Current landscape and support for practical initiation of oncological prehabilitation translatable to thyroid cancer: A position paper.

Despite a growing body of evidence for the effectiveness of prehabilitation, the uptake of prehabilitation in Europe remains low. Contributing factors range from limited awareness and understanding of prehabilitation to a lack of supporting infrastructure and reimbursement challenges. In this position paper, the authors propose a new comprehensive definition of prehabilitation and identify differentiated thyroid cancer as a type of cancer particularly well-suited for prehabilitation. To support clinicians with the implementation of prehabilitation programs in their clinics, the authors discuss the following practical solutions: a) find the most appropriate prehabilitation program for each patient; b) raise awareness among peers; c) develop evidence to demonstrate the effectiveness of prehabilitation; d) expand the interdisciplinary team; e) expand your network and make use of existing assets; f) utilize learnings from the COVID-19 pandemic.

Experiences of patients enrolled and staff involved in the prehabilitation of elective patients undergoing cardiac surgery trial: a nested qualitative study.

The purpose of this study was to understand the views and experiences of patients enrolled and staff involved in the prehabilitation of elective patients undergoing cardiac surgery trial. This sub-study was informed by normalisation process theory, a framework for evaluating complex interventions, and used consecutive sampling to recruit patients assigned to both the intervention and control groups. Patients and all staff involved in delivering the trial were invited to participate in focus groups, which were recorded, transcribed verbatim and subjected to reflexive thematic analysis. Five focus groups were held comprising 24 participants in total (nine patients assigned to the prehabilitation; seven assigned to control; and eight staff). Five themes were identified. First, preparedness for surgery reduced fear, where participants described that knowing what to expect from surgery and preparing the body physically increased feelings of control and subsequently reduced apprehension regarding surgery. Second, staff were concerned but trusted in a safe environment, describing how, despite staff's concerns regarding the risks of exercise in this population, the patients felt safe in their care whilst participating in an exercise programme in hospital. Third, rushing for recovery and the curious carer, where patients from both groups wanted to mobilise quickly postoperatively whilst staff visited patients on the ward to observe their recovery progress. Fourth, to survive and thrive postoperatively, reflecting staff and patients' expectations from the trial and what motivated them to participate. Fifth, benefits are diluted by lengthy waiting periods, reflecting the frustration felt by patients waiting for their surgery after completing the intervention and the fear about continuing exercise at home before they had been 'fixed'. To conclude, functional exercise capacity may not have improved following prehabilitation in people before elective cardiac surgery due to concerns regarding the safety of exercise that may have hindered delivery and receipt of the intervention. Instead, numerous non-physical benefits were elicited. The information from this qualitative study offers valuable recommendations regarding refining a prehabilitation intervention and conducting a subsequent trial.

A randomised controlled trial of prehabilitation in patients undergoing elective cardiac surgery.

The feasibility, safety and efficacy of prehabilitation in adult patients awaiting elective cardiac surgery are unknown. A total of 180 participants undergoing elective cardiac surgery were allocated randomly to receive either standard pre-operative care or prehabilitation, consisting of pre-operative exercise and inspiratory muscle training. The primary outcome was change in six-minute walk test distance from baseline to pre-operative assessment. Secondary outcomes included change in inspiratory muscle strength (maximal inspiratory pressure); sarcopenia (handgrip strength); quality of life and compliance. Safety outcomes were pre-specified surgical and pulmonary complications and adverse events. All outcomes were assessed at baseline; at pre-operative assessment; and 6 and 12 weeks following surgery. Mean (SD) age was 64.7 (10.2) years; 33/180 (18%) were women. In total, 65/91 (71.4%) participants who were allocated to prehabilitation attended at least four of eight supervised in-hospital exercise classes; participants aged > 50 years were more likely than younger participants to attend (odds ratio (95%CI) of 4.6 (1.0-25.1)). Six-minute walk test was not significantly different between groups (mean difference (95%CI) -7.8 m (-30.6-15.0), p = 0.503) in the intention-to-treat analysis. Subgroup analyses based on tests for interaction indicated improvements in six-minute walk test distance were larger amongst sarcopenic patients in the prehabilitation group (p = 0.004). Change in maximal inspiratory pressure from baseline to all time-points was significantly greater in the prehabilitation group, with the greatest mean difference (95%CI) observed 12 weeks after surgery (10.6 cmH2 O (4.6-16.6) cmH2 O, p < 0.001). There were no differences in handgrip strength or quality of life up to 12 weeks after surgery. There was no significant difference in postoperative mortality (one death in each group), surgical or pulmonary complications. Of 71 pre-operative adverse events, six (8.5%) were related to prehabilitation. The combination of exercise and inspiratory muscle training in a prehabilitation intervention before cardiac surgery was not superior to standard care in improving functional exercise capacity measured by six-minute walk test distance pre-operatively. Future trials should target patients living with sarcopenia and include inspiratory muscle strength training.

The association between treatment and systemic inflammation in acromegaly.

OBJECTIVE: Acromegaly is characterized by an excess of growth hormone (GH) and insulin like growth-factor 1 (IGF1), and it is strongly associated with cardiovascular diseases (CVD). Both acute and long-lasting pro-inflammatory effects have been attributed to IGF1. Previous results suggest the presence of systemic inflammation in treated patients. Here we assessed the association between treatment of acromegaly, systemic inflammation and vascular function. DESIGN: Ex vivo cytokine production and circulating inflammatory markers were assessed in peripheral blood from treated and untreated acromegaly patients (N = 120), and compared them with healthy controls. A more comprehensive prospective inflammatory and vascular assessment was conducted in a subgroup of six treatment-naive patients with follow-up during treatment. RESULTS: Circulating concentrations of VCAM1, E-selectin and MMP2 were higher in patients with uncontrolled disease, whereas the concentrations of IL18 were lower. In stimulated whole blood, cytokine production was skewed towards a more pro-inflammatory profile in patients, especially those with untreated disease. Prospective vascular measurements in untreated patients showed improvement of endothelial function during treatment. CONCLUSIONS: Acromegaly patients are characterized by a pro-inflammatory phenotype, most pronounced in those with uncontrolled disease. Treatment only partially reverses this pro-inflammatory bias. These findings suggest that systemic inflammation could contribute to the increased risk of CVD in acromegaly patients.

Fast In Situ Observation of Atomic Feshbach Resonances by Photoassociative Ionization.

We propose and experimentally investigate a scheme for observing Feshbach resonances in atomic quantum gases in situ and with a high temporal resolution of several tens of nanoseconds. The method is based on the detection of molecular ions, which are optically generated from atom pairs at small interatomic distances. As a test system we use a standard rubidium gas (^{87}Rb) with well known magnetically tunable Feshbach resonances. The fast speed and the high sensitivity of our detection scheme allows us to observe a complete Feshbach resonance within one millisecond and without destroying the gas.

The effect of treatment on quality of life in patients with acromegaly: a prospective study.

OBJECTIVE: Acromegaly has a negative influence on health-related quality of life (HRQoL). Previous studies provide limited information on the course of HRQoL during treatment. This study aims to assess the effect of treatment on the course of HRQoL at six predefined time points. DESIGN: This prospective study examines HRQoL in treatment-naive patients before and during the first 2.5 years of acromegaly treatment. METHODS: Therapy-naive acromegaly patients completed three validated questionnaires (RAND-36, AcroQoL, and the Appearance Self-Esteem (ASE)) at six predetermined time points before, during, and after treatment. Outcomes were correlated to IGF1 levels and disease control status. RESULTS: Twenty-seven acromegaly patients completed the questionnaires at all time points. After treatment, all patients had controlled acromegaly. Scores of RAND-36 domains General health, Vitality and Health change, and all AcroQoL dimensions (except for Relations) improved during treatment (P ≤ 0.003); the largest changes were detected during the first year. Gender influenced HRQoL scores, since AcroQoL scores significantly improved in males but not in females. Over time, IGF1 levels were negatively correlated with HRQoL. After 2.5 years of follow-up, HRQoL of controlled patients was still lower than in the general population. CONCLUSION: HRQoL of acromegaly patients was considerably reduced at diagnosis. Disease control was associated with an improvement of HRQoL scores. Males showed a more pronounced improvement than females. The largest changes were detected in the first year of treatment. However, HRQoL during and after treatment remained impaired in acromegaly patients, emphasizing the need of additional support.

Romidepsin suppresses monosodium urate crystal-induced cytokine production through upregulation of suppressor of cytokine signaling 1 expression.

BACKGROUND: Acute gouty arthritis currently is the most common form of inflammatory arthritis in developed countries. Treatment is still suboptimal. Dosage of urate-lowering therapy is often too low to reach target urate levels, and adherence to therapy is poor. In this study, we therefore explore a new treatment option to limit inflammation in acute gout: specific histone deacetylase (HDAC) inhibition. METHODS: Peripheral blood mononuclear cells (PBMCs) were cultured with a combination of monosodium urate crystals (MSU) and palmitic acid (C16.0) in order to activate the NLRP3 inflammasome and induce IL-1ß production. HDAC inhibitors and other compounds were added beforehand with a 1-h pre-incubation period. RESULTS: The HDAC1/2 inhibitor romidepsin was most potent in lowering C16.0+MSU-induced IL-1ß production compared to other specific class I HDAC inhibitors. At 10 nM, romidepsin decreased IL-1ß, IL-1Ra, IL-6, and IL-8 production. IL-1ß mRNA was significantly decreased at 25 nM. Although romidepsin increased PTEN expression, PBMCs from patients with germline mutations in PTEN still responded well to romidepsin. Romidepsin also increased SOCS1 expression and blocked STAT1 and STAT3 activation. Furthermore, experiments with bortezomib showed that blocking the proteasome reverses the cytokine suppression by romidepsin. CONCLUSIONS: Our results show that romidepsin is a very potent inhibitor of C16.0+MSU-induced cytokines in vitro. Romidepsin upregulated transcription of SOCS1, which was shown to directly target inflammatory signaling molecules for proteasomal degradation. Inhibiting the proteasome therefore reversed the cytokine-suppressive effects of romidepsin. HDAC1/2 dual inhibition could therefore be a highly potent new treatment option for acute gout, although safety has to be determined in vivo.

Long-term effects of radioiodine treatment on salivary gland function in adult survivors of pediatric differentiated thyroid carcinoma.

Pediatric differentiated thyroid cancer (DTC) is a rare disease. Initial treatment of DTC consists of a (near) total thyroidectomy and radioactive iodine (131I) therapy. Previous studies in adults showed that 131I treatment may result in a reduced salivary gland function. Studies regarding salivary gland function in children treated for DTC are sparse. Our aim was to assess long-term effects of 131I treatment on salivary gland function in survivors of pediatric DTC. Methods: In a nationwide cross-sectional study, salivary gland function of patients treated for pediatric DTC between 1970 and 2013 (>5 years after diagnosis, ≥18 years old at time of evaluation) was studied. Salivary gland function was assessed by sialometry, sialochemistry and a xerostomia inventory. Salivary gland dysfunction was defined as unstimulated whole saliva flow ≤0.2mL/min and/or a stimulated whole saliva flow ≤0.7 mL/min. Results: Sixty-five patients (median age at evaluation 33 [IQR, 25-40] years, 86.2% female, median follow-up period 11 [IQR, 6-22] years) underwent 131I treatment. Median cumulative 131I activity was 5.88 [IQR, 2.92-12.95] GBq, 47.7% underwent multiple 131I administrations. Salivary gland dysfunction was present in 30 (47.6%) patients. Levels of amylase and total protein in saliva were reduced. Moderate to severe xerostomia was present in 22 (35.5%) patients. Stimulated salivary secretion was lower and severity of xerostomia complaints higher in patients treated with higher cumulative 131I activity. Conclusion: In survivors of pediatric DTC, clinically significant salivary gland dysfunction was found in 35.5% and was related to the cumulative 131I activity of the treatment.

Isotensor Dibaryon in the pp→ppπ

Exclusive measurements of the quasifree pp→ppπ^{+}π^{-} reaction have been carried out at WASA@COSY by means of pd collisions at T_{p}=1.2 GeV. Total and differential cross sections have been extracted covering the energy region T_{p}=1.08-1.36 GeV, which is the region of N^{*}(1440) and Δ(1232)Δ(1232) resonance excitations. Calculations describing these excitations by t-channel meson exchange are at variance with the measured differential cross sections and underpredict substantially the experimental total cross section. An isotensor ΔN dibaryon resonance with I(J^{P})=2(1^{+}) produced associatedly with a pion is able to overcome these deficiencies.

Spin Dependence of η Meson Production in Proton-Proton Collisions Close to Threshold.

Taking advantage of the high acceptance and axial symmetry of the WASA-at-COSY detector, and the high polarization degree of the proton beam of COSY, the reaction p[over →]p→ppη has been measured close to threshold to explore the analyzing power A_{y}. The angular distribution of A_{y} is determined with the precision improved by more than 1 order of magnitude with respect to previous results, allowing a first accurate comparison with theoretical predictions. The determined analyzing power is consistent with zero for an excess energy of Q=15 MeV, signaling s-wave production with no evidence for higher partial waves. At Q=72 MeV the data reveal strong interference of Ps and Pp partial waves and cancellation of (Pp)^{2} and Ss^{*}Sd contributions. These results rule out the presently available theoretical predictions for the production mechanism of the η meson.

Embracing polygenicity: a review of methods and tools for psychiatric genetics research.

The availability of genome-wide genetic data on hundreds of thousands of people has led to an equally rapid growth in methodologies available to analyse these data. While the motivation for undertaking genome-wide association studies (GWAS) is identification of genetic markers associated with complex traits, once generated these data can be used for many other analyses. GWAS have demonstrated that complex traits exhibit a highly polygenic genetic architecture, often with shared genetic risk factors across traits. New methods to analyse data from GWAS are increasingly being used to address a diverse set of questions about the aetiology of complex traits and diseases, including psychiatric disorders. Here, we give an overview of some of these methods and present examples of how they have contributed to our understanding of psychiatric disorders. We consider: (i) estimation of the extent of genetic influence on traits, (ii) uncovering of shared genetic control between traits, (iii) predictions of genetic risk for individuals, (iv) uncovering of causal relationships between traits, (v) identifying causal single-nucleotide polymorphisms and genes or (vi) the detection of genetic heterogeneity. This classification helps organise the large number of recently developed methods, although some could be placed in more than one category. While some methods require GWAS data on individual people, others simply use GWAS summary statistics data, allowing novel well-powered analyses to be conducted at a low computational burden.

Proceedings of resources for optimal care of acute care and emergency surgery consensus summit Donegal Ireland.

BACKGROUND: Opportunities to improve emergency surgery outcomes exist through guided better practice and reduced variability. Few attempts have been made to define optimal care in emergency surgery, and few clinically derived key performance indicators (KPIs) have been published. A summit was therefore convened to look at resources for optimal care of emergency surgery. The aim of the Donegal Summit was to set a platform in place to develop guidelines and KPIs in emergency surgery. METHODS: The project had multidisciplinary global involvement in producing consensus statements regarding emergency surgery care in key areas, and to assess feasibility of producing KPIs that could be used to monitor process and outcome of care in the future. RESULTS: Forty-four key opinion leaders in emergency surgery, across 7 disciplines from 17 countries, composed evidence-based position papers on 14 key areas of emergency surgery and 112 KPIs in 20 acute conditions or emergency systems. CONCLUSIONS: The summit was successful in achieving position papers and KPIs in emergency surgery. While position papers were limited by non-graded evidence and non-validated KPIs, the process set a foundation for the future advancement of emergency surgery.

Erratum to: The management of intra-abdominal infections from a global perspective: 2017 WSES guidelines for management of intra-abdominal infections.

[This corrects the article DOI: 10.1186/s13017-017-0141-6.].

Erratum to: Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

[This corrects the article DOI: 10.1186/s13017-016-0089-y.].

Rare NOX3 Variants Confer Susceptibility to Agranulocytosis During Thyrostatic Treatment of Graves' Disease.

Agranulocytosis is a rare and serious adverse effect of antithyroid drugs, with unknown etiology. The present study aimed to uncover genetic susceptibility and underlying mechanisms of antithyroid drug-induced agranulocytosis (ATDAC). We studied two independent families with familial Graves' disease, of which several members developed ATDAC. In addition, six sporadic ATDAC patients with Graves' disease were investigated. Whole exome sequencing analysis of affected and unaffected family members was performed to identify genetic susceptibility variants for ATDAC, followed by functional characterization of primary granulocytes from patients and unrelated healthy controls. Whole exome sequencing, cosegregation analysis, and stringent selection criteria of candidate gene variants identified NOX3 as a genetic factor related to ATDAC. Functional studies revealed increased apoptosis of methimazole-treated granulocytes from patients carrying NOX3 variants. In conclusion, genetic variants in NOX3 may confer susceptibility to antithyroid drug-induced apoptosis of granulocytes. These findings contribute to the understanding of the mechanisms underlying ATDAC.

Changes in management policies for extremely preterm births and neonatal outcomes from 2003 to 2012: two population-based studies in ten European regions.

OBJECTIVE: To investigate changes in maternity and neonatal unit policies towards extremely preterm infants (EPTIs) between 2003 and 2012, and concurrent trends in their mortality and morbidity in ten European regions. DESIGN: Population-based cohort studies in 2003 (MOSAIC study) and 2011/2012 (EPICE study) and questionnaires from hospitals. SETTING: 70 hospitals in ten European regions. POPULATION: Infants born at <27 weeks of gestational age (GA) in hospitals participating in both the MOSAIC and EPICE studies (1240 in 2003, 1293 in 2011/2012). METHODS: We used McNemar's Chi2 test, paired t-tests and conditional logistic regression for comparisons over time. MAIN OUTCOMES MEASURES: Reported policies, mortality and morbidity of EPTIs. RESULTS: The lowest GA at which maternity units reported performing a caesarean section for acute distress of a singleton non-malformed fetus decreased from an average of 24.7 to 24.1 weeks (P < 0.01) when parents were in favour of active management, and 26.1 to 25.2 weeks (P = 0.01) when parents were against. Units reported that neonatologists were called more often for spontaneous deliveries starting at 22 weeks GA in 2012 and more often made decisions about active resuscitation alone, rather than in multidisciplinary teams. In-hospital mortality after live birth for EPTIs decreased from 50% to 42% (P < 0.01). Units reporting more active management in 2012 than 2003 had higher mortality in 2003 (55% versus 43%; P < 0.01) and experienced larger declines (55 to 44%; P < 0.001) than units where policies stayed the same (43 to 37%; P = 0.1). CONCLUSIONS: European hospitals reporting changes in management policies experienced larger survival gains for EPTIs. TWEETABLE ABSTRACT: Changes in reported policies for management of extremely preterm births were related to mortality declines.

Three-dimensional soft tissue analysis of the hand: a novel method to investigate effects of acromegaly.

BACKGROUND: Acral overgrowth is a highly common clinical sign in patients with active acromegaly. To what extent this overgrowth persists after long-term remission of acromegaly is largely unknown. Using the new imaging technique of three-dimensional (3D) stereophotogrammetry, it is possible to accurately investigate soft tissue changes of the hand. The aim of the recent study was to compare the 3D soft tissue characteristics of the hands of patients in long-term remission of acromegaly to those of a healthy pair matched control group. METHODS: A case-control study was performed at a tertiary referral center. Twelve patients in remission of acromegaly (58 % male, mean age 58.3 years, mean BMI 29.6 kg/m2) were compared to twelve age-, gender-, ethnicity-, and BMI-matched control subjects. Of each individual, 3D photographs of both hands were acquired and analyzed using a 3D computer software program. RESULTS: The patients in long-term remission of acromegaly have overgrowth of soft tissue of the hand compared to matched control subjects, with a larger length and width of the hand (p = 0.0025, p = 0.0017, respectively). Furthermore, the diameters measured at the proximal interphalangeal (PIP) joints of the individual fingers are larger in the acromegaly patients. CONCLUSIONS: Significant soft tissue overgrowth of the hand persists in former acromegaly patients, even after long-term remission. Analysis of 3D hand photographs is an accurate and easy tool to evaluate the acral soft tissue patterns in acromegaly. Level of Evidence: Level III, diagnostic study.

A storage ring experiment to detect a proton electric dipole moment.

A new experiment is described to detect a permanent electric dipole moment of the proton with a sensitivity of 10-29 e ⋅ cm by using polarized "magic" momentum 0.7 GeV/c protons in an all-electric storage ring. Systematic errors relevant to the experiment are discussed and techniques to address them are presented. The measurement is sensitive to new physics beyond the standard model at the scale of 3000 TeV.

Erratum to: 2016 WSES guidelines on acute calculous cholecystitis.

[This corrects the article DOI: 10.1186/s13017-016-0082-5.].