Association between muscle thickness, fat-free mass and malnutrition in patients with copd: an exploratory study

Rationale: Malnutrition is a common problem in patients with Chronic Obstructive Pulmonary Disease (COPD). Whereas estimation of fat-free muscle mass index (FFMi) with bio-electrical impedance is often used, less is known about muscle thickness measured with ultrasound (US) as a parameter for malnutrition. Moreover, it has been suggested that in this population, loss of muscle mass is characterized by loss of the lower body muscles rather than of the upper body muscles.1 Therefore, we explored the association between FFMi, muscle thickness of the biceps brachii (BB) and the rectus femoris (RF), and malnutrition in patients with COPD. Methods: Patients were assessed at the start of a pulmonary rehabilitation program. Malnutrition was assessed with the Scored Patient-Generated Subjective Global Assessment (PG-SGA). Malnutrition was defined as PG-SGA Stage B or C. FFMi (kg/m²) was estimated with bio-electrical impedance analysis BIA 101® (Akern), using the Rutten equation. Muscle thickness (mm) of the BB and the RF was measured with the handheld BodyMetrix® device (Intelametrix). Univariate and multivariate logistic regression analyses were performed to analyse associations between FFMi and muscle thickness for BB and RF, and malnutrition. Multivariate analysis corrected for sex, age, and GOLD-stage. Odds ratios (OR) and 95% confidence intervals (CI) were presented. A p-level of <0.05 was considered significant. Results: In total, 27 COPD patients (age 64±8.1 years; female 60%, GOLD-stage 3, interquartile range=3-4, BMI 27±6.6 kg/m2) were included in the analyses. In the univariate analysis, FFMi (p=0.014; OR=0.70, 95%CI: -0.12—0.15), RF thickness (p=0.021; OR=0.79, 95%CI: -0.09—0.01), and BB thickness (p=0.006; OR=0.83, 95%CI: -0.06—0.01) were all significantly associated with malnutrition. In the multivariate analysis, FFMi (p=0.031; OR=0.59, 95%CI: -0.18—0.01) and BB thickness (p=0.017; OR=0.73, 95%CI:-0.09—0.01) were significantly associated with malnutrition. None of the co-variables were significantly associated with malnutrition. Conclusion: In this relatively small sample of patients with severe COPD, low FFMi and low BB muscle thickness were both robustly associated with increased odds of being malnourished. BB muscle thickness measured with US may provide added value to the toolbox for nutritional assessment. The results of this exploratory study suggest that upper body muscles may reflect nutritional status more closely than lower body muscles. Reference: 1 Shrikrishna D, Patel M, Tanner RJ, Seymour JM, Connolly BA, Puthucheary ZA, et al. Quadriceps wasting and physical inactivity in patients with COPD. Eur Respir J. 2012;40(5):1115–22.

Community assembly in Lake Tanganyika cichlid fish:Quantifying the contributions of both niche-based and neutral processes

The cichlid family features some of the most spectacular examples of adaptive radiation. Evolutionary studies have highlighted the importance of both trophic adaptation and sexual selection in cichlid speciation. However, it is poorly understood what processes drive the composition and diversity of local cichlid species assemblages on relatively short, ecological timescales. Here, we investigate the relative importance of niche-based and neutral processes in determining the composition and diversity of cichlid communities inhabiting various environmental conditions in the littoral zone of Lake Tanganyika, Zambia. We collected data on cichlid abundance, morphometrics, and local environments. We analyzed relationships between mean trait values, community composition, and environmental variation, and used a recently developed modeling technique (STEPCAM) to estimate the contributions of niche-based and neutral processes to community assembly. Contrary to our expectations, our results show that stochastic processes, and not niche-based processes, were responsible for the majority of cichlid community assembly. We also found that the relative importance of niche-based and neutral processes was constant across environments. However, we found significant relationships between environmental variation, community trait means, and community composition. These relationships were caused by niche-based processes, as they disappeared in simulated, purely neutrally assembled communities. Importantly, these results can potentially reconcile seemingly contrasting findings in the literature about the importance of either niche-based or neutral-based processes in community assembly, as we show that significant trait relationships can already be found in nearly (but not completely) neutrally assembled communities; that is, even a small deviation from neutrality can have major effects on community patterns

Furin is a chemokine-modifying enzyme: in vitro and in vivo processing of CXCL10 generates a C-terminally truncated chemokine retaining full activity

Chemokines comprise a class of structurally related proteins that are involved in many aspects of leukocyte migration under basal and inflammatory conditions. In addition to the large number of genes, limited processing of these proteins by a variety of enzymes enhances the complexity of the total spectrum of chemokine variants. We have recently shown that the native chemokine CXCL10 is processed at the C terminus, thereby shedding the last four amino acids. The present study was performed to elucidate the mechanism in vivo and in vitro and to study the biological activity of this novel isoform of CXCL10. Using a combination of protein purification and mass spectrometric techniques, we show that the production of C-terminally truncated CXCL10 by primary keratinocytes is inhibited in vivo by a specific inhibitor of pro-protein convertases (e.g. furin) but not by inhibition of matrix metalloproteinases. Moreover, CXCL10 is processed by furin in vitro, which is abrogated by a mutation in the furin recognition site. Using GTRγS binding, C

Cleavage of von Willebrand Factor by Granzyme M Destroys Its Factor VIII Binding Capacity

Von Willebrand factor (VWF) is a pro-hemostatic multimeric plasma protein that promotes platelet aggregation and stabilizes coagulation factor VIII (FVIII) in plasma. The metalloproteinase ADAMTS13 regulates the platelet aggregation function of VWF via proteolysis. Severe deficiency of ADAMTS13 is associated with thrombotic thrombocytopenic purpura, but does not always correlate with its clinical course. Therefore, other proteases could also be important in regulating VWF activity. In the present study, we demonstrate that VWF is cleaved by the cytotoxic lymphocyte granule component granzyme M (GrM). GrM cleaved both denaturated and soluble plasma-derived VWF after Leu at position 276 in the D3 domain. GrM is unique in that it did not affect the multimeric size and pro-hemostatic platelet aggregation ability of VWF, but instead destroyed the binding of VWF to FVIII in vitro. In meningococcal sepsis patients, we found increased plasma GrM levels that positively correlated with an increased plasma VWF/FVIII ratio in vivo. We conclude that, next to its intracellular role in triggering apoptosis, GrM also exists extracellularly in plasma where it could play a physiological role in controlling blood coagulation by determining plasma FVIII levels via proteolytic processing of its carrier VWF

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

How is participation related to well-being of homeless people? An explorative qualitative study in a Dutch homeless shelter facility

status: publishe

Muscle thickness of the rectus femoris is lower in patients with copd than in healthy patients matched for sex, age and stature: an exploratory study

Rationale: Currently use of muscle thickness measured with ultrasound is suggested as an indicator for overall muscle mass in nutritional assessment. However, not much is known about how the muscle thickness measured in patients with chronic obstructive pulmonary disease (COPD) compares to the muscle thickness in healthy persons. This study explores body mass index (BMI) and rectus femoris (RF) muscle thickness in patients with advanced COPD matched with healthy controls. Methods: Patients with advanced COPD at the start of a pulmonary rehabilitation program were matched for age (5 years difference tolerance), sex (exact match), and stature (0.1 m difference tolerance) with healthy controls in a 1:4 case control ratio. BMI (kg/m2) was calculated and muscle thickness (mm) of the RF was measured with a Bodymetrix device. Paired sample t-tests were performed. BMI and RF muscle thickness of the cases were paired with the average BMI and RF of their controls. A p-level of <0.05 was considered significant and 95% CI were presented for the mean difference. Results: In total, 21 cases (median GOLD score 3 [interquartile range 3-4]; age 64.5±6.4y; female 62%; height 1.68±0.07m; BMI 26.9±6.1 kg/m2; RF 12.4±3.4mm) and 84 controls (age 64.5±6.4y; female 62%; height 1.71±0.09 m; BMI 25.8±4.5; RF 14.6±4.5mm) were included in the analyses. In the paired test, BMI was not significantly different between cases and controls (p=0.645, mean difference 0.95 kg/m2 [CI:-2.12 – 4.01]), whereas RF muscle thickness of cases was significantly lower (p=0.003, mean difference -2.33 mm [CI:-3.73 - -0.92]). Conclusion: In this limited sample of patients with COPD, RF muscle thickness in cases was significantly lower than RF muscle thickness in matched controls. Research in bigger samples is needed to confirm whether RF muscle thickness measured with US provides more useful information about body composition for clinicians than BMI in patients with COPD

Muscle thickness of the rectus femoris is lower in patients with copd than in healthy patients matched for sex, age and stature: an exploratory study

Rationale: Currently use of muscle thickness measured with ultrasound is suggested as an indicator for overall muscle mass in nutritional assessment. However, not much is known about how the muscle thickness measured in patients with chronic obstructive pulmonary disease (COPD) compares to the muscle thickness in healthy persons. This study explores body mass index (BMI) and rectus femoris (RF) muscle thickness in patients with advanced COPD matched with healthy controls. Methods: Patients with advanced COPD at the start of a pulmonary rehabilitation program were matched for age (5 years difference tolerance), sex (exact match), and stature (0.1 m difference tolerance) with healthy controls in a 1:4 case control ratio. BMI (kg/m2) was calculated and muscle thickness (mm) of the RF was measured with a Bodymetrix device. Paired sample t-tests were performed. BMI and RF muscle thickness of the cases were paired with the average BMI and RF of their controls. A p-level of <0.05 was considered significant and 95% CI were presented for the mean difference. Results: In total, 21 cases (median GOLD score 3 [interquartile range 3-4]; age 64.5±6.4y; female 62%; height 1.68±0.07m; BMI 26.9±6.1 kg/m2; RF 12.4±3.4mm) and 84 controls (age 64.5±6.4y; female 62%; height 1.71±0.09 m; BMI 25.8±4.5; RF 14.6±4.5mm) were included in the analyses. In the paired test, BMI was not significantly different between cases and controls (p=0.645, mean difference 0.95 kg/m2 [CI:-2.12 – 4.01]), whereas RF muscle thickness of cases was significantly lower (p=0.003, mean difference -2.33 mm [CI:-3.73 - -0.92]). Conclusion: In this limited sample of patients with COPD, RF muscle thickness in cases was significantly lower than RF muscle thickness in matched controls. Research in bigger samples is needed to confirm whether RF muscle thickness measured with US provides more useful information about body composition for clinicians than BMI in patients with COPD