Advances in the evaluation and treatment of autoimmune hepatitis.

PURPOSE OF REVIEW: The primary therapy of autoimmune hepatitis (AIH) has been established for over three decades. This review focuses on updates in the evaluation and management of patients with AIH. RECENT FINDINGS: The evaluation of patients has recently been updated to include more definitive screening for other autoimmune diseases, including thyroid disease and celiac disease. Antibody detection by ELISA, an easier and more commonly available method, has been incorporated into the latest iteration of the AIH scoring system. Corticosteroids and AZA remain the backbone of AIH treatment, but there is growing evidence for mycophenolate mofetil as both first-line and second-line therapy, and growing inquiry into calcineurin inhibitors. Noninvasive markers of liver disease have now been validated in AIH, with the strongest evidence for VCTE in patients with minimal hepatic inflammation. SUMMARY: Recent research of alternative immunosuppressant therapies, noninvasive markers of fibrosis, and updated society guidelines, have improved our ability to evaluate, treat, and follow patients with AIH.

Enthesitis in a European registry-based cohort of patients with psoriatic arthritis treated with tumour necrosis factor inhibitors: clinical burden, patient-reported outcomes, and treatment response.

OBJECTIVE: To explore the registration of enthesitis among biologic-naïve patients with psoriatic arthritis (PsA) initiating tumour necrosis factor inhibitor (TNFi) treatment across 12 European registries, compare the disease burden and patient-reported outcomes (PROs) between patients with and without enthesitis, and assess the enthesitis treatment response. METHOD: Demographics, clinical characteristics, and PROs at first TNFi (TNFi-1) initiation (baseline) were assessed in patients with PsA, diagnosed by a rheumatologist, with versus without assessment of entheses and between those with versus without enthesitis. Enthesitis scores and resolution frequency were identified at follow-up. RESULTS: Of 10 547 patients in the European Spondyloarthritis (EuroSpA) Research Collaboration Network initiating TNFi, 1357 underwent evaluation for enthesitis. Eight registries included a validated scoring system for enthesitis. At baseline, 874 patients underwent entheses assessment [Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 485 patients, Spondyloarthritis Research Consortium of Canada (SPARCC) 389 patients]. Enthesitis was detected by MASES in 170/485 (35%, mean score ± sd 3.1 ± 2.4) and by SPARCC in 236/389 (61%, 4 ± 3.4). Achilles enthesitis was most frequent, by both MASES (unilateral/bilateral 28%/9%) and SPARCC (48%/18%). MASES/SPARCC baseline and follow-up scores for TNFi-1 were available for 100/105 patients. Of these, 63 patients (63%) (MASES) and 46 (43.8%) (SPARCC) achieved resolution of enthesitis. The site-specific enthesitis resolution was overall lower at SPARCC sites (peripheral; 63-80%) than at MASES sites (mainly axial; 82-100%) following TNFi-1. Disease activity and PROs were worse in patients with versus without enthesitis. CONCLUSION: Entheseal assessments are only registered in a minority of patients with PsA in routine care. When assessed, enthesitis was common, and a substantial proportion demonstrated resolution following treatment with TNFi-1.

Machine learning-based immune phenotypes correlate with STK11/KEAP1 co-mutations and prognosis in resectable NSCLC: a sub-study of the TNM-I trial.

BACKGROUND: We aim to implement an immune cell score model in routine clinical practice for resected non-small-cell lung cancer (NSCLC) patients (NCT03299478). Molecular and genomic features associated with immune phenotypes in NSCLC have not been explored in detail. PATIENTS AND METHODS: We developed a machine learning (ML)-based model to classify tumors into one of three categories: inflamed, altered, and desert, based on the spatial distribution of CD8+ T cells in two prospective (n = 453; TNM-I trial) and retrospective (n = 481) stage I-IIIA NSCLC surgical cohorts. NanoString assays and targeted gene panel sequencing were used to evaluate the association of gene expression and mutations with immune phenotypes. RESULTS: Among the total of 934 patients, 24.4% of tumors were classified as inflamed, 51.3% as altered, and 24.3% as desert. There were significant associations between ML-derived immune phenotypes and adaptive immunity gene expression signatures. We identified a strong association of the nuclear factor-κB pathway and CD8+ T-cell exclusion through a positive enrichment in the desert phenotype. KEAP1 [odds ratio (OR) 0.27, Q = 0.02] and STK11 (OR 0.39, Q = 0.04) were significantly co-mutated in non-inflamed lung adenocarcinoma (LUAD) compared to the inflamed phenotype. In the retrospective cohort, the inflamed phenotype was an independent prognostic factor for prolonged disease-specific survival and time to recurrence (hazard ratio 0.61, P = 0.01 and 0.65, P = 0.02, respectively). CONCLUSIONS: ML-based immune phenotyping by spatial distribution of T cells in resected NSCLC is able to identify patients at greater risk of disease recurrence after surgical resection. LUADs with concurrent KEAP1 and STK11 mutations are enriched for altered and desert immune phenotypes.

Effectiveness of patient education as a stand-alone intervention for patients with chronic widespread pain and fibromyalgia: a systematic review and meta-analysis of randomized trials.

OBJECTIVE: Patient education is recommended as an integral component of the therapeutic plan for the management of chronic widespread pain (CWP) and fibromyalgia (FM). The key purpose of patient education is to increase the patient's competence to manage his or her own health requirements, encouraging self-management and a return to desired everyday activities and lifestyle. The aim of this systematic review was to evaluate the evidence for the benefits and potential harms associated with the use of patient education as a stand-alone intervention for individuals with CWP and FM through randomized controlled trials (RCTs). METHOD: On 24 November 2021 a systematic search of PubMed, MEDLINE, Embase, CENTRAL, PsycINFO, CINAHL, ClinicalTrials.gov, American College of Rheumatology, European League Against Rheumatism, and the World Health Organization International Clinical Trials Registry Platform identified 2069 studies. After full-text screening, five RCT studies were found to be eligible for the qualitative evidence synthesis. RESULTS: Patient education as a stand-alone intervention presented an improvement in patients' global assessment (standardized mean difference 0.79, 95% confidence interval 0.13 to 1.46). When comparing patient education with usual care, no intervention, or waiting list, no differences were found for functioning, level of pain, emotional distress in regard to anxiety and depression, or pain cognition. CONCLUSION: This review reveals the need for RCTs investigating patient education as a stand-alone intervention for patients with FM, measuring outcomes such as disease acceptance, health-related quality of life, enhancement of patients' knowledge of pain, pain coping skills, and evaluation of prioritized learning outcomes.

Unravelling the current shortfalls, challenges, and opportunities in traumatic brain injury.

The brain is the control centre of the human body. Injury to the brain can have diverse and disabling effects. Yet there remain important unanswered questions for clinicians, those affected and their families. This special collection aims to advance understanding of how we can better diagnose, treat and support those affected by brain injury across the severity spectrum.

Elective surgery in ankle and foot disorders-best practices for management of pain: a guideline for clinicians.

PURPOSE: Complex elective foot and ankle surgeries are often associated with severe pain pre- and postoperatively. When inadequately managed, chronic postsurgical pain and long-term opioid use can result. As no standards currently exist, we aimed to develop best practice pain management guidelines. METHODS: A local steering committee (n = 16) surveyed 116 North American foot and ankle surgeons to understand the "current state" of practice. A multidisciplinary expert panel (n = 35) was then formed consisting of orthopedic surgeons, anesthesiologists, chronic pain physicians, primary care physicians, pharmacists, registered nurses, physiotherapists, and clinical psychologists. Each expert provided up to three pain management recommendations for each of the presurgery, intraoperative, inpatient postoperative, and postdischarge periods. These preliminary recommendations were reduced, refined, and sent to the expert panel and "current state" survey respondents to create a consensus document using a Delphi process conducted from September to December 2020. RESULTS: One thousand four hundred and five preliminary statements were summarized into 51 statements. Strong consensus (≥ 80% respondent agreement) was achieved in 53% of statements including the following: postsurgical opioid use risk should be assessed preoperatively; opioid-naïve patients should not start opioids preoperatively unless non-opioid multimodal analgesia fails; and if opioids are prescribed at discharge, patients should receive education regarding importance of tapering opioid use. There was no consensus regarding opioid weaning preoperatively. CONCLUSIONS: Using multidisciplinary experts and a Delphi process, strong consensus was achieved in many areas, showing considerable agreement despite limited evidence for standardized pain management in patients undergoing complex elective foot and ankle surgery. No consensus on important issues related to opioid prescribing and cessation highlights the need for research to determine best practice.

RéSUMé: OBJECTIF: Les chirurgies électives complexes du pied et de la cheville sont souvent associées à une douleur intense avant et après l'opération. Lorsque cette douleur est mal prise en charge, elle peut entraîner une douleur postopératoire chronique et une consommation d'opioïdes à long terme. Comme il n'existe actuellement aucune norme, nous avons cherché à élaborer des lignes directrices sur les meilleures pratiques en matière de prise en charge de la douleur. MéTHODE: Un comité directeur local (n = 16) a interrogé 116 chirurgiens nord-américains spécialistes du pied et de la cheville pour comprendre « l'état actuel ¼ de la pratique. Un groupe d'experts multidisciplinaire (n = 35) a ensuite été formé, composé de chirurgiens orthopédistes, d'anesthésiologistes, de médecins spécialistes de la douleur chronique, de médecins de soins primaires, de pharmaciens, d'infirmières autorisées, de physiothérapeutes et de psychologues cliniciens. Chaque expert a fourni jusqu'à trois recommandations de prise en charge de la douleur pour chacune des périodes suivantes : en préchirurgie, en peropératoire, pendant l'hospitalisation postopératoire et après le congé. Ces recommandations préliminaires ont été réduites, affinées et envoyées au groupe d'experts et aux répondants du sondage sur « l'état actuel ¼ afin de créer un document de consensus à l'aide d'une méthode de Delphi réalisée entre septembre et décembre 2020. RéSULTATS: Mille quatre cent cinq déclarations préliminaires ont été résumées en 51 énoncés. Un consensus fort (≥ 80 % des répondants étaient d'accord) a été atteint concernant 53 % des énoncés, notamment les suivants : le risque de consommation postopératoire d'opioïdes devrait être évalué avant l'opération; les patients naïfs aux opioïdes ne devraient pas commencer à prendre des opioïdes avant l'opération, à moins que l'analgésie multimodale non opioïde n'échoue; et si des opioïdes sont prescrits au congé, les patients devraient être informés de l'importance de réduire leur consommation d'opioïdes. Il n'y avait pas de consensus concernant le sevrage des opioïdes en période préopératoire. CONCLUSION: À l'aide d'experts multidisciplinaires et d'une méthode de Delphi, un fort consensus a été atteint dans de nombreux aspects, montrant un accord considérable malgré des données probantes limitées pour une prise en charge standardisée de la douleur chez les patients subissant une chirurgie élective complexe du pied et de la cheville. L'absence de consensus sur des questions importantes liées à la prescription et à l'interruption des opioïdes souligne la nécessité de recherches pour déterminer les pratiques exemplaires.

The paradox-breaking panRAF plus SRC family kinase inhibitor, CCT3833, is effective in mutant KRAS-driven cancers.

BACKGROUND: KRAS is mutated in ∼90% of pancreatic ductal adenocarcinomas, ∼35% of colorectal cancers and ∼20% of non-small-cell lung cancers. There has been recent progress in targeting G12CKRAS specifically, but therapeutic options for other mutant forms of KRAS are limited, largely because the complexity of downstream signaling and feedback mechanisms mean that targeting individual pathway components is ineffective. DESIGN: The protein kinases RAF and SRC are validated therapeutic targets in KRAS-mutant pancreatic ductal adenocarcinomas, colorectal cancers and non-small-cell lung cancers and we show that both must be inhibited to block growth of these cancers. We describe CCT3833, a new drug that inhibits both RAF and SRC, which may be effective in KRAS-mutant cancers. RESULTS: We show that CCT3833 inhibits RAF and SRC in KRAS-mutant tumors in vitro and in vivo, and that it inhibits tumor growth at well-tolerated doses in mice. CCT3833 has been evaluated in a phase I clinical trial (NCT02437227) and we report here that it significantly prolongs progression-free survival of a patient with a G12VKRAS spindle cell sarcoma who did not respond to a multikinase inhibitor and therefore had limited treatment options. CONCLUSIONS: New drug CCT3833 elicits significant preclinical therapeutic efficacy in KRAS-mutant colorectal, lung and pancreatic tumor xenografts, demonstrating a treatment option for several areas of unmet clinical need. Based on these preclinical data and the phase I clinical unconfirmed response in a patient with KRAS-mutant spindle cell sarcoma, CCT3833 requires further evaluation in patients with other KRAS-mutant cancers.

Echolocation click parameters of short-finned pilot whales (Globicephala macrorhynchus) in the wild.

Short-finned pilot whales (Globicephala macrorhynchus) are large, deep-diving predators with diverse foraging strategies, but little is known about their echolocation. To quantify the source properties of short-finned pilot whale clicks, we made 15 deployments off the coast of Tenerife of a deep-water hydrophone array consisting of seven autonomous time-synced hydrophone recorders (SoundTraps), enabling acoustic localization and quantification of click source parameters. Of 8185 recorded pilot whale clicks, 47 were classified as being recorded on-axis, with a mean peak-to-peak source level (SL) of 181 ± 7 dB re 1 µPa, a centroid frequency of 40 ± 4 kHz, and a duration of 57 ± 23 µs. A fit to a piston model yielded an estimated half-power (-3 dB) beam width of 13.7° [95% confidence interval (CI) 13.2°-14.5°] and a mean directivity index (DI) of 22.6 dB (95% CI 22.5-22.9 dB). These measured SLs and DIs are surprisingly low for a deep-diving toothed whale, suggesting we sampled the short-finned pilot whales in a context with little need for operating a long-range biosonar. The substantial spectral overlap with beaked whale clicks emitted in similar deep-water habitats implies that pilot whale clicks may constitute a common source of false detections in beaked whale passive acoustic monitoring efforts.

The iPSYCH2012 case-cohort sample: new directions for unravelling genetic and environmental architectures of severe mental disorders.

The Integrative Psychiatric Research (iPSYCH) consortium has established a large Danish population-based Case-Cohort sample (iPSYCH2012) aimed at unravelling the genetic and environmental architecture of severe mental disorders. The iPSYCH2012 sample is nested within the entire Danish population born between 1981 and 2005, including 1 472 762 persons. This paper introduces the iPSYCH2012 sample and outlines key future research directions. Cases were identified as persons with schizophrenia (N=3540), autism (N=16 146), attention-deficit/hyperactivity disorder (N=18 726) and affective disorder (N=26 380), of which 1928 had bipolar affective disorder. Controls were randomly sampled individuals (N=30 000). Within the sample of 86 189 individuals, a total of 57 377 individuals had at least one major mental disorder. DNA was extracted from the neonatal dried blood spot samples obtained from the Danish Neonatal Screening Biobank and genotyped using the Illumina PsychChip. Genotyping was successful for 90% of the sample. The assessments of exome sequencing, methylation profiling, metabolome profiling, vitamin-D, inflammatory and neurotrophic factors are in progress. For each individual, the iPSYCH2012 sample also includes longitudinal information on health, prescribed medicine, social and socioeconomic information, and analogous information among relatives. To the best of our knowledge, the iPSYCH2012 sample is the largest and most comprehensive data source for the combined study of genetic and environmental aetiologies of severe mental disorders.

Perioperative pain management and chronic postsurgical pain after elective foot and ankle surgery: a scoping review.

PURPOSE: Chronic postsurgical pain (CPSP) can occur after elective mid/hindfoot and ankle surgery. Effective treatment approaches to prevent the development of CPSP in this population have not been extensively investigated. The impact of multimodal strategies to prevent CPSP following elective mid/hindfoot surgery is unknown because of both the heterogeneity of acute pain management and the lack of a recognized definition particular to this surgery. This review aimed to identify and evaluate current pain management strategies after elective mid/hindfoot and ankle surgery. SOURCES: Manual and electronic searches (MEDLINE, Embase, and Cochrane Library) were conducted of literature published between 1990 and July 2017. Comparative studies of adults undergoing elective mid/hindfoot and ankle surgery were included. Two reviewers independently reviewed studies and assessed their methodological quality. PRINCIPAL FINDINGS: We found seven randomized-controlled trials meeting our inclusion criteria. Interventions focused on regional anesthesia techniques such as continuous popliteal sciatic and femoral nerve blockade. Participants were typically followed up to 48 hr postoperatively. Only one study assessed pain six months following elective mid/hindfoot and ankle surgery. CONCLUSION: There is an overwhelming lack of evidence regarding CPSP and its management for patients undergoing elective mid/hindfoot and ankle surgery. The lack of a recognized and standard definition of CPSP after this group of surgeries precludes accurate and consistent evaluation.

RéSUMé: OBJECTIF: La douleur chronique post-chirurgicale (DCPC) peut survenir après une chirurgie non urgente de la section moyenne ou postérieure du pied, ou de la cheville. Les approches thérapeutiques efficaces pour prévenir l'apparition de DCPC dans cette population n'ont pas été examinées en profondeur. L'impact des stratégies multimodales pour prévenir la DCPC après une chirurgie non urgente de la section moyenne ou postérieure du pied est inconnu, tant en raison de l'hétérogénéité de la prise en charge de la douleur aiguë que du manque de définition reconnue spécifique à ce type de chirurgie. Ce compte-rendu a pour objectif d'identifier et d'évaluer les stratégies de prise en charge de la douleur actuellement utilisées après une chirurgie de la section moyenne ou postérieure du pied, ou de la cheville. SOURCES: Des recherches manuelles et électroniques (MEDLINE, Embase, et Librairie Cochrane) ont été menées dans la littérature publiée entre 1990 et juillet 2017. Les études comparatives portant sur des adultes subissant une chirurgie non urgente de la section moyenne ou postérieure du pied ou de la cheville ont été incluses. Deux chercheurs ont indépendamment passé en revue les études et évalué leur qualité méthodologique. CONSTATATIONS PRINCIPALES: Nous avons trouvé sept études randomisées contrôlées respectant nos critères d'inclusion. Les interventions se concentraient sur des techniques d'anesthésie régionale tels que les blocs continus des nerfs sciatiques poplités et fémoraux. Les participants bénéficiaient en général d'un suivi jusqu'à 48 h après l'opération. Une seule étude a évalué la douleur six mois après une chirurgie non urgente de la section moyenne ou postérieure du pied ou de la cheville. CONCLUSION: L'absence de données probantes est colossale en ce qui touche à la DCPC et à sa prise en charge pour les patients subissant une chirurgie non urgente de la partie moyenne ou postérieure et de la cheville. L'absence de définition normalisée et reconnue de la DCPC après ce type de chirurgie en exclut toute évaluation précise et cohérente.

T cells isolated from patients with checkpoint inhibitor-resistant melanoma are functional and can mediate tumor regression.

Background: Almost half of the patients with metastatic melanoma obtain only short-term or no benefit at all from checkpoint inhibitor (CPI) immunotherapy. In this study, we investigated whether the immune system of patients progressing following CPI treatment was able to generate functional tumor-specific immune responses. Materials and methods: Tumor-infiltrating lymphocytes (TILs) were isolated and expanded from metastatic melanoma lesions which progressed during or after anti-programmed cell death protein 1 (PD)-1 and anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) treatment. Tumor-specific immune responses were assessed with co-culture assays of TILs and autologous tumor cells. Results: TILs from 23 metastases of individual patients could be assessed for T cells recognition of autologous tumor cells. All metastases were progressive on or following anti-PD-1 (23/23, 100%), and the majority also after anti-CTLA-4 (17/23, 74%). Functional antitumor immune responses were detected in 19/23 patients (83%). Both CD8+ (in 18/23 patients, 78%) and CD4+ (in 16/23 patients, 70%) TILs were able to recognize autologous tumors. A large fraction of CD8+ TILs (median 23%, range 1.0%-84%) recognized tumor cells. This is similar to the cohorts of unselected patient populations with metastatic melanoma presented in previous studies. The localization of intratumoral immune infiltrates was heterogeneous among samples. In a phase I/II clinical trial, TILs were administered with lymphodepleting chemotherapy, pegIFNα2b and interleukin-2 to 12 patients with CPI-resistant melanoma. Out of 12 patients who previously failed CPI therapy, treatment with TILs resulted in two partial responses, of which one is ongoing. Conclusions: Tumor-reactive T cells appear to heavily infiltrate the tumor microenvironment of patients who failed previous CPI treatment. These patients can still respond to an infusion of unselected autologous TILs. Our results warrant further testing of novel immune re-activation strategies in melanoma patients who failed multiple CPI therapy.

Update from a 12-Year Nationwide Fungemia Surveillance: Increasing Intrinsic and Acquired Resistance Causes Concern.

New data from the years 2012 to 2015 from the Danish National Fungemia Surveillance are reported, and epidemiological trends are investigated in a 12-year perspective (2004 to 2015). During 2012 to 2015, 1,900 of 1,939 (98%) fungal bloodstream isolates were included. The average incidence was 8.4/100,000 inhabitants, and this appears to represent a stabilizing trend after the increase to 10.1/100,000 in 2011. The incidence was higher in males than females (10.0 versus 6.8) and in patients above 50 years, and those changes were mainly driven by an increasing incidence among 80-to-89-year-old males (65.3/100,000 in 2014 to 2015). The proportion of Candida albicans isolates decreased from 2004 to 2015 (64.4% to 42.4%) in parallel with a doubling of the proportion of Candida glabrata isolates (16.5% to 34.6%, P < 0.0001). C. glabrata was more common among females (34.0% versus 30.4% in males). Following an increase in 2004 to 2011, the annual drug use stabilized during the last 2 to 3 years of that time period but remained higher than in other Nordic countries. This was particularly true for the fluconazole and itraconazole use in the primary health care sector, which exceeded the combined national levels of use of these compounds in each of the other Nordic countries. Fluconazole susceptibility decreased (68.5%, 65.2%, and 60.6% in 2004 to 2007, 2008 to 2011, and 2012 to 2015, respectively, P < 0.0001), and echinocandin resistance emerged in Candida (0%, 0.6%, and 1.7%, respectively, P < 0.001). Amphotericin B susceptibility remained high (98.7%). Among 16 (2.7%) echinocandin-resistant C. glabrata isolates (2012 to 2015), 13 harbored FKS mutations and 5 (31%) were multidrug resistant. The epidemiological changes and the increased incidence of intrinsic and acquired resistance emphasize the importance of continued surveillance and of strengthened focus on antifungal stewardship.

Development of health-related quality of life and symptoms in patients with advanced cancer in Greenland.

A prospective national cohort study assessed the development of health-related quality of life (HRQoL) and symptoms in adult patients undergoing treatment and care for advanced cancer in Greenland. HRQol was examined by EORTC QLQ-C30 version 3.0 questionnaire monthly for 4 months. Changes over time and between-group comparisons were examined. Of 58 patients included in the study, 47% completed the questionnaire four times. Functioning was generally high, and improved social functioning was observed after 1 and 2 months. The highest symptom score was for fatigue followed by pain and nausea/vomiting. A high score for financial problems remained unchanged during the entire period. Patients with higher income had reduced pain intensity (p = .03) and diarrhoea (p = .05) than patients with income below the poverty line. After 1 month, reduction in pain intensity was observed for Nuuk citizens compared with non-Nuuk citizens (p = .05). After 2 months, non-Nuuk citizens reported improved social functioning compared with Nuuk citizens (p = .05). After 3 months, Global Health in Nuuk citizens was improved compared with non-Nuuk citizens (p = .05). An important clinical finding was that patients' needs for support are related to social status, and geographical factors should be taken into account when planning palliative care.

Treatment of first metatarsophalangeal joint arthritis using hemiarthroplasty with a synthetic cartilage implant or arthrodesis: A comparison of operative and recovery time.

BACKGROUND: First metatarsophalangeal joint (MTPJ1) hemiarthroplasty using a novel synthetic cartilage implant was as effective and safe as MTPJ1 arthrodesis in a randomized clinical trial. We retrospectively evaluated operative time and recovery period for implant hemiarthroplasty (n=152) and MTPJ1 arthrodesis (n=50). METHODS: Perioperative data were assessed for operative and anaesthesia times. Recovery and return to function were prospectively assessed with the Foot and Ankle Ability Measure (FAAM) Sports and Activities of Daily Living (ADL) subscales and SF-36 Physical Functioning (PF) subscore. RESULTS: Mean operative time for hemiarthroplasty was 35±12.3min and 58±21.5min for arthrodesis (p<0.001). Anaesthesia duration was 28min shorter with hemiarthroplasty (p<0.001). At weeks 2 and 6 postoperative, hemiarthroplasty patients demonstrated clinically and statistically significantly higher FAAM Sport, FAAM ADL, and SF-36 PF subscores versus arthrodesis patients. CONCLUSION: MTPJ1 hemiarthroplasty with a synthetic cartilage implant took less operative time and resulted in faster recovery than arthrodesis. LEVEL OF EVIDENCE: III, Retrospective case control study.

Spatiotemporal Coherent Control of Thermal Excitations in Solids.

X-ray reflectivity measurements of femtosecond laser-induced transient gratings (TG) are applied to demonstrate the spatiotemporal coherent control of thermally induced surface deformations on ultrafast time scales. Using grazing incidence x-ray diffraction we unambiguously measure the amplitude of transient surface deformations with sub-Å resolution. Understanding the dynamics of femtosecond TG excitations in terms of superposition of acoustic and thermal gratings makes it possible to develop new ways of coherent control in x-ray diffraction experiments. Being the dominant source of TG signal, the long-living thermal grating with spatial period Λ can be canceled by a second, time-delayed TG excitation shifted by Λ/2. The ultimate speed limits of such an ultrafast x-ray shutter are inferred from the detailed analysis of thermal and acoustic dynamics in TG experiments.

Pain prevalence in hospitalized children: a prospective cross-sectional survey in four Danish university hospitals.

BACKGROUND: Pain management in hospitalized children is often inadequate. The prevalence and main sources of pain in Danish university hospitals is unknown. METHODS: This prospective mixed-method cross-sectional survey took place at four university hospitals in Denmark. We enrolled 570 pediatric patients who we asked to report their pain experience and its management during the previous 24 hours. For patients identified as having moderate to severe pain, patient characteristics and analgesia regimes were reviewed. RESULTS: Two hundred and thirteen children (37%) responded that they had experienced pain in the previous 24 hours. One hundred and thirty four (24%) indicated moderate to severe pain and 43% would have preferred an intervention to alleviate the pain. In children hospitalized for more than 24 hours, the prevalence of moderate/severe pain was significantly higher compared to children admitted the same day. The single most common painful procedure named by the children was needle procedures, such as blood draw and intravenous cannulation. CONCLUSION: This study reveals high pain prevalence in children across all age groups admitted to four Danish university hospitals. The majority of children in moderate to severe pain did not have a documented pain assessment, and evidence-based pharmacological and/or integrative ('non-pharmacological') measures were not systematically administered to prevent or treat pain. Thus, practice changes are needed.

Effect of floorball training on blood lipids, body composition, muscle strength, and functional capacity of elderly men.

Floorball training consists of intense repeated exercise and may offer a motivating and social stimulating team activity in elderly individuals. However, the effect of floorball training in elderly adults on physiological adaptations important for health is not known. Thus, this study examined the effect of floorball training on blood lipids, muscle strength, body composition, and functional capacity of men aged 65-76 years. Thirty-nine recreational active men were randomized into a floorball group (FG; n = 22) or petanque group (PG; n = 17), in which training was performed 1 h twice a week for 12 weeks. In FG and PG, average heart rate (HR) during training was 80% and 57%, respectively, of maximal HR. In FG, plasma low-density lipoprotein (LDL) cholesterol and triglycerides were 11% and 8% lower (P < 0.05), respectively. Insulin resistance determined by homeostatic model assessment (HOMA-IR) was reduced (P < 0.05) by 18%. HR during submaximal cycling was 5% lower (P < 0.05), and maximal voluntary contraction force was 8% higher (P < 0.05). Total and visceral fat content was lowered (P < 0.05) by 5% and 14%, respectively, HR at rest was 8% lower (P < 0.05) and performance in four different functional capacity tests were better (P < 0.05) after compared to before the training period. No changes were observed in PG. In conclusion, 12 weeks of floorball training resulted in a number of favorable effects important for health and functional capacity, suggesting that floorball training can be used as a health-promoting activity in elderly men.

Effect of team sports and resistance training on physical function, quality of life, and motivation in older adults.

The aim of this study was to investigate the effect of team sports and resistance training on physical function, psychological health, quality of life, and motivation in older untrained adults. Twenty-five untrained men and forty-seven untrained women aged 80 (range: 67-93) years were recruited. Fifty-one were assigned to a training group (TRG) of which twenty-five performed team training (TG) and twenty-six resistance training (RG). The remaining twenty-one were allocated to a control group (CG). TRG trained for 1 hour twice a week for 12 weeks. Compared with CG, TRG improved the number of arm curls within 30 seconds (P<.05) and 30-seconds chair stand (P<.05) during the intervention. In TRG, participation in training led to higher (P<.05) scores in the subscales psychological well-being, general quality of life, and health-related quality of life, as well as decreased anxiety and depression levels. No differences between changes in TG and RG were found over the intervention period, neither in physical function tests nor psychological questionnaires. Both TG and RG were highly motivated for training, but TG expressed a higher degree of enjoyment and intrinsic motivation mainly due to social interaction during the activity, whereas RG was more motivated by extrinsic factors like health and fitness benefits. In conclusion, both team training and resistance training improved physical function, psychological well-being, and quality of life. However, team sport training motivated the participants more by intrinsic factors than resistance training.

Short-term effects of liraglutide on kidney function and vasoactive hormones in type 2 diabetes: a randomized clinical trial.

AIMS: To investigate the effects of a single dose of 1.2 mg liraglutide, a once-daily glucagon-like peptide-1 (GLP-1) receptor agonist, on key renal variables in patients with type 2 diabetes. METHODS: The study was a placebo-controlled, double-blind, crossover trial in 11 male patients with type 2 diabetes. Measurements included (51) Cr-EDTA plasma clearance estimated glomerular filtration rate (GFR) and MRI-based renal blood flow (RBF), tissue perfusion and oxygenation. RESULTS: Liraglutide had no effect on GFR [95% confidence interval (CI) -6.8 to 3.6 ml/min/1.73 m(2) ] or on RBF (95% CI -39 to 30 ml/min) and did not change local renal blood perfusion or oxygenation. The fractional excretion of lithium increased by 14% (p = 0.01) and sodium clearance tended to increase (p = 0.06). Liraglutide increased diastolic and systolic blood pressure (3 and 6 mm Hg) and heart rate (2 beats per min; all p < 0.05). Angiotensin II (ANG II) concentration decreased by 21% (p = 0.02), but there were no effects on other renin-angiotensin system components, atrial natriuretic peptides (ANPs), methanephrines or excretion of catecholamines. CONCLUSIONS: Short-term liraglutide treatment did not affect renal haemodynamics but decreased the proximal tubular sodium reabsorption. Blood pressure increased with short-term as opposed to long-term treatment. Catecholamine levels were unchanged and the results did not support a GLP-1-ANP axis. ANG II levels decreased, which may contribute to renal protection by GLP-1 receptor agonists.