The clinical and financial burden of nonhepatocellular carcinoma focal lesions detected during the surveillance of patients with cirrhosis.

BACKGROUND AND AIMS: HCC surveillance is challenged by the detection of hepatic focal lesions (HFLs) of other types. This study aimed to describe the incidence, characteristics, outcomes, and costs of non-HCC HFL detected during surveillance. APPROACH AND RESULTS: We retrospectively analyzed nonstandardized workup performed in French patients included in HCC surveillance programs recruited in 57 French tertiary centers (ANRS CirVir and CIRRAL cohorts, HCC 2000 trial). The overall cost of workup was evaluated, with an estimation of an average cost per patient for the entire population and per lesion detected. A total of 3295 patients were followed up for 59.8 months, 391 (11.9%) patients developed HCCs (5-year incidence: 12.1%), and 633 (19.2%) developed non-HCC HFLs (5-year incidence: 21.8%). Characterization of non-HCC HFL required a median additional of 0.7 exams per year. A total of 11.8% of non-HCC HFLs were not confirmed on recall procedures, and 19.6% of non-HCC HFLs remained undetermined. A definite diagnosis of benign liver lesions was made in 65.1%, and malignant tumors were diagnosed in 3.5%. The survival of patients with benign or undetermined non-HCC HFL was similar to that of patients who never developed any HFL (5-year survival 92% vs. 88%, p = 0.07). The average cost of the diagnostic workup was 1087€ for non-HCC HFL and €1572 for HCC. CONCLUSIONS: Non-HCC HFLs are frequently detected in patients with cirrhosis, and do not impact prognosis, but trigger substantial costs. This burden must be considered in cost-effectiveness analyses of future personalized surveillance strategies.

Determinants of ventricular arrhythmias in sickle cell anemia: toward better prevention of sudden cardiac death.

Sudden death is 1 of the leading causes of death in adults with sickle cell anemia (SCA) but its etiology remains mostly unknown. Ventricular arrhythmia (VA) carries an increased risk of sudden death; however, its prevalence and determinants in SCA are poorly studied. This study aimed to identify the prevalence and predictors of VA in patients with SCA. From 2019 to 2022, 100 patients with SCA were referred to the physiology department to specifically analyze cardiac function and prospectively included in the DREPACOEUR registry. They underwent a 24-hour electrocardiogram monitoring (24h-Holter), transthoracic echocardiography, and laboratory tests on the same day. The primary end point was the occurrence of VA, defined as sustained or nonsustained ventricular tachycardia (VT), >500 premature ventricular contractions (PVCs) on 24h-Holter, or a recent history of VT ablation. The mean patient age was 46 ± 13 years, and 48% of the patients were male. Overall, VA was observed in 22 (22%) patients. Male sex (81% vs 34%; P = .02), impaired global longitudinal strain (GLS): -16% ± 1.9% vs -18.3% ± 2.7%; P = .02), and decreased platelet count (226 ± 96 giga per liter [G/L] vs 316 ± 130 G/L) were independently associated with VA. GLS correlated with PVC load every 24 hours (r = 0.39; P < .001) and a cutoff of -17.5% could predict VA with a sensitivity of 82% and a specificity of 63%. VAs are common in patients with SCA, especially in men. This pilot study uncovered GLS as a valuable parameter for improving rhythmic risk stratification.

When is the use of intravenous immunoglobulin appropriate in immune thrombocytopaenia?

Intravenous immunoglobulin (IVIg) is the gold standard treatment for severe cases of immune thrombocytopaenia (ITP). However, its cost, limited duration of efficacy and market supply tension have led French guidelines to reserve IVIg for ITP patients with formal contra-indications to corticosteroids, with French bleeding score ('Khellaf score') > 8, and corticosteroid-resistant patients either with Khellaf score ≤ 8 or in preparation for an invasive procedure or during pregnancy. We studied the prescribing practices of IVIg for ITP in real-life conditions and assessed their compliance with French guidelines. A monocentric retrospective study was conducted between 2016 and 2020 among 114 patients hospitalized in our unit, for a total of 208 IVIg treatments. In 37% of cases, the Khellaf score was >8, validating IVIg prescription according to French guidelines. In the remaining cases, reasons noted for use of IVIg included corticosteroid resistance (33.7%), preparation for an invasive procedure (8.5%), context of pregnancy (6.6%) and contra-indication to corticosteroids (3.3%). After analysis, IVIg prescription was considered valid according to current French guidelines in 84.4% of cases. Non-compliant IVIg prescription was more frequent in younger patients (p = 0.027). Concomitant anti-coagulation was also noted as an argument for IVIg prescription outside of the current French guidelines.

Effectiveness of comprehensive geriatric assessment adapted to primary care when provided by a nurse or a general practitioner: the CEpiA cluster-randomised trial.

BACKGROUND: The benefits of comprehensive geriatric assessment (CGA) are well established for hospital care but less so for primary care. Our primary objective was to assess the effect of two multifaceted interventions based on a CGA adapted for primary care on a composite criterion combining all-cause mortality, emergency department visits, unplanned hospital admissions, and institutionalisation. METHODS: This open-label, pragmatic, three-arm, cluster-randomised controlled trial involved 39 general practices in France. It included 634 patients aged 70 years or over with chronic health conditions and/or an unplanned hospital admission in the past 3 months, between 05/2016 and 08/2018. Interventions were in arm 1: a systematic nurse-led CGA; arm 2: a GP-led CGA, at the GP's discretion; arm 3: standard care. The primary composite endpoint was assessed at 12 months. The secondary endpoints included: components of the composite endpoint, health-related quality of life (Duke Health Profile), functional status (Katz Activities of Daily Living Index) and medications (number) at 12 months. Pairwise comparisons between the experimental groups and the control were tested. The main analysis was performed on the intention-to-treat (ITT) population, after imputing missing information and adjusting for baseline imbalances by mixed effects regressions. RESULTS: For the primary composite outcome, no statistically significant difference was found between arm 1 and the control (adjusted odds ratio [aOR] = 0.81 [95%CI 0.54-1.21], P = 0.31), whereas arm 2 and the control differed significantly (aOR = 0.60 [0.39-0.93], P = 0.022). A statistically lower risk of unplanned hospital admission in arm 2 vs control (aOR = 0.57 [0.36-0.92], P = 0.020)) was observed, while no statistically significant differences were found for the other components and between arm 1 and the control. None of the other secondary endpoints differed between arms. CONCLUSIONS: Our study led in community-dwelling older patients with chronic conditions found no significant effect of a CGA adapted for primary care on mortality, functional independence and quality of life, but suggests that a GP-led CGA may reduce the risk of unplanned hospital admission. Our study demonstrates the feasibility of incorporating CGA into clinical practice and highlights its potential benefits when applied on a case-by-case basis, guided by the GPs who develop the resulting PCP. TRIAL REGISTRATION: NCT02664454.

Success rate of fiducial marker placement for treatment of esophageal or rectal cancers: a prospective multicenter study (FIDECHO study) (with video).

BACKGROUND AND AIMS: EUS-guided placement of fiducial markers in patients with esophageal or rectal cancer who have been referred for radiation therapy lacks data regarding its feasibility and safety. The aim of this study was to assess the success rate of EUS-guided fiducial marker placement in these indications. METHODS: This prospective multicenter study enrolled patients with rectal or esophageal tumors who were treated between March 2017 and June 2021. The primary endpoint was the success of fiducial marker placement under EUS guidance utilizing the preloaded 22-gauge EchoTip Ultra Fiducial Needle (Cook Medical, Limerick, Ireland), defined by the ability to release fiducials at least at the proximal and distal ends of the tumor. Secondary endpoints were the adverse events, length of procedure, and fiducial markers remaining throughout radiation therapy. RESULTS: A total of 33 patients were included in this study, with a mean age of 64.2 ± 11.3 years; 66.7% were male. Twenty patients had rectal adenocarcinoma, and 13 had esophageal malignancies. The success rate of fiducial marker placement was 93.9%. Markers could only be released at the proximal end of the tumor in 2 cases. The average procedure time (±SD) was 12.5 ± 4.8 minutes. The number of fiducial markers placed for each patient was 3.8 ± .5. No adverse events were reported. At the end of radiotherapy, markers were still visible on imaging in all patients. CONCLUSIONS: This prospective multicenter study highlights the safety and high success of the placement of fiducial markers under EUS guidance for rectal and esophageal tumors, with no adverse events and with a short procedure time. Fiducial markers remained in place over time during radiation therapy. (Clinical trial registration number: NCT03057288.).

14-day tailored PCR-guided triple therapy versus 14-day non-Bismuth concomitant quadruple therapy for Helicobacter pylori eradication: A multicenter, open-label randomized noninferiority controlled trial.

BACKGROUND: The systematic use of susceptibility testing and tailored first-line treatment for Helicobacter pylori eradication has yet to be established. AIM: To compare 14-day tailored PCR-guided triple therapy to 14-day non-Bismuth concomitant quadruple therapy for first-line Helicobacter pylori eradication. PATIENTS AND METHODS: We performed a multicenter, parallel-group, randomized noninferiority controlled trial. Naive adult patients with Helicobacter pylori infection were treated with 14-day tailored PCR-guided triple therapy (esomeprazole 40 mg and amoxicillin 1000 mg b.d. plus clarithromycin 500 mg or levofloxacin 500 mg b.d. according to clarithromycin susceptibility) or 14-day non-Bismuth concomitant quadruple therapy (esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg b.d.). The primary endpoint was H. pylori eradication. RESULTS: We screened 991 patients for eligibility and randomized 241 patients. The first-line eradication rate was 99.2% in the tailored PCR-guided group and 95.9% in the control group (ITT population; absolute difference of +3.30%, with a lower bound of CI at -0.68%). Both first-line therapies were well tolerated, with a formally significant difference in favor of the tailored PCR-guided group (61.4% vs. 41.2%, p = 0.003). Economic analyses revealed a lower cost of the tailored PCR-guided arm, with a 92% chance of being jointly more effective and less expensive than the control arm in the ITT population. CONCLUSION: In a country with a high level of clarithromycin resistance, the results of our study demonstrated the noninferiority of 14-day tailored PCR-guided triple therapy as a first-line H. pylori eradication therapy compared to 14-day non-Bismuth quadruple therapy (ClinicalTrials.gov NCT02576236).

Predicting frailty domain impairments and mortality with the Hospital Frailty Risk Score among older adults with cancer: the ELCAPA-EDS cohort study.

BACKGROUND: Automated frailty screening tools like the Hospital Frailty Risk Score (HFRS) are primarily validated for care consumption outcomes. We assessed the predictive ability of the HFRS regarding care consumption outcomes, frailty domain impairments and mortality among older adults with cancer, using the Geriatric 8 (G8) screening tool as a clinical benchmark. METHODS: This retrospective, linkage-based study included patients aged ≥70 years with solid tumor, enrolled in the Elderly Cancer Patients (ELCAPA) multicentre cohort study (2016-2020) and hospitalized in acute care within the Greater Paris University Hospitals. HFRS scores, which encompass hospital-acquired problems and frailty-related syndromes, were calculated using data from the index admission and the preceding 6 months. A multidomain geriatric assessment (GA), including cognition, nutrition, mood, functional status, mobility, comorbidities, polypharmacy, incontinence, and social environment, was conducted at ELCAPA inclusion, with computation of the G8 score. Logistic and Cox regressions measured associations between the G8, HFRS, altered GA domains, length of stay exceeding 10 days, 30-day readmission, and mortality. RESULTS: Among 587 patients included (median age 82 years, metastatic cancer 47.0%), 237 (40.4%) were at increased frailty risk by the HFRS (HFRS>5) and 261 (47.5%) by the G8 (G8≤10). Both HFRS and G8 were significantly associated with cognitive and functional impairments, incontinence, comorbidities, prolonged length of stay, and 30-day mortality. The G8 was associated with polypharmacy, nutritional and mood impairment. DISCUSSION: Although showing significant associations with short-term care consumption, the HFRS could not identify polypharmacy, nutritional, mood and social environment impairments and showed low discriminatory ability across all GA domains.

Immunological Efficacy of Pneumococcal Vaccination Including the 13-Valent Pneumococcal Conjugate Vaccine in Adult Patients With Sickle Cell Disease: Results of the Randomized DREVAC Controlled Trial.

BACKGROUND: Patients with sickle cell disease (SCD) are at high risk for invasive pneumococcal diseases. The immunological efficacy of 13-valent conjugate pneumococcal vaccine (PCV13) followed by a 23-valent polysaccharide vaccine (PPSV23) is poorly documented in adults with SCD. METHODS: This was a randomized open-labeled phase 2 study of the immunogenicity of PCV13 at week 0, followed by PPSV23 at week 4, compared with PPSV23 alone at week 4 in adult patients with SCD. The proportion of responders (4-fold increase in serotype-specific immunoglobulin [Ig] G antibodies) to ≥10 shared serotypes was assessed at week 8. Secondary end points were (1) geometric mean titers, (2) responders to 0-1, 2-5, 6-9, or 10-12 serotypes, (3) pneumococcal opsonophagocytic activity, and (4) response durability at weeks 24 and 96. RESULTS: In total, 128 patients were randomized in the PCV13/PPSV23 (n = 63) or PPSV23-alone groups (n = 65). At week 8, 24.56% and 8.20% of patients from the PCV13/PPSV23 and PPSV23 groups, respectively, reached the primary end point (P = .02). These numbers were 36.2% and 8.7% for opsonophagocytic activity responders (P = .002). A combined PCV13/PPSV23 strategy improved the breadth of responses to 0-1, 2-5, 6-9, or 10-12 serotypes with 15.8%, 35%, 24.6%, and 24.6% versus 52.5%, 31%, 8%, and 8% in the PPSV23 group. At week 96, geometric mean titers were significantly higher in the PCV13/PPSV23 than in the PPSV23-alone group for 5 serotypes (4, 14, 19A, 19F, 23F). CONCLUSIONS: A PCV13/PPSV23 regimen improved the breadth and magnitude of antibody responses against a large range of pneumococcal serotypes in adults with SCD. The sustainability of the immune response requires recall strategies.Clinical Trial Registration: NCT02274415.

Integrating genetic variants into clinical models for hepatocellular carcinoma risk stratification in cirrhosis.

BACKGROUND & AIMS: Identifying individuals at higher risk of developing hepatocellular carcinoma (HCC) is pivotal to improve the performance of surveillance strategies. Herein, we aimed to evaluate the ability of single nucleotide polymorphisms (SNPs) to refine HCC risk stratification. METHODS: Six SNPs in PNPLA3, TM6SF2, HSD17B13, APOE, and MBOAT7 affecting lipid turnover and one variant involved in the Wnt-ß-catenin pathway (WNT3A-WNT9A rs708113) were assessed in patients with alcohol-related and/or HCV-cured cirrhosis included in HCC surveillance programmes (prospective CirVir and CIRRAL cohorts). Their prognostic value for HCC occurrence was assessed using Fine-Gray models combined into a 7-SNP genetic risk score (GRS). The predictive ability of two clinical scores (a routine non-genetic model determined by multivariate analysis and the external aMAP score) with/without the GRS was evaluated by C-indices. The standardised net benefit was derived from decision curves. RESULTS: Among 1,145 patients, 86 (7.5%) developed HCC after 43.7 months. PNPLA3 and WNT3A-WNT9A variants were independently associated with HCC occurrence. The GRS stratified the population into three groups with progressively increased 5-year HCC incidence (Group 1 [n = 627, 5.4%], Group 2 [n = 276, 10.7%], and Group 3 [n = 242, 15.3%]; p <0.001). The multivariate model identified age, male sex, diabetes, platelet count, gamma-glutamyltransferase levels, albuminemia and the GRS as independent risk factors. The clinical model performance for 5-year HCC prediction was similar to that of the aMAP score (C-Index 0.769). The addition of the GRS to both scores modestly improved their performance (C-Indices of 0.786 and 0.783, respectively). This finding was confirmed by decision curve analyses showing only fair clinical net benefit. CONCLUSIONS: Patients with cirrhosis can be stratified into HCC risk classes by variants affecting lipid turnover and the Wnt-ß-catenin pathway. The incorporation of this genetic information modestly improves the performance of clinical scores. IMPACT AND IMPLICATIONS: The identification of patients at higher risk of developing liver cancer is pivotal to improve the performance of surveillance. Risk assessment can be achieved by combining several clinical and biological parameters used in routine practice. The addition of patients' genetic characteristics can modestly improve this prediction and will ultimately pave the way for precision medicine in patients eligible for HCC surveillance, allowing physicians to trigger personalised screening strategies.

An educational programme in neonatal intensive care units (SEPREVEN): a stepped-wedge, cluster-randomised controlled trial.

BACKGROUND: Patients in neonatal intensive care units (NICUs) are at high risk of adverse events. The effects of medical and paramedical education programmes to reduce these have not yet been assessed. METHODS: In this multicentre, stepped-wedge, cluster-randomised controlled trial done in France, we randomly assigned 12 NICUs to three clusters of four units. Eligible neonates were inpatients in a participating unit for at least 2 days, with a postmenstrual age of 42 weeks or less on admission. Each cluster followed a 4-month multifaceted programme including education about root-cause analysis and care bundles. The primary outcome was the rate of adverse events per 1000 patient-days, measured with a retrospective trigger-tool based chart review masked to allocation of randomly selected files. Analyses used mixed-effects Poisson modelling that adjusted for time. This trial is registered with ClinicalTrials.gov, NCT02598609. FINDINGS: Between Nov 23, 2015, and Nov 2, 2017, event rates were analysed for 3454 patients of these 12 NICUs for 65 830 patient-days. The event rate per 1000 patient-days reduced significantly from the control to the intervention period (33·9 vs 22·6; incidence rate ratio 0·67; 95% CI 0·50-0·88; p=0·0048). INTERPRETATION: A multiprofessional safety-promoting programme in NICUs reduced the rate of adverse events and severe and preventable adverse events in highly vulnerable patients. This programme could significantly improve care offered to critically ill neonates. FUNDING: Solidarity and Health Ministry, France.

Dynamic personalized prediction of the individual liver-related risk after sustained viral response in HCV patients.

Sustained viral response (SVR) significantly improves the prognosis in patients with hepatitis C virus (HCV) chronic infection but does not totally alleviate the risk of liver-related complications (LRC). We aimed to evaluate whether the dynamics of multiple measurements of simple parameters after SVR enable the development of a personalized prediction of prognosis in HCV patients. HCV mono-infected patients who experienced SVR in two prospective cohorts (ANRS CO12 CirVir cohort: derivation set; ANRS CO22 HEPATHER cohort: validation set) were included. The study outcome was LRC, a composite criterion including decompensation of cirrhosis and/or hepatocellular carcinoma. Joint latent class modelling accounting for both biomarker trajectory and event occurrence during follow-up was developed in the derivation set to compute individual dynamic predictions, with further evaluation in the validation set. In the derivation set (n = 695; 50 LRC during the median 3.8 [1.6-7.5] years follow-up), FIB4 was identified as a biomarker associated with LRC occurrence after SVR. Joint modelling used sex and the dynamics of FIB4 and diabetes status to develop a personalized prediction of LRC. In the validation set (n = 7064; 273 LRC during the median 3.6 [2.5-4.9] years follow-up), individual dynamic predictions from the model accurately stratified the risk of LRC. Time-dependent Brier Score showed good calibration that improved with the accumulation of visits, justifying our modelling approach considering both baseline and follow-up measurements. Dynamic modelling using repeated measurements of simple parameters predicts the individual residual risk of LRC and improves personalized medicine after SVR in HCV patients.

ERS: A simple scoring system to predict early recurrence after surgical resection for hepatocellular carcinoma.

BACKGROUND: Surgical resection (SR) is a potentially curative treatment of hepatocellular carcinoma (HCC) hampered by high rates of recurrence. New drugs are tested in the adjuvant setting, but standardised risk stratification tools of HCC recurrence are lacking. OBJECTIVES: To develop and validate a simple scoring system to predict 2-year recurrence after SR for HCC. METHODS: 2359 treatment-naïve patients who underwent SR for HCC in 17 centres in Europe and Asia between 2004 and 2017 were divided into a development (DS; n = 1558) and validation set (VS; n = 801) by random sampling of participating centres. The Early Recurrence Score (ERS) was generated using variables associated with 2-year recurrence in the DS and validated in the VS. RESULTS: Variables associated with 2-year recurrence in the DS were (with associated points) alpha-fetoprotein (<10 ng/mL:0; 10-100: 2; >100: 3), size of largest nodule (≥40 mm: 1), multifocality (yes: 2), satellite nodules (yes: 2), vascular invasion (yes: 1) and surgical margin (positive R1: 2). The sum of points provided a score ranging from 0 to 11, allowing stratification into four levels of 2-year recurrence risk (Wolbers' C-indices 66.8% DS and 68.4% VS), with excellent calibration according to risk categories. Wolber's and Harrell's C-indices apparent values were systematically higher for ERS when compared to Early Recurrence After Surgery for Liver tumour post-operative model to predict time to early recurrence or recurrence-free survival. CONCLUSIONS: ERS is a user-friendly staging system identifying four levels of early recurrence risk after SR and a robust tool to design personalised surveillance strategies and adjuvant therapy trials.

Guided Self-rehabilitation Contract vs conventional therapy in chronic peripheral facial paresis: VISAGE, a multicenter randomized controlled trial.

BACKGROUND: One year after persistent peripheral facial paresis (PFP), prescriptions of conventional rehabilitation are often downgraded into maintenance rehabilitation or discontinued, the patient entering what is seen as a chronic stage. This therapeutic choice is not consistent with current knowledge about behavior-induced plasticity, which is available all life long and may allow intense sensorimotor rehabilitation to remain effective. This prospective, randomized, multicenter single-blind study in subjects with chronic unilateral PFP evaluates changes in facial motor function with a Guided Self-rehabilitation Contract (GSC) vs. conventional therapy alone, carried out for six months. METHODS: Eighty-two adult subjects with chronic unilateral PFP (> 1 year since facial nerve injury) will be included in four tertiary, maxillofacial surgery (2), otolaryngology (1) and rehabilitation (1) centers to be randomized into two rehabilitation groups. In the experimental group, the PM&R specialist will implement the GSC method, which for PFP involves intensive series of motor strengthening performed daily on three facial key muscle groups, i.e. Frontalis, Orbicularis oculi and Zygomatici. The GSC strategy involves: i) prescription of a daily self-rehabilitation program, ii) teaching of the techniques involved in the program, iii) encouragement and guidance of the patient over time, in particular by requesting a quantified diary of the work achieved to be returned by the patient at each visit. In the control group, participants will benefit from community-based conventional therapy only, according to their physician's prescription. The primary outcome measure is the composite score of Sunnybrook Facial Grading System. Secondary outcome measures include clinical and biomechanical facial motor function quantifications (Créteil Scale and 3D facial motion analysis through the Cara system), quality of life (Facial Clinimetric Evaluation and Short-Form 12), aesthetic considerations (FACE-Q scale) and mood representations (Hospital Anxiety and Depression scale). Participants will be evaluated every three months by a blinded investigator, in addition to four phone calls (D30/D60/D120/D150) to monitor compliance and tolerance to treatment. DISCUSSION: This study will increase the level of knowledge on the effects of intense facial motor streng-          Facial paralysisthening prescribed through a GSC in patients with chronic peripheral facial paresis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04074018 . Registered 29 August 2019. PROTOCOL VERSION: Version N°4.0-04/02/2021.

TRI-SCORE: a new risk score for in-hospital mortality prediction after isolated tricuspid valve surgery.

AIMS: Isolated tricuspid valve surgery (ITVS) is considered to be a high-risk procedure, but in-hospital mortality is markedly variable. This study sought to develop a dedicated risk score model to predict the outcome of patients after ITVS for severe tricuspid regurgitation (TR). METHODS AND RESULTS: All consecutive adult patients who underwent ITVS for severe non-congenital TR at 12 French centres between 2007 and 2017 were included. We identified 466 patients (60 ± 16 years, 49% female, functional TR in 49%). In-hospital mortality rate was 10%. We derived and internally validated a scoring system to predict in-hospital mortality using multivariable logistic regression and bootstrapping with 1000 re-samples. The final risk score ranged from 0 to 12 points and included eight parameters: age ≥70 years, New York Heart Association Class III-IV, right-sided heart failure signs, daily dose of furosemide ≥125 mg, glomerular filtration rate <30 mL/min, elevated bilirubin, left ventricular ejection fraction <60%, and moderate/severe right ventricular dysfunction. Tricuspid regurgitation mechanism was not an independent predictor of outcome. Observed and predicted in-hospital mortality rates increased from 0% to 60% and from 1% to 65%, respectively, as the score increased from 0 up to ≥9 points. Apparent and bias-corrected areas under the receiver operating characteristic curves were 0.81 and 0.75, respectively, much higher than the logistic EuroSCORE (0.67) or EuroSCORE II (0.63). CONCLUSION: We propose TRI-SCORE as a dedicated risk score model based on eight easy to ascertain parameters to inform patients and physicians regarding the risk of ITVS and guide the clinical decision-making process of patients with severe TR, especially as transcatheter therapies are emerging (www.tri-score.com).

Impact of two waves of Sars-Cov2 outbreak on the number, clinical presentation, care trajectories and survival of patients newly referred for a colorectal cancer: A French multicentric cohort study from a large group of university hospitals.

The SARS-Cov2 may have impaired care trajectories, patient overall survival (OS), tumor stage at initial presentation for new colorectal cancer (CRC) cases. This study aimed at assessing those indicators before and after the beginning of the pandemic in France. In this retrospective cohort study, we collected prospectively the clinical data of the 11.4 million of patients referred to the Greater Paris University Hospitals (AP-HP). We identified new CRC cases between 1 January 2018 and 31 December 2020, and compared indicators for 2018-2019 to 2020. pTNM tumor stage was extracted from postoperative pathology reports for localized colon cancer, and metastatic status was extracted from CT-scan baseline text reports. Between 2018 and 2020, 3602 and 1083 new colon and rectal cancers were referred to the AP-HP, respectively. The 1-year OS rates reached 94%, 93% and 76% for new CRC patients undergoing a resection of the primary tumor, in 2018-2019, in 2020 without any Sars-Cov2 infection and in 2020 with a Sars-Cov2 infection, respectively (HR 3.78, 95% CI 2.1-7.1). For patients undergoing other kind of anticancer treatment, the percentages are 64%, 66% and 27% (HR 2.1, 95% CI 1.4-3.3). Tumor stage at initial presentation, emergency level of primary tumor resection, delays between the first multidisciplinary meeting and the first anticancer treatment did not differ over time. The SARS-Cov2 pandemic has been associated with less newly diagnosed CRC patients and worse 1-year OS rates attributable to the infection itself rather than to its impact on hospital care delivery or tumor stage at initial presentation.

Liver Stiffness by Transient Elastography to Detect Porto-Sinusoidal Vascular Liver Disease With Portal Hypertension.

BACKGROUND AND AIMS: Porto-sinusoidal vascular liver disease (PSVD) is a rare cause of portal hypertension. PSVD is still often misdiagnosed as cirrhosis, emphasizing the need to improve PSVD diagnosis strategies. Data on liver stiffness measurement using transient elastography (TE-LSM) in PSVD are limited. The aim of this study was to evaluate the accuracy of TE-LSM to discriminate PSVD from cirrhosis in patients with signs of portal hypertension. APPROACH AND RESULTS: Retrospective multicenter study comparing TE-LSM in patients with PSVD, according to Vascular Liver Disease Interest Group criteria, with patients with compensated biopsy-proven cirrhosis associated with alcohol (n = 117), HCV infection (n = 110), or NAFLD (n = 46). All patients had at least one sign of portal hypertension among gastroesophageal varices, splenomegaly, portosystemic collaterals, history of ascites, or platelet count < 150 × 109 /L. The 77 patients with PSVD included in the test cohort had lower median TE-LSM (7.9 kPa) than the patients with alcohol-associated, HCV-related, and NAFLD-related cirrhosis (33.8, 18.2, and 33.6 kPa, respectively; P < 0.001). When compared with cirrhosis, a cutoff value of 10 kPa had a specificity of 97% for the diagnosis of PSVD with a 85% positive predictive value. A cutoff value of 20 kPa had a sensitivity of 94% for ruling out PSVD with a 97% negative predictive value. Of the patients, 94% were well-classified. Even better results were obtained in a validation cohort including 78 patients with PSVD. CONCLUSIONS: This study including a total of 155 patients with PSVD and 273 patients with cirrhosis demonstrates that TE-LSM < 10 kPa strongly suggests PSVD in patients with signs of portal hypertension. Conversely, when TE-LSM is >20 kPa, PSVD is highly unlikely.

Identification of factors impairing exercise capacity after severe COVID-19 pulmonary infection: a 3-month follow-up of prospective COVulnerability cohort.

BACKGROUND: Patient hospitalized for coronavirus disease 2019 (COVID-19) pulmonary infection can have sequelae such as impaired exercise capacity. We aimed to determine the frequency of long-term exercise capacity limitation in survivors of severe COVID-19 pulmonary infection and the factors associated with this limitation. METHODS: Patients with severe COVID-19 pulmonary infection were enrolled 3 months after hospital discharge in COVulnerability, a prospective cohort. They underwent cardiopulmonary exercise testing, pulmonary function test, echocardiography, and skeletal muscle mass evaluation. RESULTS: Among 105 patients included, 35% had a reduced exercise capacity (VO2peak < 80% of predicted). Compared to patients with a normal exercise capacity, patients with reduced exercise capacity were more often men (89.2% vs. 67.6%, p = 0.015), with diabetes (45.9% vs. 17.6%, p = 0.002) and renal dysfunction (21.6% vs. 17.6%, p = 0.006), but did not differ in terms of initial acute disease severity. An altered exercise capacity was associated with an impaired respiratory function as assessed by a decrease in forced vital capacity (p < 0.0001), FEV1 (p < 0.0001), total lung capacity (p < 0.0001) and DLCO (p = 0.015). Moreover, we uncovered a decrease of muscular mass index and grip test in the reduced exercise capacity group (p = 0.001 and p = 0.047 respectively), whilst 38.9% of patients with low exercise capacity had a sarcopenia, compared to 10.9% in those with normal exercise capacity (p = 0.001). Myocardial function was normal with similar systolic and diastolic parameters between groups whilst reduced exercise capacity was associated with a slightly shorter pulmonary acceleration time, despite no pulmonary hypertension. CONCLUSION: Three months after a severe COVID-19 pulmonary infection, more than one third of patients had an impairment of exercise capacity which was associated with a reduced pulmonary function, a reduced skeletal muscle mass and function but without any significant impairment in cardiac function.

Diagnostic Value of Extracellular Volume Quantification and Myocardial Perfusion Analysis at CT in Cardiac Amyloidosis.

Background CT can provide information regarding myocardial perfusion and expansion of the extracellular space, which is relevant to patients with cardiac amyloidosis (CA). Purpose To evaluate the role of CT in the diagnosis and prognosis of CA. Materials and Methods In this prospective study (Commission National de l'Informatique et des Libertés registration no. 1431858), participants with CA, participants with nonamyloid cardiac hypertrophy (NACH), and participants without hypertrophy were included between April 2017 and December 2018. The confirmed diagnosis of CA was determined according to established criteria (ie, proven with positive bone scintigraphy or endomyocardial biopsy). All participants were imaged with dynamic CT perfusion imaging at whole-heart cardiac CT. Extracellular volume measured at CT and myocardial perfusion parameters calculated on CT perfusion maps were compared among different participant groups. Differences between continuous data were tested using the unpaired t test, Mann-Whitney rank-sum test, or the Kruskal-Wallis test. Results A total of 84 participants with CA, 43 participants with NACH, and 33 participants without hypertrophy were included. Participants with CA exhibited a higher value of extracellular volume measured at CT (mean, 54.7% ± 9.7 [standard deviation]) than participants with NACH (mean, 34.6% ± 9.1; P < .001) and participants without hypertrophy (mean, 35.9% ± 9.9; P = .001). Mean myocardial blood volume and mean myocardial blood flow were lower in participants with CA (mean myocardial blood volume: 4.05 mL/100 g of myocardium ± 0.80; mean myocardial blood flow: 73.2 mL/100 g of myocardium per minute ± 25.7) compared to participants with NACH (mean myocardial blood volume: 5.38 mL/100 g of myocardium ± 1.20, P < .001; mean myocardial blood flow: 89.6 mL/100 g of myocardium per minute ± 31.3, P = .007) and participants without hypertrophy (mean myocardial blood volume: 5.68 mL/100 g of myocardium ± 1.05; mean myocardial blood flow: 106.3 mL/100 g of myocardium per minute ± 29.8; P < .001 for both). Extracellular volume measured at CT (hazard ratio >0.56 vs ≤0.56 = 4.2 [95% CI: 1.4, 11.8]), mean slope (hazard ratio ≤3.0 sec-1 vs >3.0 sec-1 = 0.2 [95% CI: 0.1, 0.8]), and time to peak (hazard ratio >20 seconds vs ≤20 seconds = 11.6 [95% CI: 1.3, 101.6]) were predictive of mortality in participants with CA. Conclusion Participants with cardiac amyloidosis exhibited an increase in extracellular volume at CT and abnormal CT perfusion parameters. Extracellular volume and several perfusion parameters were predictive of mortality. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Zimmerman in this issue.

Left atrial appendage closure for stroke prevention in atrial fibrillation: Final report from the French left atrial appendage closure registry.

OBJECTIVES: The French left atrial appendage (LAA) closure registry (FLAAC) aimed to assess the safety and efficacy of LAA closure in daily practice. BACKGROUND: LAA closure has emerged as an alternative for preventing thromboembolic events (TE) in patients with non-valvular atrial fibrillation (NVAF). Clinical data in this field remains limited and few investigator-initiated, real-world registries have been reported. METHODS: This nationwide, prospective study was performed in 36 French centers. The primary endpoint was the TE rate after successful LAA closure. RESULTS: The FLAAC registry included 816 patients with a mean age of 75.5 ± 0.3 years, mean follow-up of 16.0 ± 0.3 months, high TE (CHA2 DS2 -VASc score: 4.6 ± 0.1) and bleeding risks (HAS-BLED score: 3.2 ± 0.05) and common contraindications to long-term anticoagulation (95.7%). Procedure or device-related serious adverse events occurred in 49 (6.0%) patients. The annual rate of ischemic stroke/systemic embolism was 3.3% (2.4-4.6). This suggests a relative 57% reduction compared to the risk of stroke in historical NVAF populations without antithrombotic therapy. By multivariate analysis, history of TE was the only factor associated with stroke/systemic embolism during follow-up (HR, 3.3 [1.58-6.89], p = 0.001). The annual mortality rate was 10.2% (8.4-12.3). Most of the deaths were due to comorbidities or underlying cardiovascular diseases and unrelated to the device or to TE. CONCLUSIONS: Our study suggests that LAA closure can be an option in patients with NVAF. Long-term follow-up mortality was high, mostly due to comorbidities and underlying cardiovascular diseases, highlighting the importance of multidisciplinary management after LAA closure. REGISTRATION: NCT02252861.

Circulating plasmablasts and high level of BAFF are hallmarks of minimal change nephrotic syndrome in adults.

BACKGROUND: The recent success achieved with the use of B cell-depleting agents in some patients with minimal change nephrotic syndrome (MCNS) suggests an unexpected role for B lymphocytes in the pathogenesis of this immune-mediated glomerular disease. Nevertheless, no extensive B-cell phenotyping analysis has ever been performed in untreated adult patients soon after MCNS diagnosis. METHODS: We investigated the distribution of the different B-cell subpopulations in 22 untreated adult patients with biopsy-proven MCNS [MCNS relapse (MCNS-Rel)]. We compared these data with those for 24 healthy controls, 13 MCNS patients in remission (with no specific treatment) and 19 patients with idiopathic membranous nephropathy (IMN). RESULTS: Patients with MCNS-Rel or IMN had higher proteinuria and lower serum albumin and gammaglobulin levels (P < 0.0001 for all comparisons) than MCNS patients in remission. Plasmablasts were the only B-cell subsets present at significantly higher levels in MCNS-Rel patients than in the patients of the other three groups (P < 0.05 for all comparisons). The lower albumin levels and higher proteinuria levels were positively correlated with the percentage of circulating plasmablasts (Spearman test's ρ = -0.54, P = 0.01 and ρ = 0.65, P = 0.002, respectively). Similarly, the increase of immunoglobulin M (IgM) and the decrease of IgG levels were significantly associated with the percentage of plasmablasts in MCNS-Rel patients (Spearman's ρ = 0.36, P = 0.01 and Spearman's ρ = -0.60, P = 0.01, respectively). Increased production of interleukin (IL)-21, IL-6 and B-cell activating factor (BAFF) in the serum of MCNS-Rel patients was found significantly correlated with the percentage of plasmablasts (ρ = 0.72, P = 0.0002, ρ = 0.49, P = 0.04 and ρ = 0.62, P = 0.009, respectively). CONCLUSIONS: An increase in the proportion of circulating plasmablasts seems to be a hallmark of untreated MCNS in adult patients. Further studies are required to more precisely determine the phenotype and functions of these cells.