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The majority of individuals with temporomandibular disorders (TMD) experience sleep disturbance, which can maintain and exacerbate chronic pain. However, the factors underlying the sleep-pain link have not been fully elucidated, especially beyond the laboratory. Sleep deprivation can induce threat interpretation bias, as well as impairment in positive affective functioning. Using both actigraphy and daily diaries, we examined whether morning pain expectancy and positive affect mediate the association between previous night's sleep disturbance and next-day overall pain severity. Total sleep time (TST) was selected as the primary measure of sleep. The sample included 144 women (mean age = 36 [SD = 11.1]) with TMD who displayed at least subclinical insomnia. Sleep was assessed for 14 days using actigraphy which was validated by concurrent sleep diaries. Daily diary assessments of pain-related experiences and affective states were conducted twice per day (ie, once upon participants' waking and the other prior to going to sleep) for the same 14-day period. Multilevel structural equation modeling revealed that both morning pain expectancy (95% CI: -.0004, -.00003) and positive affect (95% CI: -.0005, -.000001) mediated the association between previous night's TST and next-day's overall pain severity, such that shorter previous night TST was associated with higher next-morning pain expectancy and lower positive affect, which in turn were associated with a greater level of next-day's overall pain severity while controlling for morning pain severity. Reducing exaggerated daily pain expectancy and up-regulating positive affect may be important intervention targets for disengaging the sleep-pain link among individuals with co-occurring TMD and sleep disturbance. PERSPECTIVE: The daily link between previous night sleep duration and next day pain severity is mediated by morning pain expectancy and positive affect among women with temporomandibular disorder and sleep disturbance. Reducing pain expectancy and increasing positive affect may serve an important role in improving self-management of chronic pain.

Connective tissue disorders (CTDs) are associated with esophageal dysmotility and gastroesophageal reflux disease, which may diminish survival after lung transplantation (LTx). We studied LTx outcomes in patients with a CTD stratified by esophageal motility. We identified patients who underwent bilateral LTx from 2012 to 2017. Patients with a CTD were classified by pre-LTx diagnosis: absent esophageal motility (AEM), ineffective esophageal motility (IEM), or preserved esophageal motility (PEM). The primary endpoint was 3-year survival. Sub-analysis compared survival between the AEM group and a propensity-matched (lung allocation score), non-CTD control group. Kaplan-Meier method and log-rank test were used. In total, 495 patients underwent LTx; 33 (6.7%) had a CTD. Median (IQR) age was 62 years (55.5-67.0); 24 (72.7%) were women. Survival trended lower for recipients with a CTD than without a CTD at 1-year (84.8% vs 91.8%; p = 0.2) and 3-years (66.7% vs 73.5%; p = 0.5). Within the CTD cohort, 1- and 3-year survival was significantly higher in the PEM (100%, 87.5%) and IEM (100%, 85.7%) groups than in the AEM group (50%, 20%; p0.001). The AEM group had significantly lower survival at 1-year (50% vs 92.5%) and 3-years (20% vs 65%) than a lung allocation score-matched cohort of patients without a CTD. LTx recipients with a CTD and AEM had significantly lower survival than those with PEM or IEM as well as significantly lower survival than that of a propensity-matched cohort of patients without a CTD. Patients with a CTD and AEM should be considered for LTx with extreme caution and counseled appropriately.

Background Chronic lung allograft dysfunction in lung transplant recipients (LTxRs) has 2 phenotypes: obstructive bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Our goal was to define distinct immunologic markers of exosomes from LTxRs with BOS or RAS. Methods Plasma was collected from LTxRs with BOS (n = 18), RAS (n = 13), and from stable LTxRs (n = 5). Antibodies to lung self-antigens (SAgs) were determined by ELISA. Exosomes were isolated by ultracentrifugation. Donor specific antibodies to HLA were quantified using Luminex. Exosomes were characterized for lung SAgs, transcription factors, 20S proteasome, HLA class I and II, and polymeric immunoglobulin receptor protein using western blot. Exosome miRNA was analyzed using NanoString. The exosome-induced immune response was determined in mice. Results LTxRs with RAS, but not BOS, had donor specific antibodies at diagnosis. CIITA, NFkB, polymeric immunoglobulin receptor protein, 20S proteasome, HLA-DQ, and HLA-DR were significantly higher in RAS exosomes than in BOS exosomes. RAS plasma had high levels of proinflammatory cytokines and distinct exosomal miRNA. Immunization of C57BL/6 mice with RAS exosomes showed severe inflammation and peribronchial fibrosis, whereas BOS exosomes induced patchy inflammation and fibrosis. Conclusion LTxRs with BOS or RAS had exosomes with distinct molecular and immunologic profiles. RAS samples had a higher concentration of proinflammatory factors, HLA class II, lung SAgs, and antibodies to HLA class II molecules, indicating severe allograft injury. Mice immunized with RAS exosomes developed lesions in airways, pleura, interlobular septum, and alveoli, whereas BOS exosomes induced mild to patchy inflammation with lung fibrosis.

INTRODUCTION/AIMS: Duchenne and Becker muscular dystrophies (DBMD) are X-linked neuromuscular disorders characterized by progressive muscle weakness, leading to decreased mobility and multisystem complications. We estimate productivity costs attributable to time spent by a parent caring for a male child under the age of 18 y with DBMD, with particular focus on female caregivers of boys with Duchenne muscular dystrophy (DMD) who have already lost ambulation. METHODS: Primary caregivers of males with DBMD in the Muscular Dystrophy Surveillance and Research Tracking Network (MD STARnet) were surveyed during 2011–2012 on family quality of life measures, including labor market outcomes. Of 211 respondents, 96 female caregivers of boys with DBMD were matched on state, year of survey, respondent’s age, child’s age, and number of minor children with controls constructed from Current Population Survey extracts. Regression analysis was used to estimate labor market outcomes and productivity costs. RESULTS: Caregivers of boys with DBMD worked 296 h less per year on average than caregivers of unaffected children, translating to a $8816 earnings loss in 2020 U.S. dollars. Caregivers of boys with DMD with ≥4 y of ambulation loss had a predicted loss in annualized earnings of $23,995, whereas caregivers of boys with DBMD of the same ages who remained ambulatory had no loss of earnings. DISCUSSION: Female caregivers of non-ambulatory boys with DMD face additional household budget constraints through income loss. Failure to include informal care costs in economic studies could understate the societal cost-effectiveness of strategies for managing DMD that might prolong ambulation.

State medicaid programs provide access to effective contraception for people with lower incomes. This study examined contraception use and pregnancy among reproductive-age women enrolled in the South Carolina Medicaid, by eligibility program and socio-demographic sub-groups. A retrospective cohort of women aged 15–45 who were newly eligible for South Carolina Medicaid from 2012 to 2016 was examined. Log-binomial regression and average marginal effects assessed relationships between contraception use and pregnancies ending in live and non-live births. Contraception was categorized as permanent, long acting reversible contraception (LARC), short-acting hormonal contraception (SAC), or no contraceptive claims. Women with family planning or full-benefit medicaid coverage were included. Approximately 11% of women used LARC methods, 41% used SAC methods, and 46% had no evidence of contraceptive claims. Method utilization varied by eligibility program, race/ethnicity and age. The likelihood of pregnancy was lower among SAC users and lowest among LARC users compared to women with no evidence of contraception across all three programs (family planning APR = 0.44; 95% CI 0.41–0.49 and APR = 0.13, 95% CI 0.10–0.17; Low income families APR = 0.82; 95% CI 0.77–0.88 and APR = 0.33, 95% CI 0.28–0.38; Partners for Healthy Children APR = 0.72; 95% CI 0.68–0.77 and APR = 0.35, 95% CI 0.30–0.43, respectively). Non-Hispanic Black and Hispanic teens were less likely to experience a pregnancy than non-Hispanic white teens. The likelihood of pregnancy was lower among women using SAC methods and markedly lower among women using LARC. Variation in contraceptive use among racial/ethnic groups was noted despite Medicaid coverage. As new policies and initiatives emerge, these findings provide important context for understanding the role of Medicaid programs in reducing financial barriers to contraceptive services and ensuring access to effective contraception, while fostering reproductive health autonomy among women.

In this retrospective cohort study, we characterize the health profile of preterm males with Duchenne muscular dystrophy. Major clinical milestones (ambulation cessation, assisted ventilation use, and onset of left ventricular dysfunction) and corticosteroids use in males with Duchenne muscular dystrophy identified through a population-based surveillance system were analyzed using Kaplan-Meier survival curves and Cox proportional hazards modeling. The adjusted risk of receiving any respiratory intervention among preterm males with Duchenne muscular dystrophy was 87% higher than among the corresponding full-term males with Duchenne muscular dystrophy. The adjusted risks for ambulation cessation and left ventricular dysfunction were modestly elevated among preterm compared to full-term males, but the 95% confidence intervals contained the null. No difference in the start of corticosteroid use between preterm and full-term Duchenne muscular dystrophy males was observed. Overall, the disease course seems to be similar between preterm and full-term males with Duchenne muscular dystrophy; however, pulmonary function seems to be affected earlier among preterm males with Duchenne muscular dystrophy.

Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) is a pathogenic coronavirus causing COVID‐19 infection. The interaction between the SARS‐CoV‐2 spike protein and the human receptor angiotensin‐converting enzyme 2, both of which contain several cysteine residues, is impacted by the disulfide‐thiol balance in the host cell. The host cell redox status is affected by oxidative stress due to the imbalance between the reactive oxygen/nitrogen species and antioxidants. Recent studies have shown that Vitamin D supplementation could reduce oxidative stress. It has also been proposed that vitamin D at physiological concentration has preventive effects on many viral infections, including COVID‐19. However, the molecular‐level picture of the interplay of vitamin D deficiency, oxidative stress, and the severity of COVID‐19 has remained unclear. Herein, we present a thorough review focusing on the possible molecular mechanism by which vitamin D could alter host cell redox status and block viral entry, thereby preventing COVID‐19 infection or reducing the severity of the disease.

Background Tumour progression relies on the ability of cancer cells to penetrate and invade neighbouring tissues. E-cadherin loss is associated with increased cell invasion in gastric carcinoma, and germline mutations of the E-cadherin gene are causative of hereditary diffuse gastric cancer. Although E-cadherin dysfunction impacts cell–cell adhesion, cell dissemination also requires an imbalance of adhesion to the extracellular matrix (ECM). Methods To identify ECM components and receptors relevant for adhesion of E-cadherin dysfunctional cells, we implemented a novel ECM microarray platform coupled with molecular interaction networks. The functional role of putative candidates was determined by combining micropattern traction microscopy, protein modulation and in vivo approaches, as well as transcriptomic data of 262 gastric carcinoma samples, retrieved from the cancer genome atlas (TCGA). Results Here, we show that E-cadherin mutations induce an abnormal interplay of cells with specific components of the ECM, which encompasses increased traction forces and Integrin β1 activation. Integrin β1 synergizes with E-cadherin dysfunction, promoting cell scattering and invasion. The significance of the E-cadherin-Integrin β1 crosstalk was validated in Drosophila models and found to be consistent with evidence from human gastric carcinomas, where increased tumour grade and poor survival are associated with low E-cadherin and high Integrin β1 levels. Conclusions Integrin β1 is a key mediator of invasion in carcinomas with E-cadherin impairment and should be regarded as a biomarker of poor prognosis in gastric cancer.

Poor sleep is common in inflammatory bowel disease (IBD), predicting increased risk of flares, surgery, and/or hospitalization and reducing quality of life. To profile specific sleep disorder symptoms in IBD, informing intervention efforts. 312 adults with Crohn’s disease or ulcerative colitis were recruited from an academic medical center in New Hampshire, USA. Participants completed online surveys about sleep including well-validated measures of sleep quality, insomnia, restless leg syndrome, sleep apnea, and circadian rhythms. Participants also answered questions about IBD-related problems that could interfere with sleep. 69.4% of participants reported experiencing poor sleep and 50% reported clinically significant insomnia. Participants with active IBD symptoms were more likely to have poor sleep and insomnia. Of those with poor sleep, 67.8% met the clinical threshold for insomnia disorder and 31.3% met criteria for two or more sleep disorders. IBD-related sleep disruptions (e.g., nighttime awakenings due to bowel movements) were not significantly related to poor sleep quality, but significantly related to insomnia severity for participants with active Crohn’s disease. While poor sleep in IBD is reflective of a number of different sleep problems, it is most frequently related to insomnia. IBD symptom severity contributes to insomnia, but insomnia is also distinct from IBD-related sleep disruptions. Future research on the treatment of insomnia disorder in particular in individuals with IBD is warranted.

Background Dementia outcomes include memory loss, language impairment, reduced quality of life and personality changes. Research suggests that outcomes selected for dementia clinical trials might not be the most important to people affected. Objective One of the goals of the ‘Real world Outcomes across the Alzheimer's Disease spectrum for better care: Multi‐modal data Access Platform’ (ROADMAP) project was to identify important outcomes from the perspective of people with dementia and their caregivers. We review how ROADMAP's Public Involvement shaped the programme, impacted the research process and gave voice to people affected by dementia. Design The European Working Group of People with Dementia (EWGPWD) were invited to participate. In‐person consultations were held with people with dementia and caregivers, with advance information provided on ROADMAP activities. Constructive criticism of survey content, layout and accessibility was sought, as were views and perspectives on terminology and key concepts around disease progression. Results The working group provided significant improvements to survey accessibility and acceptability. They promoted better understanding of concepts around disease progression and how researchers might approach measuring and interpreting findings. They effectively expressed difficult concepts through real‐world examples. Conclusions The role of the EWGPWD in ROADMAP was crucial, and its impact was highly influential. Involvement from the design stage helped shape the ethos of the programme and ultimately its meaningfulness. Public contribution People with dementia and their carers were involved through structured consultations and invited to provide feedback on project materials, methods and insight into terminology and relevant concepts.

Background Several methods have been proposed to measure cerebrovascular autoregulation (CA) in traumatic brain injury (TBI), but the lack of a gold standard and the absence of prospective clinical data on risks, impact on care and outcomes of implementation of CA-guided management lead to uncertainty. Aim To formulate statements using a Delphi consensus approach employing a group of expert clinicians, that reflect current knowledge of CA, aspects that can be implemented in TBI management and CA research priorities. Methods A group of 25 international academic experts with clinical expertise in the management of adult severe TBI patients participated in this consensus process. Seventy-seven statements and multiple-choice questions were submitted to the group in two online surveys, followed by a face-to-face meeting and a third online survey. Participants received feedback on average scores and the rationale for resubmission or rephrasing of statements. Consensus on a statement was defined as agreement of more than 75% of participants. Results Consensus amongst participants was achieved on the importance of CA status in adult severe TBI pathophysiology, the dynamic non-binary nature of CA impairment, its association with outcome and the inadvisability of employing universal and absolute cerebral perfusion pressure targets. Consensus could not be reached on the accuracy, reliability and validation of any current CA assessment method. There was also no consensus on how to implement CA information in clinical management protocols, reflecting insufficient clinical evidence. Conclusion The Delphi process resulted in 25 consensus statements addressing the pathophysiology of impaired CA, and its impact on cerebral perfusion pressure targets and outcome. A research agenda was proposed emphasizing the need for better validated CA assessment methods as well as the focused investigation of the application of CA-guided management in clinical care using prospective safety, feasibility and efficacy studies.

We sought to determine the impact of the indication for shunt placement on shunt-related outcomes after major arterial injuries. We hypothesized that a shunt placed for damage control indications would be associated with an increase in shunt-related complications including shunt dislodgement, thrombosis, or distal ischemia.A prospective, multicenter study (eleven level one US trauma centers) of all adult trauma patients undergoing temporary intravascular shunts (TIVS) after arterial injury was undertaken (January 2017-May 2019). Exclusion criteria included age15years, shunt placement distal to popliteal/brachial arteries, isolated venous shunts, and death before shunt removal. Clinical variables were compared by indication and shunt-related complications. The primary endpoint was TIVS complications (thrombosis, migration, distal ischemia).The 66 patients who underwent TIVS were primarily young (30years [IQR 22-36]) men (85%), severely injured (ISS 17 [10-25]) by penetrating mechanisms (59%), and had their shunts placed for damage control (41%). After a median SDT of 198min [89-622], 9% experienced shunt-related complications. Compared by shunt placement indication (damage control shunts [n=27] compared to non-damage control shunts [n=39]), there were no differences in gender, mechanism, extremity AIS, MESS score, fractures, or surgeon specialty between the two groups (all p0.05). Patients with shunts placed for damage control indications had more severe injuries (ISS 23.5 compared to 13; SBP 100 compared to 129; GCS 11 compared to 15; lactate 11.5 compared to 3.6; all p0.05), and had more frequent shunt complication predictors, but damage control shunts did not have significantly more TIVS complications (11.1% compared to 7.7%, p=0.658). Shunt complication patients were discharged home less often (33% vs 65%; p0.05) but all survived.Shunts placed for damage control indications were not associated with shunt complications in this prospective, multicenter study.

Background Effective treatment of longstanding Complex Regional Pain Syndrome (CRPS) is a challenge, as causal mechanisms remain elusive. People with CRPS frequently report distorted subjective perceptions of their affected limb. Evidence of pain reduction when the affected limb is visually altered in size suggests that visual illusions used to target central processing could restore coherence of this disrupted limb representation. We hypothesized that using virtual reality that alters hand image to match the patient's desired hand appearance would improve body perception disturbance and pain. Also, repeated exposure would maintain any therapeutic effect. Methods A blinded randomized controlled trial of 45 participants with refractory upper-limb CRPS and body perception disturbance (BPD) viewed a digital image of their affected hand for 1 min. The image was digitally altered according to the patient's description of how they desired their hand to look in the experimental group and unaltered in the control group. BPD and pain were measured pre- and post-intervention. A subgroup was followed up 2 weeks after a course of repeated interventions. Results BPD (mean-6, ±SD 7.9, p = 0.036, effect size [ES] = 0.6) and pain intensity (mean-0.43, ±SD 1.3, p = 0.047, ES = 0.5) reduced in 23 participants after single exposure compared to controls (n = 22). At follow-up, the subgroup (experimental n = 21; control n = 18) showed sustained pain reduction only (p = 0.037, ±SD 1.9, ES = 0.7), with an overall 1.2 decrease on an 11-point scale. Conclusions Visually changing the CRPS hand to a desired appearance modulates BPD and pain suggesting therapeutic potential for those with refractory CRPS. Further research to optimize this therapeutic effect is required. Significance Visual bodily illusions that change the shape and appearance of the painful CRPS hand to that desired by the patient result in a rapid amelioration of pain and body perception disturbance in people with longstanding CRPS. These findings highlight the future potential of this drug-free approach in the treatment of refractory CRPS.

Author(s): Aktas, Orhan; Smith, Michael A; Rees, William A; Bennett, Jeffrey L; She, Dewei; Katz, Eliezer; Cree, Bruce AC; N-MOmentum scientific group and the N-MOmentum study investigators | Abstract: ObjectiveBlood tests to monitor disease activity, attack severity, or treatment impact in neuromyelitis optica spectrum disorder (NMOSD) have not been developed. This study investigated the relationship between serum glial fibrillary acidic protein (sGFAP) concentration and NMOSD activity and assessed the impact of inebilizumab treatment.MethodsN-MOmentum was a prospective, multicenter, double-blind, placebo-controlled, randomized clinical trial in adults with NMOSD. sGFAP levels were measured by single-molecule arrays (SIMOA) in 1,260 serial and attack-related samples from 215 N-MOmentum participants (92% aquaporin 4-immunoglobulin G-seropositive) and in control samples (from healthy donors and patients with relapsing-remitting multiple sclerosis).ResultsAt baseline, 62 participants (29%) exhibited high sGFAP concentrations (≥170 pg/ml; ≥2 standard deviations above healthy donor mean concentration) and were more likely to experience an adjudicated attack than participants with lower baseline concentrations (hazard ratio [95% confidence interval], 3.09 [1.6-6.1], p = 0.001). Median (interquartile range [IQR]) concentrations increased within 1 week of an attack (baseline: 168.4, IQR = 128.9-449.7 pg/ml; attack: 2,160.1, IQR = 302.7-9,455.0 pg/ml, p = 0.0015) and correlated with attack severity (median fold change from baseline [FC], minor attacks: 1.06, IQR = 0.9-7.4; major attacks: 34.32, IQR = 8.7-107.5, p = 0.023). This attack-related increase in sGFAP occurred primarily in placebo-treated participants (FC: 20.2, IQR = 4.4-98.3, p = 0.001) and was not observed in inebilizumab-treated participants (FC: 1.1, IQR = 0.8-24.6, p g 0.05). Five participants (28%) with elevated baseline sGFAP reported neurological symptoms leading to nonadjudicated attack assessments.InterpretationSerum GFAP may serve as a biomarker of NMOSD activity, attack risk, and treatment effects. ANN NEUROL 2021;89:895-910.

Background: Sleep disturbance is thought to aggravate acute postoperative pain. The influence of preoperative sleep problems on pain control in the long-term and development of chronic postsurgical pain is largely unknown. Methods: This prospective, observational study aimed to examine the links between preoperative sleep disturbance (Pittsburgh Sleep Quality Index, PSQI) and pain severity (Brief Pain Inventory, BPI) 6 months postoperative (primary outcome), objective measures of pain and postoperative pain control variables (secondary outcomes). Patients (n = 52) with disabling osteoarthritis (OA) pain undergoing total hip arthroplasty (THA) were included. Quantitative sensory testing (QST) was performed preoperatively on the day of surgery to evaluate pain objectively. Clinical data, as well as measures of sleep quality and pain, were obtained preoperatively and longitudinally over a 6-month period. Results: Preoperatively, sleep disturbance (i.e., PSQI score >5) occurred in 73.1% (n = 38) of THA patients, and pain severity was high (BPI pain severity 5.4 ± 1.3). Regression models, adjusting for relevant covariates, showed that preoperative PSQI score predicted pain severity 6 months postoperative (β = 0.091 (95% CI 0.001–0.181), p =.048, R2 = 0.35). Poor sleep quality was associated with increased pressure pain sensitivity and impaired endogenous pain inhibitory capacity (R2 range 0.14–0.33, all p's < 0.04). Moreover, preoperative sleep disturbance predicted increased opioid treatment during the first 24 hr after surgery (unadjusted β = 0.009 (95% CI 0.002–0.015) mg/kg, p =.007, R2 = 0.15). Conclusions: Preoperative sleep disturbance is prevalent in THA patients, is associated with objective measures of pain severity, and independently predicts immediate postoperative opioid treatment and poorer long-term pain control in patients who have undergone THA. Significance: Poor sleep quality and impaired sleep continuity are associated with heightened pain sensitivity, but previous work has not evaluated whether preoperative sleep problems impact long-term postoperative pain outcomes. Here, we show that sleep difficulties prior to total hip arthroplasty adversely predict postoperative pain control 6 months after surgery. Given sleep difficulties robustly predict pain outcomes, targeting and improving sleep may have salutary effects on postoperative pain reports and management. (Less)

Background Volumetric laser endomicroscopy (VLE) allows for near-microscopic imaging of the superficial esophageal wall and may improve detection of early neoplasia in Barrett’s esophagus (BE). Interpretation of a 6-cm long, circumferential VLE “full scan” may however be challenging for endoscopists. We aimed to evaluate the accuracy of VLE experts in correctly diagnosing VLE full scans of early neoplasia and non-dysplastic BE (NDBE). Methods 29 VLE full scan videos (15 neoplastic and 14 NDBE) were randomly evaluated by 12 VLE experts using a web-based module. Experts were blinded to the endoscopic BE images and histology. The 15 neoplastic cases contained a subtle endoscopically visible lesion, which on endoscopic resection showed high grade dysplasia or cancer. NDBE cases had no visible lesions and an absence of dysplasia in all biopsies. VLE videos were first scored as “neoplastic” or “NDBE.” If neoplastic, assessors located the area most suspicious for neoplasia. Primary outcome was the performance of VLE experts in differentiating between non-dysplastic and neoplastic full scan videos, calculated by accuracy, sensitivity, and specificity. Secondary outcomes included correct location of neoplasia, interobserver agreement, and level of confidence. Results VLE experts correctly labelled 73 % (95 % confidence interval [CI] 67 % – 79 %) of neoplastic VLE videos. In 54 % (range 27 % – 66 %) both neoplastic diagnosis and lesion location were correct. NDBE videos were consistent with endoscopic biopsies in 52 % (95 %CI 46 % – 57 %). Interobserver agreement was fair (kappa 0.28). High level of confidence was associated with a higher rate of correct neoplastic diagnosis (81 %) and lesion location (73 %). Conclusions Identification of subtle neoplastic lesions in VLE full scans by experts was disappointing. Future studies should focus on improving methodologies for reviewing full scans, development of refined VLE criteria for neoplasia, and computer-aided diagnosis of VLE scans.

BACKGROUND: Sleep disturbance, common in cancer survivors, is associated with obesity, eating behaviors and metabolism, and may impact weight loss treatment outcomes. Weight loss promotion in breast cancer survivors is important because it can potentially decrease cancer recurrence. We have previously demonstrated the efficacy of a behavioral weight loss (BWL) intervention for overweight/obese breast cancer survivors in the POWER-remote breast cancer trial. In the current study we aimed to evaluate the impact of baseline sleep on weight outcomes at 6 and 12 months. We hypothesized that participants with poor sleep at baseline will lose significantly less weight. METHODS: Women with a history of stage 0-III breast cancer, who completed local therapy and chemotherapy, with a body mass index ≥25 kg/m2 were randomized to a self-directed approach or the 12-month POWER-remote intervention, a BWL intervention consisting of telephone-based coaching, online educational materials and tracking of diet, physical activity and weight. Participants completed demographic questionnaires at baseline, and patient-reported outcomes (PROs) at baseline, 6 and 12 months, including the 6-item NIH PROMIS Adult Sleep Disturbance Version 1.0 Short Form, assessing sleep quality, depth, and restoration over the last week. Weight was measured at baseline, 6 and 12 months and % total weight loss (%TWL) was calculated from baseline weight. Those with poor sleep were defined as having a sleep T-score >55, and associations between sleep scores and change in weight at 6 and 12 months were made using a linear regression model, while adjusting for baseline weight. Fisher’s exact test was also used to compare the number of patients who had 5% weight-loss between sleep groups. RESULTS: A total of 48 women with early stage breast cancer received BWL. Those with poor sleep in the BWL group (n= 16) lost significantly less weight than those with normal sleep in the BWL group (n=32) at both 6 (-4.06% vs -6.77% TWL, p>0.05) and 12 months (-3.87% vs -7.54% TWL, p>0.05), respectively. Similar findings were seen in poor sleepers in the BWL group and attaining 5% weight loss at 6 (p>0.05) and 12 months (p>0.05). There were no significant differences in weight loss outcomes among those in usual care. CONCLUSION: Breast cancer survivors receiving the weight loss intervention who reported normal sleep at baseline had double the weight loss than those with sleep disturbance at 12 months (-7.54% vs -3.87%). While this is not statistically significant, it is clinically significant and leaves room for further study. These results suggest that sleep may affect weight loss. Updated data, including comparison with control group and analyses by weight loss irrespective of arm, will be reported at the conference. Further studies are need to evaluate the association between baseline sleep and weight loss, and determine if interventions that detect and treat underlying sleep disturbance may augment behavioral interventions for weight loss. FUNDING: Breast Cancer Research Foundation, Cigarette Restitution Fund Table 1: Weight Loss Summary in BWL group based on Sleep DisturbanceVariablesPoor sleep (T-score >55)Normal sleep (T-Score 0.05Percent change in weight from BL to 12mo. - Mean (SD)-3.87 (7.29)-7.54 (7.91)p>0.05 Citation Format: Jennifer Y Sheng, Amanda K Montanari, Amanda L Blackford, David D Lim, Cesar A Santa-Maria, Vered Stearns, Michael T Smith, Janelle W Coughlin. The impact of sleep on weight loss in overweight or obese breast cancer survivors [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD11-04.

Purpose The purpose of this paper is to highlight the difficulties in identifying adults with autism spectrum disorder (ASD) and to illustrate the consequences of late diagnoses in forensic settings. Design/methodology/approach This paper presents an overview of the literature relevant to the topic and presents the details of three clinical cases. Findings Delayed diagnosis is not uncommon in forensic services. Cases may remain unidentified for considerable periods despite being under evaluation from clinical teams. Diagnosis in forensic settings is challenged by case complexity. Barriers to prompt diagnosis include time, resources and clinical competency. Timely diagnosis may lessen the risk of future offences, improves clinical risk management and can bring direct benefits to those with the condition. Originality/value This is the first case series which explores the issue of late diagnosis in forensic settings. The illustration of the extent to which a diagnosis can be missed may prompt clinicians to review and identify missed cases. The discussion of the issue may also support services to review their approach to screening and diagnosis of ASD.

Porphyromonas gingivalis is a Gram-negative anaerobic periodontal microorganism strongly associated with tissue-destructive processes in human periodontitis. Following oral infection with P. gingivalis, the periodontal bone loss in mice is reported to require the engagement of Toll-like receptor 2 (TLR2). Serine-glycine lipodipeptide or glycine aminolipid classes of P. gingivalis engage human and mouse TLR2, but a novel lipid class reported here is considerably more potent in engaging TLR2 and the heterodimer receptor TLR2/TLR6. The novel lipid class, termed Lipid 1256, consists of a diacylated phosphoglycerol moiety linked to a serine-glycine lipodipeptide previously termed Lipid 654. Lipid 1256 is approximately 50-fold more potent in engaging TLR2 than the previously reported serine-glycine lipid classes. Lipid 1256 also stimulates cytokine secretory responses from peripheral blood monocytes and is recovered in selected oral and intestinal Bacteroidetes organisms. Therefore, these findings suggest that Lipid 1256 may be a microbial TLR2 ligand relevant to chronic periodontitis in humans.

Objective Esophageal aperistalsis has been considered a relative contraindication for lung transplant because of a higher risk of allograft dysfunction secondary to reflux and aspiration induced by poor esophageal clearance. We previously reported that esophageal motility improves in some patients after lung transplant. We reviewed the clinical course of lung transplant recipients diagnosed with an aperistaltic esophagus on pretransplant testing. Methods We identified patients diagnosed with pretransplant aperistaltic esophagus on high-resolution manometry who underwent lung transplant. Recipients with normal esophageal motility before lung transplant were used as the propensity score–matched control group. High-resolution manometry was repeated after lung transplant, and patients with aperistalsis were further divided into 2 subgroups: improved esophageal peristalsis and nonimproved peristalsis (ie, persistent aperistalsis after lung transplant). Results Esophageal aperistalsis was seen in 31 patients (mean age, 59.0 years; 21 men). The 1-, 3-, and 5-year post–lung transplant survivals in the aperistalsis group were 80.6%, 51.2%, and 34.9%, respectively, which was significantly lower than in the control group (90.3%, 73.4%, and 58.8%, respectively; P = .038). Post–lung transplant high-resolution manometry was performed for 29 patients in the aperistalsis group, 19 of whom demonstrated improved esophageal motility (65.5%). The 1-, 3-, and 5-year survivals after lung transplant of patients with recovery of peristalsis were similar to those of the control group (89.5%, 65.0%, and 48.8%, respectively; P = 1.000), whereas the nonimproved peristalsis group had lower survival (80.0%, 36.0%, and data unavailable, respectively; P = .012). Conclusions Esophageal aperistalsis is not necessarily a contraindication for lung transplant. Improved peristalsis can be expected in up to two-thirds of these patients and is associated with good outcomes.

Background Post-operative nausea and vomiting (PONV) is often encountered following corrective scoliosis surgery in children, frequently attributed to high-dose opiate administration. PONV is a frequent cause of prolonged hospital stay. Mechanisms related to transient partial duodenal compression by narrow angulation of the superior mesenteric artery (SMA) and aorta following scoliosis surgery are poorly understood and might be implicated in PONV. This study investigates relationships between biomechanical anatomic variations of the SMA and aorta, and its relationship with clinically significant PONV following scoliosis surgery in children. Methods Children undergoing elective spinal arthrodesis for adolescent idiopathic scoliosis were assessed by preoperative abdominal ultrasound and spinal X-ray prior to surgery. Post-operative assessment of clinically significant PONV is compared to preoperative imaging and clinical variables. Results Thirteen patients (11 female and two male), with a mean age of 14 years and 1 month were included. Five patients (38.5%) developed clinically significant PONV. A significant association was observed between the coronal aorto-mesenteric orientation and PONV (P = 0.035). Of the five patients who developed PONV, two had direct coronal angulation of the SMA, one had left angulation and two had right angulation. Patients with significant PONV had narrower aorto-mesenteric distances which approached significance (P = 0.06). No other preoperative variable reached significance. Conclusion Patients with coronal aorto-mesenteric orientation preoperatively appear at greater risk of developing significant PONV following scoliosis surgery, independent of opiate requirements, prompting consideration of transient partial duodenal obstruction as an important factor in the mechanisms of PONV. A coronal aorto-mesenteric orientation theory (CAMOT) is proposed to explain this biomechanical vascular 'scissor'.

Background There are emerging data indicating that sleep disturbance may be linked with an increase in opioid use. The majority of sickle cell disease (SCD) patients experience sleep disturbances, which can elevate pain severity and pain catastrophizing, both of which are important predictors of opioid consumption. Purpose We conducted a preliminary investigation on the association between previous night sleep disturbance and short-acting opioid use, as well as the potential mediating roles of pain severity and pain catastrophizing. Because sex is associated with sleep disturbance, pain-related experiences, and opioid use, we also explored the potential moderating role of sex. Methods Participants were 45 SCD patients who were prescribed opioids. For 3 months, sleep diaries were collected immediately upon participants’ awakening. Daily pain severity, pain catastrophizing, and prescription opioid use measures were collected before bedtime. Results Multilevel structural equation modeling revealed that wake time after sleep onset (WASO) during the previous night (Time 1) predicted greater short-acting opioid use during the next day (Time 2). Pain severity and pain catastrophizing measured during the next day (Time 2) also mediated the association between the two. Sex moderation analysis showed that the positive association between WASO and pain severity was largely driven by women. Conclusion These findings provide some preliminary evidence as to the mechanism linking sleep continuity disturbance and opioid requirement in SCD patients. Future studies should replicate and extend these findings with clearer temporal information and employing more refined measures of sleep continuity and prescription opioid use in a larger sample.

INTRODUCTION: Bronchiolitis obliterans syndrome (BOS), a subtype of chronic lung allograft dysfunction, is quite common, with up to half of all lung recipients developing BOS within five years of transplantation. Preventive efforts are aimed at alleviating known risk factors of BOS development, while the primary goal of treatment is to delay the irreversible, fibrotic airway changes and progressive loss of lung function. AREAS COVERED: This narrative review will briefly discuss the updated definition, clinical presentation, pathogenesis, risk factors, and survival after BOS, while paying particular attention to the salient evidence for optimal preventive strategies and treatments based on investigations in the modern era. EXPERT OPINION: Future translational research focused on further characterizing the complex interplay between immune and non-immune mechanisms mediating chronic lung rejection is the first step towards mitigating risk of allograft injury, improving early disease detection with non-invasive biomarkers, and ultimately, developing an effective, targeted therapy that can extend the life of the lung allograft.

This clinical policy from the American College of Emergency Physicians addresses key issues in opioid management in adult patients presenting to the emergency department. A writing subcommittee conducted a systematic review of the literature to derive evidence-based recommendations to answer the following clinical questions: (1) In adult patients experiencing opioid withdrawal, is emergency department-administered buprenorphine as effective for the management of opioid withdrawal compared with alternative management strategies? (2) In adult patients experiencing an acute painful condition, do the benefits of prescribing a short course of opioids on discharge from the emergency department outweigh the potential harms? (3) In adult patients with an acute exacerbation of noncancer chronic pain, do the benefits of prescribing a short course of opioids on discharge from the emergency department outweigh the potential harms? (4) In adult patients with an acute episode of pain being discharged from the emergency department, do the harms of a short concomitant course of opioids and muscle relaxants/sedative-hypnotics outweigh the benefits? Evidence was graded and recommendations were made based on the strength of the available data.

The mainstay of treatment in advanced cancer pain is opioids; however, non-opioid medications such as acetaminophen continue to be included in guidelines despite a lack of clear, convincing evidence for their use. The aim of our study was to determine if acetaminophen improves pain control or reduces opioid utilization in hospitalized patients receiving strong opioids for cancer pain managed by the palliative care consult service (PCCS). We carried out at single-center retrospective cohort study of 194 adult cancer patients seen by the PCCS and who received strong opioids. Patients who received acetaminophen during their admission were compared to those who did not. The primary outcome was a 30% reduction in average daily pain score from admission to discharge using a numeric rating scale. There was no difference between groups in achieving a 30% reduction in pain (35.8% vs. 35.4%, adjusted odds ratio 0.87, 95% confidence interval [CI] 0.46 to 1.63). Acetaminophen was associated with a longer LOS (8 days vs. 6 days, adjusted relative risk 1.67, 95% CI 1.30 to 2.15). In this study of cancer patients receiving strong opioids, acetaminophen use was not associated with improved pain control or reduced opioid utilization, but was associated with a greater LOS.

Background The coronavirus disease 2019 (COVID-19) pandemic has infected more than 13 million people on a global scale and claimed more than half million deaths across 213 countries and territories. While the focus is currently on recovery from the pandemic, the disease has significantly changed the way we practice medicine and neurosurgery in New York City and the United States. Apart from the emergency cases, several health systems across the country have similarly started to perform elective surgeries. Although COVID-19 screening and testing guidelines have been proposed and adopted by many hospitals, these may not adequately protect the operating room personnel who are in proximity to the patient for prolonged periods. There are concerning reports of especially high transmission rates of COVID-19 in transmucosal head and neck procedures conducted by otolaryngologists and neurosurgeons, despite attempts at wearing what constitutes appropriate personal protective equipment. Methods Here, we describe a simple technique of additional draping that can be used for all cranial, endonasal, spinal, and neurointerventional cases to limit the transmission of coronavirus. Results The proposed technique offers a simple, commonly available, cost-effective alternative that avoids the use of additional retractor systems. Moreover, this technique can be used in all neurosurgical procedures. Conclusions With the rising concerns regarding airborne spread of the virus, we expect that these precautions will prove highly useful as we enter the recovery phase of this pandemic and hospitals attempt to prevent a return to widespread infection. In addition, its availability and cost effectiveness make this technique especially attractive to practical use in centers with limited resources.

Background An estimated 38% of US adults are obese. Obesity is associated with socioeconomic disparities and increased rates of comorbidities, and is a known risk factor for development of pancreatic cancer. As a fourth leading cause of death in the United States, pancreatic cancer is commonly treated with a pancreatico-duodenectomy (PD), or Whipple procedure. Data regarding the effects of obesity on post-operative complication rate primarily comes from specialized centers, however the results are mixed. Our aim is to elucidate the effects that obesity has on outcomes after PD for pancreatic head cancer using a national prospectively maintained clinical database. Method The 2010–2015 American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) Participant Use Files (PUF) were used as the data source. We identified cases in which PD was performed (CPT code 48150) in the setting of a postoperative diagnosis of pancreatic cancer (ICD9 code 157.0). We excluded cases that had emergency admissions, BMI ≤18.5 kg/m2, intraoperative wound classification of III or IV, and disseminated cancer. Cases with missing BMI, preoperative albumin, operative time, LOS data were also excluded. Multiple imputation for missing sex, race, functional status, and ASA classification using chained equations was performed.16 Patients that had BMI ≥30 kg/m2 were considered obese, and patients with BMI Results 3484 patients underwent pancreaticoduodenectomy for pancreatic cancer. 860 patients were identified as obese. Propensity score analysis was performed matching age, sex, race, functional status, presence of dyspnea, diabetes, hypertension, acute renal failure, dialysis dependence, ascites, steroid use, bleeding disorders, history of chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), weight loss, American Society of Anesthesiologists (ASA) classification, and preoperative albumin levels. After matching, obese patients had higher risk of 30-day postoperative complications compared to control, including organ space wound infections (OR 1.38, 95% CI 1.07–1.79, p = 0.0128), returning to the operating room (OR 1.39, 95% CI 1.01–1.91, p = 0.0461), failure to extubate for greater than 48 h (OR 1.60, 95% CI 1.09–2.34, p = 0.0153), death (OR 1.68, 95% CI 1.01–2.78, p = 0.0453), septic shock (OR 2.22, 95% CI 1.46–3.38, p = 0.0002), pulmonary embolism (OR 2.42, 95% CI 1.07–5.45, p = 0.0332), renal insufficiency (OR 2.67, 95% CI 1.33–5.38, p = 0.0058). Sensitivity analysis yielded similar results with the exception of risk for return to the operating room, death, and pulmonary embolism, P > .05. Conclusion In this large observational study using a national clinical database, obese patients undergoing PD for head of pancreas cancer had increased risk of postoperative complications and mortality in comparison to controls.

The optimal medical therapy early after left atrial appendage closure (LAAC) is not well defined. A regimen that prevents thromboembolic events and device-related thrombus (DRT) while minimizing bl...

Background/Aims Barrett’s esophagus (BE) is characterized by intestinal metaplasia in the distal esophagus. The aims of this study are to: (1) Compare baseline distal esophageal impedance (DEI) using high-resolution esophageal manometry with impedance (HREMI) in patients with BE, esophagitis, and healthy volunteers and (2) Correlate length of low impedance on HREMI in patients with BE to the length of endoscopic BE. Methods Patients with BE or esophagitis who underwent HREMI were included. Ten volunteers had HREMI. Baseline DEI was calculated from HREMI using the landmark segment. In patients with BE, the impedance was plotted to measure the extent of plotted low impedance (PLI) and visual low impedance (VLI). Lengths of VLI and PLI were correlated to endoscopic length of BE by Prague score. Results Forty-five patients were included (16 BE; 19 esophagitis; 10 volunteers). BE patients had lower baseline DEI at the first, second, and third sensors above the lower esophageal sphincter (mean ± SEM: 1.37 ± 0.45, 0.97 ± 0.27, and 0.81 ± 0.20) compared to volunteers (8.73 ± 0.60, 8.20 ± 0.73, and 6.94 ± 0.99; P < 0.001). Baseline DEI was lower in BE than esophagitis patients (2.98 ± 0.65, 2.49 ± 0.56, and 2.01 ± 0.51) at the first, second, and third sensors (P < 0.052 for second and third sensors); ie, BE < esophagitis < controls. PLI and VLI had a stronger correlation to circumferential score (r2 = 0.84 and 0.83) than maximal score (r2 = 0.76 and 0.68). Conclusions Baseline DEI is lower in BE compared with esophagitis and healthy volunteers. The length of low impedance correlates to the endoscopic extent of BE. Thus, impedance values during HREMI may help suggest the presence and extent of BE or esophagitis. (J Neurogastroenterol Motil 2020;26:344-351)

Background Wide area transepithelial sampling with three-dimensional computer-assisted analysis (WATS3D) is an adjunct to the standard random 4-quadrant forceps biopsies (FB, "Seattle protocol") that significantly increases the detection of Barrett's esophagus (BE) and associated neoplasia in patients undergoing screening or surveillance. Aims To examine the cost-effectiveness of adding WATS3D to the Seattle protocol in screening patients for BE. Methods A decision analytic model was used to compare the effectiveness and cost-effectiveness of two alternative BE screening strategies in chronic gastroesophageal reflux disease patients: FB with and without WATS3D. The reference case was a 60-year-old white male with gastroesophageal reflux disease (GERD). Effectiveness was measured by the number needed to screen to avert one cancer and one cancer-related death, and quality-adjusted life years (QALYs). Cost was measured in 2019 US$, and the incremental cost-effectiveness ratio (ICER) was measured in $/QALY using thresholds for cost-effectiveness of $100,000/QALY and $150,000/QALY. Cost was measured in 2019 US$. Cost and QALYs were discounted at 3% per year. Results Between 320 and 337 people would need to be screened with WATS3D in addition to FB to avert one additional cancer, and 328-367 people to avert one cancer-related death. Screening with WATS3D costs an additional $1219 and produced an additional 0.017 QALYs, for an ICER of $71,395/QALY. All one-way sensitivity analyses resulted in ICERs under $84,000/QALY. Conclusions Screening for BE in 60-year-old white male GERD patients is more cost-effective when WATS3D is used adjunctively to the Seattle protocol than with the Seattle protocol alone.

Lung transplant recipients (LTxRs) with acute rejection (AR) and chronic rejection (bronchiolitis obliterans syndrome [BOS]) induce circulating exosomes known to contain donor human leukocyte antigens and lung-associated self-antigens. Here, we sought to identify proteomic signatures in circulating extracellular vesicles (EVs) that differentiate LTxRs in 4 groups: stable, AR, BOS, or respiratory viral infection (RVI). EVs were isolated from plasma from patients in each group via ultracentrifugation. EV protein cargoes were prepared for shotgun proteomics using liquid chromatography–tandem mass spectrometry. We identified 2 unique proteins for AR, 4 for RVI, 24 for BOS, and 8 for stable LTxRs. Differential analysis of AR, BOS, RVI, and stable proteins identified significantly deregulated proteins (p < 0.05, log2(fold change) > ±1) in each condition (31, 2, and 2, respectively). EVs from LTxRs with AR contained proteins involved in immunoglobulin, complement regulation, coagulation, and innate and adaptive immune response pathways. EVs from LTxRs with BOS revealed enriched immunoglobulin receptors and a carboxypeptidase N catalytic chain. EVs from LTxRs with RVI had an enriched macrophage-stimulating factor. We found unique signatures in LTxRs with AR, BOS, and RVI, highlighting complex immune mechanisms underlying lung allograft rejection. Proteomic signatures in LTxRs’ circulating EVs provided insights into immunological mechanisms of graft rejection and RVI.

Cisplatin is a platinum-based chemotherapy compound effective against a variety of cancers. However, it can cause increased reactive oxygen species (ROS) production in auditory and vestibular tissue leading to permanent hearing and balance loss. The amino acid, L-serine, has been shown to reduce ROS in some tissue types. In this project, we first investigated whether L-serine could reduce cisplatin-mediated ROS generation in zebrafish utricular tissue culture using spectrophotometry and the fluorescent ROS detector dye, H2DCFDA. Then, we examined whether L-serine could prevent the effect of cisplatin against cellular viability in the mouse auditory hybridoma cell line, HEI-OC1, using the spectrophotometric (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. As a final step, we used H2DCFDA dye and flow cytometry analysis to determine if L-serine could counteract the effect of cisplatin on ROS production in this cell line. We found that cisplatin and L-serine treatment may influence ROS production in utricular tissue. Further, although L-serine did not counteract the effect of cisplatin against HEI-OC1 cellular viability, the amino acid did prevent the platinum compound's effect to increase ROS in these cells. These results suggest that L-serine may act in auditory and vestibular tissues as an effective protectant against cisplatin-mediated toxicity.

Type I interferon (IFN) drives pathology in systemic lupus erythematosus (SLE) and can be tracked via IFN-inducible transcripts in blood. Here, we examined whether measurement of circulating proteins, which enter the bloodstream from inflamed tissues, also offers insight into global IFN activity. Using a novel protocol we generated 1,132 aptamer-based protein measurements from anti-dsDNApos SLE blood samples and derived an IFN protein signature (IFNPS) that approximates the IFN 21-gene signature (IFNGS). Of 82 patients with SLE, IFNPS was elevated for 89% of IFNGS-high patients (49/55) and 26% of IFNGS-low patients (7/27). IFNGS-high/IFNPS-high patients exhibited activated NK, CD4, and CD8 T cells, while IFNPS-high only patients did not. IFNPS correlated with global disease activity in lymphopenic and non-lymphopenic patients and decreased following type I IFN neutralisation with anifrolumab in the SLE phase IIb study, MUSE. In summary, we developed a protein signature that reflects IFNGS and identifies a new subset of patients with SLE who have IFN activity.

BackgroundThis article describes a novel patient care algorithm which provides a Role 1 (R1) medic with a structured approach to delivering prolonged field care (PFC) in a resource-limited environment. PFC is a vital component of the operational patient care pathway providing the continuum of care from completion of a primary survey to the delivery to hospital care. Future operational environments are likely to have more fragile or extended lines of communication, potentially delaying evacuation to hospital care. This delay may lead to increases in patient morbidity and mortality. Effective PFC offers an opportunity to improve patient outcomes and help mitigate against this risk.MethodsAn initial prototype model of a PFC care process was developed using existing hospital-based guidance. A series of medical and trauma vignettes and best available evidence were used to refine the algorithm.ResultsThe algorithm has been designed be used in conjunction with patient specific clinical guidance making the approach generalisable for all patient groups. For UK military, clinical guidance is provided by clinical guidelines for operations. The algorithm can be downloaded into a convenient format to be used on mobile devices or printed as an aide memoire.

The aim of this study was to elucidate the outcomes of percutaneous internal ring suture (PIRS) technique for inguinal hernia repair augmented with thermal peritoneal injury compared to open inguinal hernia repair (OHR) in a large population of contemporary pediatric patients. Thermal injury with PIRS has been shown to reduce recurrence in animal models and is increasingly being incorporated into clinical practice. Retrospective review of all PIRS procedures and OHR between Jan-2017 to Sept-2018 was performed. Data regarding patient characteristics, characteristics of the hernia, operative details, postoperative complications, and recurrence were collected. Non-parametric tests were used and p

Background Idiopathic spinal cord herniation is a disorder in which the spinal cord herniates through a dural defect. We present a case in which both the standard surgical method and a salvage method failed. Case Description A 36-year-old man presented with 2 years of progressive numbness and proximal hip flexion weakness of both lower extremities. Magnetic resonance imaging of the thoracic spine was suggestive for a ventral spinal cord herniation at the T6/7 level. He was initially treated with reduction of his cord herniation, placement of a ventral sling of collagen matrix over the dural defect to prevent re-herniation, with a laminoplasty. He developed a blood-pressure-dependent paraparesis that did not recover despite a return to the operating room (OR) for removal of the laminoplastic bone flap. He was again taken to the OR, the sling was removed and we enlarged the ventral dural defect rostrally and caudally to prevent strangulation of the hernia as described by Watanabe. Though in the short term he was able to recover and transfer to physical therapy, after going home he developed lower extremity weakness and low-pressure headaches. Magnetic resonance imaging showed a ventral epidural cerebrospinal fluid pocket retropulsing the spinal cord, as well as pockets of ventral cerebrospinal fluid collections remote from the surgery site. The patient returned to the OR and the initial surgery with the ventral sling was re-performed with resolution of the headaches; the patient was neurologically stable and transferred to rehabilitation. Long-term he developed left intercostal pain at the level of the surgery without radiological correlate. Conclusions In this patient there was no single satisfactory surgical treatment of his ventrally herniated spinal cord—partly related to the herniated component of the cord acting as a mass within a narrow canal at the apex of the thoracic kyphosis. We encountered previously unreported complications of the ventral defect widening technique of surgical treatment.

Pulmonary vein obstruction is a rare condition, most commonly reported following pulmonary vein catheter ablation for atrial arrhythmia. This novel technique for treatment of pulmonary venous obstruction has the advantage of utilizing an autologous vascularized flap with intact endothelium for reconstruction of the pulmonary vein and to prevent restenosis., Schematic of the pulmonary vein reconstruction. A vascularized flap from the right atrium was mobilized and gently rotated and sutured to the ventral surface of the pulmonary vein creating a non‐obstructive path through the pulmonary vein and into the left atrium. Autologous pericardium was used to reconstruct the lateral portion of the SVC and the proximal lateral part of the right atrium to prevent SVC stenosis. SVC, superior vena cava.

Epithelial-mesenchymal transition (EMT) has been implicated to play a role in chronic lung allograft dysfunction (CLAD). Liver kinase B1 (LKB1), a tumor suppressor gene, can regulate EMT. However, its role in CLAD development following lung transplantation remains unknown. Using qRT-PCR, biopsies from lung transplant recipients with bronchiolitis obliterans syndrome (BOS) demonstrated significant downregulation of LKB1 (p = .0001), compared to stable biopsies. To determine the role of LKB1 in EMT development, we analyzed EMT in human bronchial epithelial cell line BEAS-2B. Knockdown of LKB1 by siRNA significantly dysregulated mesenchymal markers expression in BEAS-2B cells. Following incubation of human primary bronchial epithelial cell or BEAS-2B cells with exosomes isolated from BOS or stable lung transplant recipients, LKB1 expression was inhibited when incubated with BOS-exosome. Incubation with BOS-exosomes also decreased LKB1 expression and induced EMT markers in air-liquid interface culture method. Our results provide novel evidence that exosomes released from transplanted lungs undergoing chronic rejection are associated with inactivated tumor suppressor gene LKB1 and this loss induces EMT leading to the pathogenesis of CLAD following human lung transplantation.

Introduction Existing data demonstrate reduced delta power during sleep in chronic pain and depressed patients. However, there has been little examination of the relationship between delta power and next-day reports of pain. We tested the extent to which nocturnal (during the concurrent sleep period) and daytime pain reports are associated with delta power during sleep, as well as the extent to which this association is moderated by depressive symptoms. We hypothesised that reduced delta power and SWS would be associated with increased pain, pain catastrophising, and pain sensitivity. Methods 149 female participants with insomnia and temporomandibular joint pain (TMD) were recruited. We examined nocturnal and daytime measures of pain (pain severity, average pain), pain catastrophizing, and objective pain sensitivity (obtained through quantitative sensory testing (QST)), and calculated relative nocturnal delta (0.5-3.4 Hz) power using polysomnography. We fit linear regression models correcting for depressive symptom severity, age, and total sleep time, and further examined the moderating effect of depression severity on these measures. Results reduced delta power was associated with increased average nocturnal pain (Unstandardized β = -17.67, p= 0.02), morning pain (Unstandardized β = -15.67, p=0.02), and average next-day pain (Unstandardized β = -16.74, p= 0.03). Depression severity did not moderate these relationships. Delta power was not significantly associated with objective pain-sensitivity, nocturnal, or daytime pain catastrophising. However the association between nocturnal pain catastrophising and delta power was moderated by depressive symptom severity (p = 0.04). Simple slopes analysis revealed that when participants had low depressive symptoms ( Discussion These findings demonstrate that delta power during sleep is associated with both nocturnal and daytime experience of pain in patients with TMD. In patients with TMD and low depressive symptoms, reduced delta power was associated with increased nocturnal pain catastrophising.

Aim Persistent pain after groin hernia repair is a major health problem. Sleep disturbance is associated with heightened pain sensitivity. The main objective of this study was to examine the role of sleep disturbance in the development and long-term maintenance of chronic postherniorrhaphy inguinal pain (CPIP), with exploration of sex differences. Material and Methods From 2012-2017, a national cohort of patients with prior groin hernia repair (n = 2084; 45.8% females) were assessed for the development of CPIP 12 months after surgery. Patients then underwent long-term (median 5.0 years) follow-up to evaluate the contribution of sex and sleep disturbance on the maintenance of CPIP. Associations between pre- and postoperative sleep problems (assessed at long-term follow-up) and CPIP were tested using logistic regression. Results Females had higher rates of CPIP with negative impact on daily activities 12 months after surgery as compared to males (14.6 vs 9.2%, p Conclusions Sleep disturbance may increase the risk for CPIP, and contribute to maintenance of postsurgical pain. Females are at heightened risk for CPIP as compared to males. Given the robust associations between sleep disturbance and CPIP, interventions which consolidate and promote sleep, especially in females, may improve long-term pain control.

Background: Sickle cell trait (SCT) has received attention as a cause of death in college athletes, leading to mandatory lab SCT screening in National Collegiate Athletic Association (NCAA) athletes. High-school athletes are commonly screened by self-report. There are no known studies for evaluating whether this method is effective as a screening tool. Hypothesis: The local prevalence rate of SCT as self-reported on the preparticipation evaluation (PPE) forms would be lower than the national accepted average. Methods: PPE forms from the Department of Orthopedics and Rehabilitation of the University of Florida (UF) were reviewed between January 1, 2017, and April 30, 2018. The Florida High School PPE form includes a yes/no question to assess the diagnosis of SCT. The prevalence established by self-report was then compared with the national prevalence for SCT in the comparable race/ethnicity groups reported by the CDC. The response rate of SCT questions was also compared to other common cardiac screening questions. Results: A total of 401 forms were reviewed. Six (1.5%) students answered “yes,” 351 answered “no,” and 44 left the SCT question blank. All six athletes who self-reported “yes” were Black and made up 3.7% of the 162 known Black respondents. This self-report rate for Black/African Americans was well below the expected 7.3% described by the CDC. Response rates were also lower than the comparable cardiac screening questions. Conclusions: Self-report SCT status rates are lower than the accepted prevalence in a similar population. Significant inconsistencies in reporting were also determined. Clinical relevance: This is a rare study to evaluate the self-reported prevalence of SCT in high-school athletes. Below average reporting of SCT and inconsistency in completion of the forms increase the concern for accuracy and effectiveness of current high-school SCT screening methods relying on self-report.

Purpose Leber's hereditary optic neuropathy (LHON) is the most common mtDNA optic neuropathy. It most frequently causes dense bilateral central scotomas that are often characterized in clinical studies by Humphrey visual field testing (HVF) using a stimulus size III. This provides numerical quantification of the visual field defect using the mean deviation. However, this size III testing strategy has limitations. We used stimulus size V to monitor these patients and evaluated intertest variability and dynamic range to determine the testing reliability and reproducibility. Methods This was a longitudinal retrospective cohort study comparing Stimulus III and Stimulus V HVF of 62 LHON patients who had reached the plateau stage of the disease. The intertest variability and mean defect were calculated for both stimulus sizes for 38 patients. The mean defect for stimulus size V was calculated using an algorithm developed by the University of Iowa Visual Field Reading Center. Results Stimulus size V HVFs had lower inter-test variability as measured by mean defect standard deviation (Z = 169, P < 0.01). The floor effect seen with Stimulus III HVF in LHON, was less pronounced with Stimulus V HVF. The correlation of stimulus size III and V mean defect was strong (r = 0.90, P < 0.01), and a mathematical model was constructed to calculate the Stimulus size V mean defect from the Stimulus size III results (MDstimV = 0.988 x MDStimIII + 1.35, R2 = 0.82 P < 0.01). Conclusions Stimulus size V HVF had lower intertest variability and a better dynamic range than Stimulus size III HVF in LHON patients. This makes the stimulus V HVF a more reliable metric to follow LHON patients especially in clinical trials. The mathematical model presented can be used to generate a Stimulus V equivalent mean defect from Stimulus III HVFs. Translational Relevance Using Stimulus V HVF in LHON patients increases its ability to detect and quantify a response to treatment, making it a useful metric for future LHON clinical trials and the clinical setting.

Background Postoperative ileus (POI) is a surgical complication resulting in increased morbidity and length of stay (LOS). Usual care for POI includes bowel rest and gastric decompression. It has been questioned if methylnaltrexone (MNTX), a peripheral opioid antagonist, could be used as treatment for POI. The purpose of this study was to determine if MNTX is effective and safe for POI treatment. Methods This single-center, retrospective cohort study included patients ⩾ 18 years with a POI. Patients with acute colonic pseudo-obstruction, small bowel obstruction, and gastrointestinal malignancy were excluded. The intervention was MNTX administration. The primary outcome was time to ileus resolution. Secondary outcomes included LOS, duration of nasogastric tube, total parenteral nutrition requirement, and incidence of gastrointestinal perforations. Results 110 patients were included in the analysis; 28 received MNTX. Time to ileus resolution was 9.9 days for the MNTX group and 11.4 days for the control group ( P = .38). Duration of gastric decompression was 4.6 days for the MNTX group and 4.2 days for the control group ( P = .71). Length of stay was 19.9 days for the MNTX group and 19.7 days for the control group ( P = .96). The percentage of TPN requirement was 17.9% in the MNTX group and 22.0% in the control group ( P = .65). No gastrointestinal perforations were observed in either group. Conclusion For the treatment of POI, MNTX did not significantly reduce time to resolution of ileus, LOS, duration of gastric decompression, or TPN requirements. However, no gastrointestinal perforations were seen, indicating that MNTX may be safely used in these patients.

BACKGROUND There has been a 291% relative increase in congenital syphilis (CS) cases in the United States from 2015 to 2019. Although the majority of affected fetuses/infants are stillborn or are asymptomatic, a subset is born with severe clinical illness. We describe a series of severe CS cases in the neonatal intensive care unit. METHODS Retrospective review of infants with CS, admitted to the Duke Intensive Care Nursery from June 2016 to February 2020. We recorded birthweight, gestational age, medications, procedures, diagnoses, laboratory data and outcomes. Severe symptoms included: birth depression, hypoxic ischemic encephalopathy (HIE), disseminated intravascular coagulopathy and/or persistent pulmonary hypertension (PPHN). RESULTS Seven infants with CS were identified and 5 with severe presentations were included. Median gestational age was 35.1 weeks (range: 29-37 weeks, median: 35 weeks). All infants required intubation at birth, 2 required chest compressions and epinephrine in the delivery room. One had hydrops fetalis and died in the delivery room. All 4 surviving infants had HIE, severe PPHN, hepatitis and seizures. All infants had a positive rapid plasma reagin, and were treated with penicillin G. Maternal rapid plasma reagin was pending for 3 of 5 infants at delivery, and later returned positive; 2 were positive during pregnancy but not treated. Other infectious work-up was negative. Three infants survived to discharge. CONCLUSION CS can be associated with HIE, PPHN and disseminated intravascular coagulopathy in affected infants. Clinicians should have a high index of suspicion and include CS in their differential diagnoses. This study also highlights the importance of adequate treatment of identified cases and screening during the third trimester and at delivery.

Air rage has the potential to threaten the safety of flight crew and passengers. We aimed to describe the occurrence of serious air rage incidents based on a recognised scale of severity, their associated factors and outcomes. A web-based content analysis of written media reports relating to air rage incidents occurring between 2000 and 2020 was conducted. Multiple variables were extracted, including year, flight details, age and nationality of passengers, involvement of flight crew, stage of air journey, flight diversions, presence of intoxication, psychiatric history or fear of flying. A total of 270 passengers were involved in this series of air rage incidents, with 76.2% (n = 204) male. The most frequent age group for unruly passengers was 30–39 years (n = 61). Precipitating factors included alcohol consumption (55.7%, n = 127) and nicotine withdrawal (9.2%, n = 21). Flight diversions were necessitated in 35.5% (n = 81) of cases. The majority (52.6%, n = 120) of air rage incidents were categorised as level 2 on a 4-point scale of severity. The findings of this study will be of interest to the aviation industry and to air passengers and crew. Further research is needed to elucidate the precipitants of air rage. Flight crew training should incorporate early recognition and de-escalation of air rage.

Providing care for people with dementia can be a highly stressful profession. Hair Cortisol Concentration (HCC) levels have been used as a biological marker for HPA axis activity to demonstrate that informal caregivers of people with dementia could be vulnerable to chronic stress. The current study aimed to progress the findings of research conducted with informal caregivers and is the first study to assess HCC as a biological indicator of stress in professional carers of people with dementia. HCC levels were compared between 32 professional dementia caregivers (30 females with a mean age of 45.83 and 2 males with a mean age of 24.50), 45 employees working in higher education settings (42 females with a mean age of 38.66 and 3 males with a mean age of 31.89) and 88 undergraduate students (67 females with a mean age of 24.04 and 21 males with a mean age of 23.91). Analysis of HCC was used to assess HPA axis activity over 1 month. A one-way ANCOVA, with age and gender being included as covariates, revealed that higher levels of HCC were observed in professional dementia carers than people who worked within higher education settings and undergraduate students. The results indicated that professional dementia caregivers may experience stress to the extent of activating biological stress responses at a greater frequency in comparison to people who work in higher education and undergraduate students. However, no significant differences were observed in the perceived stress levels reported across dementia caregivers, professionals working in higher education, and undergraduate students. These findings highlight the requirement to ascertain the extent to which work-related tasks or other factors, specific to the profession of caring for people with dementia, could elicit heightened HPA stress reactivity.

Study Objectives Considerable evidence shows that individuals from marginalized racial/ethnic groups in the United States experience greater rates of sleep disturbance and cardiovascular complications. Because sleep is a modifiable factor that is critically involved in cardiovascular health, improved understanding of the association between sleep and cardiovascular health during early adulthood can prevent cardiovascular disparities. This study examined racial/ethnic differences in cardiovascular function during sleep using heart rate and heart-rate-variability analyses. Methods Participants in this laboratory-based sleep study included healthy, “good sleepers” who were in early adulthood and resided in the United States at the time of participation (14 non-Hispanic Black [NHB; age = 30.9 (6.6), 57% female], 12 Asian [Asian, age = 26.0 (5.2), 42% female], and 24 non-Hispanic white [NHW; age = 24.6 (5.8), 79% female]). Results After adjusting for demographic factors and an apnea–hypopnea index, we found significantly higher heart rate within NREM Stage 2 (N2) (b = −22.6, p = .04) and REM sleep (b = −25.8, p =.048) and lower heart rate variability during N2 sleep (b = −22.6, p = .04) among NHB individuals compared with NHW individuals. Furthermore, NHB and Asian participants demonstrated significantly lower percent of time in slow wave sleep (SWS) compared with NHW participants (NHB: b = −22.6, p =.04; Asian: b = −22.6, p = .04). Individuals’ percent of time in SWS significantly mediated differences in heart rate during N2 (indirect = 0.94, 95% CI [0.03, 2.68]) and REM sleep (indirect = 1.02, 95% CI [0.04, 3.04]). Conclusions Our results showed disparities in sleep-related cardiovascular function in early adulthood that are mediated by SWS. These data suggest targeting sleep health in early adulthood might help reduce cardiovascular disease burden on individuals from marginalized groups.