A systematic review and meta-analysis of the clinimetric properties of the core outcome measurement instruments for clinical effectiveness trials of nutritional and metabolic interventions in critical illness (CONCISE).

BACKGROUND: CONCISE is an internationally agreed minimum set of outcomes for use in nutritional and metabolic clinical research in critically ill adults. Clinicians and researchers need to be aware of the clinimetric properties of these instruments and understand any limitations to ensure valid and reliable research. This systematic review and meta-analysis were undertaken to evaluate the clinimetric properties of the measurement instruments identified in CONCISE. METHODS: Four electronic databases were searched from inception to December 2022 (MEDLINE via Ovid, EMBASE via Ovid, CINAHL via Healthcare Databases Advanced Search, CENTRAL via Cochrane). Studies were included if they examined at least one clinimetric property of a CONCISE measurement instrument or recognised variation in adults ≥ 18 years with critical illness or recovering from critical illness in any language. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist for systematic reviews of Patient-Reported Outcome Measures was used. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were used in line with COSMIN guidance. The COSMIN checklist was used to evaluate the risk of bias and the quality of clinimetric properties. Overall certainty of the evidence was rated using a modified Grading of Recommendations, Assessment, Development and Evaluation approach. Narrative synthesis was performed and where possible, meta-analysis was conducted. RESULTS: A total of 4316 studies were screened. Forty-seven were included in the review, reporting data for 12308 participants. The Short Form-36 Questionnaire (Physical Component Score and Physical Functioning), sit-to-stand test, 6-m walk test and Barthel Index had the strongest clinimetric properties and certainty of evidence. The Short Physical Performance Battery, Katz Index and handgrip strength had less favourable results. There was limited data for Lawson Instrumental Activities of Daily Living and the Global Leadership Initiative on Malnutrition criteria. The risk of bias ranged from inadequate to very good. The certainty of the evidence ranged from very low to high. CONCLUSIONS: Variable evidence exists to support the clinimetric properties of the CONCISE measurement instruments. We suggest using this review alongside CONCISE to guide outcome selection for future trials of nutrition and metabolic interventions in critical illness. TRIAL REGISTRATION: PROSPERO (CRD42023438187). Registered 21/06/2023.

The Sheen Paajanen grOin Recommended Treatment 'SPoRT' score for groin pain.

INTRODUCTION: Evaluating groin pain still evades many clinicians at times as they have difficulty determining the cause of pain when no true hernia exists. This study's aim was to evaluate a simple and novel scoring system which is reproducible, to help determine whether conservative measures or surgery is recommended for the management of groin pain attributable to inguinal disruption. MATERIAL & METHODS: A retrospective analysis of all patients from 2018 to 2020 that underwent surgery or conservative management for inguinal disruption with at least a 1-year follow-up were evaluated. The scoring system is based on MRI and ultrasound imaging as well as clinical findings, with scores given from - 2 to + 2 based on the defined findings listed. A maximum total of four points scored for each assessment was used. Sensitivity and specificity analysis was conducted for each potential score cut off point. RESULTS: A total of 172 patients were evaluated with 33 patients (19%) undergoing conservative management and 139 patients (81%) undergoing surgery. The median SPoRT score for the surgery group was 2.0 (1.0, 3.0), and - 1.0 (- 3.0, 0.0) in the physiotherapy group which was a significant difference (p < 0.001). An optimal cut off of ≤ 0 for physio and ≥ 1 for surgery was established, yielding a sensitivity of 90.9% (95% CI 75.7%-98.1%), a specificity of 89.2% (95% CI 82.8%-93.8%) and an area under the curve (AUC) of 0.936 (95% CI 0.874-0.997). DISCUSSION: SPoRT score of ≤ 0 can recommend a patient should undergo conservative measures or physiotherapy as a mainstay of treatment with a score of ≥ 1 recommending surgery. Further validation of the score is necessary.

Core outcome measures for clinical effectiveness trials of nutritional and metabolic interventions in critical illness: an international modified Delphi consensus study evaluation (CONCISE).

BACKGROUND: Clinical research on nutritional and metabolic interventions in critically ill patients is heterogenous regarding time points, outcomes and measurement instruments used, impeding intervention development and data syntheses, and ultimately worsening clinical outcomes. We aimed to identify and develop a set of core outcome domains and associated measurement instruments to include in all research in critically ill patients. METHODS: An updated systematic review informed a two-stage modified Delphi consensus process (domains followed by instruments). Measurement instruments for domains considered 'essential' were taken through the second stage of the Delphi and a subsequent consensus meeting. RESULTS: In total, 213 participants (41 patients/caregivers, 50 clinical researchers and 122 healthcare professionals) from 24 countries contributed. Consensus was reached on time points (30 and 90 days post-randomisation). Three domains were considered 'essential' at 30 days (survival, physical function and Infection) and five at 90 days (survival, physical function, activities of daily living, nutritional status and muscle/nerve function). Core 'essential' measurement instruments reached consensus for survival and activities of daily living, and 'recommended' measurement instruments for physical function, nutritional status and muscle/nerve function. No consensus was reached for a measurement instrument for Infection. Four further domains met criteria for 'recommended,' but not 'essential,' to measure at 30 days post-randomisation (organ dysfunction, muscle/nerve function, nutritional status and wound healing) and three at 90 days (frailty, body composition and organ dysfunction). CONCLUSION: The CONCISE core outcome set is an internationally agreed minimum set of outcomes for use at 30 and 90 days post-randomisation, in nutritional and metabolic clinical research in critically ill adults.

Using genomic prediction to detect microevolutionary change of a quantitative trait.

Detecting microevolutionary responses to natural selection by observing temporal changes in individual breeding values is challenging. The collection of suitable datasets can take many years and disentangling the contributions of the environment and genetics to phenotypic change is not trivial. Furthermore, pedigree-based methods of obtaining individual breeding values have known biases. Here, we apply a genomic prediction approach to estimate breeding values of adult weight in a 35-year dataset of Soay sheep (Ovis aries). Comparisons are made with a traditional pedigree-based approach. During the study period, adult body weight decreased, but the underlying genetic component of body weight increased, at a rate that is unlikely to be attributable to genetic drift. Thus cryptic microevolution of greater adult body weight has probably occurred. Genomic and pedigree-based approaches gave largely consistent results. Thus, using genomic prediction to study microevolution in wild populations can remove the requirement for pedigree data, potentially opening up new study systems for similar research.

Genetic architecture and lifetime dynamics of inbreeding depression in a wild mammal.

Inbreeding depression is ubiquitous, but we still know little about its genetic architecture and precise effects in wild populations. Here, we combine long-term life-history data with 417 K imputed SNP genotypes for 5952 wild Soay sheep to explore inbreeding depression on a key fitness component, annual survival. Inbreeding manifests in long runs of homozygosity (ROH), which make up nearly half of the genome in the most inbred individuals. The ROH landscape varies widely across the genome, with islands where up to 87% and deserts where only 4% of individuals have ROH. The fitness consequences of inbreeding are severe; a 10% increase in individual inbreeding FROH is associated with a 60% reduction in the odds of survival in lambs, though inbreeding depression decreases with age. Finally, a genome-wide association scan on ROH shows that many loci with small effects and five loci with larger effects contribute to inbreeding depression in survival.

Totally extraperitoneal repair for the 'sportsman's groin' via 'the Manchester Groin Repair': a comparison of elite versus amateur athletes.

BACKGROUND: Surgery has a recognised role in the treatment of 'sportsman's groin'. This study hypothesises that elite athletes have a superior advantage in both pre- and post-op rehabilitation and therefore will present and resume sporting activities quicker. METHODS: A retrospective analysis on a secure database of athletes presenting with groin pain that underwent surgery for 'inguinal disruption'. All data were explored via appropriate descriptive statistics and comparisons made between elite and amateur athletes. RESULTS: All patients were male (n = 144). The median age 33 years (range 14-72). The median return to sporting activity was 4.5 weeks (range 2.0-16.0) with one amateur athlete being unable to return to sporting activity. Using the mean of both sides, a comparison of VAS pain scores at pre-operative and 1 month post-operative time points showed a significant reduction (p < 0.001). Comparing 'elite' versus 'amateur' athletes, significant differences were seen in patient age (median 26 vs 40 years; p < 0.001), lead time to clinic presentation (median 62.0 vs 111.5 days; p = 0.004), and time to return to sporting activity (4 vs 5 weeks; p = 0.019). Additional MRI findings within the groin girdle were found in 89 patients (66.4%) and 34 patients (23.6%) had an MRI finding within the adductor tendon. CONCLUSION: The Manchester Groin Rrepair is an effective surgical management for 'inguinal disruption'. Elite athletes present quicker and return to sport sooner. Given the prevalence of other findings, a multidisciplinary approach to the 'sportsman's groin' is required.

Systemic biomarkers currently implicated in the formation of abdominal wall hernia: A systematic review of the literature.

BACKGROUND: Surgery to the abdominal wall is ubiquitous worldwide and hernia treatment is challenging and expensive, posing a critical need to tailor treatment to individual patient risk-factors. In this systematic review, we consider specific systemic factors with potential as biomarkers of hernia formation. METHODS: A healthcare database-assisted search, following PRISMA guidelines, identified journal articles for inclusion and analysis. RESULTS: 14 biomarker studies were selected, comparing hernia patients and hernia-free controls, focusing on markers of extracellular matrix (ECM) remodelling and collagen turnover. Matrix metalloproteinase-2 was increased in patients with inguinal hernia. Markers of type IV collagen synthesis were increased in patients with abdominal wall hernia; while markers of fibrillar collagen synthesis were reduced. Additional other ECM signalling proteins differ significantly within published studies. CONCLUSION: We identify a lack of high-quality evidence of systemic biomarkers in tailoring treatment strategies relative to patient-specific risks, but recognise the potential held within biomarker-based diagnostic studies to improve management of hernia pathogeneses.

Contemporaneous evaluation of inguinal hernia causation: a European perspective.

AIM: The aim of the study was to evaluate any social, occupational and physical factors, which may influence the occurence or cause of a primary inguinal hernia in two European countries. METHODS: A questionnaire was completed by all the respondents in the setting of an out-patient clinic prospectively at the time of initial presentation and the data were collected on a secure database. All responses for each question were explored via appropriate descriptive statistics. Statistical comparisons were made using Fisher's exact test where appropriate. RESULTS: 537 adults completed the questionnaire and had their data analysed. Comparisons between those that presented with a primary complaint of either 'bulge/swelling' or 'discomfort/pain' found no differences in occupation, age or any other demographic data. Equal proportions of patients who described a single strenuous event presented with a bulge/swelling or discomfort/pain. The reporting of a causative single strenuous event was not significantly influenced by occupation, lifestyle or amount of activity carried out nor was there any significant influence upon when a hernia presented after the suspected strenuous event, although the majority reported a lump within 1 week. CONCLUSION: This study cannot at present support the belief that a single strenuous event will be the sole cause for the development of a primary inguinal hernia.

Senescence in immunity against helminth parasites predicts adult mortality in a wild mammal.

Our understanding of the deterioration in immune function in old age-immunosenescence-derives principally from studies of modern human populations and laboratory animals. The generality and significance of this process for systems experiencing complex, natural infections and environmental challenges are unknown. Here, we show that late-life declines in an important immune marker of resistance to helminth parasites in wild Soay sheep predict overwinter mortality. We found senescence in circulating antibody levels against a highly prevalent nematode worm, which was associated with reduced adult survival probability, independent of changes in body weight. These findings establish a role for immunosenescence in the ecology and evolution of natural populations.

Outcome of the "Manchester Groin Repair" (Laparoscopic Totally Extraperitoneal Approach With Fibrin Sealant Mesh Fixation) in 434 Consecutive Inguinal Hernia Repairs.

Introduction: This study looks at the outcome of 352 patients that underwent the "Manchester groin repair" in the period from 2007 to 2016. The effect of laterality on chronic groin pain and the reduction of pain scores post-surgery are evaluated as well as the rate of hernia recurrence for the inguinal hernia repairs. Methods: The "Manchester groin repair" is a modification of a laparoscopic totally extra-peritoneal approach with fibrin sealant mesh fixation. Data were collected prospectively. In addition to demographic data and the European Hernia Society classification grading of each hernia, pain scores were assessed prior to surgery and at 4-6 weeks post-operatively using a ten-point visual analog pain scale. Data were collected on a bespoke database and differences between time-points analyzed by non-parametric Wilcoxon signed rank tests with Kruskal-Wallis rank sum test for three-group comparisons. Significance was at the P < 0.05 level. The study was undertaken as an institutional audit. Results: Three hundred and fifty two patients underwent TEP repair as per the "Manchester Groin Repair" modification during the period of interest with a median follow-up period of 109.5 (IQR 57.0-318.5) weeks. Of these 274 (77.8%) were for the repair of true hernias and 78 (22.2%) were for inguinal disruptions. All inguinal hernia repairs patients were evaluated (254 m, 20 f); median [interquartile range] age 50 (39-65) years. There were 75 right inguinal hernias (27.4%), 39 Left inguinal hernias (14.2%), and 160 bilateral inguinal hernias (58.4%), giving a total of 434 hernia repairs. During follow-up there were 6 recurrences (1.4%).Of the 274 patients evaluated, 145 (52.9%) had both pre and post-operative pain scores available. Median pre-operative pain score was 5 [IQR 4-7]. Median post-operative pain score was 1 [IQR 1-2]. This difference was significant (P < 0.001). Pre-operative pain scores were higher for those with a bilateral hernia (median 6 vs. 5 and 4, respectively; P = 0.005), but there was no difference in post-operative scores (P = 0.347). One patient (0.3%) presented with chronic groin pain (pain after 3 months). Conclusion: This study demonstrates that the "Manchester groin repair" provides an excellent repair with a low rate of recurrence and low incidence of chronic pain. Longer-term evaluation and larger patient series will add to the understanding of the role of this procedure in groin hernia repair.

Comparison of Mesh Fixation Techniques in Elective Laparoscopic Repair of Incisional Hernia-ReliaTack™ v ProTack™ (TACKoMesh) - A double-blind randomised controlled trial.

BACKGROUND: Minimally invasive incisional hernia repair has been established as a safe and efficient surgical option in most centres worldwide. Laparoscopic technique includes the placement of an intraperitoneal onlay mesh with fixation achieved using spiral tacks or sutures. An additional step is the closure of the fascial defect depending upon its size. Key outcomes in the evaluation of ventral abdominal hernia surgery include postoperative pain, the presence of infection, seroma formation and hernia recurrence. TACKoMESH is a randomised controlled trial that will provide important information on the laparoscopic repair of an incisional hernia; 1) with fascial closure, 2) with an IPOM mesh and 3) comparing the use of an articulating mesh-fixation device that deploys absorbable tacks with a straight-arm mesh-fixation device that deploys non-absorbable tacks. METHODS: A prospective, single-centre, double-blinded randomised trial, TACKoMESH, will establish whether the use of absorbable compared to non-absorbable tacks in adult patients undergoing elective incisional hernia repair produces a lower rate of pain both immediately and long-term. Eligible and consenting patients will be randomized to surgery with one of two tack-fixation devices and followed up for a minimum one year. Secondary outcomes to be explored include wound infection, seroma formation, hernia recurrence, length of postoperative hospital stay, reoperation rate, operation time, health related quality of life and time to return to normal daily activity. DISCUSSION: With ongoing debate around the best management of incisional hernia, continued trials that will add substance are both necessary and important. Laparoscopic techniques have become established in reducing hospital stay and rates of infection and report improvement in some patient centered outcomes whilst achieving similarly low rates of recurrence as open surgical techniques. The laparoscopic method with tack fixation has developed a reputation for its tendency to cause post-operative pain. Novel additions to technique, such as intraoperative-sutured closure of a fascial defect, and developments in surgical technology, such as the evolution of composite mesh design and mesh-fixation devices, have brought about new considerations for patient and surgeon. This study will evaluate the efficacy of several new technical considerations in the setting of elective laparoscopic incisional hernia repair. TRIAL REGISTRATION: Name of registry - ClinicalTrials.gov Registration number: NCT03434301 . Retrospectively registered on 15th February 2018.

Distinct habitat use strategies of sympatric rorqual whales within a fjord system.

We used ecosystem sampling during systematic surveys and opportunistic focal follows, comparison tests, and random forest models to evaluate fin whale (Balaenoptera physalus) and humpback whale (Megaptera novaeangliae) habitat associations within an inland feeding ground (Kitimat Fjord System, British Columbia, Canada). Though these species are sympatric and share a common prey source, they were attuned to different aspects of the local habitat. The fin whales were associated with habitat properties reminiscent of the open ocean. Humpback whales, in contrast, were associated with features more commonly associated with the inland waters of fjords. Fixed habitat features, such as seafloor depth and distance from the fjord mouth, were the most important predictors of fin whale presence, but fixed and dynamic variables, such as surface properties, predicted humpback whale presence with equal (moderate) success. With the exception of strong salinity gradients for humpback whales, habitat conditions were poor predictors of feeding state. Fin whales practiced a spatially confined, seasonally stable, and thus more predictable use of certain channels within the fjord system. These findings are compatible with site loyal behavior, which is interesting in light of the species' historical, unique use of this fjord system. The relatively lackluster performance of humpback-habitat models, coupled with the importance of oceanographic properties, makes the humpback's habitat use strategy more uncertain. The fact that two sympatric species sharing a common prey source exhibited different habitat use strategies suggests that at least one species was informed by something in addition to prey. Given that the two species are attuned to different aspects of the fjord habitat, their responses to habitat changes, including anthropogenic impacts, would likely be different in both nature and degree. Our findings highlight the value of comparative studies and the complexity of rorqual habitat use, which must be understood in order for critical habitat to be identified and protected.

18F-FDG PET/CT in a cardiac metastasis in a patient with history of malignant neuroectodermal tumour of the chest wall: Case report and review of the literature. / PET/TC con 18F-FDG en metástasis cardíaca en un paciente con antecedente de tumor neuroectodérmico maligno de la pared torácica (tumor de Askin): caso clínico y revisión de la literatura.

The case presented is a 25-year-old male with a malignant neuroectodermal tumour on the left chest wall (Askin tumour), treated with surgery after neoadyuvant chemotherapy and followed by consolidation chemotherapy. After 9 years of disease free survival, the patient developed an acute pulmonary embolism. The echocardiogram, thoracic CT, and cardiac MRI scans revealed a mass in the right atrium. Recurrence of an Askin tumour versus an atrium myxoma was suspected. 18F-FDG PET/CT showed an intense hypermetabolic right atrium mass with extension to the right ventricle highly suggestive of malignancy. The result of the histopathology examination after biopsy and subsequently exeresis of the right atrium mass was consistent with a metastasis of the primary tumour.

No evidence for parental age effects on offspring leukocyte telomere length in free-living Soay sheep.

In humans, the effect of paternal age at conception (PAC) on offspring leukocyte telomere length (LTL) is well established, with older fathers thought to pass on longer telomeres to their offspring in their sperm. Few studies have looked for PAC effects in other species, but it has been hypothesised that the effect will be exacerbated in polygamous species with higher levels of sperm competition and production. We test for maternal (MAC) and paternal age at conception effects on offspring LTL in Soay sheep, a primitive breed experiencing strong sperm competition. We use qPCR to measure relative telomere length in 389 blood samples (n = 318 individuals) collected from an unmanaged population of sheep on St Kilda, where individual age and parentage are known. We find no evidence that either MAC or PAC are associated with LTL in offspring across the age range, or when considering only young lambs (n = 164). This is the first study to test for parental age effects on offspring LTL in a wild mammal population, and the results contrast with the findings of numerous human studies that find a PAC effect, as well as predictions of a stronger PAC effect in polygamous species.

Robust extraction of quantitative structural information from high-variance histological images of livers from necropsied Soay sheep.

Quantitative information is essential to the empirical analysis of biological systems. In many such systems, spatial relations between anatomical structures is of interest, making imaging a valuable data acquisition tool. However, image data can be difficult to analyse quantitatively. Many image processing algorithms are highly sensitive to variations in the image, limiting their current application to fields where sample and image quality may be very high. Here, we develop robust image processing algorithms for extracting structural information from a dataset of high-variance histological images of inflamed liver tissue obtained during necropsies of wild Soay sheep. We demonstrate that features of the data can be measured in a fully automated manner, providing quantitative information which can be readily used in statistical analysis. We show that these methods provide measures that correlate well with a manual, expert operator-led analysis of the same images, that they provide advantages in terms of sampling a wider range of information and that information can be extracted far more quickly than in manual analysis.

Physiological proteins in resource-limited herbivores experiencing a population die-off.

Nutrient availability is predicted to interact with herbivore population densities. Competition for low quality food at high density may reduce summer food intake, and in turn winter survival. Conversely, low population density may favor physiological recovery through better access to better quality spring forage. Here, we take advantage of the long-term study of the Soay sheep population of St. Kilda (Scotland) to measure plasma protein markers and immunity in two consecutive summers with contrasting population densities. We show that, following a winter die-off resulting in a shift to low population density, albumin and total proteins increased, but only in adult sheep. The effect was not solely attributable to selective disappearance of malnourished sheep. Similarly, the concentration of antibodies was higher following the die-off, potentially indicating recovery of immune function. Overall, our results are consistent with the physiological recovery of surviving individuals after a harsh winter.

Accounting for female space sharing in St. Kilda Soay sheep (Ovis aries) results in little change in heritability estimates.

When estimating heritability in free-living populations, it is common practice to account for common environment effects, because of their potential to generate phenotypic covariance among relatives thereby biasing heritability estimates. In quantitative genetic studies of natural populations, however, philopatry, which results in relatives being clustered in space, is rarely accounted for. The two studies that have been carried out so far suggest absolute declines in heritability estimates of up to 43% when accounting for space sharing by relatives. However, due to methodological limitations these estimates may not be representative. We used data from the St. Kilda Soay sheep population to estimate heritabilities with and without accounting for space sharing for five traits for which there is evidence for additive genetic variance (birthweight, birth date, lamb August weight, and female post-mortem jaw and metacarpal length). We accounted for space sharing by related females by separately incorporating spatial autocorrelation, and a home range similarity matrix. Although these terms accounted for up to 18% of the variance in these traits, heritability estimates were only reduced by up to 7%. Our results suggest that the bias caused by not accounting for space sharing may be lower than previously thought. This suggests that philopatry does not inevitably lead to a large bias if space sharing by relatives is not accounted for. We hope our work stimulates researchers to model shared space when relatives in their study population share space, as doing so will enable us to better understand when bias may be of particular concern.