc.)

Background: Not everyone who tries addictive drugs develops a substance use disorder. One of the best predictors of risk is a family history (FH) of substance use problems. In part, this might reflect perturbed mesolimbic dopamine responses., Methods: We measured amphetamine-induced changes in [(11)C]raclopride binding in 1) high-risk young adults with a multigenerational FH of substance use disorders (n = 16); 2) stimulant drug-naïve healthy control subjects with no known risk factors for addiction (n = 17); and 3) subjects matched to the high-risk group on personal drug use but without a FH of substance use problems (n = 15)., Results: Compared with either control group, the high-risk young adults with a multigenerational FH of substance use disorders exhibited smaller [(11)C]raclopride responses, particularly within the right ventral striatum. Past drug use predicted the dopamine response also, but including it as a covariate increased the group differences., Conclusions: Together, the results suggest that young people at familial high risk for substance use disorders have decreased dopamine responses to an amphetamine challenge, an effect that predates the onset of addiction., (© 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.)

Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [(11)C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87 ± 8.65) and 18 healthy male controls (age: 25.44 ± 6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a battery of neurocognitive tests. Relative to the healthy controls, the ADHD patients, as a group, showed greater d-amphetamine-induced decreases in striatal [(11)C]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [(11)C]raclopride binding potential was associated with poorer performance on measures of response inhibition and ADHD symptoms. Our findings suggest an augmented striatal dopaminergic response in treatment-naive ADHD. Though in contrast to results of a previous study, this finding appears consistent with a model proposing exaggerated phasic dopamine release in ADHD. A susceptibility to increased phasic dopamine responsivity may contribute to such characteristics of ADHD as poor inhibition and impulsivity.

Axillary artery aneurysms are rare entities that warrant surgical intervention. Reported complications include thrombosis, distal embolization, and debilitating neurologic symptoms caused by median nerve compression. Common etiologies include trauma or repetition injuries. Less recognized associations include atherosclerotic, connective tissue, or mycotic processes. We report a case of a rare tortuous axillary artery aneurysm causing neurologic symptoms in a woman with an unused arteriovenous fistula., (Published by Elsevier Inc.)

Background: The neurobiology of risk for alcohol use disorders (AUDs) remains poorly understood. Individual differences in vulnerability, though, have been indicated by subjective responses to alcohol ingestion and personality traits., Methods: To investigate the relationship between these features and striatal dopamine (DA) responses to alcohol, we studied 26 healthy young social drinkers (21.3 ± 3.0 years old; 10.7 ± 8.8 drinks/wk) at varying risk for alcoholism. Each participant received 2 positron emission tomography [(11) C]raclopride scans after administration of either placebo or oral alcohol (1 ml/kg body weight of 94% alcohol, 0.75 g/kg) in a randomized and counterbalanced design., Results: Subjects with high-risk subjective responses to alcohol had more family members with AUDs, greater alcohol use problems, and, in response to the alcohol challenge, significant decreases in [(11) C]raclopride binding indicative of increased extracellular DA. In contrast, low-risk subjects exhibited increases in [(11) C]raclopride binding in response to alcohol. The results were similar when risk groups were based on personality traits, although statistically less robust., Conclusions: Changes in striatal DA in response to alcohol ingestion may be a neurobiological marker of vulnerability to AUDs., (Copyright © 2013 by the Research Society on Alcoholism.)

Background: In laboratory animals, environmental stressors markedly activate the mesocortical dopamine system. The present study tested whether this occurs in humans., Methods: The effects of a laboratory psychological stressor (Montreal Imaging Stress Task, MIST) on mesocortical dopamine release in healthy young adults (11 males, mean age ± SD, 20.6 ± 2.4 years) was measured using positron emission tomography and [(18)F]fallypride. Each subject was scanned in two separate days in counterbalanced order: one with the MIST and one with the control task. Binding potential (BP ND ) maps of the whole brain were calculated for each scan, using a simplified reference tissue compartmental model. Then BP ND was compared between subjects. Heart rate, galvanic skin response, and salivary cortisol level were measured during the scans., Results: The psychological stressor significantly decreased [(18)F]fallypride binding values in the dorsal part of the medial prefrontal cortex (dmPFC), corresponding to the rostal part of the cingulate motor zone. The greater the stress-induced decrease in [(18)F]fallypride binding in the dmPFC, the greater the stress-induced increases in heart rate., Conclusions: The present study provides evidence of stress-induced dopamine release in the mPFC in humans, in vivo., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: The aim of this work was to create a mailable phantom with measurement accuracy suitable for Radiological Physics Center (RPC) audits of high dose-rate (HDR) brachytherapy sources at institutions participating in National Cancer Institute-funded cooperative clinical trials. Optically stimulated luminescence dosimeters (OSLDs) were chosen as the dosimeter to be used with the phantom., Methods: The authors designed and built an 8 × 8 × 10 cm(3) prototype phantom that had two slots capable of holding Al2O3:C OSLDs (nanoDots; Landauer, Glenwood, IL) and a single channel capable of accepting all (192)Ir HDR brachytherapy sources in current clinical use in the United States. The authors irradiated the phantom with Nucletron and Varian (192)Ir HDR sources in order to determine correction factors for linearity with dose and the combined effects of irradiation energy and phantom characteristics. The phantom was then sent to eight institutions which volunteered to perform trial remote audits., Results: The linearity correction factor was kL = (-9.43 × 10(-5) × dose) + 1.009, where dose is in cGy, which differed from that determined by the RPC for the same batch of dosimeters using (60)Co irradiation. Separate block correction factors were determined for current versions of both Nucletron and Varian (192)Ir HDR sources and these vendor-specific correction factors differed by almost 2.6%. For the Nucletron source, the correction factor was 1.026 [95% confidence interval (CI) = 1.023-1.028], and for the Varian source, it was 1.000 (95% CI = 0.995-1.005). Variations in lateral source positioning up to 0.8 mm and distal∕proximal source positioning up to 10 mm had minimal effect on dose measurement accuracy. The overall dose measurement uncertainty of the system was estimated to be 2.4% and 2.5% for the Nucletron and Varian sources, respectively (95% CI). This uncertainty was sufficient to establish a ± 5% acceptance criterion for source strength audits under a formal RPC audit program. Trial audits of four Nucletron sources and four Varian sources revealed an average RPC-to-institution dose ratio of 1.000 (standard deviation = 0.011)., Conclusions: The authors have created an OSLD-based (192)Ir HDR brachytherapy source remote audit tool which offers sufficient dose measurement accuracy to allow the RPC to establish a remote audit program with a ± 5% acceptance criterion. The feasibility of the system has been demonstrated with eight trial audits to date.

The meso-striatal dopamine system influences responses to rewards and the motivation to seek them out. Marked individual differences in these responses are seen in laboratory animals, related in part to input from the prefrontal cortex. Here we measured the relation between cortical morphology and drug-induced striatal dopamine release in healthy young people. Participants were 24 (17 male, 7 female; age 23.0 ± 6.2 years) stimulant drug-naive subjects who underwent PET [(11)C]raclopride scans with 0.3 mg/kg d-amphetamine orally and placebo, and an anatomical MRI scan for measuring cortical thickness. As expected, d-amphetamine produced significant reductions in [(11)C]raclopride binding potential in the striatum as a percentage of the value in the placebo condition. There was substantial individual variability in this response, which was correlated with cortical thickness in the frontal lobe as a whole. The association was strongest in the anterior part of the right lateral prefrontal cortex and bilateral supplementary motor area. A thicker cortex was correlated with a smaller dopamine response. Together, this work demonstrates in humans an association between cortical thickness and the striatal dopamine response to drugs of abuse. Although prefrontal regulation of striatal function has been well studied, it was unclear whether the thickness of the prefrontal cortex was an acceptable proxy to the function of that region. These results suggest it is.

Subclinical microembolization identified on diffusion-weighted magnetic resonance imaging is recognized as an important outcome measure for carotid revascularization procedures. It is generally believed that arch manipulation is the primary reason for developing microemboli in the contralateral hemisphere during carotid artery stenting. However, we identified three patients who developed postprocedure microemboli of the contralateral hemisphere despite a known chronic contralateral internal carotid artery occlusion. Our cases highlight that ipsilateral microemboli may be an underappreciated but an important source of contralateral lesions through patent intracranial collateral pathways., (Published by Mosby, Inc.)

Drug-related cues are potent triggers for relapse in people with cocaine dependence. Dopamine (DA) release within a limbic network of striatum, amygdala and hippocampus has been implicated in animal studies, but in humans it has only been possible to measure effects in the striatum. The objective here was to measure drug cue-induced DA release in the amygdala and hippocampus using high-resolution PET with [(18)F]fallypride. Twelve cocaine-dependent volunteers (mean age: 39.6 ± 8.0 years; years of cocaine use: 15.9 ± 7.4) underwent two [(18)F]fallypride high-resolution research tomography-PET scans, one with exposure to neutral cues and one with cocaine cues. [(18)F]Fallypride non-displaceable-binding potential (BPND) values were derived for five regions of interest (ROI; amygdala, hippocampus, ventral limbic striatum, associative striatum, and sensorimotor striatum). Subjective responses to the cues were measured with visual analog scales and grouped using principal component analysis. Drug cue exposure significantly decreased BPND values in all five ROI in subjects who had a high-, but not low-, craving response (limbic striatum: p=0.019, associative striatum: p=0.008, sensorimotor striatum: p=0.004, amygdala: p=0.040, and right hippocampus: p=0.025). Individual differences in the cue-induced craving response predicted the magnitude of [(18)F]fallypride responses within the striatum (ventral limbic: r=0.581, p=0.048; associative: r=0.589, p=0.044; sensorimotor: r=0.675, p=0.016). To our knowledge this study provides the first evidence of drug cue-induced DA release in the amygdala and hippocampus in humans. The preferential induction of DA release among high-craving responders suggests that these aspects of the limbic reward network might contribute to drug-seeking behavior.

Objective: Reintervention rates after repair of abdominal aortic aneurysm (AAA) are higher for endovascular repair (EVAR) than for open repair, mostly due to treatment for endoleaks, whereas open surgical operations for bowel obstruction and abdominal hernias are higher after open repair. However, readmission rates after EVAR or open repair for nonoperative conditions and complications that do not require an intervention are not well documented. We sought to determine reasons for all-cause readmissions within the first year after open repair and EVAR., Methods: Patients who underwent elective AAA repair in California during a 6-year period were identified from the Health Care and Utilization Project State Inpatient Database. All patients who had a readmission in California ≤1 year of their index procedure were included for evaluation. Readmission rates and primary and secondary diagnoses associated with each readmission were analyzed and recorded., Results: From 2003 to 2008, there were 15,736 operations for elective AAA repair, comprising 9356 EVARs (60%) and 6380 open repairs (40%). At 1 year postoperatively, the readmission rate was 52.1% after open repair and 55.4% after EVAR (P=.0003). The three most common principle diagnoses associated with readmission after any type of AAA repair were failure to thrive, cardiac issues, and infection. When stratified by repair type, patients who underwent open repair were more likely to be readmitted with primary diagnoses associated with failure to thrive, cardiac complications, and infection compared with EVAR (all P<.001). Those who underwent EVAR were more likely, however, to be readmitted with primary diagnoses of device-related complications (P=.05), cardiac complications, and infection., Conclusions: Total readmission rates within 1 year after elective AAA repair are greater after EVAR than after open repair. Reasons for readmission vary between the two cohorts but are related to the magnitude of open surgery after open repair, device issues after EVAR, and the usual cardiac and infectious complications after either intervention. Systems-based analysis of these causes of readmission can potentially improve patient expectations and care after elective aneurysm repair., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)