Characterizing and predicting the relationship between translaminar fracture toughness and pull-out length distributions under distinct temperatures.

The translaminar fracture toughness reflects the damage tolerance of a fibre-reinforced composite under longitudinal tension, which often governs the final failure of structures. One of the main energy-dissipation mechanisms that contributes to the translaminar toughness of composites is the fibre pull-out process. The present study aims to quantify and model the statistical distribution of fibre pull-out lengths formed on the translaminar fracture surface of composites, for the first time in the literature; this is done under different temperatures, so that the relationship between pull-out length distributions, micromechanical properties and the translaminar fracture toughness can be established. The fracture surfaces of cross-ply compact tension specimens tested under three different temperatures have been scanned through X-ray computed tomography to quantify the extent of fibre pull-out on the fracture surfaces; the distribution of pull-out lengths showed alarger average and larger variability with an increase in temperature, which also lead to an increase in translaminar fracture toughness. A similar trend has been captured by the proposed analytical model, which predicts the pull-out length distribution based on the analysis of quasi-fractal idealizations of the fracture surface, yielding an overall accuracy of more than 85%. This article is part of the theme issue 'Ageing and durability of composite materials'.

Correlation of polyp grading scales with patient symptom scores and olfaction in chronic rhinosinusitis: a systematic review and meta-analysis.

BACKGROUND: Various nasal polyp (NP) scoring systems have been proposed and used in the literature. However, no single system has been identified as superior. Correlations between NP scoring systems and patient symptoms, quality of life (QOL) or olfaction vary widely. METHODS: A systematic search of PubMed, CINAHL, Scopus, and Cochrane Library was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Any study examining endoscopy scores and symptom, QOL or olfaction measures in cross sectional manner or after therapeutic intervention were included. RESULTS: This review identified 55 studies for a pooled meta-analysis of Lund-Kennedy (LK-NP) polyp scores (N = 6), Meltzer scores (N = 6), Nasal polyp scores (NPS; N = 19), Total polyp score (TPS; N=8) Lilholdt scores (N = 8), Olfactory cleft endoscopy score (OCES; N =4), Discharge, inflammation, polyp/edema score (DIP; N = 2), and Perioperative sinus endoscopy score (POSE; N = 2). Meta-regression assessed correlations between NP grading systems and SNOT-22, nasal congestion scores, total nasal symptom scores (TNSS), and Smell Identification Test-40 (SIT40). None of the NP grading systems correlated significantly with any symptom, QOL or olfactory metric. In intervention studies of surgery or monoclonal antibody treatment, changes in NPS scores did not correlate with any patient reported outcome measure (PROM) or olfactory outcomes. CONCLUSION: Current NP endoscopic scoring systems are not associated with PROMs such as SNOT-22, nasal congestion scores, and TNSS as well as objective measures of olfaction. NP grading systems with improved clinical utility are needed.

Correlation of polyp grading scales with patient symptom scores and olfaction in chronic rhinosinusitis: a systematic review and meta-analysis.

BACKGROUND: Various nasal polyp (NP) scoring systems have been proposed and used in the literature. However, no single system has been identified as superior. Correlations between NP scoring systems and patient symptoms, quality of life (QOL) or olfaction vary widely. METHODS: A systematic search of PubMed, CINAHL, Scopus, and Cochrane Library was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Any study examining endoscopy scores and symptom, QOL or olfaction measures in cross sectional manner or after therapeutic intervention were included. RESULTS: This review identified 55 studies for a pooled meta-analysis of Lund-Kennedy (LK-NP) polyp scores (N = 6), Meltzer scores (N = 6), Nasal polyp scores (NPS; N = 19), Total polyp score (TPS; N=8) Lilholdt scores (N = 8), Olfactory cleft endoscopy score (OCES; N =4), Discharge, inflammation, polyp/edema score (DIP; N = 2), and Perioperative sinus endoscopy score (POSE; N = 2). Meta-regression assessed correlations between NP grading systems and SNOT-22, nasal congestion scores, total nasal symptom scores (TNSS), and Smell Identification Test-40 (SIT40). None of the NP grading systems correlated significantly with any symptom, QOL or olfactory metric. In intervention studies of surgery or monoclonal antibody treatment, changes in NPS scores did not correlate with any patient reported outcome measure (PROM) or olfactory outcomes. CONCLUSION: Current NP endoscopic scoring systems are not associated with PROMs such as SNOT-22, nasal congestion scores, and TNSS as well as objective measures of olfaction. NP grading systems with improved clinical utility are needed.

Nonpharmacological interventions to reduce respiratory viral transmission: an evidence-based review with recommendations.

BACKGROUND: Viral respiratory infections are a leading cause of worldwide mortality and exert the potential to cause global socioeconomic crises. However, inexpensive, efficacious, and rapidly deployable strategies to reduce viral transmission are increasingly important in the setting of an ongoing pandemic, though not entirely understood. This article provides a comprehensive review of commonly employed nonpharmacological interventions to interrupt viral spread and provides evidence-based recommendations for their use. METHODOLOGY: A systematic review of three databases was performed. Studies with defined endpoints of subjects receiving one of five interventions (nasal washing, gargling, personal protective equipment (PPE), social distancing, and hand hygiene) were included. An evidence-based review of the highest level of evidence, with recommendations, was created in accordance with a previously described, rigorous, iterative process. RESULTS: Fifty-four primary studies were included. The most commonly studied intervention was hand hygiene, followed by PPE, gargling, saline nasal washing, and social distancing. CONCLUSIONS: Mask use and hand hygiene are strong recommendations for prevention of viral transmission. Donning gloves, gowns, and eye protection are a recommendation in healthcare settings. Saline nasal washing and gargling are options in selected populations. Although an aggregate level of evidence is not provided, the authors recommend social distancing.

Association between hydroxychloroquine levels and disease activity in a predominantly Hispanic systemic lupus erythematosus cohort.

OBJECTIVES: Hydroxychloroquine (HCQ) is a key therapy in systemic lupus erythematosus (SLE). Medication non-adherence is reported in up to 80% of lupus patients and results in increased morbidity, mortality, and health care utilization. HCQ levels are a sensitive and reliable method to assess medication adherence. Our study evaluated the role of HCQ level measurement in routine clinical care and its association with disease activity in a predominantly Hispanic population. METHODS: SLE patients from the Columbia University Lupus cohort treated with HCQ for ≥ 6 months and reporting medication adherence were included. HCQ levels were measured by whole blood high performance liquid chromatography. Non-adherence was defined as an HCQ level <500 ng/ml. The association between HCQ levels and disease activity measured by Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was evaluated. RESULTS: One hundred and eight patients were enrolled; the median age was 38 years, 91% were female, and 63% were Hispanic. The median SLEDAI-2K was 4.3 (0-20). Forty-one percent of patients had an HCQ level <500 ng/ml consistent with non-adherence, of which 19% had undetectable levels. A higher SLEDAI-2K score was associated with low HCQ levels (p = 0.003). This association remained significant after adjusting for depression (p = 0.0007). CONCLUSION: HCQ levels < 500 ng/ml were associated with higher disease activity and accounted for 32% of the SLEDAI-2K variability. HCQ blood measurement is a simple and reliable method to evaluate medication adherence in SLE. Reasons for non-adherence (levels < 500 ng/ml) should be further explored and addressed.

Prognostic factors in patients treated with second-line chemotherapy for advanced gastric cancer: results from the randomized prospective phase III FFCD-0307 trial.

AIM: The aim of this study was to determine prognostic factors in patients treated with second-line therapy (L2) for locally advanced or metastatic gastric and gastro-esophageal junction (GEJ) adenocarcinoma in a randomized phase III study with predefined L2. METHODS: In the FFCD-0307 study, patients were randomly assigned to receive in L1 either epirubicin, cisplatin, and capecitabine (ECX arm) or fluorouracil, leucovorin, and irinotecan (FOLFIRI arm). L2 treatment was predefined (FOLFIRI for the ECX arm and ECX for the FOLFIRI arm). Chi square tests were used to compare the characteristics of patients treated in L2 with those of patients who did not receive L2. Prognostic factors in L2 for progression-free survival (PFS) and overall survival (OS) were analyzed using a Cox model. RESULTS: Among 416 patients included, 101/209 (48.3%) patients in the ECX arm received FOLFIRI in L2, and 81/207 (39.1%) patients in the FOLFIRI arm received ECX in L2. Patients treated in L2, compared with those who only received L1 had : a better ECOG score (0-1: 90.4% versus 79.7%; p = 0.0002), more frequent GEJ localization (40.8% versus 27.6%; p = 0.005), and lower platelet count (median: 298000 versus 335000/mm3; p = 0.02). In multivariate analyses, age < 60 years at diagnosis (HR 1.49, 95% CI 1.09-2.03, p = 0.013) and ECOG score 2 before L2 (HR 2.62, 95% CI 1.41-4.84, p = 0.005) were the only significant poor prognostic factors for OS. CONCLUSION: Age ≥ 60 years at diagnosis and ECOG score 0/1 before L2 were the only favorable prognostic factors for OS.

Letrozole and palbociclib versus chemotherapy as neoadjuvant therapy of high-risk luminal breast cancer.

Background: Palbociclib is a CDK4/6 inhibitor with demonstrated efficacy and safety in combination with endocrine therapy in advanced luminal breast cancer (LBC). We evaluated the respective efficacy and safety of chemotherapy and letrozole-palbociclib (LETPAL) combination as neoadjuvant treatment in patients with high-risk LBC. Patients and methods: NeoPAL (UCBG10/4, NCT02400567) is a randomised, parallel, non-comparative phase II study. Patients with ER-positive, HER2-negative, Prosigna®-defined luminal B, or luminal A and node-positive, stage II-III breast cancer, not candidate for breast-conserving surgery, were randomly assigned to either letrozole (2.5 mg daily) and palbociclib (125 mg daily, 3 weeks/4) during 19 weeks, or to FEC100 (5FU 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2)×3 21-day courses followed by docetaxel 100 mg/m2×3 21-day courses. Primary end point was residual cancer burden (RCB 0-I rate). Secondary end points included clinical response, proliferation-based markers, and safety. Results: Overall, 106 patients were randomised [median Prosigna® ROR Score 71 (22-93)]. RCB 0-I was observed in four and eight patients in LETPAL [7.7% (95% CI 0.4-14.9)] and chemotherapy [15.7% (95% CI 5.7-25.7)] arms, respectively. Pathological complete response rates were 3.8% and 5.9%. Clinical response (75%) and breast-conserving surgery rates (69%) were similar in both arms. Preoperative Endocrine Prognostic Index 0 scores (breast cancer-specific survival) were observed in 17.6% and 8.0% of patients in LETPAL and chemotherapy arms, respectively. Safety profile was as expected, with 2 versus 17 serious adverse events (including 11 grade 4 serious AEs in the chemotherapy arm). Conclusion: LETPAL combination was associated with poor pathological response but encouraging clinical and biomarker responses in Prosigna®-defined high-risk LBC. Contemporary chemotherapy regimen was associated with poor pathological and biomarker responses, with a much less favourable safety profile. LETPAL combination might represent an alternative to chemotherapy in early high-risk LBC. Clinical Trial Number: NCT02400567.

Novel associations between blood DNA methylation and body mass index in middle-aged and older adults.

BACKGROUND/OBJECTIVES: There is increasing evidence of a relationship between blood DNA methylation and body mass index (BMI). We aimed to assess associations of BMI with individual methylation measures (CpGs) through a cross-sectional genome-wide DNA methylation association study and a longitudinal analysis of repeated measurements over time. SUBJECTS/METHODS: Using the Illumina Infinium HumanMethylation450 BeadChip, DNA methylation measures were determined in baseline peripheral blood samples from 5361 adults recruited to the Melbourne Collaborative Cohort Study (MCCS) and selected for nested case-control studies, 2586 because they were subsequently diagnosed with cancer (cases) and 2775 as controls. For a subset of 1088 controls, these measures were repeated using blood samples collected at wave 2 follow-up, a median of 11 years later; weight was measured at both time points. Associations between BMI and blood DNA methylation were assessed using linear mixed-effects regression models adjusted for batch effects and potential confounders. These were applied to cases and controls separately, with results combined through fixed-effects meta-analysis. RESULTS: Cross-sectional analysis identified 310 CpGs associated with BMI with P<1.0 × 10-7, 225 of which had not been reported previously. Of these 225 novel associations, 172 were replicated (P<0.05) using the Atherosclerosis Risk in Communities (ARIC) study. We also replicated using MCCS data (P<0.05) 335 of 392 associations previously reported with P<1.0 × 10-7, including 60 that had not been replicated before. Associations between change in BMI and change in methylation were observed for 34 of the 310 strongest signals in our cross-sectional analysis, including 7 that had not been replicated using the ARIC study. CONCLUSIONS: Together, these findings suggest that BMI is associated with blood DNA methylation at a large number of CpGs across the genome, several of which are located in or near genes involved in ATP-binding cassette transportation, tumour necrosis factor signalling, insulin resistance and lipid metabolism.

Suppressive antibiotic therapy with oral tetracyclines for prosthetic joint infections: a retrospective study of 78 patients.

PURPOSE: This study aimed at describing the use of oral cyclines (i.e., doxycycline and minocycline) as suppressive antibiotic therapy (SAT) in patients with periprosthetic joint infections (PJIs). METHODS: Medical charts of all patients with surgical revisions for PJIs who were given cycline-based SAT because of a high failure of various origins were reviewed. Data regarding tolerability and effectiveness of cycline-based SAT were analysed. RESULTS: Seventy-eight patients of mean age 64 ± 17 years received cycline-base SAT in the period from January 2006 to January 2014. PJIs involved the knee in 37 patients (47%), the hip in 35 (45%), the elbow in 4 (5%), and the shoulder in 2 (3%) and were qualified as early in 31 patients (39.7%). Staphylococcus spp. were the most common pathogens accounting for 72.1% of the total number of bacterial strains identified. All included patients had surgery which consisted in debridement and implant retention in 59 of them (75.6%). Doxycycline and minocycline were prescribed as SAT in 72 (92%) and 6 (8%) patients, respectively. Adverse events were reported in 14 patients (18%), leading to SAT discontinuation in 6 of them (8%). After a mean follow-up of 1020 ± 597 days, a total of 22 (28.2%) patients had failed including 3 cases (3.8%) with documented acquisition of tetracycline resistance in initial pathogen(s). CONCLUSIONS: Our results suggest that oral cyclines used as SAT in patients treated for PJI have an acceptable tolerability and effectiveness and appear to be a reasonable option in this setting.

Low prevalence of Pneumocystis pneumonia in hospitalized patients with systemic lupus erythematosus: review of a clinical data warehouse.

Objective In the era of powerful immunosuppression, opportunistic infections are an increasing concern in systemic lupus erythematosus. One of the best-studied opportunistic infections is Pneumocystis pneumonia; however, the prevalence of Pneumocystis pneumonia in systemic lupus erythematosus is not clearly defined. This study evaluates the prevalence of Pneumocystis pneumonia in hospitalized systemic lupus erythematosus patients, with a focus on validating the Pneumocystis pneumonia and systemic lupus erythematosus diagnoses with clinical information. Methods This retrospective cohort study evaluates the prevalence of Pneumocystis pneumonia in all systemic lupus erythematosus patients treated at Columbia University Medical Center-New York Presbyterian Hospital between January 2000 and September 2014, using electronic medical record data. Patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and patients with renal transplants (including both early and late post-transplant patients) represented immunocompromised control groups. Patients with systemic lupus erythematosus, Pneumocystis pneumonia, HIV/AIDS, or renal transplant were identified using diagnostic codes from the International Classification of Diseases, Ninth Revision (ICD-9). Results Out of 2013 hospitalized systemic lupus erythematosus patients, nine had presumed Pneumocystis pneumonia, yielding a low prevalence of Pneumocystis pneumonia in systemic lupus erythematosus of 0.45%. Three of the nine Pneumocystis pneumonia cases were patients with concomitant systemic lupus erythematosus and HIV/AIDS. Only one of these nine cases was histologically confirmed as Pneumocystis pneumonia, in a patient with concomitant systemic lupus erythematosus and HIV/AIDS and a CD4 count of 13 cells/mm3. The prevalence of Pneumocystis pneumonia in renal transplant patients and HIV/AIDS patients was 0.61% and 5.98%, respectively. Conclusion Given the reported high rate of adverse effects to trimethoprim-sulfamethoxazole in systemic lupus erythematosus and the low prevalence of Pneumocystis pneumonia in hospitalized systemic lupus erythematosus patients, our data do not substantiate the need for Pneumocystis pneumonia prophylaxis in systemic lupus erythematosus patients, except in those with concurrent HIV/AIDS.

Effects of defaunation and dietary coconut oil distillate on fermentation, digesta kinetics and methane production of Brahman heifers.

A 2 × 2 factorial experiment was conducted to assess the effects of presence or absence of rumen protozoa and of dietary coconut oil distillate (COD) supplementation on rumen fermentation characteristics, digesta kinetics and methane production in Brahman heifers. Twelve Brahman heifers were selected to defaunate, with 6 being subsequently refaunated. After defaunation and refaunation, heifers were randomly allocated to COD supplement or no supplement treatments while fed an oaten chaff-based diet. Methane production (MP; 94.17 v 104.72 g CH4 /d) and methane yield [MY; 19.45 v 21.64 g CH4 /kg dry matter intake (DMI)] were reduced in defaunated heifers compared with refaunated heifers when measured at 5 weeks after refaunation treatment (p < 0.01). Supplement of COD similarly reduced MP and MY (89.36 v 109.53 g/d and 18.46 v 22.63 g/kg DMI, respectively; p < 0.01), and there were no significant interactions of defaunation and COD effects on rumen fermentation or methane emissions. Concentration of total volatile fatty acid (VFA) and molar proportions of acetate, propionate and butyrate was not affected by defaunation or by COD. Microbial crude protein (MCP; g/d) outflow was increased by defaunation (p < 0.01) in the absence of COD but was unaffected by defaunation in COD-supplemented heifers. There was a tendency towards a greater average daily gain (ADG) in defaunated heifers (p = 0.09), but COD did not increase ADG (p > 0.05). The results confirmed that defaunation and COD independently reduced enteric MP even though the reduced emissions were achieved without altering rumen fermentation VFA levels or gut digesta kinetics.

[Lymphedema of the lower limbs: Initial manifestation of gastric linitis plastica]. / Lymphœdème des membres inférieurs révélant une linite gastrique.

BACKGROUND: Primary lymphedemas are constitutional abnormalities of the lymphatic system. Secondary lymphedemas occur after damage to the lymphatic system, mainly after cancer treatments or tumour mass compression. There are many other causes, including filariasis, which is nonetheless very rare in France. PATIENTS AND METHODS: A 52-year-old man presented with a two-month history of increased size of the left leg. He was asymptomatic and in good general condition. Clinical examination revealed non-pitting lymphedema and ipsilateral hydrocele without loco-regional compressive lymph node. Initial extensive explorations were unremarkable. Lymphoscintigraphy revealed low tracer fixation in the left leg. The symptoms continued to worsen, with exacerbation and bilateralization of the lymphedema. Two months later, axillary lymph nodes appeared corresponding to metastasis from a signet-ring cell carcinoma. Despite two lines of chemotherapy, the patient died 8 months later due to multiple metastatic disease. DISCUSSION: Our case is remarkable because the lymphedema was not related to extrinsic compression and was the first symptom of gastric cancer. In the absence of compression, endo-lymphatic micro-metastases could constitute the causative process. Acquired lymphedema of the lower limbs must be recognized as a potential early symptom of gastric carcinoma and should therefore prompt further investigations.

Targeted B cell therapies in the treatment of adult and pediatric systemic lupus erythematosus.

Belimumab (Benlysta) is a fully-humanized monoclonal antibody that inhibits B-lymphocyte stimulator (also known as B cell activating factor) and was approved by the U.S. Federal Drug Administration and European Medicines Evaluation Agency for treatment in adults with autoantibody-positive systemic lupus erythematosus (SLE). Rituximab (Rituxan) is a chimeric anti-CD20 monoclonal antibody targeting B lymphocytes. This review discusses the key findings of the phase III trials in adults with SLE and of real-world use of belimumab and rituximab in the care of both adult and pediatric SLE patients. It highlights the safety profile of belimumab and rituximab and gives insight into the consideration of these therapies for specific SLE disease states. It concludes with a discussion of the current clinical trials investigating B cell therapies in specific SLE disease states and a look to the future, with ongoing clinical trials.

Outcome of patients with streptococcal prosthetic joint infections with special reference to rifampicin combinations.

BACKGROUND: Outcome of patients with streptococcal prosthetic joint infections (PJIs) is not well known. METHODS: We performed a retrospective multicenter cohort study that involved patients with total hip/knee prosthetic joint (THP/TKP) infections due to Streptococcus spp. from 2001 through 2009. RESULTS: Ninety-five streptococcal PJI episodes (50 THP and 45 TKP) in 87 patients of mean age 69.1 ± 13.7 years met the inclusion criteria. In all, 55 out of 95 cases (57.9 %) were treated with debridement and retention of the infected implants with antibiotic therapy (DAIR). Rifampicin-combinations, including with levofloxacin, were used in 52 (54.7 %) and 28 (29.5 %) cases, respectively. After a mean follow-up period of 895 days (IQR: 395-1649), the remission rate was 70.5 % (67/95). Patients with PJIs due to S. agalactiae failed in the same proportion as in the other patients (10/37 (27.1 %) versus 19/58 (32.7 %); p = .55). In the univariate analysis, antibiotic monotherapy, DAIR, antibiotic treatments other than rifampicin-combinations, and TKP were all associated with a worse outcome. The only independent variable significantly associated with the patients' outcomes was the location of the prosthesis (i.e., hip versus knee) (OR = 0.19; 95 % CI 0.04-0.93; p value 0.04). CONCLUSIONS: The prognosis of streptococcal PJIs may not be as good as previously reported, especially for patients with an infected total knee arthroplasty. Rifampicin combinations, especially with levofloxacin, appear to be suitable antibiotic regimens for these patients.

Association of severe placental inflammation with death prior to discharge and cerebral palsy in preterm infants.

OBJECTIVE: The objective of our study was to identify placental patterns associated with death before discharge or cerebral palsy in a large cohort of preterm infants with a high follow-up rate at 2 years of corrected age. DESIGN: Population-based monocentric study. SETTINGS: Monocentric study in the maternity unit of the University Hospital of Angers, France between 24+0 and 33+6  weeks of gestation, between January 2008 and December 2011. POPULATION: All singleton infants born alive with a placental examination were eligible. METHODS: Clinical data (obstetric and neonatal) were collected prospectively through the LIFT cohort. Placental data were collected retrospectively from medical records. The main outcome measure was death before discharge or cerebral palsy. RESULTS: We did not find any significant association between severe inflammatory lesions on the placenta and death [odds ratio (OR) 1.49; 95% CI 0.55-4.01; P = 0.43] or cerebral palsy (OR 1.41; 95% CI 0.43-4.62; P = 0.57). This lack of significant association persisted even after adjustment (aOR 0.9; 95% CI 0.20-2.30; P = 0.54; aOR 0.98; 95% CI 0.27-3.58; P = 0.97). CONCLUSION: Our results do not provide evidence for a significant association between severe inflammatory placental lesions and either death before discharge or cerebral palsy at 2 years of corrected age in preterm infants born at <34 weeks of gestational age. Further studies remain necessary to confirm this result. TWEETABLE ABSTRACT: We found no significant association between inflammatory placental lesions and death or cerebral palsy.

Effects of Rumen Protozoa of Brahman Heifers and Nitrate on Fermentation and In vitro Methane Production.

Two experiments were conducted assessing the effects of presence or absence of rumen protozoa and dietary nitrate addition on rumen fermentation characteristics and in vitro methane production in Brahman heifers. The first experiment assessed changes in rumen fermentation pattern and in vitro methane production post-refaunation and the second experiment investigated whether addition of nitrate to the incubation would give rise to methane mitigation additional to that contributed by defaunation. Ten Brahman heifers were progressively adapted to a diet containing 4.5% coconut oil distillate for 18 d and then all heifers were defaunated using sodium 1-(2-sulfonatooxyethoxy) dodecane (Empicol). After 15 d, the heifers were given a second dose of Empicol. Fifteen days after the second dosing, all heifers were allocated to defaunated or refaunated groups by stratified randomisation, and the experiment commenced (d 0). On d 0, an oral dose of rumen fluid collected from unrelated faunated cattle was used to inoculate 5 heifers and form a refaunated group so that the effects of re-establishment of protozoa on fermentation characteristics could be investigated. Samples of rumen fluid collected from each animal using oesophageal intubation before feeding on d 0, 7, 14, and 21 were incubated for in vitro methane production. On d 35, 2% nitrate (as NaNO3) was included in in vitro incubations to test for additivity of nitrate and absence of protozoa effects on fermentation and methane production. It was concluded that increasing protozoal numbers were associated with increased methane production in refaunated heifers 7, 14, and 21 d after refaunation. Methane production rate was significantly higher from refaunated heifers than from defaunated heifers 35 d after refaunation. Concentration and proportions of major volatile fatty acids, however, were not affected by protozoal treatments. There is scope for further reducing methane output through combining defaunation and dietary nitrate as the addition of nitrate in the defaunated heifers resulted in 86% reduction in methane production in vitro.

Point-of-care musculoskeletal ultrasound is critical for the diagnosis of hemarthroses, inflammation and soft tissue abnormalities in adult patients with painful haemophilic arthropathy.

We previously demonstrated in adult patients with haemophilia (PWH) that hemarthrosis is present in only ~1/3rd of acutely painful joints by using point-of-care-musculoskeletal ultrasound (MSKUS). Therefore, other unrecognized tissue abnormalities must contribute to pain. Using high resolution MSKUS, employing grey scale and power Doppler, we sought to retrospectively (i) investigate soft tissue abnormalities in painful haemophilic joints and (ii) to determine to what extent MSKUS findings, functional or radiographic joint scores correlate with biomarkers of inflammation in PWH. Findings were correlated with Hemophilia Joint Health Scores (HJHS), Pettersson scores, high sensitivity C-reactive protein and von Willebrand factor activity and antigen levels. A total of 65 MSKUS examinations for acute and chronic joint pains were performed for 34 adult haemophilia patients, mostly for chronic joint pains (72.3%). The most prominent findings (66.5%) pertained to inflammatory soft tissue changes including synovitis, tendinitis, enthesitis, bursitis and fat pad inflammation. Effusions were present in 55.5% and 46.8% of MSKUS performed for acute and chronic pain, respectively. Of those, 90.0% were bloody during acute and 47.6% during persistent pains. While inflammatory biomarkers correlated well with overall HJHS and total Pettersson scores (P < 0.05), they did not differ between those patients with synovitis and those without. MSKUS is emerging as an important modality to diagnose treatable musculoskeletal abnormalities contributing to pain in haemophilic arthropathy, and therefore seems critical for a personalized approach to haemophilia care. The role of biomarkers in this setting remains less clear and requires further investigation.

Influence of daily dosage and frequency of administration of rifampicin-levofloxacin therapy on tolerance and effectiveness in 154 patients treated for prosthetic joint infections.

Data on the tolerance and effectiveness of rifampicin-levofloxacin combination therapy (RLCT) in patients treated for prosthetic joint infections (PJIs) according to daily dosage are lacking. A review of the clinical data from patients treated with RLCT for PJIs in a French referent center for PJIs was conducted. A total of 154 patients (75 F/79 M), with a median age of 64.1 years and median body weight of 83.1 kg, were included. The median daily dosages of rifampicin and levofloxacin were, respectively, 1,200 mg (range 300-2,100) and 750 mg (range 500-1,500), corresponding to a mean daily dose per kg of, respectively, 16.2 ± 4.3 mg/kg and 10.1 ± 3.0 mg/kg. After a mean follow-up period of 55.6 ± 27.1 months (range 24-236), 127 patients (82.5 %) were in remission. Adverse events attributable to rifampicin and levofloxacin were reported in 48 (31.2 %) and 13 (8.4 %) patients (p < 0.001), respectively. Patients who experienced rifampicin-related adverse events had been given higher rifampicin daily doses than the other patients (p = 0.04). The rifampicin daily dosage did not influence patient outcome and nor did the levofloxacin daily dosage on both tolerance and patient outcome. Our results suggest that adjusting rifampicin daily doses to the patient total body weight when combined with levofloxacin for the treatment of PJIs is associated with a poor tolerance. High daily doses of rifampicin (>600 mg) and levofloxacin (750 mg) do not improve patient outcome when compared to lower daily doses in this setting.

[Nutritional assessment in primary practice in elderly patients]. / Approche ambulatoire de la dénutrition chez la personne âgée.

Undernutrition is frequent and often underdiagnosed among older adults in every setting (home, nursing home, hospital), and is associated with increased morbidity and mortality. In this context, a systematic periodical nutritional assessment is proposed in patients aged 75 years and over. Without a consensus, the most widely used diagnostic criteria is an unintentional weight loss of 5% over a month or 10% over 6 months. When undernutrition is present, multimodal interventions are provided to address each potentially contributing comorbid condition and to promote increased caloric intake. Follow-up and adaptation of interventions after 3 months are required.