Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

Pubic Osteomyelitis: Epidemiology and Factors Associated with Management Failure in Two French Reference Centers

Abstract Background Pubic osteomyelitis (PO) is a neglected bone and joint infections (BJI), as its management is still poorly codified. We aim to describe PO epidemiology and to look for factors associated with management failure. Methods We performed a retrospective cohort study in two French reference centers including patients with PO in 2010–2016. Treatment failure was defined by clinical (persistence or recurrence of clinical signs) and/or microbiological failure. Factors associated with treatment failure were determined by univariate Cox analysis (hazard ratio [HR] and 95% confidence interval calculation). Kaplan–Meier curve was compared between groups by log-rank test. Results Twenty-five patients were included over 13 years (median age 67 years; 19 men, median ASA score 3). Six (24 %) had a PO from haematogenous origin. Those were all monomicrobial infection, due to S.aureus, mostly identified in young patients without comorbidities, especially in athletes. No surgery was required if no abcess or bone sequestrum were found. Nineteen patients (76 %) had a post-operative chronic PO (developed from 1 month to 11 years after a pelvic surgery); 15 of them had history of pelvic cancer (60%); 12 received radiotherapy at the site of infection (48 %). Infection was polymicrobial in 68 % of cases, including 32 % of cases with multidrug-resistant pathogens. A clinical success was recorded in only 14 patients (56%). Treatment failure was always noticed in chronic post-operative forms. Potential risk factors associated with failure management were: pelvic cancer history (HR 3.8; &amp;#x2028;P = 0,089); pelvic radiotherapy history (HR 2.9; P = 0.122); clinical sinus tract (HR 5.1; P = 0,011); infection with multidrug-resistant bacteria (HR 2.8; P = 0,116), and polymicrobial infection (HR 70.5; P = 0,090). Conclusion Our study highlights predominant chronic complex post-operative forms of PO. They are mostly plurimicrobial, sometimes associated with multi-drug resistance, occurring in fragile patients with pelvic cancer. It frequently leads to complex antibiotherapy, with important risk of relapse. Aggressive surgical procedure with large bone resection is frequently required in patients who underwent pelvic radiotherapy. Disclosures T. Ferry, HERAEUS: Consultant, Speaker honorarium. E. Senneville, 1959: Board Member and Consultant, Consulting fee and Speaker honorarium </jats:sec

Corynebacterium Bone and Joint Infection (BJI): A Retrospective Cohort Study in a Reference Center for BJI Management

Abstract Background Corynebacterium is a rare etiologic agent of BJI. We aimed to describe this rare clinical condition and to assess treatment failure determinants. Methods All adult patients with proven Corynebacterium BJI (i.e., consistent clinical/radiological signs, AND ≥2 reliable positive bacteriological samples, AND treated as such) were included in a retrospective cohort study. After cohort description, determinants of treatment failure (i.e., infection persistence, relapse, requirement of additional surgical procedure, and BJI-related death) were determined using stepwise logistic regression and Kaplan-–Meier curve analysis. Results The 51 included BJI were more frequently chronic (88.2%), orthopaedic device related (ODI, 74.5%) and polymicrobial (78.4%). Surgery was performed in 92.2% of cases, and considered as appropriate in 76.5% of them. The main first-line antimicrobials were glycopeptides (68.6%), β-lactams (50%), and/or clindamycin (10.0%). Three (5.9%) patients received daptomycin as part of first-line regimen, and 8 (15.7%) at any point of treatment. After a follow-up of 60.7 (IQR 30.1–115.1) weeks, 20 (39.2%) treatment failures were observed, including 4 (20%) Corynebacterium-documented relapse. Independent risk factors were initial biological inflammatory syndrome (OR 16.1; P = 0,030) and inappropriate surgical management (OR 7.481; P = 0.036). Interestingly, all patients receiving daptomycin as part of first-line regimen failed (P &amp;lt; 0.001), including one patient with a Corynebacterium-documented relapse with a daptomycin increased MIC. Among patients with ODI, survival curve analysis disclosed a worst prognosis in case of prosthetic joint infection (P = 0.030), unappropriate surgical management (P = 0.029) and daptomycin use as first-line regimen (P &amp;lt; 0.001). Conclusion Corynebacterium BJI is a poorly known condition, frequently chronic, and polymicrobial. An important rate of failure was observed, associated with inappropriate surgical management and daptomycin use as part of first-line regimen. As described for other clinical conditions such as infective endocarditis, daptomycin should be avoid or used in combination therapy to prevent resistance selection and treatment failure. Disclosures T. Ferry, HERAEUS: Consultant, Speaker honorarium. S. Lustig, Heraeus: Consultant, Consulting fee </jats:sec

Association between corticosteroids and intubation or death among patients with COVID-19 pneumonia in non-ICU settings: an observational study using of real-world data from 51 hospitals in France and Luxembourg

AbstractObjectiveTo assess the effectiveness of corticosteroids on outcomes of patients with mild COVID-19 pneumonia.MethodsWe used routine care data from 51 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids at 0.8 mg/kg/day eq. prednisone (CTC group) vs standard of care (no-CTC group) among patients ≤ 80 years old with COVID-19 pneumonia requiring oxygen without mechanical ventilation. The primary outcome was intubation or death at Day 28. Baseline characteristics of patients were balanced using propensity score inverse probability of treatment weighting.ResultsAmong the 891 patients included in the analysis, 203 were assigned to the CTC group. At day 28, corticosteroids did not reduce the rate of the primary outcome (wHR 0.92, 95% CI 0.61 to 1.39) nor the cumulative death rate (wHR 1.03, 95% CI 0.54 to 1.98). Corticosteroids significantly reduced the rate of the primary outcome for patients requiring oxygen ≥ at 3L/min (wHR 0.50, 95% CI 0.30 to 0.85) or C-Reactive Protein (CRP) ≥ 100mg/L (wHR 0.44, 95%CI 0.23 to 0.85). We found a higher number of hyperglycaemia events among patients who received corticosteroids, but number of infections were similar across the two groups.ConclusionsWe found no association between the use of corticosteroids and intubation or death in the broad population of patients ≤80 years old with COVID-19 hospitalized in non-ICU settings. However, the treatment was beneficial for patients with ≥ 3L/min oxygen or CRP ≥ 100mg/L at baseline. These data support the need to confirm the right timing of corticosteroids for patients with mild COVID.Short summaryWe assessed the effectiveness of corticosteroids among patients ≤ 80 years old with COVID-19, in non-ICU settings. Our results support the use of corticosteroids for patients receiving oxygen at ≥3L/min or with a C-reactive protein ≥ 100mg/L at baseline.</jats:sec

Pressure Ulcer-Related Pelvic Osteomyelitis: Evaluation of a Two-Stage Surgical Strategy (Debridement, Negative Pressure Therapy and Flap Coverage) with Prolonged Antimicrobial Therapy

Abstract Background A two-stage surgical strategy (debridement-negative pressure therapy (NPT) and flap coverage) with prolonged antimicrobial therapy is usually proposed in pressure ulcer-related pelvic osteomyelitis but has not been widely evaluated. Methods Adult patients with pressure ulcer-related pelvic osteomyelitis treated by a two-stage surgical strategy were included in a retrospective cohort study. Determinants of superinfection (i.e.,, additional microbiological findings at reconstruction) and treatment failure were assessed using binary logistic regression and Kaplan–Meier curve analysis. Results Sixty-four pressure ulcer-related pelvic osteomyelitis in 61 patients (age, 47 [IQR 36–63]) were included. Osteomyelitis was mostly plurimicrobial (73%), with a predominance of S. aureus (47%), Enterobacteriaceae (44%), and anaerobes (44%). Flap coverage was performed after 7 (IQR 5–10) weeks of NPT, with 43 (68%) positive bone samples among which 39 (91%) were superinfections, associated with a high ASA score (OR, 5.8; P = 0.022). An increased prevalence of coagulase negative Staphylococci (P = 0.017) and Candida (P = 0.003) was observed at time of flap coverage. An ESBL Enterobacteriaceae was found in one (12%) patients, associated with fluoroquinolone consumption (OR, 32.4; P = 0.005). Treatment duration was as 20 (IQR 14–27) weeks, including 11 (IQR 8–15) after reconstruction. After a follow-up of 54 (IQR 27–102) weeks, 15 (23%) failures were observed, associated with previous pressure ulcer (OR, 5.7; P = 0.025) and Actinomyces infection (OR, 9.5; P = 0.027). Conclusion Pressure ulcer-related pelvic osteomyelitis is a difficult-to-treat clinical condition, generating an important consumption of broad-spectrum antibiotics. Carbapenem should be reserved for ESBL at-risk patients only, including those with previous fluoroquinolone use. The uncorrelation between outcome and the debridement-to-reconstruction interval argue for a short sequence to limit the total duration of treatment. Disclosures T. Ferry, HERAEUS: Consultant, Speaker honorarium </jats:sec

Arthroscopic “Debridement and Implant Retention” With Local Administration of Exebacase (Lysin CF-301) Followed by Suppressive Tedizolid as Salvage Therapy in Elderly Patients for Relapsing Multidrug-Resistant S. epidermidis Prosthetic Knee Infection

Exebacase, a recombinantly produced lysin has recently (i) reported proof-of-concept data from a phase II study in S. aureus bacteremia and (ii) demonstrated antibiofilm activity in vitro against S. epidermidis. In patients with relapsing multidrug-resistant (MDR) S. epidermidis prosthetic knee infection (PKI), the only surgical option is prosthesis exchange. In elderly patients who have undergone several revisions, prosthesis explantation could be associated with definitive loss of function and mortality. In our BJI reference regional center, arthroscopic debridement and implant retention with local administration of exebacase (LysinDAIR) followed by suppressive tedizolid as salvage therapy is proposed for elderly patients with recurrent MDR S. epidermidis PKI with no therapeutic option or therapeutic dead end (for whom revision or transfemoral amputation is not feasible and no other oral option is available). Each use was decided in agreement with the French health authority and in accordance with the local ethics committee. A written consent was obtained for each patient. Exebacase (75 mg/mL; 30 mL) was administered directly into the joint during arthroscopy. Four patients (79–89 years old) were treated with the LysinDAIR procedure. All had several previous prosthetic knee revisions without prosthesis loosening. Three had relapsing PKI despite suppressive antibiotics following open DAIR. Two had clinical signs of septic arthritis; the two others had sinus tract. After the LysinDAIR procedure, no adverse events occurred during arthroscopy; all patients received daptomycin 8 mg/kg and linezolid 600 mg bid (4–6 weeks) as primary therapy, followed by tedizolid 200 mg/day as suppressive therapy. At 6 months, recurrence of the sinus tract occurred in the two patients with sinus tract at baseline. After &amp;gt;1 year follow up, the clinical outcome was favorable in the last two patients with total disappearance of clinical signs of septic arthritis even if microbiological persistence was detected in one of them. Exebacase has the potential to be used in patients with staphylococci PKI during arthroscopic DAIR as salvage therapy to improve the efficacy of suppressive antibiotics and to prevent major loss of function.</jats:p

Progressive Multifocal Leukoencephalopathy Treated by Immune Checkpoint Inhibitors

International audienceObjective: Our aim was to assess the real-world effectiveness of immune checkpoint inhibitors for treatment of patients with progressive multifocal leukoencephalopathy (PML).Methods: We conducted a multicenter survey compiling retrospective data from 79 PML patients, including 38 published cases and 41 unpublished cases, who received immune checkpoint inhibitors as add-on to standard of care. One-year follow-up data were analyzed to determine clinical outcomes and safety profile. Logistic regression was used to identify variables associated with 1-year survival.Results: Predisposing conditions included hematological malignancy (n = 38, 48.1%), primary immunodeficiency (n = 14, 17.7%), human immunodeficiency virus/acquired immunodeficiency syndrome (n = 12, 15.2%), inflammatory disease (n = 8, 10.1%), neoplasm (n = 5, 6.3%), and transplantation (n = 2, 2.5%). Pembrolizumab was most commonly used (n = 53, 67.1%). One-year survival was 51.9% (41/79). PML-immune reconstitution inflammatory syndrome (IRIS) was reported in 15 of 79 patients (19%). Pretreatment expression of programmed cell death-1 on circulating T cells did not differ between survivors and nonsurvivors. Development of contrast enhancement on follow-up magnetic resonance imaging at least once during follow-up (OR = 3.16, 95% confidence interval = 1.20-8.72, p = 0.02) was associated with 1-year survival. Cerebrospinal fluid JC polyomavirus DNA load decreased significantly by 1-month follow-up in survivors compared to nonsurvivors (p < 0.0001). Thirty-two adverse events occurred among 24 of 79 patients (30.4%), and led to treatment discontinuation in 7 of 24 patients (29.1%).Interpretation: In this noncontrolled retrospective study of patients with PML who were treated with immune checkpoint inhibitors, mortality remains high. Development of inflammatory features or overt PML-IRIS was commonly observed. This study highlights that use of immune checkpoint inhibitors should be strictly personalized toward characteristics of the individual PML patient. ANN NEUROL 2023;93:257-270