Clinical impact and cost-consequence analysis of ePlex® blood culture identification panels for the rapid diagnosis of bloodstream infections: a single-center randomized controlled trial.

To assess clinical impact and perform cost-consequence analysis of the broadest multiplex PCR panels available for the rapid diagnosis of bloodstream infections (BSI). Single-center, randomized controlled trial conducted from June 2019 to February 2021 at a French University hospital with an institutional antimicrobial stewardship program. Primary endpoint was the percentage of patients with optimized antimicrobial treatment 12 h after transmission of positivity and Gram stain results from the first positive BC. This percentage was significantly higher in the multiplex PCR (mPCR) group (90/105 = 85.7% %, CI95% [77.5 ; 91.8] vs. 68/107 = 63.6%, CI95% [53.7 ; 72.6]; p < 10- 3) at interim analysis, resulting in the early termination of the study after the inclusion of 309 patients. For patients not optimized at baseline, the median time to obtain an optimized therapy was much shorter in the mPCR group than in the control group (6.9 h, IQR [2.9; 17.8] vs. 26.4 h, IQR [3.4; 47.5]; p = 0.001). Early optimization of antibiotic therapy resulted in a non-statistically significant decrease in mortality from 12.4 to 8.8% (p = 0.306), with a trend towards a shorter median length of stay (18 vs. 20 days; p = 0.064) and a non-significant reduction in the average cost per patient of €3,065 (p = 0.15). mPCR identified all the bacteria present in 88% of the samples. Despite its higher laboratory cost, the use of multiplex PCR for BSI diagnosis leads to early-optimised therapy, seems cost-effective and could reduce mortality and length of stay. Their impact could probably be improved if implemented 24/7.

Eosinophils are the dominant type2 marker for the current indication of biological treatment in severe uncontrolled chronic rhinosinusitis with nasal polyps.

The latest European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) defines markers for type2 inflammation in the context of indicating biological therapy in severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) as either a total serum immunoglobulin E (total-IgE) <100 kU/L, a blood eosinophil count (BEC, expressed as -109 cells / L) >=0.25, or a tissue eosinophil count >=10 per high power field (HPF) (1). Recently, an EPOS/EUFOREA expert panel advised to lower the threshold for BEC from >=0.25 (EPOS2020) to >=0.15 (EUFOREA2023) to align with thresholds used for biological indication in asthma patients (2). As far as we know, there is no literature supporting the cut-off value for total-IgE.

Hypereosinophilia during dupilumab treatment in patients with chronic rhinosinusitis with nasal polyps.

BACKGROUND: Increased blood eosinophil count (BEC) is common in patients under dupilumab treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). This study investigated the prevalence and consequences of hypereosinophilia and to help define patients at risk. METHODS: Real-life, prospective observational cohort study of patients treated with dupilumab for severe CRSwNP. Eligible patients were adult and biological-naive (N=334). All BEC values at baseline and during treatment were reported. Patients with a follow-up of >= 1 year were included to define patients at risk for hypereosinophilia by comparing baseline BEC values (N=218). Furthermore, clinical characteristics and therapeutic consequences for patients with BEC >= 3.0 were noted. RESULTS: Hypereosinophilia developed in a minority of patients, with a peak at week 12 (16.2% with BEC >= 1.5, and 1.7% >= 3.0) in cross-sectional analysis. BEC >= 1.5 developed in 28.9% and BEC >=3.0 in 4.6% of cases with a minimal 1-year follow-up. Baseline BEC was significantly higher for patients developing BEC >= 1.5 and BEC >=3.0, with an optimal cut-off point of 0.96 to predict developing BEC >= 3.0. CONCLUSIONS: Blood eosinophil count (BEC) >= 1.5 is transient and usually abates with no therapeutic interventions and BEC >= 3.0 is rare. Hypereosinophilic syndrome did not occur and switching to a different biological was rarely employed. A baseline BEC of >=1.0 can be a reason for extra caution.

Measuring control of disease in Chronic Rhinosinusitis; assessing the correlation between SinoNasal Outcome Test-22 and Visual Analogue Scale item scores.

BACKGROUND: In chronic rhinosinusitis (CRS), aim of treatment is control of disease. EPOS2020 suggests the use of visual analogue scale (VAS) measurements on several symptoms. We aim to determine if individual VAS items can be replaced by widely used SinoNasal Outcome Test-22 (SNOT-22) items when determining control of disease, to avoid using double measurements and to stimulate its use in clinical practice. METHODS: Analyses were made on correlations between individual SNOT-22 scores and symptom-specific questions from consecutive patients with CRS visiting our tertiary referral rhinologic clinic for the first time. RESULTS: 157 CRS patients were included. Correlations of individual items were strong (r greater than 0.8). Best parity in sensitivity, specificity, positive predicting value, negative predicting value, odds ratio and Receiver Operating Characteristic curves were found in individual item score of VAS greater than 5 and SNOT item-score. This cut off is valid for measuring control of disease, combining several nasal, facial pain and sleep symptoms (controlled, partially controlled and uncontrolled). CONCLUSION: There is strong correlation between individual items measured as SNOT or VAS. For the definition of CRS disease control, as proposed in EPOS2020, the use of symptoms specific SNOT 23 is predictive of VAS greater than 5.

Occupational exposure influences control of disease in patients with chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a frequent condition that is treated by endoscopic sinus surgery (ESS) when medical treatment fails. Irritating or sensitizing airborne agents can contribute to uncontrolled CRS. A prior study showed a linear correlation between occupational exposure and the number of ESS. METHODS: In this cross-sectional study we tested the hypothesis that occupational exposure is a risk for undergoing ESS. We sent questionnaires enquiring occupational exposure in patients with CRS with nasal polyps (CRSwNP) or CRS without nasal polyps (CRSsNP). An expert assessed blindly the reported work exposures to inhaled agents. The relationship between occupational exposure on undergoing ESS was analysed. RESULTS: Among all patients who underwent ESS (n=343), 30% reported a relevant occupational exposure, which is significantly higher than the 4.8% found among CRS patients that underwent no prior sinus surgery (n=21). Besides occupational exposure, self-reported doctor-diagnosed asthma were independent variables contributing to the chance of undergoing ESS. CONCLUSION: In our study we confirm occupational exposure as a risk factor for uncontrolled CRS, if defined by undergoing ESS. In CRS patients with uncontrolled symptoms, despite maximal conservative therapy, the clinician should explore the possible contribution of occupational exposure.

The Amsterdam Classification of Completeness of Endoscopic Sinus Surgery (ACCESS): a new CT-based scoring system grading the extent of surgery.

BACKGROUND: A debate is ongoing on the role of the extent of sinus surgery in disease control in chronic rhinosinusitis (CRS). The newly developed Amsterdam Classification on Completeness of Endoscopic Sinus Surgery (ACCESS) score provides a way to quantify extent of surgery. This study aimed to validate the ACCESS scoring system and to report its interrater agreement compa- red to the widely used Lund-Mackay (LM) scoring system. METHODOLOGY: Forty hand-picked anonymized computed tomography scans of sinuses of patients with varying pathology and degree of previous sinus surgery were independently scored by six rhinologists. Interrater agreement was determined by the intraclass correlation (ICC) statistic. RESULTS: The interrater agreement of the ACCESS score was excellent, comparable to the LM score. The ACCESS interrater agree- ment was not influenced by degree of opacification or diagnosis. The ACCESS score reliably measured predicted differences induced by sinus surgery. CONCLUSIONS: the ACCESS score is an easy-to-use valid tool to assess extent of sinus surgery with an excellent interrater agree- ment. Further validation in a random group of CRS cases is required.

Antifungal susceptibility testing practices in mycology laboratories in France, 2018.

A survey of mycology laboratories for antifungal susceptibility testing (AFST) was undertaken in France in 2018, to better understand the difference in practices between the participating centers and to identify the difficulties they may encounter as well as eventual gaps with published standards and guidelines. The survey captured information from 45 mycology laboratories in France on how they perform AFST (number of strains tested, preferred method, technical and quality aspects, interpretation of the MIC values, reading and interpretation difficulties). Results indicated that 86% of respondents used Etest as AFST method, with a combination of one to seven antifungal agents tested. Most of the participating laboratories used similar technical parameters to perform their AFST method and a large majority used, as recommended, internal and external quality assessments. Almost all the participating mycology laboratories (98%) reported difficulties to interpret the MIC values, especially when no clinical breakpoints are available. The survey highlighted that the current AFST practices in France need homogenization, particularly for MIC reading and interpretation.

mySinusitisCoach: patient empowerment in chronic rhinosinusitis using mobile technology.

Mobile health technology is emerging to take a prominent position in the management of chronic diseases. These technologies aim at enhancing patient empowerment via education and self-management. To date, of all the different apps available for patients with sinus disease, none were developed by medical experts dealing with chronic rhinosinusitis (CRS). The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) has undertaken a multi-stakeholder approach for designing, developing and implementing a tool to support CRS patients in monitoring their symptoms and to provide patients with a digital support platform containing reliable medical information about their disease and treatment options. mySinusitisCoach has been developed by medical experts dealing with CRS in close collaboration with patients, primary care physicians and community pharmacists, meeting the needs of both patients and health care providers. From a research perspective, the generation of real life data will help to validate clinical studies, patient stratification and improve understanding of the socio-economic impact of CRS, thereby paving the way for better treatment strategies.

Chromoblastomycosis and sporotrichosis, two endemic but neglected fungal infections in Madagascar.

Chromoblastomycosis and sporotrichosis are endemic fungal infections of tropical and subtropical regions, including Madagascar. The causal fungi develop in the soil or on plants and infect humans through wounds, either directly (wounding by the plant, through thorns, for example), or through the contact of an existing wound with contaminated soil. For this reason, the lesions predominantly occur on the limbs, and these fungi principally infect people working outside with bare hands and/or feet. The subcutaneous lesions of chromoblastomycosis are initially nodular, subsequently becoming warty, tumoral, cauliflower-like and pruriginous, which promotes dissemination. The chronic nature of the infection and its progression over long periods lead to highly disabling lesions in essentially rural and agricultural populations. The lesions of sporotrichosis are also nodular, but more ulcerous, and they form an extended chain following the route of the lymph vessels. Pus, squamous or skin biopsy specimens are used for the mycological examination of these mycoses. Treatment depends on the severity and form of the lesions and is based on antifungal drugs sometimes combined with physical methods. There has been no study of these infections for more than two decades in Madagascar, despite the large numbers of cases seen by doctors in all parts of the island. The nature, diversity and distribution of the plants responsible for contamination have not been described in Madagascar. In this review, we described these two endemic mycoses in terms of their epidemiological, mycological, clinical and therapeutic characteristics, focusing particularly on Madagascar, which is one of the leading foci of these two infections worldwide.

EUFOREA Rhinology Research Forum 2016: report of the brainstorming sessions on needs and priorities in rhinitis and rhinosinusitis.

The first European Rhinology Research Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held in the Royal Academy of Medicine in Brussels on 17th and 18th November 2016, in collaboration with the European Rhinologic Society (ERS) and the Global Allergy and Asthma European Network (GA2LEN). One hundred and thirty participants (medical doctors from different specialties, researchers, as well as patients and industry representatives) from 27 countries took part in the multiple perspective discussions including brainstorming sessions on care pathways and research needs in rhinitis and rhinosinusitis. The debates started with an overview of the current state of the art, including weaknesses and strengths of the current practices, followed by the identification of essential research needs, thoroughly integrated in the context of Precision Medicine (PM), with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key principles for improving current clinical practices. This report provides a concise summary of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2016.

Chronic rhinosinusitis: New understanding of specific and general Quality of life scores.

Our goal in treating chronic rhinosinusitis (CRS) is to reduce sinonasal symptoms and improve quality of life (QoL). In patients with CRS, sinonasal symptoms have a significant impact on QoL. Various validated measures exist to quantify QoL such as the 22-item Sinonasal Outcomes Test (SNOT- 22) and MSNOT-20 Young Persons Questionnaire (MSYPQ) specific to CRS, while others measure general QoL, such as the EuroQol 5-Dimensional general health-related QoL survey (EQ5D).

Multicenter Comparison of the Etest and EUCAST Methods for Antifungal Susceptibility Testing of Candida Isolates to Micafungin.

In vitro susceptibility of 933 Candida isolates, from 16 French hospitals, to micafungin was determined using the Etest in each center. All isolates were then sent to a single center for determination of MICs by the EUCAST reference method. Overall essential agreement between the two tests was 98.5% at ±2 log2 dilutions and 90.2% at ±1 log2 dilutions. Categorical agreement was 98.2%. The Etest is a valuable alternative to EUCAST for the routine determination of micafungin MICs in medical mycology laboratories.

Impact of systemic antifungal therapy on the detection of Candida species in blood cultures in clinical cases of candidemia.

The diagnosis and follow-up of candidemia still rely on blood cultures (BCs). In vitro studies show that antifungals can significantly modify the result of blood culture not containing adsorbing agents. We aimed to evaluate, under clinical conditions, the impact on BC yeast detection of systemic antifungal therapy (SAT). Patients (n = 125) experiencing candidemia at Grenoble University Hospital (France) were included in a 4-year retrospective study. The Plus Aerobic/F (Aerobic) and Plus Anaerobic/F (Anaerobic) bottles, which both contain adsorbing resins and the non-resin selective Mycosis IC/F (Mycosis) bottles, were compared using multivariate hierarchical models adjusted for clinical characteristics. The positivity rate (PR) is decreased in patients with SAT (p < 0.01), abdominal surgery (p = 0.01), and hemodialysis (p = 0.02). In all bottles, SAT reduces PR by a factor of 0.16 (95 % CI: [0.08; 0.32]) and increases the time to positivity (TTP) by a factor of 1.76 ([1.30; 2.40]; p < 0.01). In the presence of SAT, TTP is higher in non-resin bottles (Mycosis) than in resin bottles (RR = 1.76, [1.30; 2.40]); however, the TTP in nonresin and resin bottles remains comparable. Although discordant results are observed with and without SAT (37 and 58 % respectively), we showed that the presence of SAT decreases significantly the agreement rate by a factor of 0.29 (CI: [0.12; 0.68]). The combination of Anaerobic and Mycosis bottles allowed a 100 % positivity rate for C. glabrata. SAT significantly affects BC results. Because they provide additional and complementary results, this study supports the concomitant use of resin and selective bottles, especially in patients receiving SAT.

Frequency resolved cross-correlation between optical and terahertz pulses: application to ultrashort laser pulse characterization.

We have analyzed both theoretically and experimentally the spectrum of the optical pulses produced by the interaction of optical and THz pulses in a ZnTe crystal. Recorded as a function of the delay between the two pulses, the resulting spectrogram can be viewed as a frequency resolved cross-correlation between the optical and THz pulses making it possible to characterize the optical pulse.

Prospective Evaluation of a New Aspergillus IgG Enzyme Immunoassay Kit for Diagnosis of Chronic and Allergic Pulmonary Aspergillosis.

Anti-Aspergillus IgG antibodies are important biomarkers for the diagnosis of chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA). We compared the performance of a new commercial enzyme immunoassay (EIA) (Bordier Affinity Products) with that of the Bio-Rad and Virion\Serion EIAs. This assay is novel in its association of two recombinant antigens with somatic and metabolic antigens of Aspergillus fumigatus In a prospective multicenter study, 436 serum samples from 147 patients diagnosed with CPA (136 samples/104 patients) or ABPA (94 samples/43 patients) and from 205 controls (206 samples) were tested. We obtained sensitivities of 97%, 91.7%, and 86.1%, and specificities of 90.3%, 91.3%, and 81.5% for the Bordier, Bio-Rad, and Virion\Serion tests, respectively. The Bordier kit was more sensitive than the Bio-Rad kit (P < 0.01), which was itself more sensitive than the Virion\Serion kit (P = 0.04). The Bordier and Bio-Rad kits had similar specificity (P = 0.8), both higher than that of the Virion\Serion kit (P = 0.02). The area under the receiver operating characteristic (ROC) curves confirmed the superiority of the Bordier kit over the Bio-Rad and the Virion\Serion kits (0.977, 0.951, and 0.897, respectively; P < 0.01 for each comparison). In a subset analysis of 279 serum samples tested with the Bordier and Bio-Rad kits and an in-house immunoprecipitin assay (IPD), the Bordier kit had the highest sensitivity (97.7%), but the IPD tended to be more specific (71.2 and 84.7%, respectively; P = 0.10). The use of recombinant, somatic, and metabolic antigens in a single EIA improved the balance of sensitivity and specificity, resulting in an assay highly suitable for use in the diagnosis of chronic and allergic aspergillosis.

Prognostic value of sarcopenia in liver surgery.

Current knowledge indicates that malnutrition increases the rate of post-operative complications, particularly respiratory and infectious, after major surgery. Almost all liver surgery is performed in patients with cancer, a factor that increases the risk of malnutrition. The primary risk factors for post-operative complications are pre-operative hypo-albuminemia and a body mass index less than 20 kg/m(2). To improve the prediction of complications in these patients, some teams have suggested measurement of muscle thickness by computed tomography. Muscular mass can thus be quantified by measuring the total surface of the psoas muscle or the total surface of all muscles (i.e. external and internal oblique, transverse, psoas and paravertebral muscles) seen on an axial CT slice at L3. As well, data exist suggesting that sarcopenia is an independent predictive factor of post-operative morbidity and poor long-term survival after resection for cancer. Nonetheless, the literature on the subject is limited, there are no standardized definitions for sarcopenia, and the need of special software to calculate the surfaces limits its usefulness. Lastly, there are little if any data concerning the nutritional or pharmacologic means to treat sarcopenia. This update, based on a literature review, deals with the value and the prognostic impact of sarcopenia in surgery for liver tumors. The current definition of sarcopenia, validated internationally, the methods of measurement, and the consequences of sarcopenia on the outcome of liver resections are detailed in this review.

Cardiac safety of lacosamide: the non-clinical perspective.

OBJECTIVES: Lacosamide is indicated for the adjunctive treatment of partial-onset seizures in adult patients. Unlike other sodium channel-blocking antiepileptic drugs, lacosamide selectively enhances sodium channel slow inactivation. Potential effects of lacosamide on cardiac sodium channels and their cardiovascular consequences were comprehensively assessed. This manuscript presents the non-clinical cardiac safety profile of lacosamide. METHODS: Lacosamide was tested in vitro on sodium and L-type calcium currents from isolated human atrial myocytes and on hERG-mediated potassium currents from stably transfected HEK293 cells. Cardiac action potentials were recorded in guinea pig ventricular myocytes. In vivo, hemodynamic and ECG parameters were evaluated in anesthetized dogs and monkeys receiving acute cumulative intravenous doses of lacosamide. RESULTS: Following intravenous dosing with lacosamide, dose-dependent PR and QRS prolongation and ECG abnormalities (loss of P waves, atrioventricular and intraventricular blocks, junctional premature contractions) were observed in anesthetized dogs and monkeys. In vitro, lacosamide reduced human cardiac sodium currents in a concentration-, voltage- and state-dependent manner. Lacosamide reductions in Vmax in guinea pig myocytes were similar to lamotrigine and carbamazepine. Lacosamide showed no relevant inhibitory effects on hERG and L-type calcium channels and did not prolong QTc in vivo. CONCLUSIONS: ECG findings in anesthetized animals correlate well with in vitro sodium channel-related effects and are also consistent with those (PR prolongation, first-degree atrioventricular block) reported in healthy volunteers and patients with epilepsy. Both in vivo and in vitro effects were detected from exposure levels 1.5- to 2-fold above those achieved with the maximum-recommended human lacosamide dose (400 mg/day).

[Use of therapeutic hypothermia in sudden unexpected postnatal collapse]. / Malaise grave inopiné du nouveau-né à terme : une place possible pour l'hypothermie thérapeutique.

Sudden postnatal collapse of a full-term newborn is uncommon but may result in severe consequences: these include death; epilepsy; and motor, cognitive, or sensory impairment. Most authors suggest applying a therapeutic hypothermia approach when a previously healthy newborn develops moderate or severe encephalopathy after a sudden postnatal collapse occurring within the first hours or days after birth. However, this technique has still not been validated by randomized trials. Only a few cases have been reported in the literature. This article describes five apparently healthy newborns, born between 2007 and 2012, who suffered moderate to severe encephalopathy following a postnatal collapse on their first day of life. It describes their clinical history as well as their treatment and follow-up. The article focuses on the implementation of hypothermia in this indication and its limitations. Two newborns underwent classic therapeutic hypothermia, two others underwent temperature regulation (one at 34.5 °C, the other one for only 15 h because she quickly improved). One newborn, with severe pulmonary arterial hypertension, did not receive therapeutic hypothermia. Two newborns died (one had classic hypothermia and the other hypothermia at 34.5 °C), the outcome of the three survivors at three years, 18 months, and 15 months is good with only transient postural anomalies. Follow-up must be continued to assess their cognitive development and particularly their memorization processes. Additional research and centralization of the cases is required to evaluate the feasibility, safety, and benefits of therapeutic hypothermia in this situation.

Long-term results of functional endoscopic sinus surgery in children with chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is rare in children and has a major impact on Quality of Life (QoL). Functional endoscopic sinus surgery (FESS) has proven to be an effective treatment, but it is still unclear what long-term outcomes are in children with CRSwNP. The objective of this study was to assess long-term results of FESS in children with CRSwNP. METHODOLOGY: We performed a combined prospective and retrospective study. A QoL questionnaire was send to all children with CRSwNP who received FESS between the year 2000-2010. Almost half of these children also filled in this questionnaire preoperatively. RESULTS: Forty-four Children underwent FESS. From 18 patients, we also prospectively collected preoperative QoL questionnaires. The mean follow-up period was 4.0 years (+- 2.9). The mean age at surgery was 13 years (+-2.9). Of these children, 9 had CF and 10 children asthma. R-SOM scores showed a significant improvement both in general symptoms as well as several different domains when comparing pre- and postoperative questionnaires. Only 5 of 44 patients needed a subsequent intervention. In children with CF this was 3 of 9. CONCLUSION: This study demonstrates that long-term results of FESS in children with CRSwNP are good. QoL has improved significantly, especially in nasal symptoms, showing that FESS is a good treatment in children with CRSwNP. Furthermore, even children with CF show good results.