CRP under 130 mg/L rules out the diagnosis of Legionella pneumophila serogroup 1 (URINELLA Study).

INTRODUCTION: In case of pneumonia, some biological findings are suggestive for Legionnaire's disease (LD) including C-reactive protein (CRP). A low level of CRP is predictive for negative Legionella Urinary-Antigen-Test (L-UAT). METHOD: Observational retrospective study in Nord-Franche-Comté Hospital with external validation in Besançon University Hospital, France which included all adults with L-UAT performed during January 2018 to December 2022. The objective was to determine CRP optimal threshold to predict a L-UAT negative result. RESULTS: URINELLA included 5051 patients (83 with positive L-UAT). CRP optimal threshold was 131.9 mg/L, with a negative predictive value (NPV) at 100%, sensitivity at 100% and specificity at 58.0%. The AUC of the ROC-Curve was at 88.7% (95% CI, 86.3-91.1). External validation in Besançon Hospital patients showed an AUC at 89.8% (95% CI, 85.5-94.1) and NPV, sensitivity and specificity was respectively 99.9%, 97.6% and 59.1% for a CRP threshold at 131.9 mg/L; after exclusion of immunosuppressed patients, index sensitivity and NPV reached also 100%. CONCLUSION: In case of pneumonia suspicion with a CRP level under 130 mg/L (independently of the severity) L-UAT is useless in immunocompetent patients with a NPV at 100%. We must remain cautious in patients with symptoms onset less than 48 h before CRP dosage.

Simple Aspiration versus Drainage for Complete Pneumothorax: A Randomized Noninferiority Trial.

Rationale: Management of first episodes of primary spontaneous pneumothorax remains the subject of debate. Objectives: To determine whether first-line simple aspiration is noninferior to first-line chest tube drainage for lung expansion in patients with complete primary spontaneous pneumothorax. Methods: We conducted a prospective, open-label, randomized noninferiority trial. Adults aged 18-50 years with complete primary spontaneous pneumothorax (total separation of the lung from the chest wall), recruited at 31 French hospitals from 2009 to 2015, received simple aspiration (n = 200) or chest tube drainage (n = 202) as first-line treatment. The primary outcome was pulmonary expansion 24 hours after the procedure. Secondary outcomes were tolerance of treatment, occurrence of adverse events, and recurrence of pneumothorax within 1 year. Substantial discordance in the numerical inputs used for trial planning and the actual trial rates of the primary outcome resulted in a reevaluation of the trial analysis plan. Measurement and Main Results: Treatment failure occurred in 29% in the aspiration group and 18% in the chest tube drainage group (difference in failure rate, 0.113; 95% confidence interval [CI], 0.026-0.200). The aspiration group experienced less pain overall (mean difference, -1.4; 95% CI, -1.89, -0.91), less pain limiting breathing (frequency difference, -0.18; 95% CI, -0.27, -0.09), and less kinking of the device (frequency difference, -0.05; 95% CI, -0.09, -0.01). Recurrence of pneumothorax was 20% in this group versus 27% in the drainage group (frequency difference, -0.07; 95% CI, -0.16, +0.02). Conclusions: First-line management of complete primary spontaneous pneumothorax with simple aspiration had a higher failure rate than chest tube drainage but was better tolerated with fewer adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT01008228).

Liberal or Conservative Oxygen Therapy for Acute Respiratory Distress Syndrome.

BACKGROUND: In patients with acute respiratory distress syndrome (ARDS), the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network recommends a target partial pressure of arterial oxygen (Pao2) between 55 and 80 mm Hg. Prospective validation of this range in patients with ARDS is lacking. We hypothesized that targeting the lower limit of this range would improve outcomes in patients with ARDS. METHODS: In this multicenter, randomized trial, we assigned patients with ARDS to receive either conservative oxygen therapy (target Pao2, 55 to 70 mm Hg; oxygen saturation as measured by pulse oximetry [Spo2], 88 to 92%) or liberal oxygen therapy (target Pao2, 90 to 105 mm Hg; Spo2, ≥96%) for 7 days. The same mechanical-ventilation strategies were used in both groups. The primary outcome was death from any cause at 28 days. RESULTS: After the enrollment of 205 patients, the trial was prematurely stopped by the data and safety monitoring board because of safety concerns and a low likelihood of a significant difference between the two groups in the primary outcome. Four patients who did not meet the eligibility criteria were excluded. At day 28, a total of 34 of 99 patients (34.3%) in the conservative-oxygen group and 27 of 102 patients (26.5%) in the liberal-oxygen group had died (difference, 7.8 percentage points; 95% confidence interval [CI], -4.8 to 20.6). At day 90, 44.4% of the patients in the conservative-oxygen group and 30.4% of the patients in the liberal-oxygen group had died (difference, 14.0 percentage points; 95% CI, 0.7 to 27.2). Five mesenteric ischemic events occurred in the conservative-oxygen group. CONCLUSIONS: Among patients with ARDS, early exposure to a conservative-oxygenation strategy with a Pao2 between 55 and 70 mm Hg did not increase survival at 28 days. (Funded by the French Ministry of Health; LOCO2 ClinicalTrials.gov number, NCT02713451.).

Repeat corneal transplantation: indication, surgical technique, and early graft failures trends in France from 2004 to 2019.

PURPOSE: To investigate the repeat corneal transplantation trend in France from 2004 to 2019. METHODS: Review of the prospectively compiled French Biomedicine Agency electronic database containing all corneal transplantation records from 2004 to 2019. The surgical technique, demographic characteristics, diagnosis, and previous graft data were retrieved and analyzed using the Cochran-Armitage trend test. RESULTS: A total of 66,584 corneal transplantations were performed, 51,260 of which were first grafts and 15,324 (23%) were regrafts. For regrafts, 77% were penetrating keratoplasties (PK) and 19.6% were lamellar keratoplasties (LK). Age, hypertonia, glaucoma, trauma, lens surgery, immune disorders, diameter > 8.5 mm, and neovessels in > 2 quadrants were associated with a higher rate of repeat keratoplasty. Keratoconus, secondary endothelial dystrophy, and Fuchs' dystrophy were the principal indications for regrafting. When a previous graft failed, it occurred earlier for patients with LK (4.6 years, median = 2, SD = 7.54) than PK (8.48 years, median = 5, SD = 9.51). Failure within a year was the reason why 28.3% of the LK regrafts and 12.5% of PK regrafts were performed, while for failure within two years these values were 49.9% and 27.8%, respectively. Graft survival decreased with the number of repeat keratoplasty, being more pronounced after a second LK regraft and after a first PK regraft. CONCLUSION: The number of LK regrafts increased continuously, and 1/3 were performed for failure within the year. This rate increased until 2015, after which it stabilized until 2019, probably due to the better mastery of the technique.

Scannographic Study of Risk Factors of Abdominal Aortic Aneurysm Rupture.

BACKGROUND: Current decision about when to operate abdominal aortic aneurysms (AAAs) is based only on the maximum aneurysm diameter (MAD). However, small aneurysms still rupture and we can observe very large AAA without any symptom. A simple morphologic analysis could be a tool to assess the risk of rupture. The main objective of this study was to assess the relevance of ratios between MAD and healthy aorta on computed tomography (CT) as a risk factor of AAA rupture. The secondary objective was to evaluate CT signs as risk factors of AAA rupture. METHODS: Retrospective observational bicentric study comparing CT scans of a ruptured AAA group and a control group treated electively was conducted. Appariement 1:1 based on MAD was applied. Ratios between healthy aorta diameters at several levels, celiac trunk (CTR), superior mesenteric artery (SMA), highest renal artery (RA), and the MAD were calculated. The presence of blebs, crescent signs, ruptures of calcifications of the aneurysm sack, and draped aorta were notified. RESULTS: From 2010 to 2016, 38 ruptured AAA and 38 controls were included. Ratios were superior in the rupture group, respectively: MAD/CTR [2.77 (±0.5) versus 2.58 (±0.4) P < 0.095], MAD/SMA [2.92 (±0.7) versus 2.74 (±0.5) P < 0.194], and MAD/RA [3.02 (±0.70) versus 2.76 (±0.5) P < 0.054] but not significatively. Receiver operating characteristic curve analysis demonstrated optimal threshold to detect rupture at 2.8 for the ratio MAD/CTR (area under the curve (AUC) 0.593, sensitivity 47.4%, specificity 78.9%), at 3.3 for the ratio MAD/SMA (AUC 0.564, sensitivity 31.6%, specificity 92.1%), and at 3.3 for the ratio MAD/RA (AUC 0.591, sensitivity 31.6%, specificity 94.7%). Bivariate analysis for rupture risk factor showed significance for the three ratios (MAD/CTR > 2.8 [OR = 11 (1.42; 85.20) P < 0.0217], MAD/SMA > 3.3 [OR = 10 (1.28; 78.12) P < 0.0281], and MAD/RA >3.3 [OR = 11.00 (1.42; 85.20) P < 0.0217]). One scannographic sign was more present in the rupture group: crescent sign 36.8% versus 5.3%, P = 0.0007, as well in bivariate analysis [OR = 7 (1.59; 30.80) P < 0.0326]. CONCLUSIONS: In our experience, specific ratios when they exceed calculated threshold, seem to be more prone to rupture. We could consider that these measures, easy to apply in clinical practice, would be complementary keys for rupture risk individual assessment.

Comparison between type A and type B early adiposity rebound in predicting overweight and obesity in children: a longitudinal study.

Early adiposity rebound (EAR) predicts paediatric overweight/obesity, but current approaches do not consider both the starting point of EAR and the BMI trajectory. We compared the clinical characteristics at birth, age 3-5 and 6-8 years of children, according to the EAR and to its type (type A/type B-EAR). We assessed the children's odds of being classified as overweight/obese at age 6-8 years, according to the type of EAR as defined at age 3-5 years. As part of this two-wave observational study, 1055 children were recruited and examined at age 3-5 years. Antenatal and postnatal information was collected through interviews with parents, and weight and height from the health records. Type A and type B-EAR were defined in wave 1 according to the BMI nadir and the variation of BMI z-score between the starting point of the adiposity rebound and the last point on the curve. At 6-8 years (wave 2), 867 children were followed up; 426 (40·4 %) children demonstrated EAR. Among them, 172 had type A-EAR, higher rates of parental obesity (P < 0·05) and greater birth weight compared with other children (P < 0·001). Odds for overweight/obesity at 6-8 years, when adjusting for antenatal and postnatal factors, was 21·35 (95 % CI 10·94, 41·66) in type A-EAR children and not significant in type B-EAR children (OR 1·76; 95 % CI 0·84, 3·68) compared with children without EAR. Classification of EAR into two subtypes provides physicians with a reliable approach to identify children at risk for overweight/obesity before the age of 5 years.

Regional trends in corneal transplantation from 2004 to 2015 in France: a 12-year review on indications, technique and waiting period.

The aim of this study was to report the 12-year longitudinal trends in regional disparity in terms of indications, techniques and waiting period for corneal transplantation in France from 2004 to 2015. The records of all corneal transplantations performed from 2004 to 2015 in France were retrospectively reviewed by analasing the registry and the territorial organization [divided France into 7 interregional areas of collection and distribution of grafts (IACD)] of the French Biomedicine Agency. A total of 46,658 corneal transplantations were performed between 2004 and 2015. In 2014, there was 65.8 keratoplasties per million inhabitants (10-6 per capita in France, but there were some regional disparities, from 44.9 × 10-6 per capita in IACD 2 to 87.2 × 10-6 per capita in IACD 5. In 2014, IACD 7 performed the highest number of transplantations for keratoconus with 15.7 × 10 - 6 per capita; IACD 5 ranked first for Fuchs endothelial disease and secondary endothelial failure with, respectively, 20.5 × 10-6 per capita and 21.2 × 10-6 per capita, and IACD 4 ranked first for graft failure with 17.4 × 10-6 per capita. All regions over the years began to perform more lamellar keratoplasties (4.3% in 2004 vs 45.2% in 2015) and fewer penetrating keratoplasties (85.8% in 2004 vs 48.2% in 2015). The mean waiting time was 3.4 ± 5.2 months in France over 12 years, with minimal disparities between regions: all of them under 4 months waiting time in 2015, from 1.4 months for IACD 1-3.8 months for IACD 5. Regional disparities have changed over the years, with a modification of indications, and upgrading surgical techniques for some indications. Some disparities remain, mainly because of the variability in the number and activity of transplantation centres and eye banks. Measures could be taken to minimize these disparities, such as increasing communication between eye banks. The waiting time for keratoplasty decreasing below the 4-month mark is a good indicator of the progress made. Regional disparities have decreased over the years, but some regions remain disadvantaged in terms of needs and access to transplants. Tomorrow's challenge is to identify solutions and adapt the offer to the needs.

Impact of intravenous exenatide infusion for perioperative blood glucose control on myocardial ischemia-reperfusion injuries after coronary artery bypass graft surgery: sub study of the phase II/III ExSTRESS randomized trial.

BACKGROUND: The aim of the study was to investigate whether intravenous (iv) infusion of exenatide, a synthetic GLP-1 receptor agonist, could provide a protective effect against myocardial ischemia-reperfusion injury after coronary artery bypass graft (CABG) surgery. METHODS: A sub study analysis of patients > 18 years admitted for elective CABG and included in the ExSTRESS trial was conducted. Patients were randomized to receive either iv exenatide (1-h bolus of 0.05 µg min-1 followed by a constant infusion of 0.025 µg min-1) (exenatide group) or iv insulin therapy (control group) for blood glucose control (target range 100-139 mg dl-1) during the first 48 h after surgical incision. All serum levels of troponin I measured during routine care in the Cardiac Surgery ICU were recorded. The primary outcome was the highest value of plasma concentration of troponin I measured between 12 and 24 h after ICU admission. The proportion of patients presenting an echocardiographic left ventricular ejection fraction (LVEF) > 50% at the follow-up consultation was compared between the two groups. RESULTS: Finally, 43 and 49 patients were analyzed in the control and exenatide groups, respectively {age: 69 [61-76] versus 71 [63-75] years; baseline LVEF < 50%: 6 (14%) versus 16 (32%) patients; on-pump surgery: 29 (67%) versus 33 (67%) patients}. The primary outcome did not significantly differ between the two groups (3.34 [1.06-6.19] µg l-1 versus 2.64 [1.29-3.85] µg l-1 in the control and exenatide groups, respectively; mean difference (MD) [95% confidence interval (95% CI)] 0.16 [- 0.25; 0.57], p = 0.54). The highest troponin value measured during the first 72 h in the ICU was 6.34 [1.36-10.90] versus 5.04 [2.39-7.18] µg l-1, in the control and exenatide groups respectively (MD [95% CI] 0.20 [- 0.22; 0.61], p = 0.39). At the follow-up consultation, 5 (12%) versus 8 (16%) patients presented a LVEF < 50% in the control and in the exenatide groups respectively (relative risk [95% CI] 0.68 [0.16; 2.59], p = 0.56). CONCLUSIONS: Postoperative iv exenatide did not provide any additional cardioprotective effect compared to iv insulin in low-risk patients undergoing scheduled CABG surgery. Trial registration ClinicalTrials.gov Identifier NCT01969149, date of registration: January 7th, 2015; EudraCT No. 2009-009254-25 A, date of registration: January 6th, 2009.

Increased levels of circulating platelet-derived microparticles are associated with metastatic cutaneous melanoma.

We investigated the plasma levels of PMPs in patients with 45 stage III and 45 stage IV melanoma. PMPs were characterised by flow cytometry and their thrombogenic activity. We also investigated the link between PMPs circulating levels and tumor burden. The circulating levels of PMPs were significantly higher in stage IV (8500 µL-1 ) than in patients with stage III (2041 µL-1 ) melanoma (P=.0001). We calculated a highly specific (93.3%) and predictive (91.7%) cut-off value (5311 µL-1 ) allowing the distinction between high-risk stage III and metastatic stage IV melanoma. The thrombogenic activity of PMPs was significantly higher in patients with stage IV melanoma (clotting time: 40.7 second vs 65 second, P=.0001). There was no significant association between the radiological tumoral syndrome and the plasma level of PMPs. Our data suggest the role of PMPs in metastatic progression of melanoma.

Clinical Effectiveness of Intravenous Exenatide Infusion in Perioperative Glycemic Control after Coronary Artery Bypass Graft Surgery: A Phase II/III Randomized Trial.

BACKGROUND: We aimed to assess the clinical effectiveness of intravenous exenatide compared to insulin in perioperative blood glucose control in coronary artery bypass grafting surgery patients. METHODS: Patients more than 18 yr old admitted for elective coronary artery bypass grafting were included in a phase II/III nonblinded randomized superiority trial. Current insulin use and creatinine clearance of less than 60 ml/min were exclusion criteria. Two groups were compared: the exenatide group, receiving exenatide (1-h bolus of 0.05 µg/min followed by a constant infusion of 0.025 µg/min), and the control group, receiving insulin therapy. The blood glucose target range was 100 to 139 mg/dl. The primary outcome was the proportion of patients who spent at least 50% of the study period within the target range. The consumption of insulin (Cinsulin) and the time to start insulin (Tinsulin) were compared between the two groups. RESULTS: In total, 53 and 51 patients were included and analyzed in the exenatide and control groups, respectively (age: 70 ± 9 vs. 68 ± 11 yr; diabetes mellitus: 12 [23%] vs. 10 [20%]). The primary outcome was observed in 38 (72%) patients in the exenatide group and in 41 (80%) patients in the control group (odds ratio [95% CI] = 0.85 [0.34 to 2.11]; P = 0.30). Cinsulin was significantly lower (60 [40 to 80] vs. 92 [63 to 121] U, P < 0.001), and Tinsulin was significantly longer (12 [7 to 16] vs. 7 [5 to 10] h, P = 0.02) in the exenatide group. CONCLUSIONS: Exenatide alone at the dose used was not enough to achieve adequate blood glucose control in coronary artery bypass grafting patients, but it reduces overall consumption of insulin and increases the time to initiation of insulin.

The RAPID Neuropsychological Test Battery for Subjects Aged 50-89: From Norms to Cognitive Profile.

BACKGROUND/AIMS: It is well established that healthy adults obtain low performances when simultaneously interpreting the results of multiple tests. The aim of this study was to estimate the proportion of French-speaking healthy older adults with low scores for the RAPID (Réseau d'Aide au diagnostic et à la PrIse en charge des Détériorations cognitives et de maladies neurologiques chroniques en Franche-Comté et au niveau national) battery test and consider different combinations of test scores within a specific domain and across different domains. METHODS: The prevalence of low scores (i.e., ≤5th percentile) on the 14 RAPID primary measures was calculated from the RAPID normative sample (n = 476), based on 4 ages (50-89 years) and 3 levels of education. RESULTS: A high percentage (40.1%) of the normative sample obtained at least one or more low scores (i.e., false positives). In contrast, the risk of having low scores was much less important (<2%) when considering the combinations of 2 test-scores. CONCLUSION: Low scores are very common in healthy older subjects and are thus not necessarily pathological or indicative of truly impaired functioning. The information derived from a cognitive profile may provide a greater clinical relevance in an individual, since very few of the healthy older adults obtained low scores on combinations of 2 test-scores.

Asymptomatic subjects with airway obstruction have significant impairment at exercise.

BACKGROUND: The relevance of screening for airway obstruction in subjects not complaining of COPD symptoms may depend on the definition of airway obstruction. Response to exercise in asymptomatic subjects with persistent airway obstruction as defined by a postbronchodilator FEV1/FVC <5th centile lower limit of normal (LLN) remains unknown. METHODS: Dyspnoea (Borg scale), exercise tolerance and ventilatory constraints on tidal volume expansion were assessed in 20 consecutive asymptomatic subjects with persistent mild airway obstruction detected by screening (postbronchodilator FEV1/FVC z-score: -2.14±0.29; FEV1 z-score: -1.02±0.64) undergoing incremental cycle cardiopulmonary exercise testing, compared with 20 healthy controls with normal spirometry matched for age, sex, body mass index and smoking history (FEV1/FVC z-score: -0.13±0.57; FEV1 z-score: 0.32±0.67) and with 20 symptomatic patients with COPD matched for the same characteristics (FEV1/FVC z-score: -2.36±0.51; FEV1 z-score: -1.02±0.48). RESULTS: Asymptomatic subjects with airway obstruction had higher dyspnoea ratings than controls during incremental exercise. Asymptomatic subjects with airway obstruction had also peak oxygen consumption and peak power output that were lower than controls, and similar to those observed in patients with COPD. Although less frequent than in COPD, dynamic hyperinflation was more frequent in asymptomatic subjects with airway obstruction than in controls (85%, 50% and 10%, respectively; p=0.01 in asymptomatic subjects vs controls and p=0.04 vs COPD). CONCLUSIONS: Although they did not present with chronic activity-related dyspnoea, subjects with a postbronchodilator FEV1/FVC

Prevalence and risk factors for COPD in farmers: a cross-sectional controlled study.

There are conflicting data regarding the magnitude and determinants of chronic obstructive pulmonary disease (COPD) risk in farmers.In a cross-sectional study of 917 nonfarming working controls and 3787 farmers aged 40-75 years, we assessed respiratory symptoms, tobacco exposure, job history (without direct exposure measurement) and lung function. COPD was defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criterion (post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.70) and by the Quanjer reference equation (post-bronchodilator FEV1/FVC

Can preoperative CRP levels predict infections of bipolar hemiarthroplasty performed for femoral neck fracture? A retrospective, multicenter study.

INTRODUCTION: Current recommendations urge us to operate quickly on femoral neck fractures to reduce the risk of comorbidity decompensation. In some cases, this leads us to operate when an underlying infection is present. In this study, we evaluated the infection rate of bipolar hemiarthroplasty after femoral neck fracture and attempted to relate it to preoperative C-reactive protein (CRP) levels. MATERIALS AND METHODS: The infection rate of bipolar hemiarthroplasty was evaluated in a dual-center, retrospective study of 260 patients over a 2-year period. During the first year, the preoperative CRP levels were not taken into account when scheduling the procedure. During the second year, if preoperative CRP levels were above 50 mg/L, the procedure was delayed to look for and treat any ongoing infections. RESULTS: The overall periprosthetic infection rate in this study was 4.85 % (range 4.8-4.9), with 33 % of patients passing within 1 year due to the infection. In the group where CRP was not taken into consideration, 59 of the 143 operated away patients (41 %) had their preoperative CRP levels measured. Twenty-nine of these patients had CRP > 50 mg/L when they were operated. Of the seven infections in the group, one patient had CRP > 50 mg/L, two had CRP < 50 mg/L, and four patients did not have preoperative CRP levels measured. In the group where CRP was taken into consideration, 104 of the 117 patients (89 %) had their preoperative CRP assessment. Thirty of these patients had CRP > 50 mg/L upon admission; their procedure was delayed to determine the etiology of this CRP elevation. No cause was found in 16 of these 30 patients, and they were operated despite having CRP > 50 mg/L. There were five infections in this group: four patients had CRP > 50 mg/L and were treated accordingly; one patient had preoperative CRP < 50 mg/L. In patients where the preoperative CRP levels were taken into account, the delay before surgery was twice as long as those where CRP levels were not considered. DISCUSSION: C-reactive protein (CRP) level alone is not a good preoperative predictive factor for periprosthetic joint infection, although 80 % of the patient with an infected bipolar hemiarthroplasty had CRP > 50 mg/L upon admission. The increased delay due to the CRP analysis is not without consequence for this cohort. Two previous studies have looked into the predictive ability of CRP levels, but these involved scheduled surgical procedures. CONCLUSION: This study could not validate the use of CRP levels, nor a 50 mg/L threshold, as predictive factors for a preexisting infection during bipolar hemiarthroplasty for femoral neck fracture. As a consequence, new infection screening tools must be developed and validated.

Intensity modulated arc therapy in bilaterally irradiated head and neck cancer: a comparative and prospective multicenter planning study.

A dosimetric comparison was made of Helical Tomotherapy (HT) and Rapid'Arc(®) (RA) in 115 patients with head and neck carcinoma included in a prospective and multicentric study. HT and RA provided highly conformal plans that easily complied with dose volume constraints for organs at risk. HT reduced high doses to the planning target volumes (PTVs) compared to RA and provided a more homogeneous dose distribution but with an increased Non Tumoral Integral Dose (NTID) than RA. However, the clinical consequences of these dosimetric advantages and disadvantages need further investigation.