Urinary methotrexate dosage in rheumatoid arthritis, in patients treated for at least 6 months: a potential marker of adherence.

OBJECTIVES: Non-adherence to rheumatoid arthritis (RA) treatments must be identified. A methotrexate (MTX) urinary dosage (METU) was recently developed. The aim of our study was to assess adherence to MTX in RA using METU in real-life conditions and to compare it with indirect adherence measurement technics. METHODS: We performed a cross-sectional study at Reims University Hospital. We included over 18-year-old patients with RA treated by MTX for more than 6 months. Patients were invited to complete demographic, clinical and psychological questionnaires and adherence measurement technics (Compliance Questionnaire of Rheumatology (CQR) and Medication Possession Ratio (MPR)). A urinary sample was collected to measure MTX and information about tolerance was evaluated through Methotrexate Intolerance Severity Score. RESULTS: 84 patients were included, 26 using oral MTX, 58 subcutaneous (SC) MTX. Among them, 73% were female, mean age was 61.5 years, MTX mean dose was 15 mg/week and 61.9% were treated by biological DMARDs (Disease Modifying Antirheumatic Drugs). 77 patients (91.7%) were adherent to treatment according to METU, whereas MPR and CQR reported less adherence (69.5% and 61.9%, respectively). MPR and METU were not significantly different in SC MTX users (p=0.059). Non-adherent patients had a higher number of tender joints and C reactive protein value (p<0.05). CONCLUSION: This is the first largest study evaluating MTX adherence in patients with RA using a urinary dosage. We identified that indirect adherence measurements did not reflect real-life adherence. It would be appreciable to realise METU, in a new study, in patients with RA with unexplained response to treatment, to consider it before escalating therapeutic strategy.

"The least significant change on bone mineral density scan increased in patients with higher degrees of obesity".

BACKGROUND: The least significant change (LSC) threshold of 0.03 g/cm² is used to interpret bone mineral density (BMD) scans in the general population. Our working hypothesis was that the current LSC threshold would not be applicable in obese populations. AIMS: The aim of this study was to calculate the LSC in an obese population. METHODS: We performed an interventional study among 120 obesity patients, in whom two measurements of BMD were performed at 3 sites. Pairs of measures were used to calculate the LSC, using the Bland and Altman method. RESULTS: We calculated that the LSC was 0.046 g/cm² at the lumbar spine, 0.069 g/cm² at the femoral neck, and 0.06 g/cm² at the total hip. We also calculated the LSC for each class of obesity and observed an increase in LSC with increasing body mass index (BMI). We calculated a LSC of 0.05 g/cm² in patients with class 2 or class 3 obesity, whereas the LSC in patients with class 1 obesity is similar to the threshold used in the general population. DISCUSSION: In obese population, like BMD, LSC is higher than the threshold value of the general population, and increases with increasing BMI. CONCLUSION: LSC of 0.05 g/cm² could be used in clinical practice in patients with class 2 or 3 obesity. These findings should help to improve the interpretation of BMD scans in these patients and optimize their management. TRIAL REGISTRATION NUMBER: Comité de Protection des Personnes Ile-de France VII, France.

Predictors of Nursing Home Entry within 36 Months after Hospitalization via the Emergency Department among Persons Aged 75 Years or Older.

OBJECTIVE: We aimed to identify risk factors for nursing home (NH) entry 36 months after hospitalization via the emergency department (ED) in a population of patients aged 75 years or older. METHODS: This was a prospective multicentre cohort. Patients were recruited from the emergency departments (EDs) of nine hospitals. Subjects had been hospitalised in a medical ward in the same hospital as the ED to which they were initially admitted. Subjects who experienced NH entry prior to ED admission were excluded. NH entry has been defined as the incident admission either into an NH or other long-term care facility within the follow-up period. Variables from a comprehensive geriatric assessment of patients were entered into a Cox model with competing risks to predict NH entry during 3 years of follow-up. RESULTS: Among 1306 patients included in the SAFES cohort, 218 (16.7%) who were already in an NH were excluded. The remaining 1088 patients included in the analysis were aged 84 ± 6 years on average. During 3 years of follow-up, 340 (31.3%) entered an NH. The independent risk factors for NH entry were that they: living alone (Hazard ratio (HR) 2.00, had a 95% confidence interval (CI) 1.59-2.54, p < 0.0001), could not independently perform activities of daily living (HR 1.81, 95% CI 1.24-2.64, p = 0.002), and had balance disorders (HR 1.37, 95% CI 1.09-1.73, p = 0.007), dementia syndrome (HR 1.80, 95% CI 1.42-2.29, p < 0.0001) and a risk of pressure ulcers (HR 1.42, 95% CI 1.10-1.82, p = 0.006). CONCLUSION: The majority of the risk factors for NH entry within 3 years after emergency hospitalization are amenable to intervention strategies. It is therefore reasonable to imagine that targeting these features of frailty could delay or prevent NH entry and improve the quality of life of these individuals before and after NH entry.

Risk Factors of Progression in Low-tumor Burden Follicular Lymphoma Initially Managed by Watch and Wait in the Era of PET and Rituximab.

Patients (pts) with asymptomatic low-burden follicular lymphoma (FL) are usually observed at diagnosis. Time to lymphoma treatment (TLT) initiation can however be very heterogeneous and risk factors of progression are poorly studied. Our study evaluated 201 pts with grade 1-3a low-tumor burden FL diagnosed in four French centers between 2010 and 2020 and managed by a watch and wait strategy in real-life settings. After a median follow-up of 4.8 years, the median TLT was 4.2 years (95% confidence interval, 3.1-5.5). On multivariate analysis, elevated lactate dehydrogenase (hazard ratio [HR] = 2.2; P = 0.02), more than 4 nodal areas involved (HR = 1.7; P = 0.02) and more than 1 extranodal involvement (HR = 2.7; P = 0.01) were identified as independent predictors of TLT. The median TLT was 5.8 years for pts with no risk factor, 2.4 years for 1 risk factor, and 1.3 years for >1 risk factors (P < 0.01). In a subanalysis of 75 pts staged with positron emission tomography-computed tomography (PET-CT), total metabolic tumor volume (TMTV) ≥14 cm3 and standardized Dmax (reflecting tumor dissemination) >0.32 m-1 were also associated with shorter TLT (HR = 3.4; P = 0.004 and HR = 2.4; P = 0.007, respectively). In multivariate models combining PET-CT parameters and clinical variables, TMTV remained independent predictor of shorter TLT. These simple parameters could help to identify FL patients initially observed at higher risk of early progression. The role of PET-CT (extranodal sites and PET metrics) in low-burden FL appears promising and warrants further assessment in large cohorts.

Prognostic Factors Related to Clinical Response in 210 Knees Treated by Platelet-Rich Plasma for Osteoarthritis.

Many studies have shown the effectiveness of platelet-rich plasma (PRP) in the treatment of knee osteoarthritis. We aimed to determine the factors associated with good or poor response to PRP injections in knee osteoarthritis. This was a prospective observational study. Patients with knee osteoarthritis were recruited from a university hospital. PRP was injected twice at a one-month interval. Pain was assessed on a visual analog scale (VAS) and function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Radiographic stage was collected and defined according to the Kellgren-Lawrence classification. Patients were classified as responders if they met the OMERACT-OARSI criteria at 7 months. We included 210 knees. At 7 months, 43.8% were classified as responders. Total WOMAC and VAS were significantly improved between M0 and M7. Physical therapy and a heel-buttock distance >35 cm were the two criteria associated with poor response at M7 by multivariate analysis. Pain VAS at M7 appeared to be lower in patients with osteoarthritis for less than 24 months. No adverse effects were reported. PRP treatment in knee osteoarthritis appears to be well-tolerated and effective, even in patients who reacted poorly to hyaluronic acid. Response was not associated with radiographic stage.

Baseline 18F-FDG Metabolic Tumor Volume Predicts Response to Rituximab Induction in Post-transplant Lymphoproliferative Disorders: A Multi-institutional Retrospective Study.

Post-transplant lymphoproliferative disorder (PTLD) is a rare complication of immunosuppression. Sequential treatment is commonly proposed, combining induction with rituximab (R-induction) followed by either continuation of treatment or addition of chemotherapy depending on response. Response to R-induction, often assessed by CT scan, is a major predictor of overall survival (OS). The aim of the study was to analyze predictive factors of R-induction response, including total metabolic tumor volume (TMTV), and investigate the role of 18F-FDG PET/CT in response assessment. This retrospective multicenter study is based on patients with PTLD included in the K-VIROGREF cohort. Only patients treated by R-induction with a baseline 18F-FDG PET/CT were included. Response to R-induction was assessed by 18F-FDG PET/CT. The optimal threshold of TMTV for rituximab response was determined using receiver operating characteristic curves. Univariate and multivariate analyses were conducted to identify predictive factors of response. A total of 67 patients were included. Survival characteristics were similar to those previously reported: the complete response rate to R-induction was 30%, the 3-year OS estimate was 66%, and the treatment-related mortality was 4%. The optimal threshold for TMTV to predict R-induction response was 135 cm3. The response rate to R-induction was 38% in the 21 patients with TMTV ≥ 135 cm3 and 72% in the 46 patients with TMTV < 135 cm3. TMTV was a significant predictor of response, both at univariate and multivariate analyses (odd ratios = 3.71, P = 0.022). Baseline TMTV is predictive of response to R-induction. Early assessment of patient response is feasible with 18F-FDG PET/CT.

Association between admission biomarkers and clinical outcome in older adults diagnosed with an infection in the emergency department.

INTRODUCTION: In older adults, prognostic performances of admission biomarkers have been poorly investigated. This study aims to compare the prognostic abilities of usual admission biomarkers, especially PCT and CRP, for major clinical outcomes, comparing older to younger adults diagnosed with an infection in the ED, and to investigate the prognostic abilities of PCT and CRP depending on the glomerular filtration rate (GFR). METHODS: It was an observational, single-center, retrospective study, conducted in the Reims University Hospital, France. Endpoints were bacteremia, septic shock, and in-hospital mortality, related to the same ED visit. RESULTS: Over 1 year, 852 patients were included with 291 (34.2%) ≥75 years, and 127 (15.3%) patients had a GFR <30 mL.min-1.1.73 m2. Overall, 74 bacteremia, 56 septic shock and 82 in-hospital deaths have been observed. Prognostic abilities of admission biomarkers tended to be systematically lower in older compared to younger adults (PCT and CRP AUROC for bacteremia were, respectively, 0.71 and 0.62 in older adults vs 0.75 and 0.70 in younger adults; PCT and CRP AUROC for septic shock were, respectively, 0.71 and 0.66 in older adults vs 0.82 and 0.68 in younger adults). PCT showed a significant discriminating power for septic shock and in-hospital mortality only for GFR ≥ 30, and CRP showed a significant discriminating power for bacteremia and septic shock only for GFR ≥60. CONCLUSION: Caution must be taken when interpreting admission biomarkers, as their prognostic abilities are lower in older adults or in patients with renal insufficiency diagnosed with an infection.

ADC measurement relevance to predict hemorrhage transformation after mechanical thrombectomy.

BACKGROUND: ADC (apparent coefficient diffusion) value has been known to predict hemorrhage transformation (HT) after thrombolysis and recently, after mechanical thrombectomy (MT). We aimed to evaluate that utility separately in basal ganglia and superficial territory. We used HT occurrence with or without NIHSS change as primary outcome measures. METHODS: This single-center retrospective study included consecutive stroke patients receiving MT for internal carotid artery (ICA) or middle cerebral artery (M1 or M2) occlusion. In patient with or without HT, using the Heidelberg Bleeding Classification, on follow-up CT scan at 24-48 h, we assessed the ADC value separately in basal ganglia and superficial territory on MRI before MT to search for the correlation. Multivariable analysis was performed using variables with significant differences between the HT group and non-HT group. RESULTS: One hundred seventeen patients were included in the final analysis. HT distribution was as follows: 9 patients (7.69%) HI1 or 2; 14 patients (11.97%) PH1; 21 patients (17.95%) PH2; 29 patients (24.79%) subarachnoid hemorrhage; and 21 patients (17.95%) symptomatic intracranial hemorrhage (sICH). Mean ADC minimal value in basal ganglia in the HT group was significantly lower than in the non-HT group (377.6 × 10-6 mm2/s [± 52.4] vs 413.3 × 10-6 mm2/s [± 72.5]; p = 0.0229) with an area under the curve (AUC) of 0.6622 (95% CI: 0.5-0.8; p = 0.014). MRI-MT time was significantly longer in the HT group (p = 0.0002), but there was no association between ADC value and onset-MRI or MRI-MT times (Spearman's coefficients <0.7, p > 0.05). Glycemia at admission (>1.5 g/L) (OR = 4.2; 95% CI [1.611; 10.961]) and carotid occlusion (OR = 2.835; 95% CI [1.134; 7.091]) were independently associated with HT. CONCLUSIONS: ADC value in basal ganglia, unlike brain superficial territory, are correlated to HT risk after MT.

Fatigue and quality-of-life in the year following SARS-Cov2 infection.

BACKGROUND: The SARS-COV2 pandemic has been ongoing worldwide since at least 2 years. In severe cases, this infection triggers acute respiratory distress syndrome and quasi-systemic damage with a wide range of symptoms. Long-term physical and psychological consequences of this infection are therefore naturally present among these patients. The aim of this study was to describe the state of health of these patients at 6 (M6) and 12 months (M12) after infection onset, and compare quality-of-life (QOL) and fatigue at these time-points. METHODS: A prospective cohort study was set up at Reims University Hospital. Patients were clinically assessed at M6 and M12. Three scores were calculated to describe patient's status: the modified Medical Research Council score (mMRC) used to determine dyspnoea state, the Fatigue Severity Scale (FSS) and the Short Form 12 (SF12) that was carried out to determine the QOL both mentally and physically (MCS12 and PCS12). Descriptive analysis and comparison of scores between M6 and M12 were made. RESULTS: 120 patients completed both follow-up consultations. Overall, about 40% of the patients presented dyspnoea symptoms. The median mMRC score was 1 Interquartile ranges (IQR) = [0-2] at the two assessment. Concerning FSS scores, 35% and 44% of patients experienced fatigue at both follow-ups. The two scores of SF12 were lower than the general population standard scores. The mean PCS12 score was 42.85 (95% confidence interval (95% CI [41.05-44.65])) and mean MCS12 score of 46.70 (95% CI [45.34-48.06]) at 6 months. At 12 months, the mean PCS12 score was 42.18 (95% confidence interval (95% CI [40.46-43.89])) and mean MCS12 score of 47.13 (95% CI [45.98-48.28]). No difference was found between SF12 scores at 6 and 12 months. CONCLUSIONS: This study pinpoints the persistence of fatigue and a low mental and physical QOL compared to population norms even after 1 year following infection. It also supports the claims of mental or psychological alterations due to infection by this new virus, hence a lower overall QOL in patients.

Association between Heparin Dose and 6-Week Mortality in Patients with COVID-19.

Background: Severe forms of SARS-CoV-2 infections are associated with high rates of thromboembolic complications. Professional societies and expert consensus reports have recommended anticoagulants for COVID-19 hospitalized patients. Our study aimed to compare the effect of therapeutic, intermediate and prophylactic doses of heparin on 6-week survival in patients hospitalized for COVID-19. Methods: The study sample is a French cohort of COVID-19 patients hospitalized between Feb 25th and Apr 30th 2020. Patients were assigned to one of 3 anticoagulation dose groups based on the maximum dose they received for at least three days (prophylactic, intermediate or therapeutic). The main outcome was survival up to 42 days after hospital admission. Multivariate Cox regression models were performed to adjust analyses for confounding factors. Results: A total of 323 patients were included. The mean age of the study sample was 71.6 ± 15 years, and 56.3% were men. Treatment with the intermediate versus prophylactic dose of anticoagulation (HR = 0.50, 95%CI = [0.26; 0.99], p = 0.047) and with therapeutic versus prophylactic dose (HR = 0.58 95%CI = [0.34; 0.98], p = 0.044) was associated with a significant reduction in 6-week mortality, after adjustment for potential confounding factors. Comparison of therapeutic versus intermediate doses showed no significant difference in survival. Conclusions: Our results reported a significant positive effect of intermediate and therapeutic doses of heparin on 6-week survival for hospitalized COVID-19 patients compared with a prophylactic dose.

Impact of Pharmacists-Led Interventions in Primary Care for Adults with Type 2 Diabetes on HbA1c Levels: A Systematic Review and Meta-Analysis.

Type 2 diabetes mellitus (T2D) is responsible for an important premature mortality. Pharmacists involved in community-based pharmaceutical care services could help patients with diabetes through education and management as they participate in their regular and long-term care. This meta-analysis aimed to evaluate the association between interventions led by pharmacists in the primary care setting and mean change in HbA1c levels. Randomized controlled trials and quasi-experimental studies with a control group were included. Standardized mean differences (SMD) and their 95% confidence intervals (95% CI) were calculated to compare the mean change in HbA1c values between baseline and end of the intervention in each group. Subgroup analyses were performed to explore heterogeneity. Twelve articles were included. The results showed that pharmacist's interventions significantly reduced HbA1c compared to usual care with an overall SMD of −0.67 (95% CI = [−0.87; −0.48], p < 0.0001). Even if no significant difference between subgroups were found, the reduction of HbA1c seemed more important when baseline HbA1c was ≥8.5%, the intervention occurred monthly, in a primary care center and in countries with a lower human development index. Our results suggest that pharmacists-led interventions in the primary care setting can improve glycemic control for adults with T2D.

Association between proton pump inhibitors and severe hematological toxicity in patients receiving pemetrexed-based anticancer treatment: The prospective IPPEM study.

OBJECTIVE: Pemetrexed is associated with hematological toxicity. Drug-drug interactions (DDIs) between methotrexate and proton pump inhibitors (PPIs) induce a higher risk of hematological toxicity due to the inhibition of methotrexate excretion by PPIs. As pemetrexed and methotrexate are both excreted by human organic anion transporter 3 (hOAT3), this study investigates the hypothetical DDI between pemetrexed and PPIs in lung cancer patients. The primary objective was the occurrence of severe (grade ≥ 3) hematological toxicity. The secondary objectives were to describe the type of hematological toxicity and associated clinical consequences (NCT03537833). MATERIALS AND METHODS: PPI consumption was collected for each patient receiving pemetrexed-based anticancer chemotherapy from May 2018 to October 2020 in a prospective multicentric observational and nonrandomized study. Multivariate Cox regression and propensity score (PS) adjustment, PS matching and inverse weighting on PS (IPTW) methods were used. RESULTS: PPI consumption (55 among 156 included patients) was associated with a significantly higher risk of severe hematological toxicity in the multivariable Cox regression model (hazard ratio HR = 2.51, 95% confidence interval [1.47-4.26]; p = 0.005). Similar results were found with PS adjustment (HR = 1.91 CI95% [1.14-3.20]; p = 0.002), PS-matching (HR = 1.93 CI95% [1.08-3.45]; p = 0.02) and IPTW method (HR = 2.06 CI95% [1.27-3.35]; p = 0.004). Severe neutropenia and anemia occurred in 32.7% and 14.1% of patients, respectively. This resulted in 48 anticancer chemotherapy postponements and 24 dose adjustments, 26 growth factor prescriptions, 24 red blood cell transfusions, and 20 hospitalizations. CONCLUSIONS: The results strongly suggest an association between PPI consumption and pemetrexed-related severe hematological toxicity. Deprescription of PPIs when feasible should be considered to prevent this DDI.

Development and validation of a ready-to-use score to prioritise medication reconciliation at patient admission in an orthopaedic and trauma department.

OBJECTIVE: Medication reconciliation (MR) is recognised as an important tool in preventing medication errors such as unintentional discrepancies (UDs). The aim of this study was to identify independent predictive factors of UDs during MR at patient admission to an orthopaedic and trauma department. The secondary objective was to build and validate a ready-to-use score to prioritise patients. METHOD: A retrospective study was performed on 3.5 years of pharmacist-led MR in the orthopaedic and trauma department of a large university teaching hospital. Independent predictors of UD were identified by multivariable logistic regression. A priority score to identify patients at risk of at least one UD was constructed from the odds ratios of the risk factors, and validated in a separate cohort. Performance was assessed with sensitivity, specificity, C-statistic and Hosmer-Lemeshow goodness-of-fit. RESULTS: In total, 888 patients were included and 387 UDs were identified, mainly drug omissions (65.1%). Five independent predictors of UD were identified: age >75 years (OR 2.05, 95% CI 1.41 to 3.00; p<0.001), admission during school holidays (OR 1.69, 95% CI 1.17 to 2.44; p=0.005), female gender (OR 2.20, 95% CI 1.53 to 3.16; p<0.001), emergency hospitalisation (OR 2.05, 95% CI 1.45 to 2.92; p<0.001), and ≥5 medications on the best possible medication history (BPMH) (OR 3.29, 95% CI 2.20 to 4.94; p<0.001). Based on these predictors, a priority score ranging from 0 to 10 was built and internally and externally validated (C statistic 0.72, 95% CI 0.67 to 0.76). CONCLUSIONS: This study confirms the high prevalence of UD in patients admitted to orthopaedic and trauma surgery departments. Five independent predictive factors of UD during MR were identified (female gender, emergency hospitalisation, hospitalisation during school holidays, age ≥75 years, and ≥5 medicines on the BPMH). The developed risk score will help to prioritise MR among patients at risk of medication error and is ready-to-use in other orthopaedic and trauma departments.

Clinical Outcome Predictive Value of Procalcitonin in Patients Suspected with Infection in the Emergency Department.

Procalcitonin (PCT) may be useful for early risk stratification in the emergency department (ED), but the transposition of published data to routine emergency practice is sometimes limited. An observational retrospective study was conducted in the adult ED of the Reims University Hospital (France). Over one year, 852 patients suspected of infection were included, of mean age 61.7 years (SD: 22.6), and 624 (73.2%) were hospitalized following ED visit. Overall, 82 (9.6%) patients died during their hospitalization with an odds ratio (OR) of 5.10 (95% CI: 2.19-11.87) for PCT ≥ 0.5, in multivariate logistic regression analyses. Moreover, 78 (9.2%) patients were admitted to an ICU, 74 (8.7%) had attributable bacteremia, and 56 (6.6%) evolved toward septic shock with an OR of 4.37 (2.08-9.16), 6.38 (2.67-15.24), and 6.38 (2.41-16.86), respectively, for PCT ≥ 0.5. The highest discriminatory values were found for patients with age <65 years, but PCT lost its discrimination power for in-hospital mortality in patients with a bronchopulmonary infection site or a temperature ≥37.8°C and for ICU admission in patients with severe clinical presentations. PCT could be helpful in risk stratification, but several limitations must be considered, including being sometimes outperformed by a simple clinical examination.

The ROX index as a predictor of standard oxygen therapy outcomes in thoracic trauma.

BACKGROUND: Thoracic trauma is commonplace and accounts for 50-70% of the injuries found in severe trauma. Little information is available in the literature as to timing of endotracheal intubation. The main objective of this study was to assess the accuracy of the ROX index in predicting successful standard oxygen (SO) therapy outcomes, and in pre-empting intubation. METHODS: Patient selection included all thoracic trauma patients treated with standard oxygen who were admitted to a Level I trauma center between January 1, 2013 and April 30, 2020. Successful standard SO outcomes were defined as non-requirement of invasive mechanical ventilation within the 7 first days after thoracic trauma. RESULTS: One hundred seventy one patients were studied, 49 of whom required endotracheal intubation for acute respiratory distress (28.6%). A ROX index score ≤ 12.85 yielded an area under the ROC curve of 0.88 with a 95% CI [0.80-0.94], 81.63sensitivity, 95%CI [0.69-0.91] and 88.52 specificity, 95%CI [0.82-0.94] involving a Youden index of 0.70. Patients with a median ROX index greater than 12.85 within the initial 24 h were less likely to require mechanical ventilation within the initial 7 days of thoracic trauma. CONCLUSION: We have shown that a ROX index greater than 12.85 at 24 h was linked to successful standard oxygen therapy outcomes in critical thoracic trauma patients. It is our belief that an early low ROX index in the initial phase of trauma should heighten vigilance on the part of the attending intensivist, who has a duty to optimize management.

Diagnosis of postoperative recurrence of Crohn disease with MR-enterography: Value of diffusion-weighted imaging.

PURPOSE: To compare the diagnostic capabilities of MR enterography (MRE) using contrast-enhanced (CE) sequences with those of MRE using diffusion-weighted (DW) imaging for the diagnosis of postoperative recurrence at the neo-terminal ileum and/or anastomosis after ileocolonic resection in patients with Crohn disease (CD), and to clarify the role of additional DW imaging to CE-MRE in this context. MATERIAL AND METHODS: Forty patients who underwent ileal resection for CD, and both endoscopy and MRE within the first year after surgery were included. There were 21 men and 19 women, with a mean age of 38 years±12 (SD) years (range: 18-67 years). MRE examinations were blindly analyzed independently by one senior (R1) and one junior (R2) radiologist for the presence of small bowel postoperative recurrence at the anastomotic site. During a first reading session, T2-, steady-state- and DW-MRE were reviewed (DW-MRE or set 1). During a separate distant session, T2-, steady-state- and CE-MRE were reviewed (CE-MRE or set 2). Lastly, all sequences were analyzed altogether (set 3). Performances of each reader for the diagnosis of postoperative recurrence were evaluated using endoscopic findings as the standard of reference (Rutgeerts score≥i2b). RESULTS: Fifteen patients out of 40 (37.5%) had endoscopic postoperative recurrence at the anastomotic site. Sensitivity for the diagnosis of postoperative recurrence was 73% (95% CI: 51-96%) for R1 and 67% (95% CI: 43-91%) for R2 using set 1, and 80% (95% CI: 60-100%) for both readers using set 2. There was no significant differences in sensitivity between reading set 1 and reading set 2, for either R1 or R2 (R1, P> 0.99; R2, P=0.48). Specificity was 96% (95% CI: 88-100%) for both readers using set 1 or using set 2. Reading set 3 yielded an area under the ROC curve (AUC) of 0.93 (95% CI: 0.84-1) versus 0.89 (95% CI: 0.75-1) with set 1 (P=0.18) and versus 0.89 (95% CI: 0.78-1) with set 2 (P=0.21). No significant differences in AUC were found between set 1 or 2 and set 3 (P=0.18), nor between set 1 and 2 (P=0.76). Accuracies were 88% (95% CI: 74-95%) and 85% (95% CI: 71-93%) for DW-MRE for R1 and R2, respectively; 90% (95% CI: 77-96%) for CE-MRE for both readers; and 93% (95% CI: 80-97%) and 88% (95% CI: 74-95%) for R1 and R2 with set 3, respectively. CONCLUSION: DW-MRE has diagnostic capabilities similar to those of CE-MRE for the diagnosis of postoperative recurrence of CD at the anastomotic site.

Acquired decrease of the C3b/C4b receptor (CR1, CD35) and increased C4d deposits on erythrocytes from ICU COVID-19 patients.

In order to study the mechanisms of COVID-19 damage following the complement activation phase occurring during the innate immune response to SARS-CoV-2, CR1 (the regulating complement activation factor, CD35, the C3b/C4b receptor), C4d deposits on Erythrocytes (E), and the products of complement activation C3b/C3bi, were assessed in 52 COVID-19 patients undergoing O2 therapy or assisted ventilation in ICU units in Rheims France. An acquired decrease of CR1 density on E from COVID-19 patients was observed (Mean = 418, SD = 162, N = 52) versus healthy individuals (Mean = 592, SD = 287, N = 400), Student's t-test p < 10-6, particularly among fatal cases, and in parallel with several parameters of clinical severity. Large deposits of C4d on E in patients were well above values observed in normal individuals, mostly without concomitant C3 deposits, in more than 80% of the patients. This finding is reminiscent of the increased C4d deposits on E previously observed to correlate with sub endothelial pericapillary deposits in organ transplant rejection, and with clinical SLE flares. Conversely, significant C3 deposits on E were only observed among » of the patients. The decrease of CR1/E density, deposits of C4 fragments on E and previously reported detection of virus spikes or C3 on E among COVID-19 patients, suggest that the handling and clearance of immune complex or complement fragment coated cell debris may play an important role in the pathophysiology of SARS-CoV-2. Measurement of C4d deposits on E might represent a surrogate marker for assessing inflammation and complement activation occurring in organ capillaries and CR1/E decrease might represent a cumulative index of complement activation in COVID-19 patients. Taken together, these original findings highlight the participation of complement regulatory proteins and indicate that E are important in immune pathophysiology of COVID-19 patients. Besides a potential role for monitoring the course of disease, these observations suggest that novel therapies such as the use of CR1, or CR1-like molecules, in order to down regulate complement activation and inflammation, should be considered.