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.

Analysis of the transplacental transmission of SARS CoV-2 virus and antibody transfer according to the gestational age at maternal infection.

To quantify transplacental transmission of SARS-CoV-2 virus and antibody transfer in pregnant women and their newborns according to the gestational age at maternal infection. A prospective observational multicenter study including pregnant women with a positive RT-PCR or a positive serology for SARS-CoV-2 and compatible symptoms, from April to December 2020, in 11 French maternities. The study was designed to obtain a systematic collection of mother-infant dyad's samples at birth. SARS-CoV-2 viral load was measured by RT-PCR. IgG and IgM antibodies against the SARS-CoV-2 spike protein were measured by enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were analyzed according to the gestational age at maternal infection. The primary outcome was the rate of SARS CoV-2 materno-fetal transmission at birth. The secondary outcome was the quantification of materno-fetal antibody transfer. Maternal and neonatal outcomes at birth were additionally assessed. Among 165 dyads enrolled, one congenital infection was confirmed {n = 1 (0.63%) IC95% [0.02%; 3.48%]}. The average placental IgG antibody transfer ratio was 1.27 (IC 95% [0.69-2.89]). The transfer ratio increased with increasing time between the onset of maternal infection and delivery (P Value = 0.0001). Maternal and neonatal outcomes were reassuring. We confirmed the very low rate of SARS-CoV-2 transplacental transmission (< 1%). Maternal antibody transfer to the fetus was more efficient when the infection occurred during the first and second trimester of pregnancy.

Acute heart failure in elderly patients admitted to the emergency department with acute dyspnea: a multimarker approach diagnostic study.

BACKGROUND AND IMPORTANCE: Diagnosing acute heart failure (AHF) is difficult in elderly patients presenting with acute dyspnea to the emergency department. OBJECTIVES: To assess the diagnostic accuracy of NT-proBNP, high-sensitivity cardiac troponin-I (Hs-cTnI), soluble ST2 (ST2), galectin-3 and CD146 alone and in combination for diagnosing AHF in elderly patients presenting with acute dyspnea to the emergency department. DESIGN, SETTINGS AND PARTICIPANTS: This was a prospective, multicenter study performed between September 2016 and January 2020, including elderly patients presenting with acute dyspnea to the emergency department of 6 French hospitals. INTERVENTION: Measurement of NT-proBNP, hs-cTnI, ST2, galectin-3 and CD146. OUTCOME MEASURE AND ANALYSIS: The reference standard, AHF, was adjudicated by two independent physicians based on ED and hospitalization clinical, biological (excluding biomarkers), radiological and echocardiography data (performed by a cardiologist in the cardiology department specifically for this study). Three exploratory methods (two using a cross-sectional approach with logistic regression and counting all biomarker combinations, and one using a sequential approach with gray zone optimizations) were applied to create comprehensive combinations of the 5 biomarkers for measuring diagnostic accuracy. MAIN RESULTS: Two hundred thirty-eight patients (median age of 85 years, IQR = 8) were analyzed, and 110 (46%) were diagnosed with AHF. The accuracies of NT-proBNP, CD146, hs-cTnI, galectin-3, and ST2 were 0.72 [95% confidence interval (CI) 0.66-0.77], 0.63 (95% CI 0.57-0.69), 0.59 (95% CI 0.53-0.65), 0.55 (95% CI 0.49-0.61) and 0.51 (95% CI 0.45-0.57), respectively. Regardless of the approach used or how the 5 biomarkers were combined, the best accuracy for diagnosing AHF (0.73, 95% CI 0.67-0.78) did not differ from that of NT-proBNP alone. CONCLUSION: In this study, NT-proBNP alone exhibited the best diagnostic accuracy for diagnosing AHF in elderly patients presenting with acute dyspnea to the emergency departments. None of the other biomarkers alone or combined improved the accuracy compared to NT-proBNP, which is the only biomarker to use in this setting.

Score to Predict the Occurrence of Pneumothorax After Computed Tomography-guided Percutaneous Transthoracic Lung Biopsy.

PURPOSE: The main objective of this study was to identify risk factors for post-percutaneous transthoracic lung biopsy (PTLB) pneumothorax and to establish and validate a predictive score for pneumothorax occurrence to identify patients eligible for outpatient care. MATERIAL AND METHODS: Patients who underwent PTLB between November 1, 2012 and March 1, 2017 were retrospectively evaluated for clinical and radiologic factors potentially related to pneumothorax occurrence. Multivariate logistic regression was used to identify risk factors, and the model coefficient for each factor was used to compute a score. Then, a validation cohort was prospectively evaluated from March 2018 to October 2019. RESULTS: Among the 498 eligible patients in the study cohort, pneumothorax occurred in 124 patients (24.9%) and required drainage in 34 patients (6.8%). Pneumothorax risk factors were chronic obstructive pulmonary disease (OR 95% CI 2.28[1.18-4.43]), several passages through the pleura (OR 95% CI 7.71[1.95-30.48]), an anterior biopsy approach (OR 95% CI 6.36 3.82-10.58]), skin-to-pleura distance ≤30 mm (OR 95% CI 2.25[1.09-6.65]), and aerial effusion >10 mm (OR 95% CI 9.27 [5.16-16.65]). Among the 236 patients in the prospective validation cohort, pneumothorax occurred in 18% and 8% were drained. A negative score (<73 points) predicted a probability of pneumothorax occurrence of 7.4% and late evacuation of 2.5% (OR 95% CI respectively 0.18[0.08-0.39] and 0.15[0.04-0.55]) and suggested a reduced length of hospital stay (P=0.009). CONCLUSION: This predictive score for pneumothorax secondary to PTLB has high prognostic performance and accuracy to direct patients toward outpatient management. CLINICAL TRIALS: NCT03488043.

Efficacy of Immune Checkpoint Inhibitor (ICI) Rechallenge in Advanced Melanoma Patients' Responders to a First Course of ICI: A Multicenter National Retrospective Study of the French Group of Skin Cancers (Groupe de Cancérologie Cutanée, GCC).

BACKGROUND: The long-term effectiveness of immune checkpoint inhibitor (ICI) rechallenge for progressive or recurrent advanced melanoma following previous disease control induced by ICI has not been thoroughly described in the literature. PATIENTS AND METHODS: In this retrospective multicenter national real-life study, we enrolled patients who had been rechallenged with an ICI after achieving disease control with a first course of ICI, which was subsequently interrupted. The primary objective was to evaluate tumor response, while the secondary objectives included assessing the safety profile, identifying factors associated with tumor response, and evaluating survival outcomes. RESULTS: A total of 85 patients from 12 centers were included in the study. These patients had advanced (unresectable stage III or stage IV) melanoma that had been previously treated and controlled with a first course of ICI before undergoing rechallenge with ICI. The rechallenge treatments consisted of pembrolizumab (n = 44, 52%), nivolumab (n = 35, 41%), ipilimumab (n = 2, 2%), or ipilimumab plus nivolumab (n = 4, 5%). The best overall response rate was 54%. The best response was a complete response in 30 patients (35%), a partial response in 16 patients (19%), stable disease in 18 patients (21%) and progressive disease in 21 patients (25%). Twenty-eight adverse events (AEs) were reported in 23 patients (27%), including 18 grade 1-2 AEs in 14 patients (16%) and 10 grade 3-4 AEs in nine patients (11%). The median progression-free survival (PFS) was 21 months, and the median overall survival (OS) was not reached at the time of analysis. Patients who received another systemic treatment (chemotherapy, targeted therapy or clinical trial) between the two courses of ICI had a lower response to rechallenge (p = 0.035) and shorter PFS (p = 0.016). CONCLUSION: Rechallenging advanced melanoma patients with ICI after previous disease control induced by these inhibitors resulted in high response rates (54%) and disease control (75%). Therefore, ICI rechallenge should be considered as a relevant therapeutic option.

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).

Head-to-perineum distance measured transperineally as a predictor of failed midcavity vacuum-assisted delivery.

BACKGROUND: During the second stage of labor, in case of a need for a fetal extraction at midcavity, the choice of attempting the procedure between operative vaginal delivery and cesarean delivery is difficult. Moreover, guidelines on this subject are not clear. OBJECTIVE: This study aimed to identify antenatal and intrapartum parameters associated with a failed midcavity vacuum-assisted delivery and its association with maternal and neonatal adverse outcomes. STUDY DESIGN: This was a single-center, retrospective, cohort study conducted at a tertiary maternity hospital in France from January 2010 to December 2020. Women with singleton pregnancies under epidural analgesia with nonanomalous cephalic presenting fetuses and gestational ages at ≥37 weeks of gestation, who were submitted to midcavity vacuum-assisted delivery, were included. Following the American College of Obstetricians and Gynecologists definition, midcavity was defined as the presenting part of the fetus (ie, the fetal head) found at stations 0 and +1. For research purposes, all patients were submitted to transperineal ultrasound to evaluate the head-to-perineum distance, however, this measurement did not affect the decision to perform a midcavity vacuum-assisted delivery. The primary outcome of the study was failed midcavity vacuum-assisted delivery leading to cesarean delivery or the use of a different instrument to achieve vaginal delivery. RESULTS: Overall, 951 cases of midcavity vacuum-assisted delivery were included in this study. Failed midcavity vacuum-assisted delivery occurred in 242 patients (25.4%). Factors independently associated with failed midcavity vacuum-assisted delivery included maternal height (adjusted odds ratio, 0.96; 95% confidence interval, 0.94-0.99; P=.002), duration of the active phase of the first stage of labor (adjusted odds ratio, 1.11; 95% confidence interval, 1.05-1.17; P<.001), nonocciput anterior fetal head position (adjusted odds ratio, 1.47; 95% confidence interval, 1.06-2.04; P=.02), z score of the head-to-perineum distance (adjusted odds ratio, 1.23; 95% confidence interval, 1.05-1.43; P=.01), and birthweight of >4000 g (adjusted odds ratio, 2.04; 95% confidence interval, 1.28-3.26; P=.003). Women submitted to a failed midcavity vacuum-assisted delivery were more likely to have a major postpartum hemorrhage (7.1% vs 2.0%; P<.001), whereas neonates were more likely to have an umbilical artery pH of <7.1 (30.5% vs 19.8%; P=.001), be admitted to the neonatal intensive care unit (9.6% vs 4.7%; P=.005), and have a severe caput succedaneum (14.9% vs 0.7%; P<.001). Subgroup analysis on all patients with a fetal head station of 0 found that the head-to-perineum distance was the only independent variable associated with failed midcavity vacuum-assisted delivery (adjusted odds ratio, 1.66; 95% confidence interval, 1.29-2.12; P<.001). The area under the receiving operating characteristic curve of the head-to-perineum distance in this subgroup population was 0.67 (95% confidence interval, 0.60-0.73; P<.001), and the optimal cutoff point of the head-to-perineum distance measurement discriminating between failed and successful midcavity vacuum-assisted deliveries was 55 mm. It was associated with a 0.90 (95% confidence interval, 0.83-0.95) sensitivity, 0.19 (95% confidence interval, 0.14-0.25) specificity, 0.36 (95% confidence interval, 0.30-0.42) positive predictive value, and 0.80 (95% confidence interval, 0.66-0.90) negative predictive value. CONCLUSION: Study data showed that a high fetal head station, measured using the head-to-perineum distance, and a nonocciput anterior position of the fetal head are independently associated with failed midcavity vacuum-assisted delivery. The result supported the systematic assessment of the sonographic head station and position before performing a midcavity vacuum-assisted delivery.

Fractures reduction with osteoporotic treatments in patients over 75-year-old: A systematic review and meta-analysis.

Background: Osteoporosis consists in the reduction of bone mineral density and increased risk of fracture. Age is a risk factor for osteoporosis. Although many treatments are available for osteoporosis, there is limited data regarding their efficacy in older people. Objective: To evaluate the efficacy of osteoporosis treatments in patients over 75 years old. Methods: We reviewed all published studies in MEDLINE, Cochrane and EMBASE including patients over 75 years old, treated by osteoporosis drugs, and focused on vertebral fractures or hip fractures. Results: We identified 4,393 records for review; 4,216 were excluded after title/abstract review. After full text review, 19 records were included in the systematic review. Most studies showed a reduction in vertebral fracture with osteoporosis treatments, but non-significant results were observed for hip fractures. Meta-analysis of 10 studies showed that lack of treatment was significantly associated with an increased risk of vertebral fractures at one (OR = 3.67; 95%CI = 2.50-5.38) and 3 years (OR = 2.19; 95%CI = 1.44-3.34), and for hip fractures at one (OR = 2.14; 95%CI = 1.09-4.22) and 3 years (OR = 1.31, 95%CI = 1.12-1.53). Conclusion: A reduction in the risk of vertebral fractures with osteoporosis treatments was observed in most of the studies included and meta-analysis showed that lack of treatment was significantly associated with an increased risk of vertebral fractures. Concerning hip fractures, majority of included studies did not show a significant reduction in the occurrence of hip fractures with osteoporotic treatments, but meta-analysis showed an increased risk of hip fractures without osteoporotic treatment. However, most of the data derived from post hoc and preplanned analyses or observational studies.

Effects of long-acting bronchodilators on cardiac autonomic control in COPD.

INTRODUCTION: Several studies in COPD have shown a significant and early increase in the risk of cardiovascular mortality attributable to inhaled bronchodilators including long acting ß2 agonists (LABAs) and muscarinic antagonists (LAMAs). Cardiac autonomic system impairment may be a potential mechanism involved. METHODS: We performed a phase 4, investigator-initiated, prospective, randomized, blinded, cross-over trial (LAB-Card trial - NCT02872090) to evaluate the effect of two LAMAs and one LABA on the cardiac autonomic system in patients with COPD by using three major assessment approaches: heart rate variability (HRV, a predictor of cardiovascular death), baroreflex sensitivity (BRS) and autonomic function (tilt test). RESULTS: 34 patients attended four visits to receive either tiotropium 18µg, glycopyrronium 44µg, indacaterol 150 µg or placebo (lactose) in a randomized order followed by the assessment of HRV and BRS in supine position and after passive rising. Neither LAMAs (tiotropium or glycopyrronium) nor LABA (indacaterol) induced a higher LF/HF ratio (reflect of sympathetic/parasympathetic balance) measured in supine position at rest compared to placebo (primary outcome). Solely indacaterol induced an increase in heart rate compared to placebo. No significant differences were observed for HRV and BRS between active drugs and placebo in supine position or after passive rising. CONCLUSION: We did not found evidence of a deleterious effect of 2 LAMAs and one LABA on the autonomic cardiovascular control in COPD patients. Further investigations are needed to explore mechanisms by which long-acting bronchodilators may increase cardiovascular events in COPD.

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.

ß-lactam dosing at the early phase of sepsis: Performance of a pragmatic protocol for target concentration achievement in a prospective cohort study.

PURPOSE: We hypothesized that a protocol of standardized fixed dose using prolonged infusion during the early phase of sepsis may avoid insufficient ß-lactam concentrations. METHODS: In this single center prospective study, patients with sepsis and vasopressors were enrolled if they were treated by either piperacillin-tazobactam, meropenem or cefepime. Βeta-lactams were administered at fixed dose by prolonged infusion. Targeted plasma concentrations for piperacillin, meropenem and cefepime were above 80 mg/L, 8 mg/L and 38 mg/L respectively. Three blood samples were collected per patient over the first 48 h of treatment. Primary endpoint was target concentration achievement during the 48 first hours, defined as all plasma concentrations above the targeted threshold. RESULTS: Among the 89 patients completing the three samples, target concentrations were achieved for 61 (69%). Target concentrations were achieved in 20 (53%), 32 (89%), and 9 (60%) of the patients treated with piperacillin, meropenem and cefepime, respectively. By multivariate analysis, lower APACHE 2 score, higher baseline MDRD creatinine clearance, and piperacillin use were independently associated with insufficient ß-lactam concentrations. CONCLUSION: Despite a fixed dose antibiotic administration protocol with prolonged infusion insufficient ß-lactam concentration was frequent at the early phase of sepsis, especially in less severe patients, without renal failure, and treated with piperacillin. In septic patients with vasopressors, piperacillin dosing higher than 16 g may be needed to achieve the recommended target concentration. TRIAL REGISTRATION: NCT02820987.

COVEVOL: Natural Evolution at 6 Months of COVID-19.

Many studies have investigated post-COVID symptoms, but the predictors of symptom persistence remain unknown. The objective was to describe the natural course of the disease at 6 months and to identify possible factors favoring the resurgence or persistence of these symptoms. COVEVOL is a retrospective observational descriptive study of 74 patients. All patients with positive SARS-CoV-2 PCR from March 2020 were included. We compared a group with symptom persistence (PS group) with another group without symptom persistence (no-PS group). Fifty-three out of seventy-four patients (71.62%) described at least one persistent symptom at 6 months of SARS-CoV-2 infection. In the PS group, 56.6% were women and the average age was 54.7 years old [21-89.2] ± 16.9. The main symptoms were asthenia (56.6%, n = 30), dyspnea (34%, n = 18), anxiety (32.1% n = 17), anosmia (24.5%, n = 13) and agueusia (15.1% n = 8). Ten patients (13.51%) presented a resurgence in symptoms. Patients in the PS group were older (p = 0.0048), had a higher BMI (p = 0.0071), and were more frequently hospitalized (p = 0.0359) compared to the no-PS group. Odynophagia and nasal obstruction were less present in the inaugural symptoms of COVID-19 in the PS group (p = 0.0202 and p = 0.0332). Persistent post-COVID syndromes are common and identification of contributing factors is necessary for understanding this phenomenon and appropriate management.

Impact on antimicrobial consumption of procalcitonin-guided antibiotic therapy for pneumonia/pneumonitis associated with aspiration in comatose mechanically ventilated patients: a multicenter, randomized controlled study.

BACKGROUND: In comatose patients receiving oro-tracheal intubation for mechanical ventilation (MV), the risk of aspiration is increased. Aspiration can lead to chemical pneumonitis (inflammatory reaction to the gastric contents), or aspiration pneumonia (infection caused by inhalation of microorganisms). Distinguishing between the two types is challenging. We tested the interest of using a decisional algorithm based on procalcitonin (PCT) values to guide initiation and discontinuation of antibiotic therapies in intubated patients. METHODS: The PROPASPI (PROcalcitonin Pneumonia/pneumonitis Associated with ASPIration) trial is a multicenter, prospective, randomized, controlled, single-blind, superiority study comparing two strategies: (1) an intervention group where threshold PCT values were used to guide initiation and discontinuation of antibiotics (PCT group); and (2) a control group, where antibiotic therapy was managed at the physician's discretion. Patients aged 18 years or over, intubated for coma (Glasgow score ≤ 8), with MV initiated within 48 h after admission, were eligible. The primary endpoint was the duration of antibiotic treatment during the first 15 days after admission to the ICU. RESULTS: From 24/2/2015 to 28/8/2019, 1712 patients were intubated for coma in the 5 participating centers, of whom 166 were included in the study. Data from 159 were available for intention-to-treat analysis: 81 in the PCT group, and 78 in the control group. Overall, 67 patients (43%) received antibiotics in the intensive care unit (ICU); there was no significant difference between groups (37 (46%) vs 30 (40%) for PCT vs control, p = 0.432). The mean duration of antibiotic treatment during the first 15 days in the ICU was 2.7 ± 3.8 days; there was no significant difference between groups (3.0 ± 4.1 days vs 2.3 ± 3.4 days for PCT vs control, p = 0.311). The mean number of days under MV was significantly higher in the PCT group (3.7 ± 3.6 days) than in controls (2.7 ± 2.5 days, p = 0.033). The duration of ICU stay was also significantly longer in the PCT group: 6.4 ± 6.5 days vs 4.6 ± 3.5 days in the control group (p = 0.043). After adjustment for SAPS II score, the difference in length of stay and duration of mechanical ventilation between groups was no longer significant. CONCLUSION: The use of PCT values to guide therapy, in comparison to the use of clinical, biological (apart from PCT) and radiological criteria, does not modify exposure to antibiotics in patients intubated for coma. Trial registration Clinicaltrials.gov Identifier NCT02862314.

Cognitive Impairment in Late-Life Depression: A Comparative Study of Healthy Older People, Late-Life Depression, and Mild Alzheimer's Disease Using Multivariate Base Rates of Low Scores.

Late-Life Depression (LLD) is often associated with cognitive impairment. However, distinction between cognitive impairment due to LLD and those due to normal aging or mild Alzheimer's Disease (AD) remain difficult. The aim of this study was to present and compare the multivariate base rates of low scores in LLD, mild AD, and healthy control groups on a battery of neuropsychological tests. Participants (ages 60-89) were 352 older healthy adults, 390 patients with LLD, and 234 patients with mild AD (i.e., MMSE ≥ 20). Multivariate base rates of low scores (i.e., ≤ 5th percentile) were calculated for each participant group within different cognitive domains (verbal episodic memory, executive skills, mental processing speed, constructional praxis, and language/semantic memory). Obtaining at least one low score was relatively common in healthy older people controls (from 9.4 to 17.6%), and may thus result in a large number of false positives. By contrast, having at least two low scores was unusual (from 0.3 to 4.6%) and seems to be a more reliable criterion for identifying cognitive impairment in LLD. Having at least three low memory scores was poorly associated with LLD (5.9%) compared to mild AD (76.1%) and may provide a useful way to differentiate between these two conditions [ χ ( 1 ) 2 = 329.8, p < 0.001; Odds Ratio = 50.7, 95% CI = 38.2-77.5]. The multivariate base rate information about low scores in healthy older people and mild AD may help clinicians to identify cognitive impairments in LLD patients, improve the clinical decision-making, and target those who require regular cognitive and clinical follow-up.

Systematic Review and Subgroup Meta-analysis of Randomized Trials to Determine Tocilizumab's Place in COVID-19 Pneumonia.

INTRODUCTION: Tocilizumab randomized clinical trial results are heterogeneous because of the heterogenous population included in them. METHODS: We conducted a meta-analysis with subgroup meta-analysis (PRISMA guidelines) between severe and non-severe COVID-19. RESULTS: We included nine trials. Overall, the mortality rate was 24.5% (821/3357) in the tocilizumab group and 29.1% (908/3125) in the control group at day 28-30 (pooled OR, 0.85; 95% CI 0.76-0.96; p = 0.006). Considering the subgroup analysis, this benefit on mortality was confirmed and amplified in the severe COVID-19 group (pooled OR, 0.82; 95% CI 0.73-0.93; p = 0.001) but not in the non-severe COVID-19 group (pooled OR, 1.46; 95% CI 0.91-2.34; p = 0.12). For patients who were not mechanically ventilated at baseline (5523/6482), the pooled OR (0.74; 95% CI 0.64-0.85; p < 0.0001) for mechanical ventilation incidence at day 28-30 was in favor of tocilizumab (cumulative incidence of 14.8% versus 19.4% in tocilizumab and control arm, respectively). This benefit was confirmed in both subgroups, i.e., severe and non-severe COVID-19. CONCLUSION: Tocilizumab is an effective treatment in hospitalized patients with COVID-19 and hypoxemia by improving survival and decreasing mechanical ventilation requirement. The greatest benefit is observed in severe COVID-19.

Predictive factors for exudation of quiescent choroidal neovessels detected by OCT angiography in the fellow eyes of eyes treated for a neovascular age-related macular degeneration.

BACKGROUND: To identify predictive factors for exudation for quiescent choroidal neovessels (qCNV) in the fellow eyes of eyes treated for a neovascular age-related macular degeneration (AMD). METHODS: Prospective observational study. One hundred and forty-four contralateral eyes of 144 patients treated for wet AMD were analysed. At a baseline visit, multimodal imaging including dye angiographies and optical coherence tomography angiography (OCT-A) was performed in order to detect qCNV. Patients were followed up for 12 months with a monthly assessment. The manifestation of any type of exudation (either intra- or subretinal fluid or hyperreflective subretinal material) was monitored. RESULTS: The prevalence of qCNV in the treatment-naive eyes was 15.9% with an incidence over a 12-month period of 2.8%. In total, 40.7% of the overall neovessels remained stable with no sign of exudation, while 59.3% presented some fluid during the follow-up. A statistically significant relationship was established for the following variables preceding the exudation: increase in central macular thickness (OR = 116; 95% CI [4.74; 50530] p = 0.038), increase in pigment epithelial detachment height (OR = 1.76; 95% CI [1.17; 3.18] p = 0.021) and width (OR = 1.53; 95% CI [1.12; 2.62] p = 0.042), increase in neovessels' surface on OCT-A (OR = 6.32; 95% CI [1.62; 51.0] p = 0.033), emergence of a branching pattern (OR = 7.50; 95% CI[1.37; 61.5] p = 0.032) and appearance of a hypointense halo surrounding the lesion (OR = 10.00; 95% CI [1.41; 206] p = 0.048). CONCLUSIONS: The risk of exudation in the treatment-naive fellow eyes of eyes treated for neovascular AMD was notably increased in the presence of qCNV. The biomarkers identified will help to detect their activation in order to ensure prompt antiangiogenic therapy.