Impact of emergency physician performed ultrasound in the evaluation of adult patients with acute abdominal pain: a prospective randomized bicentric trial.

BACKGROUND: Abdominal pain is common in patients visiting the emergency department (ED). The aim of this study was to assess the diagnostic contribution of point-of-care ultrasound (POCUS) in patients presenting to the ED with acute abdominal pain. METHODS: We designed an interventional randomized, controlled, open label, parallel-group, trial in two French EDs. We included adult patients presenting to the ED with acute abdominal pain. Exclusion criteria were a documented end-of-life, an immediate need of life-support therapy and pregnant or breast-feeding women. Patients were randomized in the experimental group (i.e., workup including POCUS) or control group (usual care). The primary objective of the study was to assess the added value of POCUS on diagnostic pathway in the ED, according to the diagnostic established a posteriori by an adjudication committee. The primary endpoint was the proportion of exact preliminary diagnosis between the 2 groups. The preliminary diagnosis made after clinical examination and biological results with POCUS (intervention arm) or without POCUS (usual care) was considered exact if it was similar to the adjudication committee diagnosis. RESULTS: Between June 2021 11th and June 2022 23th, 256 patients were randomized, but five were not included in the primary analysis, leaving 125 patients in the POCUS group and 126 patients in the usual care group (130 women and 121 men, median [Q1-Q3] age: 42 [30;57]). There was no difference for exact diagnosis between the two groups (POCUS 70/125, 56% versus control 78/126 (62%), RD 1.23 [95% CI 0.74-2.04]). There was no difference in the accuracy for the diagnosis of non-specific abdominal pain nor number of biological or radiological exams. Diagnostic delays and length of stay in the ED were also similar. CONCLUSIONS: In this trial, systematic POCUS did not improve the rate of diagnostic accuracy in unselected patients presenting to the ED with acute abdominal pain. However, as it was a safe procedure, further research should focus on patients with suspected etiologies where POCUS is particularly useful. TRIAL REGISTRATION:  This trial was registered on ClinicalTrials.gov on 2022/07/20 ( https://clinicaltrials.gov/study/NCT04912206?id=NCT04912206&rank=1 ) (NCT04912206).

Immediate vs. culture-initiated antibiotic therapy in suspected non-severe ventilator-associated pneumonia: a before-after study (DELAVAP).

BACKGROUND: Ventilator-associated pneumonia (VAP) is the leading nosocomial infection in critical care and is associated with adverse outcomes. When VAP is suspected, starting antibiotic therapy (AT) immediately after pulmonary sampling may expose uninfected patients to unnecessary treatment, whereas waiting for bacteriological confirmation may delay AT in infected patients. As no robust data exist to choose between these strategies, the decision must balance the pre-test diagnostic probability, clinical severity, and risk of antimicrobial resistance. The objective of this study in patients with suspected non-severe VAP was to compare immediate AT started after sampling to conservative AT upon receipt of positive microbiological results. The outcomes were antibiotic sparing, AT suitability, and patient outcomes. METHODS: This single-center, before-after study included consecutive patients who underwent distal respiratory sampling for a first suspected non-severe VAP episode (no shock requiring vasopressor therapy or severe acute respiratory distress syndrome). AT was started immediately after sampling in 2019 and upon culture positivity in 2022 (conservative strategy). The primary outcome was the number of days alive without AT by day 28. The secondary outcomes were mechanical ventilation duration, day-28 mortality, and AT suitability (active necessary AT or spared AT). RESULTS: The immediate and conservative strategies were applied in 44 and 43 patients, respectively. Conservative and immediate AT were associated with similar days alive without AT (median [interquartile range], 18.0 [0-21.0] vs. 16.0 [0-20.0], p = 0.50) and without broad-spectrum AT (p = 0.53) by day 28. AT was more often suitable in the conservative group (88.4% vs. 63.6%, p = 0.01), in which 27.9% of patients received no AT at all. No significant differences were found for mechanical ventilation duration (median [95%CI], 9.0 [6-19] vs. 9.0 [6-24] days, p = 0.65) or day-28 mortality (hazard ratio [95%CI], 0.85 [0.4-2.0], p = 0.71). CONCLUSION: In patients with suspected non-severe VAP, waiting for microbiological confirmation was not associated with antibiotic sparing, compared to immediate AT. This result may be ascribable to low statistical power. AT suitability was better with the conservative strategy. None of the safety outcomes differed between groups. These findings would seem to allow a large, randomized trial comparing immediate and conservative AT strategies.

Covid-19-associated pulmonary aspergillosis in mechanically ventilated patients: incidence and outcome in a French multicenter observational cohort (APICOVID).

BACKGROUND: Recent studies identified coronavirus disease 2019 (COVID-19) as a risk factor for invasive pulmonary aspergillosis (IPA) but produced conflicting data on IPA incidence and impact on patient outcomes. We aimed to determine the incidence and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) in mechanically ventilated patients. METHODS: We performed a multicenter retrospective observational cohort study in consecutive adults admitted to 15 French intensive care units (ICUs) in 2020 for COVID-19 requiring mechanical ventilation. CAPA was diagnosed and graded according to 2020 ECMM/ISHAM consensus criteria. The primary objective was to determine the incidence of proven/probable CAPA, and the secondary objectives were to identify risk factors for proven/probable CAPA and to assess associations between proven/probable CAPA and patient outcomes. RESULTS: The 708 included patients (522 [73.7%] men) had a mean age of 65.2 ± 10.8 years, a median mechanical ventilation duration of 15.0 [8.0-27.0] days, and a day-90 mortality rate of 28.5%. Underlying immunosuppression was present in 113 (16.0%) patients. Corticosteroids were used in 348 (63.1%) patients. Criteria for probable CAPA were met by 18 (2.5%) patients; no patient had histologically proven CAPA. Older age was the only factor significantly associated with probable CAPA (hazard ratio [HR], 1.04; 95% CI 1.00-1.09; P = 0.04). Probable CAPA was associated with significantly higher day-90 mortality (HR, 2.07; 95% CI 1.32-3.25; P = 0.001) but not with longer mechanical ventilation or ICU length of stay. CONCLUSION: Probable CAPA is a rare but serious complication of severe COVID-19 requiring mechanical ventilation and is associated with higher day-90 mortality.

Impact of dupilumab on patch test results and allergic contact dermatitis: A prospective multicenter study.

BACKGROUND: Limited and conflicting data have been reported on the impact of dupilumab (DUPI) on patch test (PT) results and its efficacy against allergic contact dermatitis (ACD). OBJECTIVE: This study was undertaken to analyze PT reactivities and relevance during treatment with DUPI to determine whether they could detect ACD in patients with uncontrolled or worsened atopic dermatitis (AD) who were receiving this agent. METHODS: This prospective, multicenter study examined 76 DUPI-treated patients who had undergone PTs. The relevant information was collected during 3 visits. RESULTS: Overall, 36 patients (47%) had ≥1 positive PT reaction, and 142 PT results were positive. Twenty-three patients (30%) had ≥1 positive and clinically relevant PT result. Five of them had clinical eczema improvement after allergen avoidance. We compared the PT results of 36 patients before and during DUPI therapy, representing 1230 paired PT allergens, of which 1022 were the same, 34 were positive, 44 were lost, and 130 were uninterpretable. LIMITATIONS: Because the number of patients included remains limited, our findings should be confirmed with a larger sample. CONCLUSION: Our results confirmed the usefulness of PTs for patients receiving DUPI, with good PT reproducibility. We suggest that all DUPI-treated patients with AD developing partial responses or experiencing symptom worsening should undergo PTs to look for contact sensitization.

Complications and risk factors on midline catheters' follow-up about non-ICU patients: study protocol for a multicentre observational study (the midDATA study).

INTRODUCTION: The midline catheter (MC) is an increasingly popular device used commonly for patients with difficult venous access or those who require infusion for more than 6 days. Little is known about complications such as infection, thrombosis or occlusion for inpatient and home care patient. This protocol presents the follow-up of non-intensive care unit patients with an MC. The aim is to identify complications and search for risk factors associated with these complications. METHOD AND ANALYSIS: A prospective observational design is used for the follow-up of 2000 patients from 13 centres in France. Each practitioner (inserting clinician, anaesthetist nurse, hospital nurse and home nurse) will fill out a logbook to report each care made (eg, number of saline flushes, dress maintenance) on the MC and if any complications occurred. The incidence of complications (ie, infections, thrombosis or occlusions) will be expressed by the total number of events per 1000 catheter days. The period of recruitment began in December 2019 for a duration of 2 years. An extension of the inclusion period of 1 year was obtained. ETHICS AND DISSEMINATION: This study received the approval of the Committee for the Protection of Persons of Nord Ouest IV (No EudraCT/ID-RCB : 2019-A02406-51). It was registered at clinical trials (NCT04131088). It is planned to communicate results at conferences and in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04131088.

A comparative study of three-dimensional cone-beam CT sialography and MR sialography for the detection of non-tumorous salivary pathologies.

BACKGROUND: Imaging of the salivary ductal system is relevant prior to an endoscopic or a surgical procedure. Various imaging modalities can be used for this purpose. The aim of this study was to compare the diagnostic capability of three-dimensional (3D)-cone-beam computed tomography (CBCT) sialography versus magnetic resonance (MR) sialography in non-tumorous salivary pathologies. METHODS: This prospective, monocenter, pilot study compared both imaging modalities in 46 patients (mean age 50.1 ± 14.9 years) referred for salivary symptoms. The analyses were performed by two independent radiologists and referred to identification of a salivary disease including sialolithiasis, stenosis, or dilatation (primary endpoint). The location and size of an abnormality, the last branch of division of the salivary duct that can be visualized, potential complications, and exposure parameters were also collected (secondary endpoints). RESULTS: Salivary symptoms involved both the submandibular (60.9%) and parotid (39.1%) glands. Sialolithiasis, dilatations, and stenosis were observed in 24, 25, and 9 patients, respectively, with no statistical differences observed between the two imaging modalities in terms of lesion identification (p1 = 0.66, p2 = 0.63, and p3 = 0.24, respectively). The inter-observer agreement was perfect (> 0.90) for lesion identification. MR sialography outperformed 3D-CBCT sialography for visualization of salivary stones and dilatations, as evidenced by higher positive percent agreement (sensitivity) of 0.90 [95% CI 0.70-0.98] vs. 0.82 [95% CI 0.61-0.93], and 0.84 [95% CI 0.62-0.94] vs. 0.70 [95% CI 0.49-0.84], respectively. For the identification of stenosis, the same low positive percent agreement was obtained with both procedures (0.20 [95% CI 0.01-0.62]). There was a good concordance for the location of a stone (Kappa coefficient of 0.62). Catheterization failure was observed in two patients by 3D-CBCT sialography. CONCLUSIONS: Both imaging procedures warrant being part of the diagnostic arsenal of non-tumorous salivary pathologies. However, MR sialography may be more effective than 3D-CBCT sialography for the identification of sialolithiasis and ductal dilatations. TRIAL REGISTRATION: NCT02883140.

Association between radiographic and functional outcome in vertebral osteomyelitis SPONDIMMO, a 6-month prospective multicenter cohort.

OBJECTIVES: This study aimed to describe radiographic and functional evolution over 6 months in a large cohort of VO patients. METHODS: We prospectively recruited patients with VO from 2016 to 2019 in 11 French centers. X-rays were performed at baseline, 3 months, and 6 months to assess progression using structural and static criteria. Functional impairment was evaluated using the Oswestry Disability Index (ODI) at 3 months and 6 months. RESULTS: Two hundred and twenty-two patients were included. Mean age was 67.8±14 years, mostly men (67.6%). After 3 months, there was a significant increase in vertebral fusion (16.4% vs 52.7%), destruction of vertebral bodies (10.1% vs 22.8%), and of all the static features (frontal angulation (15.2% vs 24.4%), segmental (34.6% vs 56%) and regional (24.5% vs 41%) kyphosis). From 3 to 6 months, among the different X-ray abnormalities, only the complete fusion progressed significantly (16.6% vs 27.2%). Median ODI showed significant improvement from 3 to 6 months (24, IQR [11.5-38] vs 16, IQR [6-34]). At 6 months, 14.1% of the patients had a severe disability, 2% a major disability. The persistence of vertebral destruction at 6 months was associated with a higher ODI (16, IQR [7.5-30.5] vs 27, IQR [11.5-44.5]). No differences in radiological progression were observed with immobilization using a rigid brace. CONCLUSION: Our study demonstrates structural and static radiographic progression after 3 months. Only the complete fusion progressed over the long-term. Functional impairment was associated with persistence of vertebral destruction.

A comparative study of three-dimensional cone beam computed tomographic sialography and ultrasonography in the detection of non-tumoral salivary duct diseases.

OBJECTIVES: To compare the overall diagnostic outcomes of 3D-CBCT sialography and ultrasonography (US) in the detection of sialolithiasis, ductal dilatation, and ductal stenosis. METHODS: This retrospective monocentric study compared the two imaging modalities carried out in the same patients referred for salivary symptoms of the parotid and submandibular glands. The primary endpoint was the capacity of the imaging procedure to diagnose a lesion. The secondary objectives were the detection rates according to the type of lesion, analysis of the causes of failure, and the parameters of radiation exposure and safety (for 3D-CBCT sialography). RESULTS: Of the 236 patients who received a 3D-CBCT sialography in our institution, 157 were ultimately included in the per-protocol analysis. 3D-CBCT sialography allowed detection of ductal lesions in 113 patients versus 86 with US. The two imaging modalities yielded congruent interpretations in 104 out of 157 subjects (66.2%). Higher sensitivity and negative predictive value were observed with 3D-CBCT sialography compared with US, irrespective of the lesions studied: 0.85 vs 0.65 and 0.70 vs 0.44, respectively. Regarding the sialolithiasis, both 3D-CBCT sialography and US allowed identification of lesions with high sensitivity and negative predictive value (0.80 vs 0.75 and 0.88 vs 0.78, respectively). CONCLUSIONS: US remains the first-line examination for exploration of the salivary lesions. 3D-CBCT sialography is an alternative in case of inconclusive US, and prior to any endoscopic procedure.

Association of early dexamethasone therapy with mortality in critically Ill COVID-19 patients: a French multicenter study.

BACKGROUND: Dexamethasone is recommended for COVID-19 patients who require oxygen therapy. However, its effectiveness in reducing mortality and intubation, and its safety, remain debated. We aimed to investigate whether dexamethasone reduces day-28 mortality in unselected patients with critical COVID-19. METHODS: We performed an observational cohort study in consecutive COVID-19 patients admitted to any of 13 French intensive care units (ICUs) in 2020. The primary objective was to determine whether early dexamethasone therapy was associated with day-28 mortality and the secondary objectives were to assess whether early dexamethasone decreased intubation requirements and to collect adverse events. RESULTS: Of 1058 included patients, 611 (57.75%) received early dexamethasone (early dexamethasone group), 358 (33.83%) did not receive any steroids (no steroids group), and 89 (8.41%) received late dexamethasone or other steroids. Day-28 mortality was similar between the early dexamethasone and the no steroids groups (15.06% and 14.25%, respectively; P = 0.59). Factors associated with day-28 mortality were older age (adjusted hazard ratio [aHR], 1.06; 1.04-1.09; P < 0.001), worse SOFA score (aHR, 1.13; 1.06-1.20; P < 0.001), and immunocompromised status (aHR, 1.59; 1.01-2.50; P = 0.043). Early dexamethasone was associated with fewer intubations (48.55% vs. 61.49%, P < 0.001) and more ventilator-free days by day 28 (22 [2-28] vs. 17 [1-28] days, P = 0.003), compared to no steroids. Ventilator-associated pneumonia (VAP) was more common with early dexamethasone (HR, 1.29 [1.01-1.63], P = 0.04) than with no steroids, whereas no differences were noted for bloodstream infection, fungal infection, or gastrointestinal bleeding. CONCLUSIONS: Early dexamethasone in critically ill COVID-19 patients was not associated with lower day-28 mortality. However, early dexamethasone was associated with lower intubation needs and more ventilator-free days by day 28. In patients treated with invasive mechanical ventilation, early dexamethasone was associated with a higher risk of VAP.

Outcomes of mild-to-moderate postresuscitation shock after non-shockable cardiac arrest and association with temperature management: a post hoc analysis of HYPERION trial data.

BACKGROUND: Outcomes of postresuscitation shock after cardiac arrest can be affected by targeted temperature management (TTM). A post hoc analysis of the "TTM1 trial" suggested higher mortality with hypothermia at 33 °C. We performed a post hoc analysis of HYPERION trial data to assess potential associations linking postresuscitation shock after non-shockable cardiac arrest to hypothermia at 33 °C on favourable functional outcome. METHODS: We divided the patients into groups with vs. without postresuscitation (defined as the need for vasoactive drugs) shock then assessed the proportion of patients with a favourable functional outcome (day-90 Cerebral Performance Category [CPC] 1 or 2) after hypothermia (33 °C) vs. controlled normothermia (37 °C) in each group. Patients with norepinephrine or epinephrine > 1 µg/kg/min were not included. RESULTS: Of the 581 patients included in 25 ICUs in France and who did not withdraw consent, 339 had a postresuscitation shock and 242 did not. In the postresuscitation-shock group, 159 received hypothermia, including 14 with a day-90 CPC of 1-2, and 180 normothermia, including 10 with a day-90 CPC of 1-2 (8.81% vs. 5.56%, respectively; P = 0.24). After adjustment, the proportion of patients with CPC 1-2 also did not differ significantly between the hypothermia and normothermia groups (adjusted hazards ratio, 1.99; 95% confidence interval, 0.72-5.50; P = 0.18). Day-90 mortality was comparable in these two groups (83% vs. 86%, respectively; P = 0.43). CONCLUSIONS: After non-shockable cardiac arrest, mild-to-moderate postresuscitation shock at intensive-care-unit admission did not seem associated with day-90 functional outcome or survival. Therapeutic hypothermia at 33 °C was not associated with worse outcomes compared to controlled normothermia in patients with postresuscitation shock. Trial registration ClinicalTrials.gov, NCT01994772.

Functional and Survival Outcomes of Patients following the Harrington Procedure for Complex Acetabular Metastatic Lesions.

BACKGROUND: The Harrington surgical technique makes it possible to manage complex, extensive bone lesions using pins and cement to consolidate bone for acetabular cup positioning. However, it may be associated with a high reoperation rate, and the functional results of this surgery are not precisely described in the literature. METHODS: In a monocentric retrospective study including all patients operated on using the Harrington procedure associated with THA between 2005 and 2020, we aimed to assess preoperative and postoperative function, reoperation-free survival, and overall survival. RESULTS: Functional improvement was significant for Parker scores (preoperative: 3.6 ± 2.0; 6-month follow-up: 6.6 ± 3.2; 12-month follow-up: 7.6 ± 2.1) and Musculoskeletal Tumor Society (MSTS) scores (preoperative: 31.1 ± 16.2%; 6-month follow-up: 67.7 ± 30.6%; 12-month follow-up: 82.4 ± 24.0%). Of the 21 patients included, the reoperation-free survival rate was 76.1% [CI 95%: 58.1-99.7] at six and twelve months, with the main complications being pin migration (50.0%) and infection (25%). The patient overall survival rate was 76.2% [95% CI: 59.9-96.7] at six months and 61.9% [95% CI: 59.9-96.7] at 12 months. DISCUSSION: These results underlined significant functional improvements following a conventional Harrington procedure, with acceptable reoperation rates.

Impact of early nutrition route in patients receiving extracorporeal membrane oxygenation: A retrospective cohort study.

BACKGROUND: Early nutrition management in patients receiving extracorporeal membrane oxygenation (ECMO) remains controversial. Despite its potentially beneficial effect, enteral nutrition (EN) could be associated with gastrointestinal (GI) complications. Total daily energy requirements remain difficult to achieve with ECMO support. Analysis of nutrition practices could improve nutrition management of this particular population. METHODS: A monocentric retrospective study of patients requiring ECMO in a cardiac surgery intensive care unit (ICU) between 2010 and 2014 with follow-up ≥6 days. Nutrition support was monitored daily until ECMO weaning. We compared patients exposed (EN group, n = 49) and unexposed (No EN group (NEN), n = 63) with EN, as well as the energy and protein intakes within 4 days after initiation of ECMO. Vital status and nosocomial infections were followed up until ICU discharge. Primary outcome was the incidence of GI intolerance and risk-factor identification. Secondary outcomes included impact of nutrition inadequacy and clinical outcome. RESULTS: A total 112 patients were analyzed, representing 969 nutrition days. Median ratio of energy and protein prescribed/required daily was 81% (58-113) and 56% (36-86), respectively. GI intolerance was experienced by 53% (26 of 49) of patients in the EN group and was only associated with ECMO duration (odds ratio, 1.14: 95% CI, 1.00-1.31; P = .05). Low-energy and protein days were not associated with clinical outcomes such as nosocomial infections. CONCLUSION: EN is associated with almost 50% GI intolerance without clinical benefit for patients receiving ECMO. Adequacy in energy and protein amounts did not affect clinical outcome.

Spine immobilization and neurological outcome in vertebral osteomyelitis SPONDIMMO, a prospective multicentric cohort.

OBJECTIVE: The aim of our study was to describe spine immobilization in a multicentric cohort of vertebral osteomyelitis (VO), and evaluate its association with neurological complications during follow-up. METHODS: We prospectively included patients from 2016 to 2019 in 11 centers. Immobilization, imaging, and neurological findings were specifically analyzed during a 6-month follow-up period. RESULTS: 250 patients were included, mostly men (67.2%, n=168). Mean age was 66.7±15 years. Diagnosis delay was 25 days. The lumbo-sacral spine was most frequently involved (56.4%). At diagnosis, 25.6% patients (n=64) had minor neurological signs and 9.2% (n=23) had major ones. Rigid bracing was prescribed for 63.5% (n=162) of patients, for a median of 6 weeks, with variability between centers (P<0.001). The presence of epidural inflammation and abscess on imaging was associated with higher rates of rigid bracing prescription (OR 2.33, P=0.01). Frailness and endocarditis were negatively associated with rigid bracing prescription (OR 0.65, P<0.01, and OR 0.42, P<0.05, respectively). During follow up, new minor or major neurological complications occurred in respectively 9.2% (n=23) and 6.8% (n=17) of patients, with similar distribution between immobilized and non-immobilized patients. CONCLUSION: Spine immobilization prescription during VO remains heterogeneous and seems associated inflammatory lesions on imaging but negatively associated with frailness and presence of endocarditis. Neurological complications can occur despite rigid bracing. Our data suggest that in absence of any factor associated with neurological complication spine bracing might not be systematically indicated. We suggest that spine immobilization should be discussed for each patient after carefully evaluating their clinical signs and imaging findings.

Preterm Birth and Small-for-Gestational Age Neonates among Prepregnancy Underweight Women: A Case-Controlled Study.

The aim of our study was to investigate whether prepregnancy underweight body mass index (BMI) is associated with preterm birth (PTB) and small-for-gestational age (SGA). This retrospective case-control study included 814 women with live singleton fetuses in vertex presentation that gave birth between January 2016 and November 2016 in two tertiary care hospitals. The study group (n = 407) comprised all women whose prepregnancy BMI was underweight (<18.5 kg/m2) and who delivered during the study period. A control group (n = 407) was established with women whose prepregnancy BMI was normal (18.5-24.9 kg/m2) by matching age and parity. Univariate and multivariate analyses were performed to compare PTB and SGA associated with prepregnancy underweight BMI. Compared with the control group, the study group had higher rates of overall PTB (10.1% vs. 5.7%, p = 0.02), iatrogenic PTB (4.2% vs. 1.5%, p = 0.02), and SGA (22.1% vs. 11.1%, p < 0.001). In a multivariable analysis, prepregnancy underweight BMI was associated with PTB (aOR 2.32, 95% CI 1.12-4.81) and with SGA (aOR 2.38, 95% CI 1.58-3.58). In singleton pregnancies, women's prepregnancy underweight compared with normal BMI was associated with an increase in PTB and in SGA neonates. Identifying this specific high-risk group is pragmatic and practical for all physicians, and they should be aware about perinatal outcome among underweight women.

Comparison of four channelled videolaryngoscopes to Macintosh laryngoscope for simulated intubation of critically ill patients: the randomized MACMAN2 trial.

BACKGROUND: Videolaryngoscopes with an operating channel may improve the intubation success rate in critically ill patients. We aimed to compare four channelled videolaryngoscopes to the Macintosh laryngoscope used for intubation of a high-fidelity simulation mannikin, in a scenario that simulated critical illness due to acute respiratory failure. RESULTS: Of the 79 residents who participated, 54 were considered inexperienced with orotracheal intubation. Each participant used all five devices in random order. The first-pass success rate was 97.5% [95% CI 91.1-99.7] for Airtraq™, KingVision™, and Pentax AWS200™, 92.4% [95% CI 84.2-97.2] for VividTrac VT-A100™, and 70.9% [95% CI 59.6-80.6] for direct Macintosh laryngoscopy. The first-pass success rate was significantly lower with direct Macintosh laryngoscopy than with the videolaryngoscopes (p < 0.0001 for Airtraq™, KingVision™, Pentax AWS200™, and VividTrac VT-A100™). CONCLUSION: The Airtraq™, KingVision™, and Pentax AWS200™ channelled videolaryngoscopes produced high first-pass success rates with a lower boundary of the 95% CI above 90%. A multicentre, randomised controlled clinical study comparing channelled videolaryngoscopy to direct laryngoscopy should include one of these three videolaryngoscopes.

Oxygen reserve index for non-invasive early hypoxemia detection during endotracheal intubation in intensive care: the prospective observational NESOI study.

BACKGROUND: To evaluate the ability of the oxygen reserve index (ORI) to predict the occurrence of mild hypoxemia (defined as SpO2 < 97%) during endotracheal intubation (ETI) of patients in the intensive care unit (ICU). METHODS: This observational single-centre study included patients without hypoxemia (defined as SpO2/FiO2 > 214) who required ETI in the ICU. Patients were followed during preoxygenation and ETI then until hospital discharge and/or day 28. We recorded cases of mild hypoxemia, moderate (SpO2 < 90%) and severe (SpO2 < 80%) hypoxemia, moderate arterial hypotension (systolic arterial pressure < 90 mmHg), oesophageal intubation, aspiration, cardiac arrest, and death. RESULTS: Between January 2019 and July 2020, 56 patients were included prospectively and 51 patients were analysed. Twenty patients had mild hypoxemia between the end of preoxygenation and the end of intubation; in 10 of these patients, the decrease in SpO2 below 97% was preceded by an ORI < 0.4, the median time difference being 81 s [interquartile range, 34-146]. By multivariable analysis, a higher ORI (by 0.1 increase) value during preoxygenation was associated with absence of hypoxemia (odds ratio, 0.76; 95% confidence interval, 0.61;0.95; P = 0.0141). CONCLUSION: In non-hypoxemic patients, the 81-s [34-146] median time between the ORI decrease below 0.4 and the SpO2 decrease below 97% during apnoea may allow preventive action. A higher ORI value during preoxygenation was independently protective against hypoxemia. Whether these findings also apply to hypoxemic patients, and the clinical impact of a preoxygenation strategy based on ORI monitoring, remain to be evaluated prospectively. Trial Registration ClinicalTrial.gov, #NCT03600181.

Etiological Work-Up for Adults with Bronchiectasis: A Predictive Diagnostic Score for Primary Ciliary Dyskinesia and Cystic Fibrosis.

BACKGROUND: etiological investigations are not done for all adult patients with bronchiectasis because of the availability and interpretation of tests. The aim of the study was to elaborate a score to identify patients at high risk of having cystic fibrosis or primary ciliary dyskinesia (CF/PCD), which require appropriate management. METHODS: diagnostic work-ups were carried out on a French monocenter cohort, and results were subjected to logistic-regression analyses to identify the independent factors associated with CF/PCD diagnosis and, thereby, elaborate a score to validate in a second cohort. RESULTS: among 188 patients, 158 had no obvious diagnosis and were enrolled in the algorithm-construction group. In multivariate analyses, age at symptom onset (8.69 (2.10-35.99); p = 0.003), chronic ENT symptoms or diagnosed sinusitis (10.53 (1.26-87.57); p = 0.03), digestive symptoms or situs inversus (5.10 (1.23-21.14); p = 0.025), and Pseudomonas. aeruginosa and/or Staphylococcus aureus isolated from sputum (11.13 (1.34-92.21); p = 0.02) are associated with CF or PCD. Receiver operating characteristics curve analysis, using a validation group of 167 patients with bronchiectasis, confirmed the score's performance with AUC 0.92 (95% CI: 0.84-0.98). CONCLUSIONS: a clinical score may help identify adult patients with bronchiectasis at higher risk of having CF or PCD.

Pharmacokinetics and Safety of XAV-19, a Swine Glyco-humanized Polyclonal Anti-SARS-CoV-2 Antibody, for COVID-19-Related Moderate Pneumonia: a Randomized, Double-Blind, Placebo-Controlled, Phase IIa Study.

We assessed the pharmacokinetics and safety of XAV-19, a swine glyco-humanized polyclonal antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in coronavirus disease 2019 (COVID-19)-related moderate pneumonia. The objective was to evaluate the optimal dose and safety of XAV-19 during this first administration to patients with COVID-19-related moderate pneumonia. In this phase IIa trial, adults with COVID-19-related moderate pneumonia with a duration of ≤10 days were randomized to receive an infusion of XAV-19 at 0.5 mg/kg of body weight at day 1 and day 5 (group 1), 2 mg/kg at day 1 and day 5 (group 2), or 2 mg/kg at day 1 (group 3) or placebo. Eighteen patients (n = 7 for group 1, n = 1 for group 2, n = 5 for group 3, and n = 5 for placebo) were enrolled. Baseline characteristics were similar across groups; median XAV-19 serum concentrations (ranges) at the time of the maximum serum concentration of the drug (Cmax) and at day 8 were 9.1 (5.2 to 18.1) and 6.4 (2.8 to 11.9) µg/ml, 71.5 and 47.2 µg/ml, and 50.4 (29.1 to 55.0) and 20.3 (12.0 to 22.7) µg/ml for groups 1, 2, and 3, respectively (P = 0.012). The median terminal half-life (range) was estimated at 11.4 (5.5 to 13.9) days for 2 mg/kg of XAV-19 at day 1. Serum XAV-19 concentrations were above the target concentration of 10 µg/ml (2-fold the in vitro 100% inhibitory concentration [IC100]) from the end of perfusion to more than 8 days for XAV-19 at 2 mg/kg at day 1. No hypersensitivity or infusion-related reactions were reported during treatment, and there were no discontinuations for adverse events and no serious adverse events related to the study drug. A single intravenous dose of 2 mg/kg of XAV-19 demonstrated high serum concentrations, predictive of potent durable neutralizing activity with good tolerability. (This study has been registered at ClinicalTrials.gov under identifier NCT04453384.).

Evaluation of the impact of HMS Plus on postoperative blood loss compared with ACT Plus in cardiac surgery.

BACKGROUND: The standardized management of anticoagulation during the cardiopulmonary bypass seems inaccurate because of patients and surgeries variability. This study evaluates if an individualized management of heparin and protamine guided by the HMS Plus system during cardiopulmonary bypass could reduce postoperative blood loss. METHODS: We conducted a prospective, controlled, unblinded, single-center study. One-hundred and eighthy-eight patients operated for cardiac surgery were included. Patients were divided in ACT Plus group (standardized approach) and HMS Plus group (individualized approach). The primary outcome was blood-loss volume during the first 24 postoperative hours. The main secondary outcomes were the need for allogeneic blood transfusions and the final protamine/heparin ratio. RESULTS: There was no difference between the two groups for baseline characteristics. Medium blood-loss volume in the ACT Plus group was 522±260 mL vs. 527±255 mL in the HMS Plus group (P=0.58). The final protamine/heparin ratio in the ACT Plus group was 0.94±0.1 vs. 0.58±0.1 in the HMS Plus group (P<0.0001). The transfusion rate during surgery in the ACT Plus group was 25% vs. 14% in the HMS Plus group (P=0.09). CONCLUSIONS: HMS Plus did not reduce the mean blood-loss volume during the first 24 postoperative hours compared with ACT Plus. Its utility for potential transfusion rate reduction remains to be proven.

Evaluation of the safety and efficacy of XAV-19 in patients with COVID-19-induced moderate pneumonia: study protocol for a randomized, double-blinded, placebo-controlled phase 2 (2a and 2b) trial.

BACKGROUND: Early inhibition of entry and replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a very promising therapeutic approach. Polyclonal neutralizing antibodies offers many advantages such as providing immediate immunity, consequently blunting an early pro-inflammatory pathogenic endogenous antibody response and lack of drug-drug interactions. By providing immediate immunity and inhibiting entry into cells, neutralizing antibody treatment is of interest for patient with COVID-19-induced moderate pneumonia. Convalescent plasma to treat infected patients is therefore a relevant therapeutic option currently under assessment (CORIMUNO-PLASM NCT04324047). However, the difficulties of collecting plasma on the long term are not adapted to a broad use across all populations. New polyclonal humanized anti-SARS-CoV2 antibodies (XAV-19) developed by Xenothera and administered intravenous. XAV-19 is a heterologous swine glyco-humanized polyclonal antibody (GH-pAb) raised against the spike protein of SARS-CoV-2, blocking infection of ACE-2-positive human cells with SARS-CoV-2. METHODS: Pharmacokinetic and pharmacodynamic studies have been performed in preclinical models including primates. A first human study with another fully representative GH-pAb from Xenothera is ongoing in recipients of a kidney graft. These studies indicated that 5 consecutive administrations of GH-pAbs can be safely performed in humans. The objectives of this 2-step phase 2 randomized double-blinded, placebo-controlled study are to define the safety and the optimal XAV-19 dose to administrate to patients with SARS-CoV-2 induced moderate pneumonia, and to assess the clinical benefits of a selected dose of XAV-19 in this population. DISCUSSION: This study will determine the clinical benefits of XAV-19 when administered to patients with SARS-CoV-2-induced moderate pneumonia. As a prerequisite, a first step of the study will define the safety and the dose of XAV-19 to be used. Such treatment might become a new therapeutic option to provide an effective treatment for COVID-19 patients (possibly in combination with anti-viral and immunotherapies). Further studies could later evaluate such passive immunotherapy as a potential post-exposure prophylaxis. TRIAL REGISTRATION: ClinicalTrials.gov NCT04453384 , registered on 1 July 2020, and EUDRACT 2020-002574-27, registered 6 June 2020.