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Traumatic brain injury (TBI) and blunt thoracic aortic injury (BTAI) are the top two leading causes of death after blunt force trauma. Patients presenting with concomitant BTAI and TBI pose a specific challenge with respect to management strategy, because the optimal hemodynamic parameters are conflicting between the two pathologies. Early thoracic endovascular aortic repair (TEVAR) is often performed, even for minimal aortic injuries, to allow for the higher blood pressure parameters required for TBI management. However, the optimal timing of TEVAR for the treatment of BTAI in patients with concomitant TBI remains an active matter of controversy.The Aortic Trauma Foundation international prospective multicenter registry was used to identify all patients who had undergone TEVAR for BTAI in the setting of TBI from 2015 to 2020. The primary outcomes included delayed ischemic or hemorrhagic stroke, in-hospital mortality, and aortic-related mortality. The outcomes were examined among patients who had undergone TEVAR at emergent (6 vs ≥6 hours) or urgent (24 vs ≥24 hours) intervals.A total of 100 patients (median age, 43 years; 79% men; median injury severity score, 41) with BTAI (Society for Vascular Surgery BTAI grade 1, 3%; grade 2, 10%; grade 3, 78%; grade 4, 9%) and concomitant TBI who had undergone TEVAR were identified. Emergent repair was performed for 51 patients (51%). Comparing emergent repair (6 hours) to urgent repair (≥6 hours), no difference was found in delayed cerebral ischemic events (2.0% vs 4.1%; P = .614), in-hospital mortality (15.7% vs 22.4%; P = .389), or aortic-related mortality (2.0% vs 2.0%; P = .996) and no patient had experienced delayed hemorrhagic stroke. Likewise, repairs conducted in an urgent (24 hours) setting showed no differences compared with those completed in an emergent (≥24 hours) setting regarding delayed ischemic stroke (2.6% vs 4.3%; P = .548), in-hospital mortality (18.2% vs 21.7%; P = .764), or aortic-related mortality (1.3% vs 4.3%; P = .654), and no patient had experienced delayed hemorrhagic stroke.In contrast to prior retrospective efforts, results from the Aortic Trauma Foundation international prospective multicenter registry have demonstrated that neither emergent nor urgent TEVAR for patients with concomitant BTAI and TBI was associated with delayed stroke, in-hospital mortality, or aortic-related mortality. In these patients, the timing of TEVAR did not have an effect on the outcomes. Therefore, the decision to intervene should be guided by individual patient factors rather than surgical timing.

Objective Damage associated molecular patterns (DAMPs) are pathological mediators linking local tissue damage to systemic inflammation in various diseases. Some DAMPs, such as mitochondrial DNA (mtDNA), can be recognized by the cytoplasmic cGAS protein to trigger the activation of the stimulator of interferon genes (STING)-dependent innate immune pathway responsible for infection or sterile inflammation. The objective of our study was to evaluate the association between circulating mtDNA and cGAS-STING pathway activation in mediating inflammation following burn injury. Methods 48 adult Sprague-Dawley male rats were divided into eight groups (Sham, 2, 4, 8, 12, 24, 48, 72 h after burn injury). The animals underwent 40% total body surface area scald injury to produce a full-thickness burn. Plasma samples were collected via cardiac puncture under deep anesthesia. Tissues were harvested and placed in formalin, followed by paraffin embedment. Total plasma DNA was isolated followed by measurement of mtDNA using quantitative polymerase chain reaction. Haemotoxylin-Eosin stain and Western blot was used for lung histology and protein assays, respectively. Statistical analyses were performed using ANOVA and student’s t-test and represented as mean ± s.d. Results Plasma mtDNA trended upward at early time-points following burn injury with peak levels at 8 h after burn when compared to the control group (345 ± 83.4 copies/μl vs. 239 ± 43.1 copies/μl, p = 0.07) and followed a bell-shaped distribution. Lung slices from burned rats showed acute injury marked by increased inflammatory infiltrate, with the maximum changes seen at 24 h, accompanied with significant upregulation of neutrophil elastase (p = 0.04). Compared with sham animals, cGAS and STING protein levels in lung tissue were up-regulated at 4 and 8 h after burn (p = 0.03 and p Conclusion Activation of the cGAS-STING pathway by increased plasma mtDNA is an important pathway driving neutrophil infiltration in burn-induced acute lung injury in rats. A further understanding of the STING-mediated immunopathology in lung and other susceptible organs may be important for the development of novel therapies for burn injury.

Background Cognitive behavioral therapy for targeted-therapy related fatigue (CBT-TTF) has demonstrated preliminary efficacy in reducing fatigue in patients treated with tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML). Purpose The aim of the current analyses was to explore whether fatigue perpetuating factors (disturbed sleep/wake cycle, dysregulated activity patterns, maladaptive cognitions about fatigue and cancer, insufficient processing of cancer and treatment, inadequate social support and interactions, heightened fear of cancer progression) changed over time in patients receiving CBT-TTF, and whether the effect of CBT-TTF on fatigue was mediated by these factors. Methods Secondary data analyses were conducted from a pilot randomized controlled trial. Patients with CML treated with a TKI who reported moderate to severe fatigue were randomized 2:1 to CBT-TTF delivered via FaceTime for iPad or a waitlist control condition (WLC). Self-report measures of fatigue and fatigue perpetuating factors were obtained before randomization and post-intervention (i.e., approximately 18 weeks later). Mixed model and mediation analyses using bootstrap methods were used. Results A total of 36 participants (CBT-TTF n = 22, WLC n = 14) who had baseline and 18-week follow-up data and attended >5 sessions for CBT-TTF were included. Participants randomized to CBT-TTF reported improvements in activity (mental, physical, social, p’s ≤ .023) and cognitions (helplessness, catastrophizing, focusing on symptoms, self-efficacy, p’s ≤ .003) compared to WLC. Mental activity, social activity, self-efficacy, helplessness, and focusing on symptoms, as well as sleep and insufficient processing (avoidance) mediated the relationship between treatment group and fatigue. Conclusions CBT-TTF appears to improve TKI-related fatigue in CML patients through changes in behavior (sleep, activity patterns) and cognitions about fatigue and cancer. A larger randomized controlled trial is warranted to confirm these findings.

Aging is accompanied by declining lung function and increasing susceptibility to lung diseases. The role of endothelial dysfunction and vascular remodeling in these changes is supported by growing evidence, but underlying mechanisms remain elusive. In this review we summarize functional, structural, and molecular changes in the aging pulmonary vasculature and explore how interacting aging and mechanobiological cues may drive progressive vascular remodeling in the lungs.

Objectives While there is growing evidence of an association between depressive symptoms and postoperative delirium, the underlying pathophysiological mechanisms remain unknown. The goal of this study was to explore the association between depression and postoperative delirium in hip fracture patients, and to examine Alzheimer's disease (AD) pathology as a potential underlying mechanism linking depressive symptoms and delirium. Methods Patients 65 years old or older (N = 199) who were undergoing hip fracture repair and enrolled in the study “A Strategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients” completed the 15-item Geriatric Depression Scale (GDS-15) preoperatively. Cerebrospinal fluid (CSF) was obtained during spinal anesthesia and assayed for amyloid-beta (Aβ) 40, 42, total tau (t-tau), and phosphorylated tau (p-tau)181. Results For every one point increase in GDS-15, there was a 13% increase in odds of postoperative delirium, adjusted for baseline cognition (MMSE), age, sex, race, education and CSF AD biomarkers (OR = 1.13, 95%CI = 1.02–1.25). Both CSF Aβ42/t-tau (β = −1.52, 95%CI = −2.1 to −0.05) and Aβ42/p-tau181 (β = −0.29, 95%CI = −0.48 to −0.09) were inversely associated with higher GDS-15 scores, where lower ratios indicate greater AD pathology. In an analysis to identify the strongest predictors of delirium out of 18 variables, GDS-15 had the highest classification accuracy for postoperative delirium and was a stronger predictor of delirium than both cognition and AD biomarkers. Conclusions In older adults undergoing hip fracture repair, depressive symptoms were associated with underlying AD pathology and postoperative delirium. Mild baseline depressive symptoms were the strongest predictor of postoperative delirium, and may represent a dementia prodrome.

The developing brain is particularly vulnerable to foetal growth restriction (FGR) and abnormal neurodevelopment is common in the FGR infant ranging from behavioural and learning disorders to cerebral palsy. No treatment exists to protect the FGR newborn brain. Recent evidence suggests inflammation may play a key role in the mechanism responsible for the progression of brain impairment in the FGR newborn, including disruption to the neurovascular unit (NVU). We explored whether ibuprofen, an anti-inflammatory drug, could reduce NVU disruption and brain impairment in the FGR newborn. Using a preclinical FGR piglet model, ibuprofen was orally administered for 3 days from birth. FGR brains demonstrated a proinflammatory state, with changes to glial morphology (astrocytes and microglia), and blood-brain barrier disruption, assessed by IgG and albumin leakage into the brain parenchyma and a decrease in blood vessel density. Loss of interaction between astrocytic end-feet and blood vessels was evident where plasma protein leakage was present, suggestive of structural deficits to the NVU. T-cell infiltration was also evident in the parenchyma of FGR piglet brains. Ibuprofen treatment reduced the pro-inflammatory response in FGR piglets, reducing the number of activated microglia and enhancing astrocyte interaction with blood vessels. Ibuprofen also attenuated plasma protein leakage, regained astrocytic end-feet interaction around vessels, and decreased T-cell infiltration into the FGR brain. These findings suggest postnatal administration of ibuprofen modulates the inflammatory state, allowing for stronger interaction between vasculature and astrocytic end-feet to restore NVU integrity. Modulation of the NVU improves the FGR brain microenvironment and may be key to neuroprotection.

Purpose: To evaluate the association between neutrophil-to-lymphocyte ratio (NLR) and efficacy of avelumab plus axitinib or sunitinib. Experimental Design: Adult patients with untreated advanced renal cell carcinoma (RCC) with a clear-cell component, ≥1 measurable lesions, Eastern Cooperative Oncology Group performance status of 0 or 1, fresh or archival tumor specimen, and adequate renal, cardiac, and hepatic function were included. Retrospective analyses of the association between baseline NLR and progression-free survival (PFS) and overall survival (OS) in the avelumab plus axitinib or sunitinib arms were performed using the first interim analysis of the phase 3 JAVELIN Renal 101 trial (NCT02684006). Multivariate Cox regression analyses of PFS and OS were conducted. Translational data were assessed to elucidate the underlying biology associated with differences in NLR. Results: Patients with below-median NLR had longer observed PFS with avelumab plus axitinib [stratified HR, 0.85; 95% confidence interval (CI), 0.634–1.153] or sunitinib (HR, 0.56; 95% CI, 0.415–0.745). In the avelumab plus axitinib or sunitinib arms, respectively, median PFS was 13.8 and 11.2 months in patients with below-median NLR, and 13.3 and 5.6 months in patients with median-or-higher NLR. Below-median NLR was also associated with longer observed OS in the avelumab plus axitinib (HR, 0.51; 95% CI, 0.300–0.871) and sunitinib arms (HR, 0.30; 95% CI, 0.174–0.511). Tumor analyses showed an association between NLR and key biological characteristics, suggesting a role of NLR in underlying mechanisms influencing clinical outcome. Conclusions: Current data support NLR as a prognostic biomarker in patients with advanced RCC receiving avelumab plus axitinib or sunitinib.

Australian aerial skiers are recruited from other acrobatic sports through a nationally coordinated transition program. However, there is limited understanding of how to train transferring athletes for both optimal performance and injury prevention. The aim of this study was to test whether an athletic profile could be used to identify which skills that gymnasts possess are more and less likely to transfer to aerial skiing based on similarities and differences in the athletes’ physical attributes. Six elite female aerial skiers and five state- and national-level female gymnasts completed a test protocol involving drop-landing, countermovement jump, isokinetic strength of the knee flexors and extensors, flexibility and anthropometrical profile. Aerial skiers and gymnasts had an anthropometrical profile ideal for acrobatic efficiency, but gymnasts had smaller thigh girth and greater knee range of motion. These results suggest that gymnasts are more likely to succeed in transferring to aerial skiing's acrobatic skills than skiing and landing skills. We suggest that gymnasts transferring to aerial skiing undertake pretransfer training designed to improve hamstring isometric strength and dynamic stability of the knee to reduce the risk of knee injury and improve their ability to maintain a crouched position.

Background Hysteroscopy requires accurate collection of unabsorbed distension media to measure patient fluid absorption. We assessed the effectiveness and usability of a novel total capture drape compared with a standard drape during hysteroscopy. Method Simulation trials were followed by an early-phase study to compare fluid-capture efficiency and measures of drape usability during hysteroscopy randomizing the total capture drape compared with a standard drape. Experience Simulation trials indicated complete collection of unabsorbed fluid with the total capture drape and progressive loss of unabsorbed fluid with the standard drape. An early-phase study with 68 women found no statistical difference between groups for the hysteroscopic fluid deficit, but saw fewer cases with lost fluid in the total capture drape compared with the standard drape. Direct observation and focus group data indicated a trend for better capture of unabsorbed fluid with the total capture drape, along with increased usability once surgeons became familiar with correct placement. Conclusion Simulation and early-phase study results are favorable for the total capture drape, demonstrating comparable fluid collection with the standard drape. With repeated use and in-service training, surgeons expressed greater confidence in the accuracy of the hysteroscopic fluid deficit with the total capture drape compared with the standard drape. Design modifications should improve overall usability and fluid-capture efficiency.

BACKGROUND AND OBJECTIVES Length of stay is a common measure of efficiency of care. We aimed to reduce length of stay on a general medicine service through a structured quality improvement project. METHODS A reliable design strategy was implemented in successive stages at a 238-bed academically-affiliated VA hospital. Over a 2-year period, continuous improvement efforts were directed at discrete cohorts of patients deemed medically appropriate for discharge but who remained hospitalized because of discharge barriers. We compared the mean length of stay and medically-ready bed days of care for a hospital in statistical control charts. Pre- and post-intervention comparisons were made using t-tests. RESULTS In total, 5321 discharges were included in this improvement project, accounting for 35 852 bed days of care. Overall, average length of stay was reduced by 15.7%, from 7.62 to 6.40 days (P < .05). There was a significant reduction in the mean number of medically-ready bed days of care from 2.3 to 1.72. Statistical process control charts demonstrated special cause variation across patient cohorts. CONCLUSION A quality improvement project using reliable design principles was associated with shorter length of stay.

Summary Inhibin-positive hepatic carcinoma is a rare primary liver neoplasm that resembles sex cord–stromal tumor and thyroid follicular tumors. The term “cholangioblastic variant of intrahepatic cholangiocarcinoma” has been proposed. This study describes the clinicopathologic, immunophenotypic, and molecular features of a small series (n = 6) of this rare tumor. Albumin in situ hybridization (ISH) and capture-based next-generation sequencing (NGS) were also performed. All tumors occurred in young women (mean age 32.5 years, range 19–44 years) as a solitary large mass (mean 15.8 cm, range 6.9–23.5 cm). All tumors showed a highly distinctive morphology with sheets and large nests of tumor cells alternating with tubular and cystic areas imparting a sex cord–like or thyroid follicle–like morphology. Cytologic atypia was mild, and mitotic activity was low. All cases were positive for inhibin, as well as pancytokeratin, CK7, CK19, and albumin ISH. Synaptophysin and chromogranin showed focal or patchy staining, whereas INSM1 was negative. Markers for hepatocellular differentiation, thyroid origin, and sex cord–stromal tumor were negative. There were no recurrent genomic changes based on capture-based NGS of ∼500 cancer genes. Recurrence and/or metastasis was seen in three (50%) cases (follow-up time range for all cases: 5 months to 2 years). In conclusion, this series describes the distinctive morphology, immunophenotypic features, and diffuse albumin staining in six cases of a rare inhibin-positive primary liver carcinoma that runs an aggressive course similar to intrahepatic cholangiocarcinoma. Genomic changes typical of cholangiocarcinoma or hepatocellular carcinoma were not identified, and there were no recurrent genetic abnormalities. We propose the term “solid-tubulocystic variant of intrahepatic cholangiocarcinoma” to reflect the spectrum of morphologic patterns observed in this tumor.

Obsessive-compulsive disorder (OCD) is a chronic, disabling mental health condition with limited treatment options available to date. Numerous randomized controlled trials have explored the efficacy of repetitive transcranial magnetic stimulation (rTMS) in OCD. This meta-analysis synthesized data from selected randomized controlled trials and examined the impact of different treatment parameters to generate hypotheses that would direct future randomized controlled trials.A database search was performed to identify studies published in English up to October 2020. Randomized, sham-controlled studies that used rTMS to treat OCD were included. Effect sizes were calculated using Hedges' g for pre- to post-treatment Yale-Brown Obsessive Compulsive Scale scores. Subgroup analyses were conducted to assess the effects of variations in rTMS treatment parameters.A total of 26 studies with 781 participants were included. Overall, rTMS demonstrated a modest effect on reduction of Yale-Brown Obsessive Compulsive Scale scores (Hedges' g = 0.64, 95% confidence interval = 0.39-0.89; p.0001). The largest significant effect size was obtained by targeting the bilateral dorsolateral prefrontal cortex. High- and low-frequency rTMS showed comparable effects. Studies with follow-up data suggested that the effects of active rTMS remain significantly superior to those of sham 4 weeks after treatment.The therapeutic effects of rTMS are superior to those of sham in the treatment of OCD. Targeting the bilateral dorsolateral prefrontal cortex was the most favorable approach in administering rTMS. Further research is required to determine the optimal frequency, total pulses per session, and duration of treatment with rTMS for OCD.

The objective of this study was to systematically review the literature to determine the effect of combined hypothermia (HTH) and mesenchymal stem cell (MSC) therapy (administered during or immediately before or after HTH) compared with HTH alone on brain injury and neurobehavioural outcomes in animal models of neonatal hypoxic-ischaemic encephalopathy. Primary outcomes assessed were neuropathological measures and neurobehavioural measures of brain outcome. Secondary outcomes were brain protein proinflammatory cytokine status. Risk of bias (ROB) was assessed with the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) ROB assessment tool. Of 393 studies identified, 3 studies in postnatal day 7 (P7) male Sprague-Dawley rats met the inclusion criteria. Meta-analyses were undertaken for neuropathological measures (apoptotic cells, astrocytes, microglia), neurobehavioral measures (rotarod test and negative geotaxis), and proinflammatory cytokine levels. Two of the three studies scored low or unclear ROB across all measures. Treatment with HTH-MSCs together significantly improved astrocyte optical density by standardised mean difference (SMD) of 0.71 [95% confidence interval (CI) -1.14, -0.28]. No other measures showed significant differences. There is insufficient preclinical data to confirm the efficacy of combined HTH-MSC therapy over HTH alone. Future studies should utilise a reporting checklist such as in SYRCLE or Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines to improve reporting standards. Very few articles investigating the use of MSCs for the treatment of hypoxic-ischaemic encephalopathy are clinically relevant. Continuing to publish studies in models of hypoxic-ischaemic encephalopathy without the inclusion of HTH therapy does not progress the field towards improved clinical outcomes. This study shows that HTH and MSC therapy improves measures of astrogliosis. More studies are required to establish the efficacy of HTH and MSCs on measures of neuropathology and neurobehavior. The reporting of preclinical data in this space could be improved by using reporting checklists such as the SYRCLE or ARRIVE tools.

Background High-frequency rTMS over the dorsolateral prefrontal cortex (DLPFC) has demonstrated mixed effects on chronic and provoked pain. Objectives/Methods In this study, a meta-analysis was conducted to characterise the potential analgesic effects of high-frequency rTMS over the DLPFC on both chronic and provoked pain. Results A total of 626 studies were identified in a systematic search. Twenty-six eligible studies were included for the quantitative review, among which 17 modulated chronic pain and the remaining investigated the influence on provoked pain. The left side DLPFC was uniformly targeted in the chronic pain studies. While our data identified no overall effect of TMS across chronic pain conditions, there was a significant short-term analgesia in neuropathic pain conditions only (SMD = −0.87). In terms of long-lasting analgesia, there was an overall pain reduction in the midterm (SMD = −0.53, 24.6 days average) and long term (SMD = −0.63, 3 months average) post DLPFC stimulation, although these effects were not observed within specific chronic pain conditions. Surprisingly, the number of sessions was demonstrated to have no impact on rTMS analgesia. In the analysis of provoked pain, our data also indicated a significant analgesic effect following HF-rTMS over the DLPFC (SMD = −0.73). Importantly, we identified a publication bias in the studies of provoked pain but not for chronic pain conditions. Conclusions Overall, our findings support that HF-DLPFC stimulation is able to induce an analgesic effect in chronic pain and in response to provoked pain. These results highlight the potential of DLPFC-rTMS in the management of certain chronic pain conditions and future directions are discussed to enhance the potential long-term analgesic effects.

Despite more than 25 years of research establishing the antidepressant efficacy of repetitive transcranial magnetic stimulation, there remains uncertainty about the depth and breadth of this evidence base, resulting in confusion as to where repetitive transcranial magnetic stimulation fits in the therapeutic armamentarium in the management of patients with mood disorders. The purpose of this article is to provide a concise description of the evidence base supporting the use of repetitive transcranial magnetic stimulation in the context of the stages of research that typically accompanies the development of evidence for a new therapy. The antidepressant efficacy for the use of repetitive transcranial magnetic stimulation in the treatment of depression has been established through a relatively traditional pathway beginning with small case series, progressing to single-site clinical trials and then to larger multisite randomised double-blind controlled trials. Antidepressant effects have been confirmed in numerous meta-analyses followed more recently by large network meta-analysis and umbrella reviews, with evidence that repetitive transcranial magnetic stimulation may have greater efficacy than alternatives for patients with treatment-resistant depression. Finally, repetitive transcranial magnetic stimulation has been shown to produce meaningful response and remission rates in real-world samples of greater than 5000 patients. The evidence for the antidepressant efficacy of repetitive transcranial magnetic stimulation therapy is overwhelming, and it should be considered a routine part of clinical care wherever available.

Many individual and team sport events require extended periods of exercise above the speed or power associated with maximal oxygen uptake (i.e., maximal aerobic speed/power, MAS/MAP). In the absence of valid and reliable measures of anaerobic metabolism, the anaerobic speed/power reserve (ASR/APR) concept, defined as the difference between an athlete's MAS/MAP and their maximal sprinting speed (MSS)/peak power (MPP), advances our understanding of athlete tolerance to high speed/power efforts in this range. When exercising at speeds above MAS/MAP, what likely matters most, irrespective of athlete profile or locomotor mode, is the proportion of the ASR/APR used, rather than the more commonly used reference to percent MAS/MAP. The locomotor construct of ASR/APR offers numerous underexplored opportunities. In particular, how differences in underlying athlete profiles (e.g., fiber typology) impact the training response for different 'speed', 'endurance' or 'hybrid' profiles is now emerging. Such an individualized approach to athlete training may be necessary to avoid 'maladaptive' or 'non-responses'. As a starting point for coaches and practitioners, we recommend upfront locomotor profiling to guide training content at both the macro (understanding athlete profile variability and training model selection, e.g., annual periodization) and micro levels (weekly daily planning of individual workouts, e.g., short vs long intervals vs repeated sprint training and recovery time between workouts). More specifically, we argue that high-intensity interval training formats should be tailored to the locomotor profile accordingly. New focus and appreciation for the ASR/APR is required to individualize training appropriately so as to maximize athlete preparation for elite competition.

Background: Age may affect treatment outcome in trials of mild probable Alzheimer’s disease (AD). Objective: We examined age as a moderator of outcome in an exploratory study of deep brain stimulation targeting the fornix (DBS-f) region in participants with AD. Methods: Forty-two participants were implanted with DBS electrodes and randomized to double-blind DBS-f stimulation (“on”) or sham DBS-f (“off”) for 12 months. Results: The intervention was safe and well tolerated. However, the selected clinical measures did not differentiate between the “on” and “off” groups in the intent to treat (ITT) population. There was a significant age by time interaction with the Alzheimer’s Disease Assessment Scale; ADAS-cog-13 (p = 0.028). Six of the 12 enrolled participants

PURPOSE: The ASCO Quality Oncology Practice Initiative (QOPI) project was established to evaluate the influence of guideline recommendations on routine clinical practice. METHODS: QOPI provided summary data from 839 unique practices in which data were collected every six months from the Fall of 2015 to the Spring of 2019. From these data, six items were chosen based on their relationship to domains of survivorship. A zero-inflated negative binomial regression model was used to test for trends in QOPI measures adherence rates over time. The models were adjusted for the time period, region, practice-ownership, multispecialty site, fellowship program, and hospital type. RESULTS: Smoking cessation counseling recommended and smoking cessation counseling administered or referred both increased over time, 50%-61% (adjusted incidence rate ratios (IRR), 1.028; 95% CI, 1.016 to 1.040; P < .001) and 34%-49% (adjusted IRR, 1.052; 95% CI, 1.035 to 1.070; P < .001), respectively. Infertility risks discussed before chemotherapy increased from 36% to 53% (adjusted IRR, 1.056; 95% CI, 1.035 to 1.078; P < .001) and fertility options discussed or referred to specialists increased from 23% to 38% (adjusted IRR, 1.074; 95% CI, 1.046 to 1.102; P < .001). Twenty-nine percent documented a positron emission tomography, computed tomography, or bone scan within the first 12 months for women diagnosed with early breast cancer treated for curative intent (adjusted IRR, 1.000; 95% CI, 0.977 to 1.024; P = .971). Tumor marker surveillance within 12 months increased from 78% to 87% (adjusted IRR, 1.018; 95% CI, 1.002 to 1.033; P = .023). CONCLUSION: As scientific evidence to guide cancer survivorship care grows, the role of guideline recommendations permeating clinical practice using quality metrics will become increasingly important.

PURPOSE: To compare the characteristics and outcomes of rectal cancer patients with local recurrence at a perianastomotic site (PA), a surgical field (SF) site, or in lateral lymph nodes (LLN). METHODS: A total of 114 consecutive patients who underwent surgery for recurrent, non-metastatic rectal cancer at a single comprehensive cancer center between 1997 and 2012 were grouped on the basis of radiographic assessment of type of recurrence: PA, 76 (67%) patients; SF, 25 (22%) patients; LLN, 13 (11%) patients. Demographic, clinical, and pathological features were compared between the three groups, as were disease-free survival (DFS) and overall survival (OS). RESULTS: Recurrence type was associated with positive circumferential margin in the primary resection (PA, 4 [6%]; SF, 4 [19%]; LLN, 3 [25%]; P = 0.027), prior neoadjuvant therapy for the primary tumor (PA, 57 [75%]; SF, 18 [72%]; LLN, 4 [31%]; P = 0.007) and location of the primary tumor in the upper rectum (PA, 33 [45%]; SF, 5 [23%]; LLN, 1 [8%]; P < 0.001). Patients with PA had longer median DFS (PA, 5.1 years; SF, 1.5 years; LLN, 1.2 years; P = 0.036). There was a non-significant trend toward longer OS and higher rates of R0 resection for PA. CONCLUSION: Type of recurrence after salvage surgery for locally recurrent rectal cancer is associated with longer DFS in patients with PA recurrence.

Cognitive impairment is highly prevalent in schizophrenia and treatment options are severely limited. A greater understanding of the pathophysiology of impaired cognition would have broad implications, including for the development of effective treatments. In the current study we used a multimodal approach to identify neurophysiological markers of cognitive impairment in schizophrenia. Fifty-seven participants (30 schizophrenia, 27 controls) underwent neurobiological assessment (electroencephalography [EEG] and Transcranial Magnetic Stimulation combined with EEG [TMS-EEG]) and assessment of cognitive functioning using an n-back task and the MATRICS Consensus Cognitive Battery. Neurobiological outcome measures included oscillatory power during a 2-back task, TMS-related oscillations and TMS-evoked potentials (TEPs). Cognitive outcome measures were d prime and accurate reaction time on the 2-back and MATRICS domain scores. Compared to healthy controls, participants with schizophrenia showed significantly reduced theta oscillations in response to TMS, and trend level decreases in task-related theta and cortical reactivity (i.e. reduced N100 and N40 TEPs). Participants with schizophrenia also showed significantly impaired cognitive performance across all measures. Correlational analysis identified significant associations between cortical reactivity and TMS-related oscillations in both groups; and trend level associations between task-related oscillations and impaired cognition in schizophrenia. The current study provides experimental support for possible neurophysiological markers of cognitive impairment in schizophrenia. The potential implications of these findings, including for treatment development, are discussed.

Abstract. Background: The World Health Organization (WHO) estimates that an individual dies by suicide every 40 s. Aim: Our aim was to analyze how suicide is portrayed on the visual social media platform Pinterest. Method: This study used a quantitative content analysis of 500 suicide-related Pinterest posts. Content codes included the presence of factors related to the WHO media reporting guidelines. Results: The majority of posts were published by individual Pinterest users, with public and mental health entities rarely present. Suicidal ideation content was more prevalent in visuals than in accompanying text on Pinterest. Considering the WHO media suicide-reporting guidelines, posts featured more helpful than harmful content, but explicit details of suicides and suicide attempts were still prevalent. Finally, comments were more likely to identify with suicidal ideation or post negative content than post supportive content. Limitations: Content analysis cannot discern motivations behind posts; future studies should include other methods. Conclusion: This study suggests there is a critical need for further research into Pinterest and suicide-related topics.

Background The COVID-19 pandemic has quickly spread around the world, and since currently no treatments that are safe and effective for large groups of people nor a vaccine are available, the best way to prevent the illness is to avoid being exposed to the virus causing it. The purpose of this study was to examine the predictive effects of both demographic and psychosocial factors originating with the Health Belief Model on reported intent to adhere to COVID-19 preventive behaviors (e.g., social distancing, hand washing, and not attending large gatherings). Method A Qualtrics survey of 500 U.S. adults was conducted to explore the relationships of demographics and psychosocial factors with the intent to adhere to COVID-19 preventive measures. Results Gender was a predictor of taking preventive action, with women more likely to take action. Health Belief Model constructs predicted uptake of most COVID-19 preventive actions, but the constructs often appeared to work independent of the model. Race/ethnicity was an infrequent predictor, but when it did, minorities were less likely to report intent to adhere to COVID-19 preventive behaviors. Conclusion/Implications While not a perfect model for this pandemic, the Health Belief Model and its constructs should continue to be considered for use by public health communicators focusing on preventive measure campaign design in both the COVID-19 pandemic era and beyond.

To evaluate acute stress disorder (ASD) symptoms and their predictors in Neonatal Intensive Care Unit (NICU) mothers. In this cross-sectional study, 119 mothers (~72% Medicaid) completed surveys during the first month of their infants’ hospitalizations. Correlations and structural equation models (SEMs) evaluated relations among mothers’ childhood trauma history, infant health appraisals, objective infant health, and ASD. ASD symptoms (~55%) and childhood trauma (~33%) were prevalent. ASD was correlated with childhood trauma, infant health, and infant health appraisals. All SEMs had good fit, indicating that (a) infant health appraisals partially mediated relations between childhood trauma and ASD, and (b) infant health appraisals fully mediated relations between objective infant health and ASD. ASD symptoms are prevalent among NICU mothers regardless of infant health severity. Recognition of childhood trauma history and appraisals of infant health is critical for trauma-informed care.

Introduction The 2017 European Union-North American Clinical Trials in Alzheimer's Disease Task Force recommended development of clinician-rated primary outcome measures for Alzheimer's disease (AD) agitation trials, incorporating International Psychogeriatric Association (IPA) criteria. Methods In a modified Delphi process, Cohen-Mansfield Agitation Inventory (CMAI) and Neuropsychiatric Inventory-Clinician (NPI-C) items were mapped to IPA agitation domains generating novel instruments, CMAI-IPA and NPI-C-IPA. Validation in the Agitation and Aggression AD Cohort (A3C) assessed minimal clinically important differences (MCIDs), change sensitivity, and predictive validity. Results MCID was -17 (odds ratio [OR] = 14.9, 95% confidence interval [CI] = 6.8-32.6) for CMAI; -5 (OR = 9.3, 95% CI = 4.0-21.2) for CMAI-IPA; -3 (OR = 11.9, 95% CI = 4.1-34.8) for NPI-C-A+A; and -5 (OR = 7.8, 95% CI = 3.4-17.9) for NPI-C-IPA at 3 months. Areas under the curve suggested no scale better predicted global clinician ratings. Sensitivity to change for all measures was high. Conclusion Internal consistency and reliability analyses demonstrated better accuracy for the NPI-C-IPA than for the CMAI-IPA and can be used for agitation clinical trial inclusion, and for response to intervention.

Objective Blood-brain barrier (BBB) breakdown has been suggested to be an early biomarker in human cognitive impairment. However, the relationship between BBB breakdown and brain pathology, most commonly Alzheimer disease (AD) and vascular disease, is still poorly understood. The present study measured human BBB function in mild cognitive impairment (MCI) patients on 2 molecular scales, specifically BBB's permeability to water and albumin molecules. Methods Fifty-five elderly participants were enrolled, including 33 MCI patients and 22 controls. BBB permeability to water was measured with a new magnetic resonance imaging technique, water extraction with phase contrast arterial spin tagging. BBB permeability to albumin was determined using cerebrospinal fluid (CSF)/serum albumin ratio. Cognitive performance was assessed by domain-specific composite scores. AD pathology (including CSF Aβ and ptau) and vascular risk factors were examined. Results Compared to cognitively normal subjects, BBB in MCI patients manifested an increased permeability to small molecules such as water but was no more permeable to large molecules such as albumin. BBB permeability to water was found to be related to AD markers of CSF Aβ and ptau. On the other hand, BBB permeability to albumin was found to be related to vascular risk factors, especially hypercholesterolemia, but was not related to AD pathology. BBB permeability to small molecules, but not to large molecules, was found to be predictive of cognitive function. Interpretation These findings provide early evidence that BBB breakdown is related to both AD and vascular risks, but their effects can be differentiated by spatial scales. BBB permeability to small molecules has a greater impact on cognitive performance. ANN NEUROL 2021;90:227-238.

Importance The COVID-19 pandemic disrupted graduate medical education, compelling training programs to abruptly transition to virtual educational formats despite minimal experience or proficiency. We surveyed residents from a national sample of internal medicine (IM) residency programs to describe their experiences with the transition to virtual morning report (MR), a highly valued core educational conference. Objective Assess resident views about virtual MR content and teaching strategies during the COVID-19 pandemic. Design Anonymous, web-based survey. Participants Residents from 14 academically affiliated IM residency programs. Main Measures The 25-item survey on virtual MR included questions on demographics; frequency and reason for attending; opinions on who should attend and teach; how the virtual format affects the learning environment; how virtual MR compares to in-person MR with regard to participation, engagement, and overall education; and whether virtual MR should continue after in-person conferences can safely resume. The survey included a combination of Likert-style, multiple option, and open-ended questions. Results Six hundred fifteen residents (35%) completed the survey, with a balanced sample of interns (39%), second-year (31%), and third-year (30%) residents. When comparing their overall assessment of in-person and virtual MR formats, 42% of residents preferred in-person, 18% preferred virtual, and 40% felt they were equivalent. Most respondents endorsed better peer-engagement, camaraderie, and group participation with in-person MR. Chat boxes, video participation, audience response systems, and smart boards/tablets enhanced respondents’ educational experience during virtual MR. Most respondents (72%) felt that the option of virtual MR should continue when it is safe to resume in-person conferences. Conclusions Virtual MR was a valued alternative to traditional in-person MR during the COVID-19 pandemic. Residents feel that the virtual platform offers unique educational benefits independent of and in conjunction with in-person conferences. Residents support the integration of a virtual platform into the delivery of MR in the future. Supplementary Information The online version contains supplementary material available at 10.1007/s11606-021-06963-7.

Pancreatic ductal adenocarcinoma is the main cause of cancer-related mortality, with a lack of effective treatments and overall survival rates far lower than other solid cancers. This clinical challenge is related to late diagnosis as well as primary or acquired resistance to therapy-induced apoptosis. Targeting nonapoptotic cell death pathways may provide alternative therapeutic strategies to overcome drug resistance. In particular, recent studies have suggested that ferroptosis, a type of iron-dependent nonapoptotic cell death, is a promising target for pancreatic ductal adenocarcinoma. Ferroptosis can be triggered by inhibiting or activating the redox or iron metabolism-related pathways, mediated by extrinsic/membrane transports (e.g., solute carrier family 7 member 11) or intrinsic/enzymes (e.g., glutathione peroxidase 4). Although the exact effector molecule remains obscure, reactive oxygen species-induced lipid peroxidation and subsequent plasma membrane damage appears to play a central role in mediating ferroptotic death. While treatment-induced ferroptosis is beneficial to suppress tumor growth, inflammation-related immunosuppression caused by ferroptotic damage may promote the occurrence of pancreatic ductal adenocarcinoma. In this review, we outline the latest knowledge about the regulation and function of ferroptosis in pancreatic tumorigenesis and therapy.

Background Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for patients with depression who have not achieved optimal outcomes with one or more trials of antidepressant medication. It is an effective antidepressant treatment but there remains considerable scope for improving clinical outcomes. One method to potentially enhance the efficacy of rTMS is through the improvement of methods of stimulation localization. Objective The purpose of this paper is to review the literature pertaining to rTMS localization methods and approaches relevant to the treatment of major depressive disorder (MDD) and provide specific opinions on the state of the art in regards to targeting of rTMS treatment in depression. Methods A targeted review of the literature on rTMS targeting in depression. Results There is emerging evidence that optimal rTMS treatment outcomes are likely to be achieved with stimulation at a relatively anterior stimulation site in the left dorsolateral prefrontal cortex (DLPFC). However, some lines of research suggest that there may be two effective stimulation sites: one quite posterior, and one more anterior, in the DLPFC. The ‘Beam F3’ method provides reasonable localization to the anterior stimulation site and the posterior stimulation site corresponds to that typically used in studies using the ‘5 cm method’. Neuro-navigational methods are generally most likely to consistently ensure placement of the TMS coil such that it results in stimulation of a selected cortical site. fMRI – connectivity based approaches to targeting specific circuits in the DLPFC are intellectually attractive but it may not be possible to demonstrate differential effectiveness of these over the methods most commonly been used in clinical practice. Conclusions There is an emerging literature helping to improve our understanding of the optimal methods for targeting rTMS treatment for depression. However, we lack substantive prospective clinical trials demonstrating improved clinical outcomes with these techniques.

Background Increased risk of a second primary malignancy (SPM) before or after diagnosis of anal squamous cell carcinoma (ASCC) has been reported in a previous single‐institution study. We hypothesize that patients diagnosed with ASCC are at increased risk for developing SPMs before or after the diagnosis of ASCC. The primary objective of this study was to identify the diagnoses of cancer most likely to occur as SPMs before or after ASCC. Methods This work employs the Surveillance, Epidemiology, and End Results (SEER) Program registry data to conduct a US‐population‐based study of patients diagnosed with ASCC between 1975 and 2016. In patients diagnosed with ASCC, we evaluated the risk of SPMs and the risk of developing ASCC as an SPM after another cancer using standardized incidence ratios (SIR) for all SPMs by calculating the ratio of observed events in the ASCC cohort compared to expected (O/E) events in a matched reference cohort of the general population. Results A total of 7,594 patients with primary ASCC were included. Patients with ASCC were at increased risk of the diagnosis of an SPM (SIR = 1.45), particularly cancers of the lung, vulva, oropharynx, or colon. Patients with ASCC had an increased rate of previous malignancy (SIR = 1.23), especially Kaposi sarcoma or vulvar cancer. Overall elevated incidence of SPMs was unrelated to prior radiation treatment. Radiation treatment was associated with increased risk for SPMs in the female genital system but appeared protective against prostate cancer as SPMs. Conclusions Our findings support increased surveillance and screening for second malignancies in patients with these diagnoses, as patients with ASCC are often either survivors of a prior cancer diagnosis or are at increased risk of developing later malignancies., Survivors of anal squamous cell carcinoma are at increased risk for particular second malignancies and should be screened for these. Risk of second malignancies is sometimes related to radiation therapy, but radiation can also be protective against second cancers in some cases.

Background We assessed the prevalence and clinical characteristics of patients with acute decompensated heart failure (ADHF) who live alone and how they were different from patients who lived with someone else. Methods We analyzed patients in the REHAB-HF Trial. Patients were ≥60 years with preserved or reduced ejection fraction who were hospitalized with ADHF. Results Of 202 patients, 67 (33.2%) lived alone. Patients who lived alone had a mean age of 72.4±7.8 years, 64% (n=43) of whom were female, 52% (n=35) were non-white and had a mean 6.1±5.5 comorbidities. Patients living alone were largely similar in baseline characteristics, comorbid burden and prescribed medications to patients living with someone else. However, patients living alone were more likely to be female than patients living with someone else (63% [n=43] vs. 49% [n=66], p=0.04). Patients living alone had severe impairments in physical function and QoL. Cognitive dysfunction was present in 81% of those living alone. However, after adjusting for sex, no differences in physical function, depression, cognitive dysfunction or QoL were noted between patients who lived alone or those who lived with someone else. Conclusions In this diverse population of older ADHF patients, 33% lived alone (versus 26% in the general population). Those living alone were more often female, non-white, and had >6 comorbidities. Treatment strategies for older ADHF patients should consider the potential impact of social determinants.

This paper provides an overview of Malaysian mental health in light of COVID-19. It discusses some of the current treatment options and how the crisis is being managed. A focused literature review was conducted. All relevant articles were included in the review. It offers research, policy, and multicultural practice suggestions for reducing the predicted upcoming mental health pandemic. There needs to be a multiculturally competent, multi-pronged public health strategy to address the psychological damage caused both during and after the pandemic. The government, health and mental health sectors, policymakers, and academic experts need to engage in a meaningful collaboration that leads to policies, resources, and actions to prevent future distress. This paper contributes to the knowledge about the mental health impact and response to the COVID-19 pandemic in a less studied country.

Neuroblastoma (NB) is a common solid extracranial tumor developing in pediatric populations. NB can spontaneously regress or grow and metastasize displaying resistance to therapy. This tumor is derived from primitive cells, mainly those of the neural crest, in the sympathetic nervous system and usually develops in the adrenal medulla and paraspinal ganglia. Our understanding of the molecular characteristics of human NBs continues to advance documenting abnormalities at the genome, epigenome, and transcriptome levels. The high-risk tumors have MYCN oncogene amplification, and the MYCN transcriptional regulator encoded by the MYCN oncogene is highly expressed in the neural crest. Studies on the biology of NB has enabled a more precise risk stratification strategy and a concomitant reduction in the required treatment in an expanding number of cases worldwide. However, newer treatment strategies are mandated to improve outcomes in pediatric patients who are at high-risk and display relapse. To improve outcomes and survival rates in such high-risk patients, it is necessary to use a multicomponent therapeutic approach. Accuracy in clinical staging of the disease and assessment of the associated risks based on biological, clinical, surgical, and pathological criteria are of paramount importance for prognosis and to effectively plan therapeutic approaches. This review discusses the staging of NB and the biological and genetic features of the disease and several current therapies including targeted delivery of chemotherapy, novel radiation therapy, and immunotherapy for NB.

Purpose To determine whether anterior cable tears could be identified at the time of arthroscopic rotator cuff repair and determine the characteristics of the anterior cable tears identified. Methods From 2016 to 2017 all shoulder arthroscopies had data collected prospectively at the time of surgery, specifically including injury to the capsular and tendon zones of insertion on the greater tuberosity. Anterior cable position and degree of injury and medialization were recorded, as well as complete findings of the diagnostic arthroscopy. The inclusion criterion was primary shoulder arthroscopy. The exclusion criterion was any revision shoulder arthroscopy. All arthroscopic rotator cuff repairs (ARCR) were grouped together and all other nonarthroscopic rotator cuff repair surgeries (non-ARCR) were grouped together. Results In total, 118 shoulder arthroscopies had data collected prospectively at the time of surgery: 90 primary shoulder arthroscopies met the inclusion criteria; 28 were excluded because they were revision surgeries. There were 42 patients in the ARCR group (Group 1). Six of these were partial tears, and 36 were full-thickness tears. There were 48 patients in the non-ARCR group (Group 2). The non-ARCR Group 2 served as an anatomic baseline for ARCR Group 1. In all 90 shoulders, the rotator cable and anterior cable were identified. Group 1 (ARCR) incidence of anterior cable tears with abnormal position was 71.4% compared to 2.1% in group 2 (non-ARCR) (P < .001) Group 1 (ARCR) incidence of anterior cable tears with normal anterior cable position (n = 12) was compared to abnormal anterior cable position (n = 30). Injury to the anterior footprint capsular and tendon zones were compared. Normal anterior cable position correlated with no or low-grade injury to anterior footprint capsular zone. (Nimura zone C1). Abnormal anterior cable displacement graded as moderate (n = 20) and severe (n = 10) were compared for injury to the anterior footprint. Moderate displacement correlated with complete or high grade injury to C1 in 85% and complete injury to R1 in 45% (P < .001 and .049). In severe displacement complete C1 injury was 100%, and complete R1 injury was 100% (P < .001 and .001). Conclusions Anterior cable tears are universally identified in ARCR. Three patterns of medial displacement severity correlated with injury to a crucial insertion zone (C1) at the anterior footprint. The degree of anterior cable disruption at the anterior footprint and displacement was commonly disproportionately greater than the injury to the supraspinatus. Level of Evidence Level III, diagnostic study.

Background To improve and compare outcomes in healthcare, it is necessary to standardise outcome measurements. There are no widely accepted standardised outcome measures reflecting quality of care for bladder cancer (BCa) patients. Objective The aim of this study was to create a standardised set of outcomes for patients with muscle-invasive or metastatic BCa, using the value-based healthcare principles. Design, setting, and participants A multidisciplinary working group of 25 healthcare professionals and patient representatives was assembled, to develop the set. Outcome measurements and statistical analysis We used an online RAND-modified Delphi process to prioritise, discuss, and reach consensus regarding the outcomes, case-mix variables, and treatment factors. Results and limitations Recognising the heterogeneity of patients with BCa, the working group defined the scope as patients with muscle-invasive and metastatic BCa. A total of 24 outcomes, including ten patient-reported outcomes, were included in the standard set of outcomes, covering survival, complication rates, recurrence of disease, readmissions after treatment, and quality of life (QoL). Fourteen case-mix variables were included. The EQ-5D and European Organisation for Research and Treatment of Cancer quality of life (EORTC-QLQ) questionnaires were recommended to measure QoL. Conclusions We developed the first standardised set of patient-centred outcomes for muscle-invasive and metastatic BCa. The sue of this set enables institutions to monitor, compare, and improve the quality of BCa care, on an international level. Patient summary Our group of healthcare professionals and patient representatives recommended a standardised set of patient-centred outcomes to be followed during the treatment of patients with muscle-invasive or metastatic bladder cancer, in order to monitor, compare, and improve the quality of care., Take Home Message We developed the first standardised set of patient-centred outcomes for muscle-invasive and metastatic bladder cancer. The use of this set enables institutions to monitor, compare, and improve the quality of bladder cancer care on an international level.

Background/Aims Research has shown that health literacy can influence an individual's ability to practise self-care, particularly for patients with heart failure. This study aimed to assess health literacy and its relationship with heart failure knowledge and self-care practices in this patient group. Methods An observational sub-study was conducted with the data from a large randomised control trial that evaluated the relationship between patients' health literacy, general literacy, knowledge of heart failure and self-care. Results A total of 36 participants were recruited, of which 33 (89.9%) had adequate levels of health literacy. Health literacy was positively associated with heart failure knowledge. However, 67.7% of participants with adequate health literacy were found to have inadequate levels of self-care management. Conclusions Health literacy may facilitate better heart failure knowledge, but it does not necessarily lead to improved self-care management in patients with heart failure. This suggest that clinicians need to put more emphasis on translating knowledge into behavioural changes for self-care in this patient group.

The National Cancer Institute has supported cancer survivorship science for many years, yet few funded studies have examined the needs of individuals living with cancer that is advanced or has metastasized. This report analyzes currently active National Institutes of Health (NIH) grants focused on survivorship for patients living with advanced or metastatic cancers to identify emerging research topics in this population and gaps in current science. A search of all NIH research grants that received funding in Fiscal Year 2020 focused on this population was conducted, excluding grants with a primary focus on end-of-life care, tumor progression or staging and grants for which the only outcome was survival. A total of 25 active grants met the inclusion criteria. Most were funded using the R01 grant mechanism and included a range of cancer types and topics such as palliative/supportive care, psychosocial support, health services, and symptom sequelae. Although currently funded grants focus on several important topics, gaps in the portfolio remain. There is a need to enhance the grant portfolio of research studies focused on the longitudinal examination of unmet needs, models of care delivery, impact of innovative therapies, and the impact of financial hardship for individuals living with advanced or metastatic cancer. This review of current NIH studies suggests a need for expanded research on individuals living with advanced or metastatic cancer. Moving forward, enhancing research focused on key gap areas will be critical to improve care and outcomes for this growing population.

IntroductionDuring military service, many household costs for both married and single service personnel are subsidised, and transition can leave veterans unprepared for the financial demands of civilian life. Armed Forces organisations such as Sailor, Soldier, Air Force Association (SSAFA) play a central role in understanding the financial challenges that UK veterans face and provide an insight into the financial hardship experienced by veterans. The aim of this study was to use SSAFA beneficiary data as a proxy to identify the nature of financial benefit, the spatial distribution of financial hardship in the Scottish SSAFA beneficiary community and explore factors that might predict where those recipients are located.MethodsUsing an anonymised data set of Scottish SSAFA financial beneficiaries between 2014 and 2019, this study used a geographical methodology to identify the geospatial distribution of SSAFA benefit recipients and exploratory regression analysis to explore factors to explain where SSAFA beneficiaries are located.ResultsOver half of benefit applicants (n=10 735) were concentrated in only 50 postcode districts, showing evidence of a clustered pattern, and modelling demonstrates association with area-level deprivation. The findings highlight strong association between older injured veterans and need for SSAFA beneficiary assistance.ConclusionThe findings demonstrate that beneficiaries were statistically clustered into areas of high deprivation, experiencing similar challenges to that of the wider population in these areas. Military service injury or disability was strongly associated with areas of high SSAFA benefit use and in those areas high unemployment was also a significant factor to consider.

The aim of this study was to report outcomes following percutaneous microwave and cryoablation of lung metastases from adenoid cystic carcinoma (ACC) of the head and neck. This bi-institutional retrospective cohort study included 10 patients (6 females, median age 59 years [range 28–81]) who underwent 32 percutaneous ablation sessions (21 cryoablation, 11 microwave) of 60 lung metastases (median 3.5 tumors per patient [range 1–16]) from 2007 to 2019. Median tumor diameter was 16 mm [range 7–40], significantly larger for cryoablation (22 mm, p = 0.002). A median of two tumors were treated per session [range 1–7]. Technical success, local control, complications, and overall survival were assessed. Primary technical success was achieved for 55/60 tumors (91.7%). Median follow-up was 40.6 months (clinical) and 32.5 months (imaging, per tumor). Local control at 1, 2, and 3 years was 94.7%, 80.8%, and 76.4%, respectively, and did not differ between ablation modalities. Five of fifteen recurrent tumors underwent repeat ablation, and secondary technical success was achieved in four (80%). Assisted local tumor control at 1, 2, and 3 years was 96.2%, 89.8%, and 84.9%, respectively. Complications occurred following 24/32 sessions (75.0%) and 57.2% Common Terminology Criteria for Adverse Events (CTCAE) lower than grade 3. Of 13 pneumothoraces, 7 required chest tube placements. Hemoptysis occurred after 7/21 cryoablation sessions, and bronchopleural fistula developed more frequently with microwave (p = 0.037). Median length of hospital stay was 1 day [range 0–10], and median overall survival was 81.5 months (IQR 40.4–93.1). Percutaneous computed tomography-guided microwave and cryoablation can treat lung metastases from ACC of the head and neck. Complications are common but manageable, with full recovery expected.

Objectives Brain MRIs are considered essential in the evaluation of children diagnosed with growth hormone deficiency (GHD), but there is uncertainty about the appropriate cut-off for diagnosis of GHD and little data about the yield of significant abnormal findings in patients with peak growth hormone (GH) of 7–10 ng/mL. We aimed to assess the frequency of pathogenic MRIs and associated risk factors in relation to peak GH concentrations. Methods In this retrospective multicenter study, charts of patients diagnosed with GHD who subsequently had a brain MRI were reviewed. MRIs findings were categorized as normal, incidental, of uncertain significance, or pathogenic (pituitary hypoplasia, small stalk and/or ectopic posterior pituitary and tumors). Charges for brain MRIs and sedation were collected. Results In 499 patients, 68.1% had normal MRIs, 18.2% had incidental findings, 6.6% had uncertain findings, and 7.0% had pathogenic MRIs. Those with peak GH Conclusions Pathogenic MRIs were uncommon in patients diagnosed with GHD except in the group with peak GH

To evaluate 18F-fluorodeoxyglucose (FDG) perfusion PET during FDG PET/CT-guided liver tumor microwave ablation procedures for assessing the ablation margin and correlating minimum margin measurements with local progression. This IRB-approved, HIPAA-compliant study included 20 adult patients (11 M, 9 F; mean age 65) undergoing FDG PET/CT-guided liver microwave ablation to treat 31 FDG-avid tumors. Intraprocedural FDG perfusion PET was performed to assess the ablation margin. Intraprocedural decisions regarding overlapping ablations were recorded. Two readers retrospectively interpreted intraprocedural perfusion PET and postprocedural contrast-enhanced MRI. Assessability of the ablation margin and minimum margin measurements were recorded. Imaging follow-up for local progression ranged from 30 to 574 days (mean 310). Regression modeling of minimum margin measurements was performed. Hazard ratios were calculated to correlate an ablation margin threshold of 5 mm with outcomes. Intraprocedural perfusion PET prompted additional overlapping ablations of two tumors, neither of which progressed. Incomplete ablation or local progression occurred in 8/31 (26%) tumors. With repeat ablation, secondary efficacy was 26 (84%) of 31. Both study readers deemed ablation margins fully assessable more often using perfusion PET than MRI (OR 69.7; CI 6.0, 806.6; p = 0.001). Minimum ablation margins ≥ 5 mm on perfusion PET correlated with a low risk of incomplete ablation/local progression by both study readers (HR 0.08 and 0.02, p

Background Proton beam radiation therapy (PBRT) has dosimetric advantages compared to photon radiation therapy for the treatment of major salivary gland tumors (MSGTs). Methods Patients with non-metastatic MSGTs treated at a single proton therapy center from October 2013 to October 2018 were retrospectively reviewed. Results Sixty-eight patients with MSGTs were included and the most common site and histology were the parotid gland (75.0%) and adenoid cystic carcinoma (22.1%), respectively. The 3-year rates of locoregional control, progression-free survival, and overall survival were 95.1% (95% CI: 89.9%-100.0%), 80.7% (70.2%-92.7%), and 96.1% (95% CI: 90.9%-100.0%), respectively. Conclusion In a large cohort of MSGTs treated with PBRT, the rates of locoregional control were high in short-term follow-up and treatment was well tolerated.

Objective: There is a high prevalence of obstructive sleep apnea (OSA) in pediatric and adult Down Syndrome (DS) patients that is refractory to adenotonsillectomy and continuous positive airway pressure. Newer treatment modalities have emerged with improved outcomes. The objective is to provide an updated systematic review and meta-analysis to analyze the clinical outcomes of OSA in pediatric and adult DS patients with hypoglossal nerve stimulation using Inspire, midline posterior glossectomy plus lingual tonsillectomy (MPG + LT), and combined genioglossus advancement plus radiofrequency (GGS + RF). Methods: A comprehensive literature search of PubMed and Google Scholar was performed followed by a meta-analysis. Studies with preoperative and post-operative Apnea Hypopnea Index (AHI) values were included with patients serving as their own control. Results: Across 5 studies, 56 patients were analyzed. The mean reduction in AHI was statistically significant before vs. after procedure ( P

Contains fulltext : 231309.pdf (Publisher’s version ) (Open Access) Objective: The aim of the current study was to attempt to replicate the finding that the individual alpha frequency (IAF) as well as the absolute difference between IAF and 10 Hz stimulation frequency (IAF-prox) is related to treatment outcome. Methods: Correlations were performed to investigate the relationship between IAF-prox and percentage symptom improvement in a sample of 153 patients with major depressive disorder treated with 10 Hz (N = 59) to the left dorsolateral prefrontal cortex (DLPFC) or 1 Hz (N = 94) to the right DLPFC repetitive Transcranial Magnetic Stimulation (rTMS). Results: There was a significant negative correlation between IAF-prox and the percentage of symptom improvement only for the 10 Hz group. Curve fitting models revealed that there was a quadratic association between IAF and treatment response in the 10 Hz group, with a peak at 10 Hz IAF. Conclusion: The main result of Corlier and colleagues was replicated, and the findings suggest that the distance between 10 Hz stimulation frequency and the IAF may influence clinical outcome in a non-linear manner. Significance: rTMS is often administered at a frequency of 10 Hz, which is the center of the EEG alpha frequency band. The results can make a significant contribution to optimizing the clinical application of rTMS. 7 p.

Injection of high-viscosity fluids into subcutaneous tissues may lead to a granulomatous reaction called sclerosing lipogranuloma (SL). Poly-(d,l-lactide-co-glycolide) (PLG or PLGA) microspheres are used as vehicles for extended-release drugs. Here we describe the histopathologic features of a case of SL induced by exenatide extended-release injections, and the staining pattern of PLG microspheres and microsphere remnants with carbol fuchsin.

Acute cerebellitis is a rare condition with a highly heterogenous clinical course, ranging from self-limiting mild symptoms to a fulminant presentation. Symptoms include headache, vomiting, fever, ataxia, dysarthria, intention tremor, meningism, seizures, and altered level of consciousness. It warrants a high level of suspicion because of the risk of intracranial hypertension and acute hydrocephalus due to compression of the posterior fossa. We present the case of a 7-year-old boy who presented emergently with new-onset left head turn and horizontal nystagmus. Acute inflammation of a single cerebellar hemisphere (hemicerebellitis) in childhood is extremely rare, diagnosed in this case with magnetic resonance imaging. Symmetrical, diffuse cerebellar hemisphere involvement is more typical of cerebellitis. Our patient was unusual in that he presented initially with predominantly ophthalmological signs, with an otherwise normal neurological assessment. Subsequent positive serological Borrelia burgdorferi antibodies led to a diagnosis of Lyme neuroborreliosis.

Late-life depression is common and often inadequately managed using existing therapies. Depression is also associated with increased markers of inflammation, suggesting a potential role for anti-inflammatory agents. ASPREE-D is a sub-study of ASPREE, a large multi-centre, population-based, double-blind, placebo-controlled trial of aspirin vs placebo in older Australian and American adults (median follow-up: 4.7 years) of whom 1,879 were depressed at baseline. Participants were given 100mg daily dose of aspirin or placebo. Depressive symptoms were assessed annually using the validated, self-rated short version of the Center for Epidemiological Studies Depression (CES-D-10) scale. There was a significant increase in depressive scores (0.6; 95% CI 0.2 to 0.9; Chi-square (1) = 10.37; p = 0.001) and a decreased score in the mental health component of a quality of life scale (−0.7; 95% CI −1.4 to −0.1; Chi-square (1) =4.74; p = 0.029) in the aspirin group compared to the placebo group. These effects were greater in the first year of follow-up and persisted throughout the study, albeit with small to very small effect sizes. This study failed to demonstrate any benefit of aspirin in the long-term course of depression in this community-dwelling sample of older adults over a 5-year period, and identified an adverse effect of aspirin in the course of depression in those with pre-existing depressive symptoms., One Sentence Summary: Contrary to hypotheses, this study demonstrates for the first time that aspirin might have an adverse effect on the mood of older adults with pre-existing depression.