Combination of serum and peritoneal 1.3-beta-D-glucan can rule out intra-abdominal candidiasis in surgical critically ill patients: a multicenter prospective study.

BACKGROUND: Intra-abdominal candidiasis (IAC) is difficult to predict in critically ill patients with intra-abdominal infection, leading to the overuse of antifungal treatments. Serum and peritoneal 1.3-beta-D-glucan (sBDG and pBDG) have been proposed to confirm or invalidate the diagnosis of IAC, but clinical studies have reported inconsistent results, notably because of heterogeneous populations with a low IAC prevalence. This study aimed to identify a high-risk IAC population and evaluate pBDG and sBDG in diagnosing IAC. METHODS: This prospective multicenter noninterventional French study included consecutive critically ill patients undergoing abdominal surgery for abdominal sepsis. The primary objective was to establish the IAC prevalence. The secondary objective was to explore whether sBDG and pBDG could be used to diagnose IAC. Wako® beta-glucan test (WT, Fujifilm Wako Chemicals Europe, Neuss, Germany) was used for pBDG measurements. WT and Fungitell® beta-D-glucan assay (FA, Associate of Cape Cod, East Falmouth, USA) were used for sBDG measurements. RESULTS: Between 1 January 2020 and 31 December 2022, 199 patients were included. Patients were predominantly male (63%), with a median age of 66 [54-72] years. The IAC prevalence was 44% (87/199). The main IAC type was secondary peritonitis. Septic shock occurred in 63% of cases. After multivariate analysis, a nosocomial origin was associated with more IAC cases (P = 0.0399). The median pBDG level was significantly elevated in IAC (448 [107.5-1578.0] pg/ml) compared to non-IAC patients (133 [16.0-831.0] pg/ml), P = 0.0021. For a pBDG threshold of 45 pg/ml, the negative predictive value in assessing IAC was 82.3%. The median sBDG level with WT (n = 42) at day 1 was higher in IAC (5 [3.0-9.0] pg/ml) than in non-IAC patients (3 [3.0-3.0] pg/ml), P = 0.012. Similarly, median sBDG level with FA (n = 140) at day 1 was higher in IAC (104 [38.0-211.0] pg/ml) than in non-IAC patients (50 [23.0-141.0] pg/ml), P = 0.009. Combining a peritonitis score < 3, sBDG < 3.3 pg/ml (WT) and pBDG < 45 pg/ml (WT) yielded a negative predictive value of 100%. CONCLUSION: In critically ill patients with intra-abdominal infection requiring surgery, the IAC prevalence was 44%. Combining low sBDG and pBDG with a low peritonitis score effectively excluded IAC and could limit unnecessary antifungal agent exposure. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (ID number 03997929, first registered on June 24, 2019).

Accurate and Reliable Assessment of Heart Rate in Real-Life Clinical Settings Using an Imaging Photoplethysmography.

Remote photoplethysmography imaging (rPPGc) is a new method measuring essential parameters, such as heart rate (HR), which uses a video camera during teleconsultation. Our work aimed to evaluate the accuracy of such remote measurements compared with existing contact point measurement methods in real-life clinical settings. The prospective hospital-based study recruited 1045 patients who required a pulmonary function test. For each patient, measurements of HR using a standard electrocardiogram acquisition system (gold standard) were carried out concomitantly with the measurements made by the rPPGc system (Caducy v1.0.0) taken within a 60 s timeframe. Age, gender, and skin phototype were collected. We performed an intraclass coefficient correlation (ICC) and Bland-Altman plotting to determine the accuracy and precision of the rPPGc algorithm readings. We achieved measurement of HR using the two methods in 963 patients. The ICC measured at a 60 s timeframe, and when we compared the rPPGc with the gold standard, it had a 95% confidence interval (CI95) value of 0.886 [0.871:0.899]. In all, 94.6% (n = 911) patients showed promising results with a CI95 in Bland-Altman plotting. Fifty-two measurements were discordant, and further analysis established the method's accuracy at 96.2%. Our results described a good accuracy and correlation between the rPPGc system and the gold standard, thus paving the way for more precise care via telemedicine.

Innovative measurement of routine physiological variables (heart rate, respiratory rate and oxygen saturation) using a remote photoplethysmography imaging system: a prospective comparative trial protocol.

INTRODUCTION: Physiological signals are essential for assessing human health. The absence of a medical device to carry out these measurements remotely is one of the main limitations of telemedicine. Remote photoplethysmography imaging (rPPG) makes it possible to use a camera video to measure some of the most valuable physiological variables: heart rate (HR), respiratory rate (RR) and oxygen saturation (SpO2). Our objective was to evaluate the value of such remote measurements compared with existing contact point measurements techniques in real-life clinical settings. METHODS AND ANALYSIS: Prospective hospital-based study that will recruit 1045 patients who require a pulmonary function test. For each patient, measurements of HR, RR and SpO2, using a standard acquisition system, will be carried out concomitantly with the measurements made by the rPPG system. 30, 60 and 120 s time frames will be used to take measurements. Age, gender and skin phototype will also be collected. The intraclass coefficient correlation will be performed to determine the accuracy and precision of the rPPG algorithm readings. ETHICS AND DISSEMINATION: The study protocol has been approved by the French Agency for the Safety of Health Products (ANSM registration no. ID RCB 2020-A02428-31) and by a French ethics committee (CPP OUEST I-TOURS-2020T1-30 DM at 30 October 2020). Results will be published in peer-reviewed journals, at scientific conferences and through press releases. TRIAL REGISTRATION NUMBER: NCT04660318.

Dermatological opinions are imperative in ambulatory and acute care settings for pediatric skin disorders - HL-SkinPed.

BACKGROUND: Children with skin disorders usually receive care from a pediatrician, despite their limited training in this discipline. The advice of a dermatologist is frequently requested. OBJECTIVES: To estimate the degree of concordance in the diagnosis, treatment, advice, and recommended follow-up of skin disorders between pediatricians (in private practice or a pediatric emergency department [PED]) and a dermatologist. METHODS: This prospective study was carried out between June 25 and September 13, 2018. All patients younger than 18 years consulting at the PED of the University Children's Hospital or a pediatric private practice in Nancy, France, for a dermatological disorder (primary complaint) were included. Photographs, medical data, diagnosis, treatment, advice and follow-up recommended by the pediatricians were recorded in a dedicated anonymous medical file. Clinical data and photographs were subsequently reviewed by a dermatologist who provided a diagnosis. RESULTS: A total of 103 patients were included and 99 were analyzed: 53 from the PED and 46 from private practice (three patients were excluded because of unclear photographs and one was referred for maxillofacial advice). The median age was 4 years and there was a slight predominance of females (53.5%). The seven main diagnoses were: atopic dermatitis, insect bites, nonspecific viral rash, viral urticaria, hand-foot-and-mouth disease, impetigo, and contact dermatitis. The rate of agreement between the pediatricians and the dermatologist was 55% for diagnosis (73% for atopic dermatitis, 53% for insect bites, 33% for nonspecific viral rash), 40% for treatment, 54% for advice, and 58% for recommended follow-up. Reinterpretation by the dermatologist changed patient management in 15% of cases. CONCLUSIONS: The significant discordance between the pediatricians and the dermatologist suggests the need for a greater emphasis on dermatological disorders in medical training programs and for closer collaboration between disciplines for the benefit of younger patients.

Protocol of DEXPED trial: efficacy of intravenous dexamethasone, administered at the time of analgesic blocking of the lower limb, on postoperative pain in children: a randomised, placebo-controlled, double-blind trial.

INTRODUCTION: Dexamethasone is a drug used to prolong the postoperative analgesia in children after peripheral nerve blockade, although the dose usually used (0.2 mg/kg) has not been studied yet. This study is a monocentric, prospective, randomised, placebo-controlled, double-blinded study in a university hospital in France. The primary objective of the study is to evaluate the efficacy of 0.2 mg/kg intravenous dexamethasone on early postoperative pain in children aged 6-15 years, who require a lower limb peripheral nerve block following general anaesthesia. METHODS AND ANALYSIS: Eighty children, aged 6-15 years, undergoing surgery for which peripheral nerve lower limb blockade with ropivacaine following general anaesthesia are included. The inclusion criteria are: children aged 6-15 years, with American Society of Anaesthesiologists physical status I or II and scheduled for surgery requiring a peripheral block of the lower limb for analgesic purposes, with a preoperative anaesthetic evaluation between 90 and 2 days before the surgery, with informed consent from legal representatives. General anaesthesia is performed. The patient receives, according to his group, either 0.2 mg/kg of dexamethasone intravenously at the start of anaesthetic induction or the same volume of placebo. Then, the peripheral block of the lower limb is performed with ropivacaine. The primary outcome is the total doses of opioid administered (in mg/kg of morphine equivalent) within 24 hours postoperatively. The secondary objectives are the evaluation of the effect of a single-dose intravenous dexamethasone at the time of anaesthetic induction, on the following parameters: onset of postoperative pain, duration of motor block, postoperative nausea and vomiting within 24 hours. ETHICS AND DISSEMINATION: This study is conducted according to the principles of the Declaration of Helsinki and has been approved by the French national ethics committee and the National Drug Safety Agency. Findings of this study will be widely disseminated through conference presentations, reports, factsheets and academic publications. TRIAL REGISTRATION NUMBER: NCT03618173.

Flavaglines as potent anticancer and cytoprotective agents.

Flavaglines represent a family of plant natural products that display potent anticancer, cardioprotective, and neuroprotective activities. Novel flavagline derivatives were synthesized and examined for their cytotoxicity on a panel of human cancer cell lines, their cardioprotection against doxorubicin-induced apoptosis in cardiomyocytes, and their neuroprotection in culture models of Parkinson's disease and cisplatin-induced neurotoxicity. The structural requirements of flavaglines for cardio- and neuroprotection were for the first time unraveled and appeared to be slightly different from those for cytotoxicity on cancer cells. We provide also the first evidence that flavaglines may alleviate cisplatin-induced neurotoxicity, suggesting a prophylactic potential of these compounds to prevent this frequently encountered adverse effect of cancer chemotherapies.

Flavaglines alleviate doxorubicin cardiotoxicity: implication of Hsp27.

BACKGROUND: Despite its effectiveness in the treatment of various cancers, the use of doxorubicin is limited by a potentially fatal cardiomyopathy. Prevention of this cardiotoxicity remains a critical issue in clinical oncology. We hypothesized that flavaglines, a family of natural compounds that display potent neuroprotective effects, may also alleviate doxorubicin-induced cardiotoxicity. METHODOLOGY/PRINCIPAL FINDINGS: Our in vitro data established that a pretreatment with flavaglines significantly increased viability of doxorubicin-injured H9c2 cardiomyocytes as demonstrated by annexin V, TUNEL and active caspase-3 assays. We demonstrated also that phosphorylation of the small heat shock protein Hsp27 is involved in the mechanism by which flavaglines display their cardioprotective effect. Furthermore, knocking-down Hsp27 in H9c2 cardiomyocytes completely reversed this cardioprotection. Administration of our lead compound (FL3) to mice attenuated cardiomyocyte apoptosis and cardiac fibrosis, as reflected by a 50% decrease of mortality. CONCLUSIONS/SIGNIFICANCE: These results suggest a prophylactic potential of flavaglines to prevent doxorubicin-induced cardiac toxicity.

Synthetic analogue of rocaglaol displays a potent and selective cytotoxicity in cancer cells: involvement of apoptosis inducing factor and caspase-12.

Flavaglines constitute a family of natural anticancer compounds. We present here 3 (FL3), the first synthetic flavagline that inhibits cell proliferation and viability (IC(50) approximately 1 nM) at lower doses than did the parent compound, racemic rocaglaol. Compound 3 enhanced doxorubicin cytotoxicity in HepG2 cells and retained its potency against adriamycin-resistant cell lines without inducing cardiomyocyte toxicity. Compound 3 induced apoptosis of HL60 and Hela cells by triggering the translocation of Apoptosis Inducing Factor (AIF) and caspase-12 to the nucleus. A fluorescent conjugate of 3 accumulated in endoplasmic reticulum (ER), suggesting that flavaglines bind to their target in the ER, where it triggers a cascade of events that leads to the translocation of AIF and caspase-12 to the nucleus and probably inhibition of eIF4A. Our studies highlight structural features critical to their antineoplastic potential and suggest that these compounds would retain their activity in cells refractory to caspase activation.

Co-cultures of human coronary smooth muscle cells and dimethyl sulfoxide-differentiated HL60 cells upregulate ProMMP9 activity and promote mobility-modulation by reactive oxygen species.

Vascular cells and leukocytes, involved in the development of atherosclerosis, produce cytokines and/or reactive oxygen species (ROS) and matrix metalloproteinases (MMPs) implicated in cell mobility. We investigated by co-culture experiments the effects of human coronary smooth muscle cells (HCSMC) on MMPs characteristics and mobility of neutrophil-like dimethyl sulfoxide-differentiated HL60 cells (not equal HL60). The effects of superoxide dismutase (SOD) and catalase were also analyzed. All the studied MMP2 characteristics remained unchanged. HCSMC stimulated MMP9 protein level, activity and mobility of not equal HL60 cells and expressed and secreted a variety of cytokines implicated in atherosclerosis. SOD and catalase increased MMP9 expression, protein level and activity of not equal HL60, but migration of not equal HL60 cells was only decreased by catalase, demonstrating that ROS are more efficient in modulating MMP9 activity of not equal HL60 than their mobility. Finally, HCSMC being able to stimulate not equal HL60, their co-cultures may represent an in vitro approach to study cellular interactions occurring in vivo during atherosclerosis.