Multiscale Structure and Function of the Aortic Valve Apparatus.

While studying the aortic valve in isolation has facilitated the development of life-saving procedures and technologies, the dynamic interplay of the aortic valve and its surrounding structures is vital to preserving their function across the wide range of conditions encountered in an active lifestyle. Our view is that these structures should be viewed as an integrated functional unit, herein referred to as the aortic valve apparatus (AVA). The coupling of the aortic valve and root, left ventricular outflow tract, and blood circulation is crucial for AVA's functions: unidirectional flow out of the left ventricle, coronary perfusion, reservoir function, and supporting left ventricular function. In this review, we explore the multiscale biological and physical phenomena that underly the simultaneous fulfilment of these functions. A brief overview of the tools used to investigate the AVA is included, such as: medical imaging modalities, experimental methods, and computational modelling, specifically fluid-structure interaction (FSI) simulations, is included. Some pathologies affecting the AVA are explored, and insights are provided on treatments and interventions that aim to maintain quality of life. The concepts explained in this paper support the idea of AVA being an integrated functional unit and help identify unanswered research questions. Incorporating phenomena through the molecular, micro, meso and whole tissue scales is crucial for understanding the sophisticated normal functions and diseases of the AVA.

Pyridostigmine to Reduce the duration of postoperative Ileus after Colorectal surgery (PyRICo-RCT): randomized clinical trial.

BACKGROUND: Postoperative ileus, driven by the cholinergic anti-inflammatory pathway, is the most common complication in patients undergoing colorectal surgery. By inhibiting acetylcholinesterase, pyridostigmine can potentially modulate the cholinergic anti-inflammatory pathway and accelerate gastrointestinal recovery. This study aimed to assess the efficacy of pyridostigmine in improving gastrointestinal recovery after colorectal surgery. METHODS: This double-blinded RCT enrolled adult patients undergoing elective colorectal surgery at two hospitals in South Australia. Patients were randomized to 60 mg oral pyridostigmine or placebo twice daily starting 6 h after surgery until the first passage of stool. The primary outcome was GI-2, a validated composite measure of time to first stool and tolerance of oral diet. Secondary outcomes included incidence of postoperative ileus (defined as GI-2 greater than 4 days), duration of hospital stay, and 30-day complications, evaluated by intention-to-treat univariate analysis. RESULTS: Of 130 patients recruited (mean(s.d.) age 58.4(16.4) years; 73 men, 56%), 65 were allocated to each arm. The median GI-2 was 1 day shorter with pyridostigmine compared with placebo (2 (i.q.r. 1-3) versus 3 (2-4) days; P = 0.015). However, there were no significant differences in postoperative ileus (17.2 versus 21.5%; P = 0.532) or duration of hospital stay (median 5 (i.q.r. 4-8.75) versus 5 (4-7.5) days; P = 0.921). Similarly, there were no significant differences in overall complications, anastomotic leak, cardiac complications, or patient-reported side effects. CONCLUSION: Pyridostigmine resulted in a quicker return of GI-2 and was well tolerated. Larger multicentre studies are required to determine the optimal dosing and evaluate the impact of pyridostigmine in different surgical settings. Registration number: ACTRN12621000530820 (https://anzctr.org.au).

Mistranslation-associated perturbations of proteostasis do not promote accumulation of amyloid beta and plaque deposition in aged mouse brain.

A common perception in age-related neurodegenerative diseases posits that a decline in proteostasis is key to the accumulation of neuropathogenic proteins, such as amyloid beta (Aß), and the development of sporadic Alzheimer's disease (AD). To experimentally challenge the role of protein homeostasis in the accumulation of Alzheimer's associated protein Aß and levels of associated Tau phosphorylation, we disturbed proteostasis in single APP knock-in mouse models of AD building upon Rps9 D95N, a recently identified mammalian ram mutation which confers heightened levels of error-prone translation together with an increased propensity for random protein aggregation and which is associated with accelerated aging. We crossed the Rps9 D95N mutation into knock-in mice expressing humanized Aß with different combinations of pathogenic mutations (wild-type, NL, NL-F, NL-G-F) causing a stepwise and quantifiable allele-dependent increase in the development of Aß accumulation, levels of phosphorylated Tau, and neuropathology. Surprisingly, the misfolding-prone environment of the Rps9 D95N ram mutation did not affect Aß accumulation and plaque formation, nor the level of phosphorylated Tau in any of the humanized APP knock-in lines. Our findings indicate that a misfolding-prone environment induced by error-prone translation with its inherent perturbations in protein homeostasis has little impact on the accumulation of pathogenic Aß, plaque formation and associated phosphorylated Tau.

Use of Acetylcholinesterase Inhibitors in Reducing Time to Gastrointestinal Function Recovery following Abdominal Surgery: A Systematic Review.

INTRODUCTION: Postoperative ileus (POI) is a significant complication following abdominal surgery, increasing morbidity and mortality. The cholinergic anti-inflammatory response is one of the major pathways involved in developing POI, but current recommendations to prevent POI do not target this. This review aims to summarise evidence for the use of acetylcholinesterase inhibitors, neostigmine and pyridostigmine, to reduce the time to return of gastrointestinal function (GI) following abdominal surgery. METHODS: A systematic search of various databases was performed from 1946 to May 2023. Randomised controlled trials (RCTs) on acetylcholinesterase inhibitors in intra-abdominal surgery were included. Data on time to flatus and/or stool and side effects were extracted. RESULTS: Among 776 screened manuscripts, 8 RCTs (703 patients) investigating acetylcholinesterase inhibitors in intra-abdominal surgery were analysed. Five studies showed a significant reduction in time to flatus and/or stool by 17-47.6 h. Methodological variations, differing procedure types, and potential bias were observed. Limited studies reported side effects or length of stay. CONCLUSION: Acetylcholinesterase inhibitors may reduce the time for GI to return. However, current evidence is limited and biased. Further studies incorporating acetylcholinesterase inhibitors in an enhanced recovery protocol are required to address this question, especially for patients undergoing colorectal surgery.

Evaluation of a mobile COVID-19 vaccination van outreach service in an outer South London borough.

BACKGROUND: This study aimed to explore differences in users of a COVID-19 mobile vaccine van service and users of a COVID-19 static vaccination hub, and the impact of changes in national COVID-19 vaccine policy on vaccine uptake. METHODS: The age distribution of male and female service users in each service was compared. The average number of vaccines administered per hour per week was analysed. RESULTS: Females aged 80-89 represented 51.9% (95% CI 49.5-54.3%) of female vaccine van users compared with 2.8% (95% CI 2.5-3.1%) of female static hub users. The static hub had significantly greater proportions of female service users in all other age brackets.For males, the greatest difference was in those aged 70-79 who represented 29.8% (95% CI 27-32.6%) of vaccine van users and 16.6% (95% CI 16-17.2%) static hub users.Fewer vaccines were administered 2-3 weeks before the COVID-19 autumn booster policy change compared with 2-3 weeks after; 1.92 versus 6.25 vaccines per hour, respectively (Mann-Whitney U = 7, n1 = 11, n2 = 8, P < 0.01 two-tailed). CONCLUSIONS: These findings suggest that a mobile vaccine van service is an effective model for increasing COVID-19 vaccination uptake in elderly residents, particularly after a national policy change.

Improvement of Emergency Department Chest Pain Evaluation Using Hs-cTnT and a Risk Stratification Pathway.

BACKGROUND: Chest pain is among the most common reasons for presentation to the emergency department (ED) worldwide. Additional studies on most cost-effective ways of differentiating serious vs. benign causes of chest pain are needed. OBJECTIVES: Our study aimed to evaluate the effectiveness of a novel risk stratification pathway utilizing 5th generation high-sensitivity cardiac troponin T assay (Hs-cTnT) and HEART score (History, Electrocardiogram, Age, Risk factors, Troponin) in assessing nontraumatic chest pain patients in reducing ED resource utilization. METHODS: A retrospective chart review was performed 6 months prior to and after the implementation of a novel risk stratification pathway that combined hs-cTnT with HEART score to guide evaluation of adult patients presenting with nontraumatic chest pain at a large academic quaternary care ED. Primary outcome was ED length of stay (LOS); secondary outcomes included cardiology consult rates, admission rates, number of ED boarders, and number of eloped patients. RESULTS: A total of 1707 patients and 1529 patients were included pre- and postimplementation, respectively. Median overall ED LOS decreased from 317 to 286 min, an absolute reduction of 31 min (95% confidence interval 22-41 min), after pathway implementation (p < 0.001). Furthermore, cardiology consult rate decreased from 26.9% to 16.0% (p < 0.0001), rate of admission decreased from 30.1% to 22.7% (p < 0.0001), and number of ED boarders as a proportion of all nontraumatic chest pain patients decreased from 25.13% preimplementation to 18.63% postimplementation (p < 0.0001). CONCLUSIONS: Implementation of our novel chest pain pathway improved numerous ED throughput metrics in the evaluation of nontraumatic chest pain patients.

Multicenter Assessment of Cryoanalgesia Use in Minimally Invasive Repair of Pectus Excavatum: A 20-center Retrospective Cohort Study.

OBJECTIVE: To assess the clinical implications of cryoanalgesia for pain management in children undergoing minimally invasive repair of pectus excavatum (MIRPE). BACKGROUND: MIRPE entails significant pain management challenges, often requiring high postoperative opioid use. Cryoanalgesia, which blocks pain signals by temporarily ablating intercostal nerves, has been recently utilized as an analgesic adjunct. We hypothesized that the use of cryoanalgesia during MIRPE would decrease postoperative opioid use and length of stay (LOS). MATERIALS AND METHODS: A multicenter retrospective cohort study of 20 US children's hospitals was conducted of children (age below 18 years) undergoing MIRPE from January 1, 2014, to August 1, 2019. Differences in total postoperative, inpatient, oral morphine equivalents per kilogram, and 30-day LOS between patients who received cryoanalgesia versus those who did not were assessed using bivariate and multivariable analysis. P value <0.05 is considered significant. RESULTS: Of 898 patients, 136 (15%) received cryoanalgesia. Groups were similar by age, sex, body mass index, comorbidities, and Haller index. Receipt of cryoanalgesia was associated with lower oral morphine equivalents per kilogram (risk ratio=0.43, 95% confidence interval: 0.33-0.57) and a shorter LOS (risk ratio=0.66, 95% confidence interval: 0.50-0.87). Complications were similar between groups (29.8% vs 22.1, P =0.07), including a similar rate of emergency department visit, readmission, and/or reoperation. CONCLUSIONS: Use of cryoanalgesia during MIRPE appears to be effective in lowering postoperative opioid requirements and LOS without increasing complication rates. With the exception of preoperative gabapentin, other adjuncts appear to increase and/or be ineffective at reducing opioid utilization. Cryoanalgesia should be considered for patients undergoing this surgery.

Sodium Bicarbonate for Metabolic Acidosis in the ICU: Results of a Pilot Randomized Double-Blind Clinical Trial.

OBJECTIVES: To identify the best population, design of the intervention, and to assess between-group biochemical separation, in preparation for a future phase III trial. DESIGN: Investigator-initiated, parallel-group, pilot randomized double-blind trial. SETTING: Eight ICUs in Australia, New Zealand, and Japan, with participants recruited from April 2021 to August 2022. PATIENTS: Thirty patients greater than or equal to 18 years, within 48 hours of admission to the ICU, receiving a vasopressor, and with metabolic acidosis (pH < 7.30, base excess [BE] < -4 mEq/L, and Pa co2 < 45 mm Hg). INTERVENTIONS: Sodium bicarbonate or placebo (5% dextrose). MEASUREMENTS AND MAIN RESULT: The primary feasibility aim was to assess eligibility, recruitment rate, protocol compliance, and acid-base group separation. The primary clinical outcome was the number of hours alive and free of vasopressors on day 7. The recruitment rate and the enrollment-to-screening ratio were 1.9 patients per month and 0.13 patients, respectively. Time until BE correction (median difference, -45.86 [95% CI, -63.11 to -28.61] hr; p < 0.001) and pH correction (median difference, -10.69 [95% CI, -19.16 to -2.22] hr; p = 0.020) were shorter in the sodium bicarbonate group, and mean bicarbonate levels in the first 24 hours were higher (median difference, 6.50 [95% CI, 4.18 to 8.82] mmol/L; p < 0.001). Seven days after randomization, patients in the sodium bicarbonate and placebo group had a median of 132.2 (85.6-139.1) and 97.1 (69.3-132.4) hours alive and free of vasopressor, respectively (median difference, 35.07 [95% CI, -9.14 to 79.28]; p = 0.131). Recurrence of metabolic acidosis in the first 7 days of follow-up was lower in the sodium bicarbonate group (3 [20.0%] vs. 15 [100.0%]; p < 0.001). No adverse events were reported. CONCLUSIONS: The findings confirm the feasibility of a larger phase III sodium bicarbonate trial; eligibility criteria may require modification to facilitate recruitment.

Reduction in the prevalence of methicillin-resistant Staphylococcus aureus in tissue and wound swab samples taken from outpatients attending a specialist diabetic foot clinic 2005-2021.

AIMS: To assess annual change in prevalence of methicillin resistant Staphylococcus aureus (MRSA) from tissue and wound swab samples from foot ulcers (DFUs) in people with diabetes between 2005 and 2021. METHODS: A retrospective analysis of everyone with MRSA positive wound or tissue swabs taken from our specialist multidisciplinary foot clinic between July 2005 and July 2021. RESULTS: A total of 406 MRSA positive isolates from DFU swabs were identified from 185 individuals attending the foot clinic. There were 22 hospital-acquired infections (HAIs) and 159 community-acquired infections (CAIs). Fifty-two per cent (n = 37) of these individuals from 2010 to 2021 (n = 71) had presence of at least three risk factors for MRSA. The total number of swabs sent was 6312 from 1916 individuals living with diabetes. Annual MRSA DFU prevalence peaked in 2008 at 14.6% (n = 38), decreased in 2013 to 5.2% (n = 20) and did not exceed 4% (n = 6) from 2015 to 2021. Hospital MRSA was lowest in 2021 (n = 211), a 76% fall from 2007 (n = 880). Incidence of MRSA HAI from 2015 to 2021 ranged from 5.4% (n = 14) in 2020 to 11.5% (n = 41) in 2018. CONCLUSIONS: Prevalence of MRSA in DFU infections treated as outpatients is decreasing in line with falls in hospital acquired blood-borne infections and with overall hospital MRSA incidence. This is likely a reflection of the combination of interventions, including stringent antibiotic prescribing and decolonisation strategies. Reduction in prevalence should have positive impact on outcomes in people living with diabetes, reducing the complication of osteomyelitis and necessity for long-term antibiotic administration.

Thermoregulation and golden hour practices in extremely preterm infants: an international survey.

BACKGROUND: Are thermoregulation and golden hour practices in extremely preterm (EP) infants comparable across the world? This study aims to describe these practices for EP infants based on the neonatal intensive care unit's (NICUs) geographic region, country's income status and the lowest gestational age (GA) of infants resuscitated. METHODS: The Director of each NICU was requested to complete the e-questionnaire between February 2019 and August 2021. RESULTS: We received 848 responses, from all geographic regions and resource settings. Variations in most thermoregulation and golden hour practices were observed. Using a polyethylene plastic wrap, commencing humidity within 60 min of admission, and having local protocols were the most consistent practices (>75%). The odds for the following practices differed in NICUs resuscitating infants from 22 to 23 weeks GA compared to those resuscitating from 24 to 25 weeks: respiratory support during resuscitation and transport, use of polyethylene plastic wrap and servo-control mode, commencing ambient humidity >80% and presence of local protocols. CONCLUSION: Evidence-based practices on thermoregulation and golden hour stabilisation differed based on the unit's region, country's income status and the lowest GA of infants resuscitated. Future efforts should address reducing variation in practice and aligning practices with international guidelines. IMPACT: A wide variation in thermoregulation and golden hour practices exists depending on the income status, geographic region and lowest gestation age of infants resuscitated. Using a polyethylene plastic wrap, commencing humidity within 60 min of admission and having local protocols were the most consistent practices. This study provides a comprehensive description of thermoregulation and golden hour practices to allow a global comparison in the delivery of best evidence-based practice. The findings of this survey highlight a need for reducing variation in practice and aligning practices with international guidelines for a comparable health care delivery.

Does Sarcopenia Predict Local Response Rates After Chemoradiotherapy for Locally Advanced Rectal Cancer?

BACKGROUND: The predictive value of sarcopenia for tumor response to neoadjuvant chemoradiotherapy is unclear. OBJECTIVE: This study aimed to investigate the association between sarcopenia and pathological tumor regression grade after neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. DESIGN: Retrospective cohort study from a prospectively collected database. Univariate logistic regression was performed to assess the association between sarcopenia and tumor response. SETTINGS: This study was conducted at 2 tertiary care centers. PATIENTS: Participants were patients undergoing neoadjuvant chemoradiotherapy for locally advanced rectal cancer (T3/4, N0/+) between 2007 and 2018. INTERVENTION: Sarcopenia was diagnosed using sex-specific cutoffs of lean muscle mass. Using the initial staging CT, lean muscle mass was estimated using the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra, normalized for patient height. MAIN OUTCOME MEASURES: The primary end point was pathological tumor regression grade, defined as good (tumor regression grade 0/1) vs poor (tumor regression grade 2/3). RESULTS: The study included 167 patients with locally advanced rectal cancer with a median age of 60 (20-91) years, with 132 in the nonsarcopenia group and 35 in the sarcopenia group. Eighty-nine percent of patients had stage 3 cancer. Nine patients (5.4%) had a complete clinical response, 1 patient did not respond to treatment and opted for nonoperative management, and the remaining 157 patients (94.0%) proceeded to surgery. Pathological data revealed no significant difference between good tumor regression grade patients in the sarcopenia group compared with the nonsarcopenia group. Univariate analysis revealed BMI ≥25 kg/m 2 to be a risk factor for good tumor regression grade ( p = 0.002). LIMITATIONS: This study was limited by its retrospective design and small sample size. CONCLUSIONS: Sarcopenia is not a predictor of poor neoadjuvant chemoradiotherapy response in patients with locally advanced rectal cancer. Increasing BMI was associated with good tumor regression grade. Future multicentered studies are warranted to validate this finding. See Video Abstract at http://links.lww.com/DCR/C78 . LA SARCOPENIA PREDICE LAS TASAS DE RESPUESTA LOCAL DESPUS DE LA QUIMIORRADIOTERAPIA PARA EL CNCER DE RECTO LOCALMENTE AVANZADO: ANTECEDENTES:El valor predictivo de la sarcopenia para la respuesta tumoral a la quimiorradioterapia neoadyuvante no está claro.OBJETIVO:Este estudio investiga la asociación entre la sarcopenia y el grado de regresión tumoral patológica después de la quimiorradioterapia neoadyuvante en pacientes con cáncer de recto localmente avanzado.DISEÑO:Estudio de cohorte retrospectivo a partir de una base de datos recolectada prospectivamente. Se realizó una regresión logística univariante para evaluar la asociación entre la sarcopenia y la respuesta tumoral.ENTORNO CLINICO:Este estudio se realizó en dos centros de atención terciaria.PACIENTES:Pacientes sometidos a quimiorradioterapia neoadyuvante por cáncer de recto localmente avanzado (T3/4, N0/+) entre 2007-2018.INTERVENCIÓNES:La sarcopenia se diagnosticó utilizando puntos de corte de masa muscular magra específicos por género. Utilizando la tomografía computarizada de estadificación inicial, se estimó la masa muscular magra utilizando el área transversal del músculo psoas a nivel de la tercera vértebra lumbar, normalizada para la altura del paciente.PRINCIPALES MEDIDAS DE VALORACIÓN:El criterio principal de valoración fue el grado de regresión tumoral patológica, definido como bueno (grado de regresión tumoral 0/1) frente a malo (grado de regresión tumoral 2/3).RESULTADOS:El estudio incluyó a 167 pacientes con cáncer de recto localmente avanzado con una mediana de edad de 60 años (20-91), 132 en el grupo sin sarcopenia y 35 en el grupo con sarcopenia. Ochenta y nueve por ciento estaban en etapa III. Seis pacientes (5,4%) tuvieron respuesta clínica completa sostenida, un paciente no respondió al tratamiento y optó por manejo conservador, los 157 restantes (94,0%) procedieron a cirugía. Los datos patológicos no revelaron diferencias significativas entre los pacientes con buen grado de regresión tumoral en el grupo de sarcopenia en comparación con el grupo sin sarcopenia. El análisis univariado reveló que un IMC ≥25 kg/m2 era un factor de riesgo para un buen grado de regresión tumoral (p = 0,002).LIMITACIONES:Este estudio estuvo limitado por su diseño retrospectivo y tamaño de muestra pequeño.CONCLUSIÓNES:La sarcopenia no es un predictor de mala respuesta a la quimiorradioterapia neoadyuvante en pacientes con cáncer de recto localmente avanzado. El aumento del IMC se asoció con un buen grado de regresión tumoral. Se justifican futuros estudios multicéntricos para validar este hallazgo. Consulte Video Resumen en http://links.lww.com/DCR/C78 . (Traducción-Dr. Ingrid Melo ).

Can sarcopenia predict complete response after total neoadjuvant therapy in advanced rectal cancer? A multicentre observational cohort study.

BACKGROUND: The association between sarcopenia and response to neoadjuvant treatment remains unclear. This study investigates sarcopenia as a predictor of overall complete response (oCR) after Total Neoadjuvant Therapy (TNT) for advanced rectal cancer. METHOD: A prospective observational study was performed of patients with rectal cancer undergoing TNT at three South Australian hospitals between 2019 and 2022. Sarcopenia was diagnosed by pretreatment computed tomography measurement of psoas muscle cross-sectional area at the third lumbar vertebra level, normalised for patient height. The primary endpoint was oCR rate defined as the proportion of patients who achieved either clinical complete response (cCR) or pathological complete response. RESULTS: This study included 118 rectal cancer patients with an average age of 59.5 years, 83 (70.3%) of whom formed the non-sarcopenic group (NSG) and 35 (29.7%) the sarcopenic group (SG). The oCR rate was significantly higher in NSG compared with the SG (p < 0.001). cCR rate was significantly greater in NSG compared with the SG (p = 0.001). Multivariate analysis revealed sarcopenia (p = 0.029) and hypoalbuminemia (p = 0.040) were risk factors for cCR and sarcopenia was an independent risk factor for oCR (p = 0.020). CONCLUSION: Sarcopenia and hypoalbuminemia were negatively associated with tumour response following TNT in advanced rectal cancer patients.

The Role of Diversity in Mediating Microbiota Structural and Functional Differences in Two Sympatric Species of Abalone Under Stressed Withering Syndrome Conditions.

Withering syndrome (WS) is a gastro-intestinal (GI) infectious disease likely affecting all abalone species worldwide. Structural and functional changes in abalone GI microbiotas under WS-stressed conditions remain poorly investigated. It is unclear if interspecific microbiota differences, such as the presence of certain microbes, their abundance, and functional capabilities, may be involved in the occurrence of this disease. Bacterial microbiotas of healthy Haliotis fulgens and Haliotis corrugata are mainly composed by Tenericutes, Proteobacteria, Fusobacteria, and Spirochaetes. We previously reported species-specific structural and functional profiles of those communities and suggested that they are of consequence to the different susceptibility of each species to WS. Here, we address this question by comparing the structure and function of healthy and dysbiotic microbiota through 454 pyrosequencing and PICRUSt 2, respectively. Our findings suggest that the extent to which WS-stressed conditions may explain structural and functional differences in GI microbiota is contingent on the microbiota diversity itself. Indeed, microbiota differences between stressed and healthy abalone were marginal in the more complex bacterial communities of H. corrugata, in which no significant structural or functional changes were detected. Conversely, significant structural changes were observed in the less complex bacterial microbiota of H. fulgens. Moreover, structural alterations led to a significant downregulation of some metabolic activities conducted by GI bacteria. Accordingly, results suggest that gastro-intestinal bacterial diversity appears to be related with both the health of abalone and the etiology of WS.

Incidence and associated morbidity of sarcopenia in non-malignant small and large bowel anastomosis: propensity score-matched analysis.

PURPOSE: Sarcopenia is a prognostic factor for poor outcomes in colorectal cancer, but data are scarce in colorectal surgery for benign conditions where patients could benefit from a deferral of surgery to enter a prehabilitation programme. We assessed the incidence of sarcopenia and complications in patients with benign colorectal disease. METHODS: Patients who underwent elective non-malignant colorectal surgery during 2018-2022 were retrospectively identified. The cross-sectional psoas area was calculated using computed tomography (CT) imaging mid-3rd lumbar vertebrae. Sarcopenia was determined using gender-specific cut-offs. The primary outcome was complications measured by the comprehensive complication index (CCI). RESULTS: Of 188 patients identified, 39 (20.7%) were sarcopenic. Patients diagnosed with sarcopenia were older (63 vs. 58 years, p = 0.047) and had a reduced BMI (24.7 vs. 27.38 kg/m2, p = 0.001). Sarcopenic patients had more complications (82.1 vs. 64.4%, p = 0.036), and CCI was statistically but not clinically higher (20.9 vs. 20.9, p = 0.047). On univariate linear regression analysis, age ≥ 65 years old, ASA grade ≥ 3, active smokers, sarcopenia, and preoperative anaemia were predictive of CCI. Propensity score-matched analysis was performed, matching 78 cases to remove selection bias, which demonstrated sarcopenia had no impact on postoperative complications. On multivariate analysis, age (p = 0.022), smoking (p = 0.005), and preoperative anaemia (p = 0.008) remained predictive of CCI. CONCLUSION: Sarcopenia is prevalent in one-fifth of patients undergoing benign colorectal surgery. Taking advantage of the longer preoperative waiting periods, sarcopenia could be explored as a target for prehabilitation programmes to improve outcomes.

Episodic kinematics in continental rifts modulated by changes in mantle melt fraction.

Oceanic crust is created by the extraction of molten rock from underlying mantle at the seafloor 'spreading centres' found between diverging tectonic plates. Modelling studies have suggested that mantle melting can occur through decompression as the mantle flows upwards beneath spreading centres, but direct observation of this process is difficult beneath the oceans. Continental rifts, however-which are also associated with mantle melt production-are amenable to detailed measurements of their short-term kinematics using geodetic techniques. Here we show that such data can provide evidence for an upwelling mantle flow, as well as information on the dimensions and timescale of mantle melting. For North Island, New Zealand, around ten years of campaign and continuous GPS measurements in the continental rift system known as the Taupo volcanic zone reveal that it is extending at a rate of 6-15 millimetres per year. However, a roughly 70-kilometre-long segment of the rift axis is associated with strong horizontal contraction and rapid subsidence, and is flanked by regions of extension and uplift. These features fit a simple model that involves flexure of an elastic upper crust, which is pulled downwards or pushed upwards along the rift axis by a driving force located at a depth greater than 15 kilometres. We propose that flexure is caused by melt-induced episodic changes in the vertical flow forces that are generated by upwelling mantle beneath the rift axis, triggering a transient lower-crustal flow. A drop in the melt fraction owing to melt extraction raises the mantle flow viscosity and drives subsidence, whereas melt accumulation reduces viscosity and allows uplift-processes that are also likely to occur in oceanic spreading centres.

The divergent fates of primitive hydrospheric water on Earth and Mars.

Despite active transport into Earth's mantle, water has been present on our planet's surface for most of geological time. Yet water disappeared from the Martian surface soon after its formation. Although some of the water on Mars was lost to space via photolysis following the collapse of the planet's magnetic field, the widespread serpentinization of Martian crust suggests that metamorphic hydration reactions played a critical part in the sequestration of the crust. Here we quantify the relative volumes of water that could be removed from each planet's surface via the burial and metamorphism of hydrated mafic crusts, and calculate mineral transition-induced bulk-density changes at conditions of elevated pressure and temperature for each. The metamorphic mineral assemblages in relatively FeO-rich Martian lavas can hold about 25 per cent more structurally bound water than those in metamorphosed terrestrial basalts, and can retain it at greater depths within Mars. Our calculations suggest that in excess of 9 per cent by volume of the Martian mantle may contain hydrous mineral species as a consequence of surface reactions, compared to about 4 per cent by volume of Earth's mantle. Furthermore, neither primitive nor evolved hydrated Martian crust show noticeably different bulk densities compared to their anhydrous equivalents, in contrast to hydrous mafic terrestrial crust, which transforms to denser eclogite upon dehydration. This would have allowed efficient overplating and burial of early Martian crust in a stagnant-lid tectonic regime, in which the lithosphere comprised a single tectonic plate, with only the warmer, lower crust involved in mantle convection. This provided an important sink for hydrospheric water and a mechanism for oxidizing the Martian mantle. Conversely, relatively buoyant mafic crust and hotter geothermal gradients on Earth reduced the potential for upper-mantle hydration early in its geological history, leading to water being retained close to its surface, and thus creating conditions conducive for the evolution of complex multicellular life.

Australasian impact crater buried under the Bolaven volcanic field, Southern Laos.

The crater and proximal effects of the largest known young meteorite impact on Earth have eluded discovery for nearly a century. We present 4 lines of evidence that the 0.79-Ma impact crater of the Australasian tektites lies buried beneath lavas of a long-lived, 910-km3 volcanic field in Southern Laos: 1) Tektite geochemistry implies the presence of young, weathered basalts at the site at the time of the impact. 2) Geologic mapping and 40Ar-39Ar dates confirm that both pre- and postimpact basaltic lavas exist at the proposed impact site and that postimpact basalts wholly cover it. 3) A gravity anomaly there may also reflect the presence of a buried ∼17 × 13-km crater. 4) The nature of an outcrop of thick, crudely layered, bouldery sandstone and mudstone breccia 10-20 km from the center of the impact and fractured quartz grains within its boulder clasts support its being part of the proximal ejecta blanket.

London International Consensus and Delphi study on hamstring injuries part 3: rehabilitation, running and return to sport.

Hamstring injuries (HSIs) are the most common athletic injury in running and pivoting sports, but despite large amounts of research, injury rates have not declined in the last 2 decades. HSI often recur and many areas are lacking evidence and guidance for optimal rehabilitation. This study aimed to develop an international expert consensus for the management of HSI. A modified Delphi methodology and consensus process was used with an international expert panel, involving two rounds of online questionnaires and an intermediate round involving a consensus meeting. The initial information gathering round questionnaire was sent to 46 international experts, which comprised open-ended questions covering decision-making domains in HSI. Thematic analysis of responses outlined key domains, which were evaluated by a smaller international subgroup (n=15), comprising clinical academic sports medicine physicians, physiotherapists and orthopaedic surgeons in a consensus meeting. After group discussion around each domain, a series of consensus statements were prepared, debated and refined. A round 2 questionnaire was sent to 112 international hamstring experts to vote on these statements and determine level of agreement. Consensus threshold was set a priori at 70%. Expert response rates were 35/46 (76%) (first round), 15/35 (attendees/invitees to meeting day) and 99/112 (88.2%) for final survey round. Statements on rehabilitation reaching consensus centred around: exercise selection and dosage (78.8%-96.3% agreement), impact of the kinetic chain (95%), criteria to progress exercise (73%-92.7%), running and sprinting (83%-100%) in rehabilitation and criteria for return to sport (RTS) (78.3%-98.3%). Benchmarks for flexibility (40%) and strength (66.1%) and adjuncts to rehabilitation (68.9%) did not reach agreement. This consensus panel recommends individualised rehabilitation based on the athlete, sporting demands, involved muscle(s) and injury type and severity (89.8%). Early-stage rehab should avoid high strain loads and rates. Loading is important but with less consensus on optimum progression and dosage. This panel recommends rehabilitation progress based on capacity and symptoms, with pain thresholds dependent on activity, except pain-free criteria supported for sprinting (85.5%). Experts focus on the demands and capacity required for match play when deciding the rehabilitation end goal and timing of RTS (89.8%). The expert panellists in this study followed evidence on aspects of rehabilitation after HSI, suggesting rehabilitation prescription should be individualised, but clarified areas where evidence was lacking. Additional research is required to determine the optimal load dose, timing and criteria for HSI rehabilitation and the monitoring and testing metrics to determine safe rapid progression in rehabilitation and safe RTS. Further research would benefit optimising: prescription of running and sprinting, the application of adjuncts in rehabilitation and treatment of kinetic chain HSI factors.

London International Consensus and Delphi study on hamstring injuries part 2: operative management.

The key indications for surgical repair of hamstring injuries (HSIs) remain unclear in the literature due to a lack of high-level evidence and expert knowledge. The 2020 London International Hamstring Consensus meeting aimed to highlight clear surgical indications and to create a foundation for future research. A literature review was conducted followed by a modified Delphi process, with an international expert panel. Purposive sampling was used with two rounds of online questionnaires and an intermediate round involving a consensus meeting. The initial information gathering (round 1) questionnaire was sent to 46 international experts, which comprised open-ended questions covering decision-making domains in HSI. Thematic analysis of responses outlined key domains, which were evaluated by a smaller international subgroup (n=15) comprising clinical academic sports medicine physicians, physiotherapists and orthopaedic surgeons in a consensus meeting. After group discussion of each domain, a series of consensus statements were prepared, debated and refined. A round 2 questionnaire was sent to 112 international hamstring experts to vote on these statements and determine level of agreement. The consensus threshold was set a priori at 70% agreement. Rounds 1 and 2 survey respondents were 35/46 (76%) and 99/112 (88.4%), respectively. The consensus group agreed that the indications for operative intervention included: gapping at the zone of tendinous injury (87.2% agreement) and loss of tension (70.7%); symptomatic displaced bony avulsions (72.8%); and proximal free tendon injuries with functional compromise refractory to non-operative treatment (72.2%). Other important considerations for operative intervention included: the demands of the athlete/patient and the expected functional outcome (87.1%) based on the anatomy of the injury; the risk of functional loss/performance deficit with non-operative management (72.2%); and the capacity to restore anatomy and function (87.1%). Further research is needed to determine whether surgery can reduce the risk of reinjury as consensus was not reached within the whole group (48.2%) but was agreed by surgeons (70%) in the cohort. The consensus group did not support the use of corticosteroids or endoscopic surgery without further evidence. These guidelines will help standardise treatment of HSIs, specifically the indications and decision-making for surgical intervention.

London International Consensus and Delphi study on hamstring injuries part 1: classification.

Muscle injury classification systems for hamstring injuries have evolved to use anatomy and imaging information to aid management and prognosis. However, classification systems lack reliability and validity data and are not specific to individual hamstring muscles, potentially missing parameters vital for sport-specific and activity-specific decision making. A narrative evidence review was conducted followed by a modified Delphi study to build an international consensus on best-practice decision-making for the classification of hamstring injuries. This comprised a digital information gathering survey to a cohort of 46 international hamstring experts (sports medicine physicians, physiotherapists, surgeons, trainers and sports scientists) who were also invited to a face-to-face consensus group meeting in London . Fifteen of these expert clinicians attended to synthesise and refine statements around the management of hamstring injury. A second digital survey was sent to a wider group of 112 international experts. Acceptance was set at 70% agreement. Rounds 1 and 2 survey response rates were 35/46 (76%) and 99/112 (88.4%) of experts responding. Most commonly, experts used the British Athletics Muscle Injury Classification (BAMIC) (58%), Munich (12%) and Barcelona (6%) classification systems for hamstring injury. Issues identified to advance imaging classifications systems include: detailing individual hamstring muscles, establishing optimal use of imaging in diagnosis and classification, and testing the validity and reliability of classification systems. The most used hamstring injury classification system is the BAMIC. This consensus panel recommends hamstring injury classification systems evolve to integrate imaging and clinical parameters around: individual muscles, injury mechanism, sporting demand, functional criteria and patient-reported outcome measures. More research is needed on surgical referral and effectiveness criteria, and validity and reliability of classification systems to guide management.