Computed tomography measures of nutrition in patients with end-stage liver disease provide a novel approach to characterize deficits

Aim Patients with cirrhosis and end-stage liver disease (ESLD) develop severe nutrition deficits that impact on morbidity and mortality. Laboratory measures of nutrition fail to fully assess clinical deficits in muscle mass and fat stores. This study employs computed tomography imaging to assess muscle mass and subcutaneous and visceral fat stores in patients with ESLD. Methods This 1:1 case-control study design compares ESLD patients with healthy controls. Study patients were selected from a database of ESLD patients using a stratified method to assure a representative sample based on age, body mass index (BMI), gender, and model for end-stage liver disease score (MELD). Control patients were trauma patients with a low injury severity score (<10) who had a CT scan during evaluation. Cases and controls were matched for age +/- 5 years, gender, and BMI +/- 2. Results There were 90 subjects and 90 controls. ESLD patients had lower albumin levels (p<0.001), but similar total protein levels (p=0.72). ESLD patients had a deficit in muscle mass (-19%, p<0.001) and visceral fat (-13%, p<0.001), but similar subcutaneous fat (-1%, p=0.35). ESLD patients at highest risk for sarcopenia included those over age 60, BMI< 25.0, and female gender. We found degree of sarcopenia to be independent of MELD score. Conclusions These results support previous research demonstrating substantial nutrition deficits in ESLD patients that are not adequately measured by laboratory testing. Patients with ESLD have significant deficits of muscle and visceral fat stores, but a similar amount of subcutaneous fat

Match physical performance of elite female soccer players during international competition.

The purpose of the present study was to provide a detailed analysis of the physical demands of competitive international female soccer match-play. A total of 148 individual match observations were undertaken on 107 outfield players competing in competitive international matches during the 2011-2012 and 2012-2013 seasons, using a computerized tracking system (Prozone Sports Ltd., Leeds, England). Total distance (TD) and total high-speed running distances (THSR) were influenced by playing position, with central midfielders (CM) completing the highest (10985±706 m and 2882±500 m) and central defenders (CD) the lowest (9489±562 m and 1901±268 m) distances, respectively. Greater total very high-speed running (TVHSR) distances were completed when a team was without (399±143 m) compared to with (313±210 m) possession of the ball. The majority of sprints were over short distances with 76 % and 95 % being less than 5 m and 10 m, respectively. Between half reductions in physical performance were present for all variables, independent of playing position. The current study provides novel findings regarding the physical demands of different playing positions in competitive international female match-play and provides important insights for physical coaches preparing elite female players for competition

Radiologic Assessment of Muscle and Fat Stores in Long-Term Type I Diabetics Referred for Pancreas Transplant Compared to Healthy Controls

Type 1 diabetes (DM1) is associated with loss of skeletal muscle and bone mass and may affect body fat stores. This study employs computed tomography (CT) scans to assess the body composition of DM1 patients referred for pancreas transplant compared to healthy controls. A 1:1 case–control design matched study patients with otherwise healthy patients from the trauma database. Matching criteria included age ± 5 years, gender, and body mass index (BMI) ± 2kg/m2. Nutrition variables included serum albumin and protein levels, BMI, and CT measures of muscle mass and fat stores. There were 22 subjects and 22 controls (median DM1 duration 24 years). DM1 patients had less muscle mass and less subcutaneous fat but no difference in visceral fat. Patients with the greatest muscle deficit were those with DM1 greater than 20 years and those younger than age 40. DM1 patients maintain similar BMI and protein levels compared to healthy controls but have marked deficits of muscle and subcutaneous fat. These results inform the nutritional management of DM1 patients and quantify the muscle and fat deficits present in these patients. At highest risk are young patients and those with duration of DM1 over 20 years

Profiling the Responses of Soccer Substitutes: A Review of Current Literature.

Depending upon competition regulations, the laws of soccer allow between three and an unlimited number of substitutions that can be made on either a permanent or rolling basis. Substitutes are typically introduced to minimise/offset the effects of fatigue, alter tactics, replace players deemed as underperforming or injured, and/or give playing time to youth players or to squad members returning from injury. While the match-day practices of substitutes include participation in the pre-match warm-up, and sporadic periods of rewarm-up activity, it is currently unclear as to whether these pre-entry preparations facilitate optimal match performance thereafter. Acknowledging the contextual factors that possibly influence substitutes' performance, this review summarises the presently available literature on soccer substitutes, and makes recommendations for future research. Literature searching and screening yielded 13 studies, which have typically focused on characterising: (1) the patterns, including timing, of substitutes' introduction; (2) indices of match-performance; and (3) the emotional experiences of soccer substitutes. The majority of substitutions occur after the first-half has ended (i.e. at half-time or during the second-half), with introduced players exceeding the second-half physical performances of those who started the match. Observations of progressive improvements in running performance as playing time increases, and findings that substitutes mostly experience negative emotions, highlight the potential inadequacies of pre-match preparations, and present future research opportunities. Additional work is therefore needed to confirm these findings and to determine the efficacy of current preparation strategies, thereby providing opportunities to assess then address substitutes' pre-pitch entry preparations, on-field performance and emotional responses

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation &lt;92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p&lt;0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p&lt;0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Minimal Improvement in Glomerular Filtration Rate in the First Year After Liver Transplantation

Renal function is an important predictor of liver transplantation (LT) outcome. This study examines the change in glomerular filtration rate (GFR, mL/min per m) in the first year after LT, with subgroup analysis by baseline GFR, model for end-stage liver disease (MELD), age, sex, race, and diabetes/hypertension. The records of 1275 consecutive deceased donor, liver, and liver/kidney transplants were reviewed retrospectively, with the liver/kidney data analyzed separately. Glomerular filtration rate was calculated using the modification of diet in renal disease equation. Among liver only patients, 25% had GFR less than 60 (mL/min per 1.73 m) at LT, and this increased to 39% at 1 year. There were 42% of patients with normal renal function (GFR > 90) at baseline, and this decreased to 18% at 1 year. Only patient subgroups with MELD > 25 experienced any 1-year improvement in GFR, whereas all lower MELD groups experienced a significant decline in GFR. At 1 year after transplantation, there were 42% of recipients that had an absolute GFR decrease greater than 20 mL/min per 1.73 m, and 39% that decreased greater than 25% from their transplant baseline. Only 22% had an absolute improvement in GFR greater than 5 mL/min per 1.73 m. Sixty-four percent of liver transplant recipients overall experience a decrease in GFR 1 year after transplantation. Recipients with severe kidney disease at transplant (GFR < 30) are the group most likely to experience improvement in GFR after transplantation. However, at 1 year, as a group, they remain at GFR less than 60 (stage III chronic kidney disease). These results suggest that severe renal dysfunction may be marginally reversible after LT, but only 22% of the recipients in this cohort experienced any post-LT improvement in renal function

Tracheostomy Post Liver Transplant: Predictors, Complications, and Outcomes

BACKGROUND Liver transplant (LT) patients have an increased risk of postoperative respiratory failure requiring tracheostomy. This study sought to characterize objective clinical predictors of tracheostomy. MATERIAL AND METHODS The records for 2017 LT patients at a single institution were reviewed. Patients requiring tracheostomy were first compared with all other patients. A case-control subgroup analysis was conducted in which 98 tracheostomy patients were matched with 98 non-tracheostomy LT patients. For the case-control study, muscle mass was assessed using preoperative computed tomography scans. RESULTS Among 2017 LT patients, 98 required tracheostomy (5%), with a 19% complication rate. Tracheostomy patients were older and had a higher model for end-stage liver disease score, a lower body mass index (BMI), and a greater smoking history. Tracheostomy patients had a longer hospital stay (45 vs. 10 days, P<0.001) and worse 1-year survival (65% vs. 91%, P<0.001). Ten-year Cox regression patient survival for tracheostomy patients was significantly worse (32% vs. 68%, P<0.001). In the case-control analysis, respiratory failure patients were older (P<0.01) and had a lower BMI (P=0.05). They also had a muscle mass deficit of -39% compared with matched LT controls (P<0.001). No significant differences were seen with pre-LT total protein or albumin or with forced expiratory volume in 1 s divided by forced vital capacity (FEV1/FVC) values. CONCLUSIONS Predictors for respiratory failure requiring post-LT tracheostomy include higher model for end-stage liver disease score, older age, lower BMI, greater smoking history, and worse sarcopenia. Patients requiring tracheostomy have dramatically longer hospital stays and worse survival

Multimodular Penicillin-Binding Proteins: An Enigmatic Family of Orthologs and Paralogs

The monofunctional penicillin-binding DD-peptidases and penicillin-hydrolyzing serine beta-lactamases diverged from a common ancestor by the acquisition of structural changes in the polypeptide chain while retaining the same folding, three-motif amino acid sequence signature, serine-assisted catalytic mechanism, and active-site topology. Fusion events gave rise to multimodular penicillin-binding proteins (PBPs). The acyl serine transferase penicillin-binding (PB) module possesses the three active-site defining motifs of the superfamily; it is linked to the carboxy end of a non-penicillin-binding (n-PB) module through a conserved fusion site; the two modules form a single polypeptide chain which folds on the exterior of the plasma membrane and is anchored by a transmembrane spanner; and the full-size PBPs cluster into two classes, A and B. In the class A PBPs, the n-PB modules are a continuum of diverging sequences; they possess a five-motif amino acid sequence signature, and conserved dicarboxylic amino acid residues are probably elements of the glycosyl transferase catalytic center. The PB modules fall into five subclasses: A1 and A2 in gram-negative bacteria and A3, A4, and A5 in gram-positive bacteria. The full-size class A PBPs combine the required enzymatic activities for peptidoglycan assembly from lipid-transported disaccharide-peptide units and almost certainly prescribe different, PB-module specific traits in peptidoglycan cross-linking. In the class B PBPs, the PB and n-PB modules cluster in a concerted manner. A PB module of subclass B2 or B3 is linked to an n-PB module of subclass B2 or B3 in gram-negative bacteria, and a PB module of subclass B1, B4, or B5 is linked to an n-PB module of subclass B1, B4, or B5 in gram-positive bacteria. Class B PBPs are involved in cell morphogenesis. The three motifs borne by the n-PB modules are probably sites for module-module interaction and the polypeptide stretches which extend between motifs 1 and 2 are sites for protein-protein interaction. The full-size class B PBPs are an assortment of orthologs and paralogs, which prescribe traits as complex as wall expansion and septum formation. PBPs of subclass B1 are unique to gram-positive bacteria. They are not essential, but they represent an important mechanism of resistance to penicillin among the enterococci and staphylococci. Natural evolution and PBP- and beta-lactamase-mediated resistance show that the ability of the catalytic centers to adapt their properties to new situations is limitless. Studies of the reaction pathways by using the methods of quantum chemistry suggest that resistance to penicillin is a road of no return