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Background Atypical arousal regulation may explain slower mean reaction time (MRT) in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder compared with typical development. The locus coeruleus–norepinephrine system (LC-NE) underlies arousal regulation and adapts its activity to the utility of a task. LC-NE tonic and phasic activity are indexed by baseline pupil size (BPS) and stimulus-evoked pupillary response (SEPR). Methods The study assessed pupillometry in ASD (n = 31, 3 female/28 male), attention-deficit/hyperactivity disorder (n = 28, 3 female/25 male), and typically developing control subjects (n = 31, 16 female/15 male) during a visuospatial reaction-time task that manipulates arousal by conditions with low and high task utility. We estimated linear mixed models of BPS, SEPR, and MRT in a per-trial analysis to investigate arousal regulation of task performance. Results Slower MRT occurred in the ASD group compared with the typically developing control group during low-utility conditions while controlling for dimensional ASD and attention-deficit/hyperactivity disorder symptoms. In low-utility conditions, BPS and SEPR were inversely related and both were associated with faster MRT. Increased ASD symptoms across groups were associated with higher BPS during low-utility conditions. Changes in BPS and SEPR between task-utility conditions were smaller in the ASD group. Conclusions Slower visuospatial task performance in ASD is specific to low task utility. Arousal was associated with task performance and showed altered activity in ASD. Increased BPS during low-utility conditions suggested increased LC-NE tonic activity as an ASD symptom marker in children. Smaller changes in BPS and SEPR in ASD indicated attenuated LC-NE activity adaptation in response to high-utility conditions. Slower performance and atypical arousal regulation are probably associated with attenuated LC-NE activity adaptation.

Background: The optimal vasopressor management for septic patients with left ventricular (LV) dysfunction has not been well established, and current evidence is conflicting regarding the optimal vasopressor discontinuation order. Objective: The objective was to evaluate the impact of LV dysfunction on the hemodynamic management of septic shock by assessing the incidence of clinically significant hypotension after vasopressor discontinuation. Methods: In this single-center, retrospective cohort study, adult patients were included if they met the Sepsis-3 definition of septic shock, had LV dysfunction (defined as an ejection fraction ≤40%), and received norepinephrine and vasopressin as the last vasopressors discontinued. The primary outcome was the incidence of clinically significant hypotension following discontinuation of vasopressin or norepinephrine. Clinically significant hypotension was defined as a MAP less than 60 mmHg and the need for either: 1) the reinstitution of the previously discontinued agent at any dosage, 2) the receipt of at least 500 mL of a crystalloid at a rate of at least 500 mL/hour, 3) or the receipt of at least 25 grams of albumin 5% at a rate of at least 25 gram/hour. Secondary outcomes included intensive care unit (ICU) and hospital lengths of stay, and ICU and hospital mortality. Results: A total of 78 patients met inclusion criteria, with 37 patients having vasopressin discontinued first and 41 having norepinephrine discontinued first. Clinically significant hypotension occurred in 28 patients (76%) following the discontinuation of vasopressin, compared to 28 patients (81%) following the discontinuation of norepinephrine (p = 0.61). ICU length of stay was 9 days in the vasopressin discontinued first cohort, compared to 15 days in the norepinephrine discontinued first cohort (p = 0.01). There was no statistically significant difference in mortality observed. Conclusion: The discontinuation order of norepinephrine and vasopressin did not impact the incidence of clinically significant hypotension in patients with septic shock and LV dysfunction, but may influence ICU length of stay, although other factors may have impacted this finding.

Aggressiveness, assertiveness, and sexual deviance: An empirical-quantitative examination of Stoller's perversion theoryObjectives: The main aim of the present study was to empirically examinate the psychodynamic-founded perversion theory of Robert D. Stoller (1979), particularly his assumption of a transformation of aggressive impulses into sexual deviant fantasies due to traumatic experiences. Methods: In the present study different aspects of the theory were examined by using a sample (N = 954) of individuals convicted of sexually motivated offenses who had been clinically and forensically assessed between 2002 and 2018 at the Federal Evaluation Centre for Violent and Sexual Offenders (FECVSO) in the Austrian Prison System. As a part of the psychological testing procedure, German-speaking questionnaires for the assessment of aggressiveness and assertiveness were applied. Results: The results indicated that participants with a diagnosis of paraphilia showed significantly less spontaneously expressed aggression and less social competence compared to individuals without such a diagnosis. Conclusions: The findings of the present study are in line with the core assumptions of Stoller's perversion theory by demonstrating an inverse relationship between the diagnosis of paraphilia and self-reported aggression.

The advent of immunotherapy has revolutionised the treatment of metastatic lung cancer and it has recently been established as the standard of care in the radical treatment of lung cancer. However, immune-related adverse events (IrAEs) frequently occur in patients treated with immunotherapy, and rare IrAEs continue to be identified. We report a case of immunotherapy-induced coeliac disease due to adjuvant durvalumab post-chemoradiotherapy in a patient receiving curative treatment for lung cancer. The patient had raised anti-tissue transglutaminase IgA and histological findings consistent with coeliac disease. This is the first published case report of probable immunotherapy-induced coeliac disease both with the immunotherapy drug durvalumab and in the curative lung cancer setting.

A 55-year-old Caucasian woman presented with a 1-week history of left eye redness and blurred vision. Her medical history included previous small bowel resection and ileostomy for ischaemic bowel. Ophthalmic examination revealed a left corneal ulcer requiring hospital admission for intensive topical antibiotics. Overnight she became systemically unwell and was diagnosed with urinary tract infection requiring intravenous antibiotics. Her corneal condition deteriorated resulting in corneal perforation, which required a surgical gluing procedure. Despite surgery, the cornea perforated on two further occasions. At this stage, vitamin A deficiency (VAD) was suspected, due to the corneal melting response that was occurring. VAD was subsequently confirmed by serology and had occurred in this case due to malabsorption as a result of short bowel syndrome caused by previous small bowel surgery. The patient was treated with intramuscular vitamin A and eventually made a good visual and systemic recovery.

Objective Examine the association between personality measures and perceived mental fatigability. Methods We performed a cross-sectional analysis in N=1670 men, age 84.3±4.1 years. Multivariable linear regression models were used to examine the covariate adjusted association between personality measures (conscientiousness, optimism, goal reengagement, and goal disengagement) and perceived mental fatigability (measured with the validated 10-item Pittsburgh Fatigability Scale, PFS). Results One standard deviation lower conscientiousness (β=−0.91, pDiscussion Lower conscientiousness, optimism, and higher goal reengagement were linked with more severe perceived mental fatigability in older men. Personality traits may potentially contribute to early risk assessment for fatigability in later life. Future work should be longitudinal in nature and include personality assessments to confirm the temporality of the relationships observed.

Pediatric extreme thrombocytosis (EXT, platelet count > 1000 × 10(3)/μL) is rare. In a single center retrospective analysis of hospitalized children with EXT, infants with congenital diaphragmatic hernia (CDH) were overrepresented. In general pediatric patients, EXT is usually secondary to infection or inflammation, but most of the 14 CDH patients with EXT had no identifiable inciting factor. Instead, there was evidence that splenic dysfunction and bone marrow hyperactivity underlied EXT in CDH patients. None were associated with bleeding or thrombosis. Our findings identify mechanisms underlying EXT, and aid clinical interpretation and management of EXT in the pediatric population.

Background There is a need for evidence-based guidance on complementary medicines and therapies (CMT) use during pregnancy due to high prevalence of use and lack of guidance on the balance of benefit and harms. Aim Evaluate the extent to which current clinical practice guidelines relevant to Australian healthcare professionals make clear and unambiguous recommendations about CMT use in pregnancy, and synthesise these recommendations. Methods The search included EMBASE, PubMed, the National Health and Medical Research Council’s Clinical Practice Guidelines Portal, and websites of Australian maternity hospitals and professional/not-for-profit organisations for published guidelines on pregnancy care. Data were synthesised narratively. Guidelines were appraised by two independent reviewers using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Findings A total of 48 guidelines were found, of which 41% provided recommendations that were not limited to routine vitamin and mineral supplementation. There were wide variations in recommendations, particularly for vitamin D and calcium. There was some consensus on recommending ginger and vitamin B6 for nausea and vomiting, and additional supplementation for women with obesity. Guidelines generally scored poorly in the domains of editorial independence and rigour of development. Discussion There is a lack of guidance with regard to appropriate CMT use during pregnancy, which may result in less-than-optimal care. Inconsistency between guidelines may lead to variations in care. Conclusion Guidelines should include clear and unambiguous guidance on appropriate CMT use during pregnancy, be based on a structured search of the evidence and informed by stakeholder engagement.

OBJECTIVES Maximizing quality of life (QoL) is the ultimate goal of long-term dementia care. However, routine QoL measurement is rare in nursing home (NH) and assisted living (AL) facilities. Routine QoL measurement might lead to improvements in resident QoL. Our objective was to assess the feasibility of using DEMQOL-CH, completed by long-term care staff in video calls with researchers, to assess health-related quality of life (HrQoL) of NH and AL residents with dementia or other cognitive impairment. DESIGN Cross-sectional study. SETTING AND PARTICIPANTS We included a convenience sample of 5 NHs and 5 AL facilities in the Canadian province of Alberta. Forty-two care staff who had worked in the facility for ≥3 months completed DEMQOL-CH assessments of 183 residents who had lived in the facility for 3 months or more and were aged ≥65 years. Sixteen residents were assessed independently by 2 care staff to assess inter-rater reliability. METHODS We assessed HrQoL in people with dementia or other cognitive impairment using DEMQOL-CH, and assessed time to complete, inter-rater reliability, internal consistency reliability, and care staff ratings of feasibility of completing the DEMQOL-CH. RESULTS Average time to complete DEMQOL-CH was

Gestational diabetes mellitus (GDM) diagnosed during the first trimester of pregnancy is called 'early pregnancy Gestational Diabetes Mellitus' (eGDM). The burden of eGDM has only been studied sporadically. This review aims to understand the global burden of eGDM in terms of prevalence, risk factors, pregnancy outcomes, treatment and postpartum dysglycemia. METHODS: A review of epidemiologic studies reporting on early GDM screening as per Joanna Briggs Institute (JBI) methodology for prevalence reviews was conducted. A customized search strategy was used to search electronic databases namely, PubMed, CINAHL, EMBASE, Cochrane Library, Scopus, MEDLINE, Ovid, ScienceDirect, and Google Scholar. Three independent reviewers reviewed studies using Covidence software. Observational studies irrespective of study design and regardless of diagnostic criteria were included. Quality of evidence was appraised, and findings were synthesized.Of 58 included studies, 41 reported a prevalence of eGDM, ranging from 0.7 to 36.8%. Body mass index (BMI), previous history of GDM, family history of diabetes and multiparity were reported as eGDM risk factors. Adverse pregnancy outcomes associated with eGDM were macrosomia, caesarean delivery, induction of labour, hypertension, preterm delivery, and shoulder dystocia. The incidence of postpartum dysglycemia and the need for insulin was higher in women with eGDM. The risk of bias was moderate. Heterogeneity of studies is a limitation. Meta-analysis was not performed.There is heterogeneity in the prevalence of eGDM and intrapartum and postpartum ill effects for the mother and the offspring. There is a need to develop a universal screening protocol for eGDM.

Objective To explore birth stories of autistic women to understand how they make sense of the experience of childbirth. Design Narrative analysis. Setting Online interviews. Participants Sixteen women on the autism spectrum shared 19 birth stories. Methods Participants were recruited from online autism forums and were invited to share their birth stories via online asynchronous interviews. Using Burke’s approach to narrative analysis, we identified five elements within each story, including Scene (when/where), Agents (who), Act (what), Agency (how), and Purpose (why). We explored parts of the narratives where two or more elements were out of balance with each other. Results Tension most often occurred when actions taken by the health care team (Act) were out of balance with their approach to care (Agency), which left participants feeling that their concerns were minimized, their wishes were ignored, and they were left out of critical communication and education. Participants also struggled when their own autistic traits (Agent), such as sensory sensitivities, were out of balance with the birth environment (Scene), which impaired their ability to communicate with providers and participate in the birth. Conclusion Poor communication, untreated pain, and sensory overload dominated the birth narratives of participants. Nurses should trust women’s reports of pain and anxiety because autistic women may appear calm even when in severe distress. Environmental adjustments, such as dimming the lights, can help minimize sensory overload. Nurses need to provide thorough and nonjudgmental education about the birth process to ensure that autistic women feel safe and in control and do not withdraw from care.

This paper explores the impact of dementia on the selfhood of women, specifically the ways in which changes occur as a result of such a diagnosis. Interviews were conducted with 12 women (recruited from the Improving the Experience of Dementia and Enhancing Active Life programme dataset), and analysed using interpretative phenomenological analysis. Emergent themes concerned the process of receiving and adjusting to a dementia diagnosis, the emotional and psychological impact of dementia, self-presentation and stigma and the self-enforcement of new boundaries. The analysis showed that dementia had a wide-ranging impact on the selfhood and identity of women, with newfound characteristics associated with the disease leading to a loss of self-esteem, sadness and anger. The women subsequently engaged in the modification of their behaviour, as a means of coming to terms with the losses experienced.

Heterotopic heart transplantation (HHT) is rare in the modern era. When used as a biologic left ventricular assist, HHT provides pulsatile flow, supports the left ventricle with a physiologic cardiac output, responds to humoral stimuli, and with modern immunosuppression may offer long-term untethered survival. This study was undertaken to compare survival of HHT with orthotopic heart transplantation (OHT) to assess its viability in the modern era. In the United Network for Organ Sharing database, from January 1999 to December 2020, there were 27691 bicaval OHT, 13836 biatrial OHT, 1271 total OHT, and 51 HHT with sufficient follow-up. Survival was analyzed using restricted mean survival time (RMST) through 4 years as the outcome. In the first 4 years after transplant, compared with HHT, differences in RMST were 0.1 years (99% CI: -0.4 to 0.5 years) for bicaval OHT, 0.0 years (99% CI: -0.4 to 0.5 years) for biatrial OHT, and 0.0 years (99% CI: -0.5 to 0.4 years) for total OHT. In this cohort, survival was indistinguishable between HHT and OHT recipients in the first four years. Thus, HHT might be a viable alternative to durable mechanical circulatory assist particularly with size mismatched grafts or for patients with refractory pulmonary hypertension.

BACKGROUND Living liver donation is generally considered safe, but donors may experience short or long-term complications. The purpose of this study was to assess healthcare resource utilization after liver donation in living liver donors in comparison to the general population. METHODS Outpatient or emergency department visits and hospital admissions were compared between living liver donors who underwent hepatic resection for living liver donation between 2004 and 2018 and the matched general population. Healthcare resource utilization data for 5 years after liver donation were collected from the National Health Insurance Service (NHIS) database. For every living liver donor, 4 individually matched nondonors were selected from the NHIS database using age, sex, preexisting comorbidities, and previous healthcare utilization history. RESULTS A total of 1886 living liver donors and 7309 nondonors were included. In the first year after donation, living liver donors required more outpatient department visits (7 [4-13] vs. 3 [1-7], P < 0.001) and more emergency department visits (13.33% vs. 0.15%, P < 0.001) compared to matched nondonors. A similar trend persisted for 5 years after donation. The number of hospital admissions of living liver donors was higher for up to 2 years after donation with longer hospital length of stay (13.0 [10.5-16.0] vs. 5.0 [3.0-9.0] days, P < 0.0001). CONCLUSIONS Healthcare resource utilization in living liver donors for 5 years after donation were higher compared to matched nondonors. The higher healthcare resource demand may be related to postoperative complications or lowered threshold for healthcare resource utilization after donation.Supplemental Visual Abstract; http://links.lww.com/TP/C291.

Background and aims: Studies have indicated that maternal prenatal substance use may be associated with offspring attention deficit hyperactivity disorder (ADHD) via intrauterine effects. We measured associations between prenatal smoking, alcohol and caffeine consumption with childhood ADHD symptoms accounting for shared familial factors. Design: First, we used a negative control design comparing maternal and paternal substance use. Three models were used for negative control analyses: unadjusted (without confounders), adjusted (including confounders) and mutually adjusted (including confounders and partner's substance use). The results were meta-analysed across the cohorts. Secondly, we used polygenic risk scores (PRS) as proxies for exposures. Maternal PRS for smoking, alcohol and coffee consumption were regressed against ADHD symptoms. We triangulated the results across the two approaches to infer causality. Setting: We used data from three longitudinal pregnancy cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) in the United Kingdom, Generation R study (GenR) in the Netherlands and Norwegian Mother, Father and Child Cohort study (MoBa) in Norway. Participants: Phenotype data available for children were: N ALSPAC = 5455–7751; N GENR = 1537–3119; N MOBA = 28 053–42 206. Genotype data available for mothers was: N ALSPAC = 7074; N MOBA = 14 583. Measurements: A measure of offspring ADHD symptoms at age 7–8 years was derived by dichotomizing scores from questionnaires and parental self-reported prenatal substance use was measured at the second pregnancy trimester. Findings: The pooled estimate for maternal prenatal substance use showed an association with total ADHD symptoms [odds ratio (OR) SMOKING = 1.11, 95% confidence interval (CI) = 1.00–1.23; OR ALCOHOL = 1.27, 95% CI = 1.08–1.49; OR CAFFEINE = 1.05, 95% CI = 1.00–1.11], while not for fathers (OR SMOKING = 1.03, 95% CI = 0.95–1.13; OR ALCOHOL = 0.83, 95% CI = 0.47–1.48; OR CAFFEINE = 1.02, 95% CI = 0.97–1.07). However, maternal associations did not persist in sensitivity analyses (substance use before pregnancy, adjustment for maternal ADHD symptoms in MoBa). The PRS analyses were inconclusive for an association in ALSPAC or MoBa. Conclusions: There appears to be no causal intrauterine effect of maternal prenatal substance use on offspring attention deficit hyperactivity disorder symptoms.

OBJECTIVES: Three-dimensional transesophageal echocardiography (TEE) is widely used to guide decision-making for mitral repair - relative impact of surgical mitral valve repair (MVr) and MitraClip on annular remodeling is unknown. The aim was to determine the impact of both mitral repair strategies on annular geometry, including the primary outcome of annular circumference and area. DESIGN: This was a retrospective observational study of patients who underwent mitral intervention between 2016 and 2020. SETTING: Weill Cornell Medicine, a single large academic medical center. PARTICIPANTS: The population comprised of 50 degenerative mitral regurgitation (MR) patients undergoing MVr. INTERVENTIONS: Elective MVr and transesophageal echocardiography (TEE) MEASUREMENTS AND MAIN RESULTS: MitraClip or surgical MVr patients were matched (1:1) for gender and CAD. Mitral annular geometry indices were quantified on intra-procedural 3D TEE. Mild or less MR on follow-up TTE defined optimal response. MitraClip patients were older (80±8 vs. 66±6;p

Objectives To evaluate contemporary clinical presentations of priapism, their association with socioeconomic characteristics, and the role of prescribing providers in priapism episodes in a large cohort of patients managed at 3 major academic health systems. Methods We identified all consecutive patients presenting with ischemic priapism to the emergency departments of three major academic health systems (2014 –2019). Demographic characteristics, priapism etiologies, and clinical management were evaluated. Univariable and multivariable analyses were used to assess the contribution of socioeconomic characteristics and the role of prescribing providers in priapism episodes. Results We identified 102 individuals with a total of 181 priapism encounters. Hispanic race, lower income quartile, sickle-cell disease, and illicit drug use were associated with increased risk of recurrent episodes. Of ICI users, 57% received their prescriptions from non-urological medical professionals (NUMPs); the proportion with recurrent episodes was higher for NUMPs compared to urologists (24% vs 0%, P = 0.06) with no demographic differences identified between patients treated by either group. Conclusion Socioeconomic disparities exist among patients presenting with recurrent episodes of priapism, potentially highlighting systemic issues with access to care and patient education. With most patients who developed ischemic priapism from ICI being prescribed these medications by NUMPs, further investigation is required to elucidate the prescribing and counseling patterns of these providers. Increased awareness of disparities and complications may improve patient safety.

Background and aimsSeveral studies have indicated that there is an association between maternal prenatal substance use and offspring externalising disorders. However, it is uncertain whether this relationship is causal. Therefore, we updated a previously conducted systematic review to determine if the literature supports 1) a causal role of maternal prenatal substance use on offspring externalising disorders and 2) whether these associations differ across externalising disorders.MethodsWe searched Web of Science, Embase, PsycINFO and Medline databases. We included studies that examined smoking, alcohol or caffeine use during pregnancy as an exposure, and diagnosis of attention-deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional-defiant disorder (ODD) in offspring as an outcome. Studies on non-English language, fetal alcohol syndrome and comorbid autism spectrum disorders were excluded. Risk of bias assessment was conducted using Newcastle Ottawa Scale (NOS) and where possible meta-analysis was conducted for studies classed as low risk of bias.ResultsWe included 63 studies. All studies were narratively synthesised, and 7 studies were meta-analysed on smoking and ADHD. The majority of studies (46 studies) investigated the association between smoking and ADHD. Studies which accounted for genetic effects indicate that the association between smoking and ADHD is unlikely to be causal. Studies on alcohol exposure in all the outcomes reported inconsistent findings and no strong conclusions on causality can be made. Studies on caffeine exposure were mostly limited to ADHD and these studies do not support a causal effect.ConclusionsThere is no causal relationship between maternal smoking during pregnancy and attention-deficit hyperactivity (ADHD) in offspring. However, given that the majority of identified studies investigated the association between ADHD and smoking exposure, findings with alcohol and caffeine exposures and conduct disorder (CD) and oppositional-defiant disorder (ODD) need more research, especially using more genetically sensitive designs.

The composition of the gut microbiome is linked to multiple diseases, including Parkinson’s disease (PD). Bacteria producing short-chain fatty acids (SCFAs) and fecal SCFA concentrations are reduced in PD. SCFAs exert various beneficial functions in humans. In the interventional, monocentric, open-label clinical trial RESISTA-PD (NCT02784145) we aimed at altering fecal SCFAs by an 8-week prebiotic intervention with resistant starch (RS). We enrolled 87 subjects in three study-arms: 32 PD patients receiving RS (PD + RS), 30 control subjects receiving RS, and 25 PD patients receiving solely dietary instructions. We performed paired-end 100 base pair length metagenomic sequencing of fecal samples using the BGISEQ platform at an average of 9.9 GB. RS was well-tolerated. In PD + RS, fecal butyrate concentrations increased significantly and fecal calprotectin concentrations dropped significantly after 8 weeks of RS. Clinically, we observed a reduction in non-motor symptoms load in PD + RS. The reference-based analysis of metagenomes highlighted stable alpha-diversity and beta-diversity across the three groups, including bacteria producing SCFAs. Reference-free analysis suggested punctual, yet pronounced differences in the metagenomic signature in PD + RS. RESISTA-PD highlights that a prebiotic treatment with RS is safe and well-tolerated in PD. The stable alpha-diversity and beta-diversity alongside altered fecal butyrate and calprotectin concentrations calls for long-term studies, also investigating whether RS is able to modify the clinical course of PD.

International audience; OBJECTIVES: To describe the investigation, follow-up, management and outcomes in a cohort of chronic kidney disease and kidney transplant recipients exposed to a case of pulmonary tuberculosis. METHODS: Contacts were investigated following a concentric circles approach and followed-up according to their level of priority. In those with an evidence of latent tuberculous infection, treatment decision was based on the level of exposure, individual vulnerability, as well as the results of an interferon-gamma release assay. RESULTS: 130 patients with chronic kidney disease and 180 kidney transplant recipients were identified as contacts and followed-up over a two-year period.Only few vulnerable high-priority contacts received an anti-tuberculosis treatment, including the 2 (100%)highly exposed patients in circle 1, 11/78(14.1%)chronic kidney disease patients and 4/142 (2.8%) kidney transplant recipients in circle 2, and10/52 (19.2%) chronic kidney disease patients and 2/36 (5.6%) kidney transplant recipients in circle 3;all having a positive interferon-gamma release assay result. No incident case of tuberculosis disease occurred. CONCLUSIONS: These findings suggest that latent tuberculosis treatment, as recommended in European guidelines, might be reasonably avoided in vulnerable high-priority contacts of circle 2 with a negative interferon-gamma release assay in countries with low prevalence of tuberculosis.

PURPOSE: The COVID-19 pandemic led to rapid shifts in cancer survivorship care, including the widespread use of telehealth. Given the swift transition and limited data on preferences and experiences around telehealth, we surveyed oncology providers and post-treatment survivors to better understand experiences with the transition to telehealth. METHODS: We distributed provider (MD, PA or NP, nurse, navigator, and social worker) and survivor surveys through the American College of Surgeons Commission on Cancer in mid-October 2020. Survivor surveys were also disseminated through patient advocacy organizations. We included questions on demographics, experiences with telehealth, and preferences for future telehealth utilization. RESULTS: Among N = 607 providers and N = 539 cancer survivors, there was overwhelmingly more support from providers than from survivors for delivery of various types of survivorship care via telehealth and greater comfort with telehealth technologies. The only types of appointments deemed appropriate for survivorship care by both > 50% of providers and survivors were discussion of laboratory results or imaging, assessment and/or management of cancer treatment symptoms, nutrition counseling, and patient navigation support. Only a quarter of survivors reported increased access to health care services (25.5%), and 32.0% reported that they would use telehealth again. CONCLUSION: Although there have been drastic changes in technological capabilities and billing reimbursement structures for telehealth, there are still concerns around delivery of a broad range of survivorship care services via telehealth, particularly from the patient perspective. Still, offering telehealth services, where endorsed by providers and if available and acceptable to cancer survivors, may provide more efficient and accessible care following the COVID-19 pandemic.

Because of the limited published information on complications that obstructive sleep apnea (OSA) patients experience during and after cardiac surgery, we investigated OSA as a risk factor for postoperative outcomes.This project used the Northern New England Cardiovascular Disease Study Group's data collected between 2011 and 2017 based on The Society of Thoracic Surgeons Adult Cardiac Surgery Database Data Collections form. A retrospective analysis of 1555 patients with OSA and 10,450 patients without OSA across 5 medical centers undergoing isolated coronary artery bypass grafting, isolated valve surgery, and combined coronary artery bypass grafting valve surgery was conducted. We used 1:1 nearest-neighbor propensity score matching with no replacement to balance characteristics among patients with and without OSA.There was a statistically significant increased risk of postoperative pneumonia, increased length of total and postoperative stay, and time to initial extubation. Two outcomes trended toward significance: intra- and postoperative intraaortic balloon pump use. Outcomes that failed to show statistical significance were surgical site infection, atrial fibrillation, cerebrovascular accident, permanent pacemaker placement, and blood products given. A chart review conducted on a subset of the study cohort revealed that more than 40% of OSA patients did not receive continuous positive airway pressure or bilevel positive airway pressure therapy postoperatively during their hospitalization.Our study aligns with the literature in concluding that OSA has deleterious effects on postoperative outcomes of cardiac surgery patients. Further research to better stratify OSA patients by severity are still needed. Additionally heightened awareness of the need to screen, diagnose, and properly treat patients for OSA is needed.

Risk stratification of gastrointestinal stromal tumors (GISTs) is based on experience with tumors of the stomach, small bowel, and rectum, which are far more common than GISTs of other sites. In this study from 47 institutions, we analyzed GISTs of the esophagus (n = 102), colon (n = 136), and appendix (n = 27) for their size, mitotic rate, morphology, and outcome to determine which criteria predict their behavior. Esophageal GISTs were small (median: 2.5 cm) with spindle cell morphology and a low mitotic rate (mean: 3.6/5 mm2). Twelve (12%) tumors progressed, including 11 with a mitotic rate >5/5 mm2 and one large (6.8 cm) GIST with a mitotic rate of 2/5 mm2. Colonic GISTs were smaller (median: 1.4 cm) and presented with abdominal pain or bleeding in 29% of cases. Most (92%) were composed of spindle cells with a mean mitotic rate of 4.6/5 mm2. Sixteen (12%) tumors progressed: 14 had mitotic rates >5/5 mm2, and two were >5.0 cm with a mitotic rate 5/5 mm2) and size >5.0 cm. These findings support the use of size and mitotic rate for prognostication of GISTs in these locations, similar to tumors of the stomach, small bowel, and rectum.

Context In 2018, the US military developed the Military Acute Concussion Evaluation-2 (MACE-2) to inform the acute evaluation of mild traumatic brain injury (mTBI). However, researchers have yet to investigate false-positive rates for components of the MACE-2, including the Vestibular-Ocular Motor Screening (VOMS) and modified Balance Error Scoring System (mBESS), in military personnel. Objective To examine factors associated with false-positive results on the VOMS and mBESS in US Army Special Operations Command (USASOC) personnel. Design Cross-sectional study. Setting Military medical clinic. Patients or Other Participants A total of 416 healthy USASOC personnel completed the medical history, VOMS, and mBESS evaluations. Main Outcome Measure(s) False-positive rates for the VOMS (≥2 on VOMS symptom items, >5 cm for near point of convergence [NPC] distance) and mBESS (total score >4) were determined using χ2 analyses and independent-samples t tests. Multivariable logistic regressions (LRs) with adjusted odds ratios (aORs) were performed to identify risk factors for false-positive results on the VOMS and mBESS. The VOMS item false-positive rates ranged from 10.6% (smooth pursuits) to 17.5% (NPC). The mBESS total score false-positive rate was 36.5%. Results The multivariable LR model supported 3 significant predictors of VOMS false-positives, age (aOR = 1.07; 95% CI = 1.02, 1.12; P = .007), migraine history (aOR = 2.49; 95% CI = 1.29, 4.81; P = .007), and motion sickness history (aOR = 2.46; 95% CI = 1.34, 4.50; P = .004). Only a history of motion sickness was a significant predictor of mBESS false-positive findings (aOR = 2.34; 95% CI = 1.34, 4.05; P = .002). Conclusions False-positive rates across VOMS items were low and associated with age and a history of mTBI, migraine, or motion sickness. False-positive results for the mBESS total score were higher (36.5%) and associated only with a history of motion sickness. These risk factors for false-positive findings should be considered when administering and interpreting VOMS and mBESS components of the MACE-2 in this population.

ispartof: Intensive Care Medicine vol:47 issue:9 pages:1037-1040 ispartof: location:United States status: published

Introduction: There are no prospective studies looking at complications of pleural procedures. Previous British Thoracic Society Pleural audits and retrospective case series inform current practice. Incidence of any complication is between 1–15%. We sought to add to the existing literature and inform local practice with regards to intercostal drains and thoracocenteses. Methods: Local Caldicott approval was sought for a review of all inpatient adult pleural procedures coded as ‘T122 drainage of pleural cavity’ and ‘T124 insertion of tube drain into pleural cavity’. Those undergoing thoracocentesis (all with a Rocket 6 Fg catheter) and intercostal drain insertion (ICD, all with Rocket 12 Fg drain) were identified. Continuous variables are presented as mean (±range) and categorical variables as percentages where appropriate. Results: 1159 procedures were identified. A total of 199 and 960 were done for pneumothorax and effusions respectively. Mean age was 68.1 years (18–97). There were 280 thoracocenteses and 879 ICDs. Bleeding occurred in 6 (0.5%), all ICDs (clotting and platelets were within normal range, one patient was on aspirin and one on aspirin and clopidogrel). All settled except for one who had intercostal artery rupture needing cardiothoracic intervention (no anti-coagulation). Nine pneumothoraces occurred (0.78%) in seven ICDs and two aspirations). There were three definite pleural space infections (0.3%) with three ICDs. Fall out rates for ICDs were 35 (3%). Nine were not sutured, and out of those, seven inserted in the Accident and Emergency department, out of hours. All others ‘came out’ due to patient factors (previous quoted rates up to 14%). Surgical emphysema occurred in 43 (41 ICDs), 3.7%. Eight were due to fall outs and three required surgical intervention. There was no re-expansion pulmonary oedema nor direct deaths. Conclusions: Complication rates of ICD and thoracocenteses are low. Checklists might help to remind operators of the need for suturing. Limitations of this study are its retrospective nature and reliance on correct hospital coding. We are currently contributing to a prospective observational study on pleural complications.

Pseudomalignancies are benign or reactive lesions that mimic malignant neoplasms either clinically or histologically. In the head and neck region there are a number of pseudomalignancies that may present to a histopathologist, including soft tissue lesions, benign odontogenic tumours and salivary gland pathology. In this review we discuss common pseudomalignant lesions that may present in the head and neck, including their clinical presentation, histopathological features and differential diagnosis.

Summary Background There is a paucity of evidence to support safe and effective management of patients with acute severe ulcerative colitis during the COVID-19 pandemic. We sought to identify alterations to established conventional evidence-based management of acute severe ulcerative colitis during the early COVID-19 pandemic, the effect on outcomes, and any associations with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes. Methods The PROTECT-ASUC study was a multicentre, observational, case-control study in 60 acute secondary care hospitals throughout the UK. We included adults (≥18 years) with either ulcerative colitis or inflammatory bowel disease unclassified, who presented with acute severe ulcerative colitis and fulfilled the Truelove and Witts criteria. Cases and controls were identified as either admitted or managed in emergency ambulatory care settings between March 1, 2020, and June 30, 2020 (COVID-19 pandemic period cohort), or between Jan 1, 2019, and June 30, 2019 (historical control cohort), respectively. The primary outcome was the proportion of patients with acute severe ulcerative colitis receiving rescue therapy (including primary induction) or colectomy. The study is registered with ClinicalTrials.gov , NCT04411784 . Findings We included 782 patients (398 in the pandemic period cohort and 384 in the historical control cohort) who met the Truelove and Witts criteria for acute severe ulcerative colitis. The proportion of patients receiving rescue therapy (including primary induction) or surgery was higher during the pandemic period than in the historical period (217 [55%] of 393 patients vs 159 [42%] of 380 patients; p=0·00024) and the time to rescue therapy was shorter in the pandemic cohort than in the historical cohort (p=0·0026). This difference was driven by a greater use of rescue and primary induction therapies with biologicals, ciclosporin, or tofacitinib in the COVID-19 pandemic period cohort than in the historical control period cohort (177 [46%] of 387 patients in the COVID-19 cohort vs 134 [36%] of 373 patients in the historical cohort; p=0·0064). During the pandemic, more patients received ambulatory (outpatient) intravenous steroids (51 [13%] of 385 patients vs 19 [5%] of 360 patients; p=0·00023). Fewer patients received thiopurines (29 [7%] of 398 patients vs 46 [12%] of 384; p=0·029) and 5-aminosalicylic acids (67 [17%] of 398 patients vs 98 [26%] of 384; p=0·0037) during the pandemic than in the historical control period. Colectomy rates were similar between the pandemic and historical control groups (64 [16%] of 389 vs 50 [13%] of 375; p=0·26); however, laparoscopic surgery was less frequently performed during the pandemic period (34 [53%] of 64] vs 38 [76%] of 50; p=0·018). Five (2%) of 253 patients tested positive for SARS-CoV-2 during hospital treatment. Two (2%) of 103 patients re-tested for SARS-CoV-2 during the 3-month follow-up were positive 5 days and 12 days, respectively, after discharge from index admission. Both recovered without serious outcomes. Interpretation The COVID-19 pandemic altered practice patterns of gastroenterologists and colorectal surgeons in the management of acute severe ulcerative colitis but was associated with similar outcomes to a historical cohort. Despite continued use of high-dose corticosteroids and biologicals, the incidence of COVID-19 within 3 months was low and not associated with adverse COVID-19 outcomes. Funding None.

Deregulation such as overexpression of adhesion molecules influences cancer progression and survival. Metastasis of malignant cells from their primary tumor site to distant organs is the most common reason for cancer-related deaths. Junctional adhesion molecule-C (JAM-C), a member of the immunoglobulin-like JAM family, can homodimerize and aid cancer cell migration and metastasis. Here we show that this molecule is dynamically expressed on multiple myeloma (MM) cells in the bone marrow and co-localizes with blood vessels within the bone marrow of patients and mice. In addition, upregulation of JAM-C inversely correlates with the downregulation of the canonical plasma cell marker CD138 (syndecan-1), whose surface expression has recently been found to dynamically regulate a switch between MM growth in situ and MM dissemination. Moreover, targeting JAM-C in a syngeneic in vivo MM model ameliorates MM progression and improves outcome. Overall, our data demonstrate that JAM-C might serve not only as an additional novel diagnostic biomarker but also as a therapeutic target in MM disease.

We tested the hypothesis that obesity influences the pharmacodynamics of volatile general anesthetics (VGAs) by comparing effects of anesthetic exposure on mortality from traumatic brain injury (TBI) in lean and obese Drosophila melanogaster. We induced TBI with a high-impact trauma device. Starvation-selection over multiple generations resulted in an obese phenotype (SS flies). Fed flies served as lean controls (FC flies). Adult (1–8-day-old) SS and FC flies were exposed to equianesthetic doses of isoflurane or sevoflurane either before or after TBI. The principal outcome was percent mortality 24 hours after injury, expressed as the Mortality Index at 24 hours (MI(24)). TBI resulted in a lower MI(24) in FC than in SS flies [21 (2.35) and 57.8 (2.14), respectively n = 12, P = 0.0001]. Pre-exposure to isoflurane or sevoflurane preconditioned FC flies to TBI, reducing the risk of death to 0.53 (0.25 to 1.13) and 0.82 (0.43 to 1.58), respectively, but had no preconditioning effect in SS flies. Postexposure to isoflurane or sevoflurane increased the risk of death in SS flies, but only postexposure to isoflurane increased the risk in FC flies [1.39 (0.81 to 2.38)]. Thus, obesity affects the pharmacodynamics of VGAs, thwarting the preconditioning effect of isoflurane and sevoflurane in TBI. SIGNIFICANCE STATEMENT: Inadvertent preconditioning in models of traumatic brain injury (TBI) is a recognized confounder. The findings in a fruit fly (Drosophila melanogaster) model of closed-head TBI indicate that anesthetic pharmacodynamics are profoundly affected by obesity. Specifically, obesity thwarts the brain-protective effect of anesthetic preconditioning. This finding is important for experimental studies of TBI and supports the versatility of the fruit fly as a model for the exploration of anesthetic pharmacodynamics in a wide parameter space.

Current guidelines recommend restaging with MRI after neoadjuvant therapy for rectal cancer, but the accuracy of restaging MRI in estimating circumferential margin involvement requires additional clarification.The objective of this study was to measure the accuracy of circumferential resection margin assessment by MRI after neoadjuvant therapy and identify characteristics associated with accuracy.MRI data were retrospectively analyzed for concordance with the findings of whole-mount pathology analysis of the corresponding surgical specimens. Univariate and multivariate logistic regression analyses were performed to identify characteristics associated with accuracy.This study was conducted at a comprehensive cancer center.Included in the study were consecutive patients who underwent total mesorectal excision for rectal cancer between January 2018 and March 2020 after receiving neoadjuvant therapy and undergoing restaging with MRI.The primary outcome of this study included accuracy, sensitivity, specificity, and positive and negative predictive values for categorizing the circumferential resection margin as threatened; mean and paired mean differences were in proximity of the margin.Of the 94 patients included in the analysis, 39 (41%) had a threatened circumferential resection margin according to MRI at restaging, but only 17 (18%) had a threatened margin based on pathology. The accuracy of MRI in identifying a threatened margin was 63.8%, with margin proximity overestimated by 0.4 cm on average. In multivariate logistic regression, anterior location of the margin and tumor proximity to the anal verge were independently associated with reduced MRI accuracy.A limitation was the retrospective design at a single institution.The knowledge that MRI-based restaging after neoadjuvant therapy overestimates circumferential margin proximity may render some surgical radicality unnecessary and thereby help avoid the associated morbidity. With the recognition that MRI-based assessment of margin proximity may not be reliable for anterior margin and for distal tumors, radiologists may want to use greater caution in interpreting images of tumors with these characteristics and to acknowledge the uncertainty in their reports. See Video Abstract at http://links.lww.com/DCR/B814.ANTECEDENTES:Las pautas actuales recomiendan la re-estadificación por medio de la resonancia magnética luego de terapia neoadyuvante en los casos de cáncer de recto, pero la precisión de la reevaluación con la IRM para estimar el grado de implicación del margen circunferencial requiere aclaraciones adicionales.OBJETIVO:Medir el grado de exactitud en la evaluación del margen de resección circunferencial mediante resonancia magnética después de la terapia neoadyuvante e identificar las características asociadas con la precisión.DISEÑO:Se analizaron retrospectivamente los datos de resonancia magnética para determinar la concordancia entre los hallazgos del análisis de la pieza de anatamopatología y las muestras quirúrgicas correspondientes. Se realizó el análisis de regresión logística univariada y multivariada para identificar las características asociadas con la exactitud.AJUSTE:Centro oncológico integral.PACIENTES:Todos aquellos que se sometieron consecutivamente a una excisión total del mesorrecto por cáncer rectal entre Enero 2018 y Febrero 2020 luego de recibir terapia neoadyuvante y someterse a una re-estadificación por imágenes de resonancia magnética (IRM).PRINCIPALES MEDIDAS DE RESULTADO:La exactitud, la sensibilidad y especificidad; los valores predictivos positivos y negativos para categorizar el margen de resección circunferencial como amenazado; la diferencia media y las medias pareadas de proximidad a los margenes.RESULTADOS:De los 94 pacientes incluidos en el análisis, 39 (41%) tenían un margen de resección circunferencial amenazado según la resonancia magnética en la re-estadificación, pero solo 17 (18%) tenían un margen amenazado basado en la patología. La precisión de la resonancia magnética para identificar un margen amenazado fue del 63,8%, con la proximidad del margen sobreestimada en 0,4 cm en promedio. En la regresión logística multivariada, la ubicación anterior de los bordes de resección y la proximidad del tumor al margen anal se asociaron de forma independiente con la reducción en la precisión de la resonancia magnética.LIMITACIONES:Diseño retrospectivo en una institución única.CONCLUSIONES:El saber que la re-estadificación basada en la IRM, luego de terapia neoadyuvante sobreestima la proximidad de la lesión a los márgenes circunferenciales, hace innecesaria cierta radicalidad quirúrgica complementaria, lo que ayuda a evitar morbilidad asociada. Reconociendo que la evaluación de proximidad de los márgenes de resección basada en la resonancia magnética, no puede ser confiable en casos de márgenes anteriores y en casos de tumores distales. Los radiólogos recomiendan tener más precaución en la interpretación de imágenes de tumores con estas características y reconocen cierto desasosiego en sus informes. Consulte Video Resumen en http://links.lww.com/DCR/B814.

Clinical Scenario: Athletic trainers must be confident when performing life-saving skills, such as a cardiovascular assessment and cardiopulmonary resuscitation. Learning and performing skills on high-fidelity simulation manikins may improve athletic training students’ self-confidence and self-efficacy. Clinical Question: What are the effects of high-fidelity manikin simulation on athletic training students’ self-confidence and self-efficacy in performing emergency cardiovascular care? Summary of Key Findings: Three good-quality cohort studies were included. Two studies assessed the effect of high-fidelity cardiopulmonary resuscitation simulation, and one study assessed the effect of high-fidelity cardiovascular assessment. Two studies evaluated self-confidence, while the other study evaluated self-efficacy. All three studies found that high-fidelity simulation improved athletic training students’ self-confidence and self-efficacy. Clinical Bottom Line: There is currently consistent, good-quality evidence that supports the use of high-fidelity manikin simulation to improve athletic training students’ self-confidence and self-efficacy in performing cardiovascular skills and assessment. Future research should examine the effects of high-fidelity manikin simulation on the same academic levels of athletic training students to ensure generalizability of results. Strength of Recommendation: The grade of B is recommended by the Strength of Recommendation Taxonomy for consistent, good-quality evidence.

Although studies have found that autism is underdiagnosed in women and that autistic women have poorer well-being outcomes than men, less is known about autistic women's experiences with self-identification or diagnosis or how they feel such experiences affect their mental health.We explored autistic women's experiences of coming to recognize and understand themselves as autistic. We used data collected from blogs written by autistic women about their diagnostic or self-identification experiences. We were particularly interested in well-being, and how this contributed to, was affected by, and interacted with the identification and diagnostic process. We used thematic analysis to explore and document experiences described in blogs from 20 blogsites (representing the views of 23 autistic women).Acceptance was a central issue. We developed themes of self-understanding and self-acceptance, being understood and accepted by others (including peers, clinicians, and others in the autism community), and the exhaustion resulting from trying to be accepted and be understood. These issues arose both when going through the diagnostic process, and after receiving a formal diagnosis.Diagnosis and identification may have both positive and negative effects on autistic women's well-being, with women often describing difficulties after diagnosis as stemming from facing male stereotypes of autism. We consider the implications of our findings for clinicians, researchers, and those who work with autistic women.Research shows that autistic women are under-recognized and underdiagnosed. This can lead to a lack of support. Other research indicates worse mental health outcomes in autism. Exploring the perspectives of autistic women could help us understand how diagnosis may relate to mental well-being.This study examined the experiences of autistic women. We focused on well-being, mental health, and the role of diagnosis. We wanted to gain insight into how to support autistic women to achieve positive well-being.The researchers read blogs from 20 blogsites, reflecting the views and experiences of 23 autistic women. Women were either self-identifying or clinically diagnosed. The researchers then used a qualitative research technique called “thematic analysis” to summarize what women often said about well-being and diagnosis.Acceptance and feelings of belonging were important. We developed three themes: (1) self-understanding and self-acceptance, (2) being understood and accepted by others, and (3) exhaustion. Study participants felt that diagnosis often helped them understand their needs and be kinder to themselves. Diagnosis also helped women make sense of what had happened to them in the past. Finally, it helped them connect with a community, and improved relationships. However, stereotypes of autism affected women's own acceptance of their diagnosis. In some cases, feelings that they did not fit an autism diagnosis led to imposter syndrome. They described the struggle for acceptance, before and after their autism diagnosis, as exhausting. They felt this exhaustion came from trying to hide their difficulties or having to explain why they did not fit stereotypes.These findings support research that has identified high levels of exhaustion in autistic women due to trying to hide their difficulties and conform to societal expectations. Our findings suggest that acceptance is important for autistic women's well-being after their diagnosis. Facing a lack of acceptance from others could impact on women's self-acceptance. This could disrupt the positive effects a diagnosis has for women's well-being.In their blogs, women were remembering their experiences. Therefore, time may have impacted these women's views, and changed what is important to them. Our sample was limited as it did not include women who publicly identified as having intellectual disabilities, it only contained adult women (mainly aged 20–50 years), and it did not include nonbinary individuals. Experiences of autistic women who write blogs may be different from those of other autistic women.We suggest that when women seek diagnosis, acknowledgment of the difficulties they have faced coping without the recognition of being autistic is crucial. Clinicians should be aware that women may mask their difficulties, and they should avoid minimizing underlying problems. This study suggests that challenging the stereotypes associated with autism and educating professionals about autism in women are highly important. Women may benefit from support after diagnosis that helps them to manage experiences of being told they do not appear autistic, or do not fit people's expectations of autism.

Ewing's Sarcoma family of tumors are rare, malignant round cell tumors arising from undifferentiated mesenchymal cells. This aggressive neoplastic disease has a quick metastatic onset often resulting in a poor prognosis. In this case study we present a 21-year-old female diagnosed with Ewing's sarcoma of the third metatarsal bone. She initially presented in the emergency room with a 2-day onset of right foot pain following a minor injury. Radiographs taken in the emergency room revealed a cystic lesion in the third metatarsal. The patient presented to the author's clinic and following evaluation, surgical excision and curettage of the bone cyst was performed supplemented with allogenic bone graft. Due to a high clinical suspicion of malignancy, intraoperative culture and biopsy of the third metatarsal were sent to pathology and microbiology. Following evaluation of the bone biopsy with immunohistochemical staining as well as fluorescent in-situ hybridization studies, a diagnosis was made for Ewing's Sarcoma. This case report serves to display the significance of a timely workup as well as the importance of multiple pathology assessments to obtain a definitive pathologic diagnosis when clinical suspicion of malignancy is high.

BACKGROUND: While sex-related differences in transplant outcomes have been well characterized amongst adults, there are no sex-specific pediatric heart transplant studies over the last decade and none evaluating waitlist outcomes. In a contemporary cohort of children undergoing heart transplantation in the United States, this analysis was performed to determine if there were sex disparities in waitlist and/or post-transplant outcomes. METHODS: Retrospective review of Scientific Registry of Transplant Recipients database from December 16, 2011 to February 28, 2019 to compare male and female children after listing and after transplant. Demographic, clinical characteristics and outcomes were compared unadjusted and after 1:1 propensity matching for selected covariates. RESULTS: Of 4089 patients, 2299 (56%) were males. At listing, males were more likely to be older, have congenital heart disease (58% vs 48%), renal dysfunction (49% vs 44%) and implantable cardioverter defibrillator (9% vs 7%). At transplant, males were more likely to have renal (42 % vs 35%) and liver dysfunction (13% vs 10%), PRA >10% (29% vs 22%) and ischemic time >3.5 hours (p

Background Brain functional alterations during emotion processing in patients with major depressive disorder (MDD) compared with healthy control subjects (HCs) are frequently reported. However, evidence for functional correlates of emotion processing with regard to MDD trajectories is scarce. This study investigates the role of lifetime disease course for limbic brain activation during negative emotional face processing in patients with MDD. Methods In a large sample of patients with MDD (n = 333; 58.55% female) and HCs (n = 333; 60.06% female), brain activation was investigated during a negative emotional face-processing task within a cross-sectional design. Differences between HC and MDD groups were analyzed. Previous disease course, characterized by 2 components, namely hospitalization and duration of illness, was regressed on brain activation of the amygdala, (para-)hippocampus, and insula in patients with MDD. Results Patients with MDD showed increased activation in the amygdala, insula, and hippocampus compared with HCs (all p values corrected for familywise error [pFWE] .057). Conclusions This study investigated negative emotion processing in a large sample of patients with MDD and HCs. Our results confirm limbic hyperactivation in patients with MDD during negative emotion processing; however, this hyperactivation may resolve with a more severe lifetime disease course in the insula and (para-)hippocampus—brain regions involved in emotion processing and regulation. These findings need further replication in longitudinal studies.

ObjectiveTo compare key seizure and outcome characteristics between neonates with and without cardiopulmonary disease.Study designThe Neonatal Seizure Registry is a multicenter, prospectively acquired cohort of neonates with clinical or electroencephalographic (EEG)-confirmed seizures. Cardiopulmonary disease was defined as congenital heart disease, congenital diaphragmatic hernia, and exposure to extracorporeal membrane oxygenation. We assessed continuous EEG monitoring strategy, seizure characteristics, seizure management, and outcomes for neonates with and without cardiopulmonary disease.ResultsWe evaluated 83 neonates with cardiopulmonary disease and 271 neonates without cardiopulmonary disease. Neonates with cardiopulmonary disease were more likely to have EEG-only seizures (40% vs 21%, P&nbsp

Sickle cell disease (SCD) is the most common hereditary blood disorder in the United States. SCD is frequently associated with osteonecrosis, osteoporosis, osteopenia, and other bone-related complications such as vaso-occlusive pain, ischemic damage, osteomyelitis, and bone marrow hyperplasia known as sickle bone disease (SBD). Previous SBD models have failed to distinguish the age- and sex-specific characteristics of bone morphometry. In this study, we use the Townes mouse model of SCD to assess the pathophysiological complications of SBD in both SCD and sickle cell trait. Changes in bone microarchitecture and bone development were assessed by using high-resolution quantitative micro–computed tomography and the three-dimensional reconstruction of femurs from male and female mice. Our results indicate that SCD causes bone loss and sex-dependent anatomical changes in bone. SCD female mice in particular are prone to trabecular bone loss, whereas cortical bone degradation occurs in both sexes. We also describe the impact of genetic knockdown of cathepsin K– and E-64–mediated cathepsin inhibition on SBD.

Purpose: Severe viral pneumonia is associated with significant morbidity and mortality. Recent COVID-19 pandemic continues to impose significant health burden worldwide, and individual pandemic waves often lead to a large surge in the intensive care unit (ICU) admissions for respiratory support. Comparisons of severe SARS-CoV-2 pneumonia with other seasonal and nonseasonal severe viral infections are rarely studied in an intensive care setting. Methods: A retrospective cohort study comparing patients admitted to ICU with COVID-19 between March and June 2020 and those with viral pneumonias between January and December 2019. We compared patient specific demographic variables, duration of illness, ICU organ supportive measures and outcomes between both groups. Results: Analysis of 93 COVID-19 (Group 1) and 52 other viral pneumonia patients (Group 2) showed an increased proportion of obesity (42% vs. 23%, p = 0.02), non-White ethnicities (41% vs. 6%, p < 0.001) and diabetes mellitus (30% vs. 13%, p = 0.03) in Group 1, with lower prevalence of chronic obstructive pulmonary disease (COPD)/asthma (16% vs. 34%, p = 0.02). In Group 1, the neutrophil to lymphocyte ratio was much lower (6.7 vs. 10, p = 0.006), and invasive mechanical ventilation (58% vs. 26%, p < 0.001) was more common. Length of ICU (8 vs. 4, p < 0.001) and hospital stay (22 vs. 11, p < 0.001) was prolonged in Group 1, with no significant difference in mortality. Influenza A and rhinovirus were the most common pathogens in Group 2 (26% each). Conclusions: Key differences were identified within demographics (obesity, ethnicity, age, ICU scores, comorbidities) and organ support. Despite these variations, there were no significant differences in mortality between both groups. Further studies with larger sample sizes would allow for further assessment of clinical parameters in these patients.

Dementia is a progressive disorder that affects how the brain works, and in particular the ability to remember, think, and reason. It affects speech, mood, mobility, behavior, and how people perceive and respond to the world around them. Contemporary approaches to understanding dementia encourage society to think about how people can live well in their communities. These approaches focus on ensuring that people with dementia see the diagnosis not as the end of their life, but rather as the beginning of a new chapter of their life. This study explores how arts events specifically tailored for people with dementia can help those with a dementia diagnosis to live well after their diagnosis. In this study, we have undertaken qualitative research in the form of semistructured interviews with festival organizers and event managers in order to understand the value of arts festivals and events in the context of dementia care. In this article, we present areas of best practice within the Arts and Culture sector and offer recommendations for improvement in how festival and event managers make their arts events accessible and a positive experience for those living with dementia. The key theoretical contribution of this article is the proposition of a theoretical framework that explores dementia arts events as they relate to a palliative model on relationship-centered care for people living with dementia—the "Senses Framework"—and we apply this framework from social care in an arts events context.

Classic adenoid cystic carcinomas (C-AdCCs) of the breast are rare, relatively indolent forms of triple negative cancers, characterized by recurrent MYB or MYBL1 genetic alterations. Solid and basaloid adenoid cystic carcinoma (SB-AdCC) is considered a rare variant of AdCC yet to be fully characterized. Here, we sought to determine the clinical behavior and repertoire of genetic alterations of SB-AdCCs. Clinicopathologic data were collected on a cohort of 104 breast AdCCs (75 C-AdCCs and 29 SB-AdCCs). MYB expression was assessed by immunohistochemistry and MYB-NFIB and MYBL1 gene rearrangements were investigated by fluorescent in-situ hybridization. AdCCs lacking MYB/MYBL1 rearrangements were subjected to RNA-sequencing. Targeted sequencing data were available for 9 cases. The invasive disease-free survival (IDFS) and overall survival (OS) were assessed in C-AdCC and SB-AdCC. SB-AdCCs have higher histologic grade, and more frequent nodal and distant metastases than C-AdCCs. MYB/MYBL1 rearrangements were significantly less frequent in SB-AdCC than C-AdCC (3/14, 21% vs 17/20, 85% P

Objective The current study examined the unique influences of romantic relationship status and episodic and chronic stress associated with relationships in predicting changes in alcohol consumption and drinking motivations from college to post-college life. Method Moderate to heavy college student drinkers reported their drinking level and drinking motives using an Internet-based daily diary for 30 days in college and again 5 years later. At the post-college wave, participants also completed a semi-structured phone-based interview to assess romantic relationship stress. Results Multiple regression analysis indicated that chronic relationship stress and relationship dissolution stress were uniquely related to mean daily levels of post-college drinking to cope (DTC) motivation, but not to mean daily levels of enhancement motivation. Some evidence was found for the effect of relationship status, but not stress, on mean daily heavy drinking levels. We also found evidence that chronic stress moderated the effect of relationship dissolution stress, with individuals showing higher mean daily chronic stress levels displaying a stronger positive association between relationship dissolution and post-college DTC motivation. Conclusions Results are discussed in terms of how negative reinforcement processes might be an important mechanism underlying commonly found associations between romantic relationship status and problematic drinking during young adulthood. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Summary: Background: Obesity is associated with suboptimal levels in vitamin D, a nutrient important for bone health and immune function. Seasonal variation in vitamin D may exacerbate this deficiency in persons with obesity, as exposure to ultraviolet B rays in sunlight is necessary for the conversion of vitamin D to its active form in the body. The aim of this study was to determine the relationship between season and vitamin D levels in persons with obesity pursuing bariatric surgery. Materials and Methods: This retrospective cohort study from a single academic medical center investigated adult patients undergoing either primary sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) over a 20-year period. Demographics and serum 25-hydroxyvitamin D3 levels were collected from the first presenting visit to the bariatrics center. Continuous vitamin D3 levels were compared across seasons using a one-way Analysis of Variance (ANOVA). Vitamin D3 categories were examined across seasons using a Chi square test of independence. Results: 1,256 persons pursuing bariatric surgery (SG: N=697, RYGB: N=559) met the inclusion criteria. Baseline vitamin D values were available in 1,071 of the eligible patients. Overall, serum 25-hydroxyvitamin D3 levels showed a significant variation across the seasons of the year (P

BACKGROUND: Repair of complete atrioventricular canal (CAVC) is often complicated by atrioventricular valve regurgitation, particularly of the left-sided valve. Understanding the three-dimensional (3D) structure of the atrioventricular canal annulus prior to repair may help to inform optimized repair. However, the 3D shape and movement of the CAVC annulus has yet to be quantified nor has it been rigorously compared to a normal mitral valve annulus. METHODS: The complete annuli of 43 patients with CAVC were modeled in 4 cardiac phases using transthoracic 3D echocardiograms and custom code. The annular structure was compared to the annuli of 20 normal pediatric mitral valves using 3D metrics and statistical shape analysis (Procrustes analysis). RESULTS: The unrepaired CAVC annulus varied in shape significantly throughout the cardiac cycle. Procrustes analysis visually demonstrated that the average normalized CAVC annular shape is more planar than the normal mitral annulus. Quantitatively, the annular height to valve width ratio of the native left CAVC atrioventricular valve was significantly lower than that of a normal mitral valve in all systolic phases(p

Introduction Heart Transplantation (HT) is a rational therapy for advanced transthyretin cardiac amyloidosis (ATTR-CA), but the impact of ongoing amyloid deposition is not well defined. We evaluated a cohort of patients who underwent HT for ATTR-CA to determine the incidence of de novo or progression of post-HT ATTR deposition. Methods All patients who were followed post-HT for ATTR-CA at our center were included. Baseline demographics and post-HT manifestations of TTR deposition were collected. All patients completed the Composite Autonomic Symptom Score (COMPASS-31 quantifies autonomic symptoms, with a higher score [0 – 100] indicating more severe autonomic dysfunction) and Polyneuropathy Disability Score (PND, range from 0 [asymptomatic] to IV [confined to wheelchair/bed]) questionnaires. Results Twelve patients (5 wild-type, 7 variant [6 p.Val142Ile, 1 p.Thr80Ala]) were included. Mean age at HT was 64.6 (SD: 4.8) years, 83.3% male, and 50% Black. At a median of 4.0 years (IQR 2.4, 5.9) post-HT, 8 patients had symptoms of ATTR deposition (5 with gastrointestinal involvement, 4 orthopedic and 4 neurologic), with 4 patients having ≥ 2 body systems involved. There were no patients with recurrent cardiac involvement. Median COMPASS-31 score was 17.3 (IQR 11.3, 23.5) at 3.9 years (IQR 2.4, 5.9) post-HT. Four patients had a PND score of stage 1 (sensory disturbance), 1 patient was stage 2 (impaired walking) and 1 patient stage 3b (required a walking aid). Conclusion More than 50% of patients had evidence of progressive or de novo ATTR deposition post-HT, impairing quality of life despite a well-functioning cardiac allograft. These observations highlight an unmet need to establish the role of formal surveillance and treatment of TTR using TTR disease-modifying therapies, which may maintain or improve quality of life post-HT for ATTR-CA.

BACKGROUND: Therapeutic drug monitoring (TDM) supports personalized treatment. For successful implementation, TDM must have a turnaround time suited to the clinical needs of patients and their health care settings. Here, the authors share their views of how a TDM strategy can be tailored to specific settings and patient groups.METHODS: The authors selected distinct scenarios for TDM: high-risk, complex, and/or critically ill patient population; outpatients; and settings with limited laboratory resources. In addition to the TDM scenario approach, they explored potential issues with the legal framework governing dose escalation.RESULTS: The most important issues identified in the different scenarios are that critically ill patients require rapid turnaround time, outpatients require an easy sampling procedure for the sample matrix and sample collection times, settings with limited laboratory resources necessitate setting-specific analytic techniques, and all scenarios warrant a legal framework to capture the use of escalated dosages, ideally with the use of trackable dosing software.CONCLUSIONS: To benefit patients, TDM strategies need to be tailored to the intended population. Strategies can be adapted for rapid turnaround time for critically ill patients, convenient sampling for outpatients, and feasibility for those in settings with limited laboratory resources.

Extradomain-B Fibronectin (EDB-FN) is an oncomarker that can be visualized with magnetic resonance molecular imaging (MRMI) to detect pancreatic ductal adenocarcinoma (PDAC) metastasis. In this study, we sought to assess the expression of EDB-FN in clinical samples of PDAC and to evaluate MRMI of PDAC metastasis with an EDB-FN-specific gadolinium-based contrast agent (MT218) in an orthotopic KPC-GFP-Luc mouse model. EDB-FN expression was evaluated in PDAC tissue samples through immunohistochemistry. RNA-Seq data obtained from the GEPIA2 project was evaluated to demonstrate EDB-FN expression in large patient cohorts. FLASH-3D MRI at 3 T of the KPC-GFP-Luc metastasis model was performed following injection of MT218. Tumor enhancement in MR images was correlated to postmortem distribution of KPC-GFP-Luc tumors using fluorescent and bright-field cryo-imaging and anatomical landmarks. EDB-FN immunohistochemical staining scores of human metastatic tumor stroma, (2.17 ± 0.271), metastatic tumor parenchyma (2.08 ± 0.229), primary tumor stroma (1.61 ± 0.26), and primary tumor parenchyma (1.61 ± 0.12) were significantly (p

Malaria is a leading cause of death in children less than 5 years of age globally, and a common cause of fever in the returning North American traveler. New tools in the fight against malaria have been developed over the past decades: potent artemisinin derivatives; rapid diagnostic tests; long-lasting insecticidal bed nets; and a new vaccine, RTS,S/AS01. Thwarting these advances, parasite and Anopheles vector resistance are emerging. In the meantime, clinicians will continue to see malaria among febrile travelers from the tropics. Early recognition, diagnosis, and treatment can be lifesaving, but rely on the vigilance of frontline clinicians.

Testicular germ cell tumors (TGCTs) are aggressive but sensitive to cisplatin‐based chemotherapy. Alternative therapies are needed for tumors refractory to cisplatin with hypomethylating agents providing one possibility. The mechanisms of cisplatin hypersensitivity and resistance in TGCTs remain poorly understood. Recently, it has been shown that TGCTs, even those resistant to cisplatin, are hypersensitive to very low doses of hypomethylating agents including 5‐aza deoxy‐cytosine (5‐aza) and guadecitabine. We undertook a pharmacogenomic approach in order to better understand mechanisms of TGCT hypomethylating agent hypersensitivity by generating a panel of acquired 5‐aza‐resistant TGCT cells and contrasting these to previously generated acquired isogenic cisplatin‐resistant cells from the same parent. Interestingly, there was a reciprocal relationship between cisplatin and 5‐aza sensitivity, with cisplatin resistance associated with increased sensitivity to 5‐aza and 5‐aza resistance associated with increased sensitivity to cisplatin. Unbiased transcriptome analysis revealed 5‐aza‐resistant cells strongly downregulated polycomb target gene expression, the exact opposite of the finding for cisplatin‐resistant cells, which upregulated polycomb target genes. This was associated with a dramatic increase in H3K27me3 and decrease in DNMT3B levels in 5‐aza‐resistant cells, the exact opposite changes seen in cisplatin‐resistant cells. Evidence is presented that reciprocal regulation of polycomb and DNMT3B may be initiated by changes in DNMT3B levels as DNMT3B knockdown alone in parental cells resulted in increased expression of H3K27me3, EZH2, and BMI1, conferred 5‐aza resistance and cisplatin sensitization, and mediated genome‐wide repression of polycomb target gene expression. Finally, genome‐wide analysis revealed that 5‐aza‐resistant, cisplatin‐resistant, and DNMT3B‐knockdown cells alter the expression of a common set of polycomb target genes. This study highlights that reciprocal epigenetic changes mediated by DNMT3B and polycomb may be a key driver of the unique cisplatin and 5‐aza hypersensitivity of TGCTs and suggests that distinct epigenetic vulnerabilities may exist for pharmacological targeting of TGCTs., Alternative therapies are needed for testicular germ cell tumors (TGCTs) refractory to cisplatin. Recent preclinical and clinical studies suggest that cisplatin refractory TGCTs are distinctly sensitive to hypomethylating agents. The current study suggests a reciprocal relationship between cisplatin and hypomethylation agent sensitivity in TGCTs involving DNMT3B and the polycomb pathway that could lead to biomarkers for future clinical trials.