Analysis of 15 cases from a monocentric cohort of 307 liver abscesses.

BACKGROUND: Out of the context of haematological patients, Candida sp. is rarely retrieved from pyogenic liver abscesses (PLA). OBJECTIVES: Our objective was to assess the risk factors for occurrence, and clinical, microbiological characteristics, management and outcome of Candida pyogenic liver abscesses (C-PLA). PATIENTS/METHODS: We retrospectively analysed C-PLA cases and compared them to pyogenic liver abscesses exclusively due to bacteria (B-PLA) included in our monocentric database on liver abscesses. Unfavourable course was defined as the occurrence of a primary treatment failure (PTF), recurrence after an initial cure, or death within 3 months after diagnosis. RESULTS: Between 2010 and 2018, 15 C-PLA and 292 B-PLA were included. All C-PLA had a biliary origin and were polymicrobial. All patients with C-PLA had at least one comorbidity at risk for Candida infection and 7 (53.3%) presented with sepsis requiring an admission in intensive care unit. Median duration of antifungal treatment was 42 days [24-55]. In multivariate analysis, compared with B-PLA, a medical history of malignancy (OR 4.16; 95%CI 1.15-18.72) or liver abscess (OR 7.39; 95%CI 2.10-26.62), and sepsis with severity criteria (OR 3.52; 95%CI 1.07-11.90) were independently associated with the occurrence of C-PLA. In multivariate analysis, C-PLA was associated with a higher risk of recurrence (HR 3.08; 95%CI 1.38-11.22). CONCLUSION: Candida liver abscesses in non-neutropenic is a rare and severe disease. The high rate of recurrence should lead to discuss a more intensive treatment.

Evaluation of the contribution of shotgun metagenomics in the microbiological diagnosis of liver abscesses.

BACKGROUND: Shotgun metagenomics (SMg) sequencing has gained a considerable interest, as it enables the detection of any microorganisms through a single analysis. Due to the limitations of standard microbiological approaches, the microbial documentation of liver abscesses (LA), which is crucial for their medical management, can be difficult. Here we aimed to compare the performance of SMg with standard approaches for the microbiological documentation of LA. METHODS: In this retrospective study conducted at two centers, we compared the results of standard microbiology with metagenomics analysis of consecutive LA samples. For samples tested positive for Klebsiella pneumoniae, we compared the analysis of virulence and resistance genes using metagenomics data to whole-genome sequencing of corresponding isolates obtained in culture. RESULTS: Out of the 62 samples included, standard approaches and SMg yielded documentation in 80.6% and 96.8%, respectively. In 37.1% (23/62) of cases, both methods showed identical results, whereas in 43.5% (27/62) of cases, the samples were positive by both methods, but SMg found additional species in 88.9% (24/27), mostly anaerobes. When the standard approaches were negative, the SMg was able to detect microorganisms in 80.0% of cases (8/10). Overall, SMg identified significantly more microorganisms than culture (414 vs.105; p<0.05). K. pneumoniae genome analysis was able to detect resistance and virulence genes with a level of sensitivity depending on the depth of sequencing. DISCUSSION: Overall, we showed that SMg had better performance in detecting and identifying microorganisms from LA samples and could help characterizing strain's resistome and virulome. Although still costly and requiring specific skills and expensive equipment, MGs methods are set to expand in the future.

[Clinical and radiological differences between amoebic and pyogenic liver abscess: A case-control study]. / Analyse des différences cliniques et radiologiques entre abcès hépatiques amibiens et à pyogènes à partir d'une étude cas-témoin.

INTRODUCTION: Amoebic liver abscess (ALA) is the fourth cause of mortality by parasitic infection. This study aimed to assess clinical, radiological and therapeutic characteristics of patients admitted for amoebic liver abscess compared to pyogenic abscess in a French digestive tertiary care-centre. MATERIAL AND METHOD: The charts of patients hospitalized for a liver abscess between 2010 and 2020 were retrospectively assessed then separated in two groups: amoebic liver abscess and pyogenic liver abscess from portal underlying cause. Clinical and radiological data were collected for univariate comparison. RESULTS: Twenty-one patients were hospitalized during the time of the study for ALA, and 21 patients for pyogenic liver abscess with a portal mechanism. All patients hospitalized for ALA lived in and/or had travelled recently in an endemic area. In comparison with patients hospitalized for pyogenic abscess, patients admitted for ALA were younger (44years old vs. 63years old, P<0.001), had less comorbidities (5% vs. 43% of patients with at least one comorbidity, P<0.01), a longer median duration of symptoms (10days vs. 3days, P=0.015), abdominal pain (86% vs. 52%, P=0.019), and a slighter leucocytosis (9600G/L vs. 15,500G/L, P=0.041) were more frequent. On the abdominal tomodensitometry, density of ALA was higher (34 vs. 25 UH, P<0.01), associated with a focal intra-hepatic biliary dilatation and less often multiloculated. CONCLUSION: While rare in western countries, amoebic liver abscess care should not be underestimated. The presence of a solitary liver abscess of intermediate density on computed tomography, occurring on a patient returning from an endemic zone should lead the physician to a possible diagnosis of ALA.

Prior participation as a standardized patient improves OSCE scores of third-year medical students: A pilot comparative study at Université Paris Cité Medical School.

OBJECTIVE: Objective structured clinical examinations (OSCE) are one of the main modalities of skills' assessment of medical students. We aimed to evaluate the educational value of the participation of third-year medical students in OSCE as standardized patients. METHODS: We conducted a pilot OSCE session where third-year students participated in sixth-year students' OSCE as standardized patients (cases). Their scores in their own subsequent OSCE exams were compared with third-year students who had not participated (controls). Students' perceptions (stress, preparedness, ease) regarding their OSCE were compared with self-administered questionnaires. RESULTS: A total of 42 students were included (9 cases and 33 controls). Median [IQR] overall score (out of 20 points) obtained by the cases was 17 [16.3-18] versus 14.5 [12.7-16.3] for controls (p < 0.001). Students' perception of their evaluation (difficulty, stress, communication) was not significantly different between cases and controls. Most cases agreed that their participation was beneficial in reducing their stress (67%), increasing their preparedness (78%) and improving their communication skills (100%). All cases agreed that this participation should be offered more widely. CONCLUSION: Students' participation in OSCE as standardized patients led to better performance on their own OSCE and were considered beneficial. This approach could be more broadly generalized to improve student performance.

Enterococcal pyogenic liver abscesses: high risk of treatment failure and mortality.

Enterococci are the most frequent gram-positive bacteria recovered from pyogenic liver abscesses (PLA). This study aims to analyze the impact of the presence of Enterococcus spp. on PLA outcome. We retrospectively analyzed the characteristics and outcome of all PLA cases in which Enterococcus spp. was isolated between January 2010 and September 2019 in a French university hospital and compared them to PLA without Enterococcus spp. Enterococci were recovered from 68 of the 359 (19%) PLA cases. Among the 78 isolates, Enterococcus faecalis (n = 37, 47.7%) and Enterococcus faecium (n = 32, 41%) were the most frequent. Enterococcal PLA were more often of biliary origin (79.4% versus 54.6%, p < 0.001) or post-surgical (35.3% versus 18.6%, p = 0.004). Multivariate analysis showed an independent association between the isolation of Enterococcus spp. and 3-month mortality (HR 2.51, p = 0.011), primary failure (HR 2.15, p = 0.006), but not with relapses (HR 0.86, p = 0.739). In the subgroup of enterococcal PLA, portal vein thrombosis was the only factor significantly associated with 3-month mortality (univariate HR 3.45, p = 0.023) or primary treatment failure (multivariate, HR 4.02, p = 0.006). Enterococcus spp. identification in a PLA is associated with a higher mortality and primary treatment failure.

Prospective Comparison Between Shotgun Metagenomics and Sanger Sequencing of the 16S rRNA Gene for the Etiological Diagnosis of Infections.

Bacteriological diagnosis is traditionally based on culture. However, this method may be limited by the difficulty of cultivating certain species or by prior exposure to antibiotics, which justifies the resort to molecular methods, such as Sanger sequencing of the 16S rRNA gene (Sanger 16S). Recently, shotgun metagenomics (SMg) has emerged as a powerful tool to identify a wide range of pathogenic microorganisms in numerous clinical contexts. In this study, we compared the performance of SMg to Sanger 16S for bacterial detection and identification. All patients' samples for which Sanger 16S was requested between November 2019 and April 2020 in our institution were prospectively included. The corresponding samples were tested with a commercial 16S semi-automated method and a semi-quantitative pan-microorganism DNA- and RNA-based SMg method. Sixty-seven samples from 64 patients were analyzed. Overall, SMg was able to identify a bacterial etiology in 46.3% of cases (31/67) vs. 38.8% (26/67) with Sanger 16S. This difference reached significance when only the results obtained at the species level were compared (28/67 vs. 13/67). This study provides one of the first evidence of a significantly better performance of SMg than Sanger 16S for bacterial detection at the species level in patients with infectious diseases for whom culture-based methods have failed. This technology has the potential to replace Sanger 16S in routine practice for infectious disease diagnosis.

Large retrospective study analysing predictive factors of primary treatment failure, recurrence and death in pyogenic liver abscesses.

PURPOSE: Pyogenic liver abscess (PLA) is a severe disease, which unfavourable evolution remains frequent. Our objective was to assess predictive factors of unfavourable outcome in patients with PLA. METHODS: We conducted a retrospective study in a French tertiary care centre. All patients admitted for PLA between 2010 and 2018 were included. Unfavourable course was defined as the occurrence of a primary treatment failure (PTF), recurrence of PLA after an initial cure, or death within 3 months after diagnosis. Hazard ratios (95% CI) were calculated with multivariable Cox proportional hazard models. RESULTS: 302 patients were included among which 91 (30.1%) patients had an unfavourable outcome because of PTF, recurrence or death in 55 (18.2%), 28 (9.2%) and 32 (10.6%) patients, respectively. Hepatic metastases (HR 2.08; 95% CI 1.04-4.15), a nosocomial infection (2.25; 1.14-4.42), portal thrombosis (2.12; 1.14-3.93), and the isolation of Enterococcus spp. (2.18; 1.22- 3.90) were independently associated with PTF. Ischemic cholangitis (6.30; 2.70-14.70) and the isolation of Streptococcus spp. (3.72; 1.36-10.16) were associated with the risk of recurrence. Charlson comorbidity index (HR 1.30 per one point; 95% CI 1.15-1.46; p < 0.001), portal thrombosis (3.53; 1.65-7.56) and the presence of multi-drug-resistant organisms (3.81; 1.73-8.40) were associated with mortality within 3 months following PLA diagnosis. PLA drainage was the only factor associated with a lower mortality (0.14; 0.06-0.34). CONCLUSION: Identification of specific risk factors may help to improve the management of PLA and to elaborate targeted recommendations according to patient's and disease's characteristics.

Hepatic sarcoidosis with symptomatic portal hypertension: A report of 12 cases with review of the literature.

Introduction: Sarcoidosis is a systemic granulomatosis of unknown etiology, characterized by the presence of immune granulomas. Liver damage is a relatively common extra-pulmonary manifestation, occurring in 3.6-30% of cases. Some patients can develop symptomatic portal hypertension (PH). Few series have evaluated the prognosis of symptomatic PH as well as the efficacy and safety of specific treatment on this complication. Methods: This is a multicenter retrospective study of cases of histologically proven hepatic sarcoidosis with symptomatic PH (ascites, digestive hemorrhage) and/or hepatic encephalopathy. Demographic characteristics, comorbidities, clinical manifestations of sarcoidosis, biological data, imaging study of the liver, treatment, and clinical outcomes were collected. Results: Twelve patients were identified, with a mean follow-up of 140 months. The M/F ratio was 1 and Caucasian origin was the most represented (75%). Seven patients presented with hepatic comorbidities: metabolic syndrome, chronic alcoholism or chronic viral hepatitis. Apart from hepatic involvement, mediastino-pulmonary involvement was the most common followed by osteoarticular and skin. Liver damage was inaugural in two thirds of cases. Nine patients developed ascites, six presented esophageal varices complicated by gastrointestinal bleeding. Three patients presented with both ascites and variceal bleeding. One case of hepatic encephalopathy was observed. Five patients presented signs of hepatocellular insufficiency during follow-up, of whom three had hepatic comorbidities. Eight out of 12 patients required second-line treatment after failure of corticosteroids, three patients underwent ligation of esophageal varices but with recurrent digestive bleeding in all cases. Two patients benefited from a transjugular intrahepatic portosystemic shunt (TIPS), also with poor result. At the end of follow-up, five patients were alive and seven patients died. Two patients received a liver transplant, with good result and without recurrence of sarcoidosis on the transplant thereafter. Two patients had quiet sarcoidosis on low dose of corticosteroids and one patient was lost to follow-up. Conclusion: Symptomatic PH related to hepatic sarcoidosis is a severe complication, with high morbidity and mortality, and frequent failure of specific treatments of PH. Early management of these patients, with detection of hepatic comorbidities seems important. In case of therapeutic failure, liver transplantation is an option to consider.

Rituximab-resistant splenic memory B cells and newly engaged naive B cells fuel relapses in patients with immune thrombocytopenia.

Rituximab (RTX), an antibody targeting CD20, is widely used as a first-line therapeutic strategy in B cell-mediated autoimmune diseases. However, a large proportion of patients either do not respond to the treatment or relapse during B cell reconstitution. Here, we characterize the cellular basis responsible for disease relapse in secondary lymphoid organs in humans, taking advantage of the opportunity offered by therapeutic splenectomy in patients with relapsing immune thrombocytopenia. By analyzing the B and plasma cell immunoglobulin gene repertoire at bulk and antigen-specific single-cell level, we demonstrate that relapses are associated with two responses coexisting in germinal centers and involving preexisting mutated memory B cells that survived RTX treatment and naive B cells generated upon reconstitution of the B cell compartment. To identify distinctive characteristics of the memory B cells that escaped RTX-mediated depletion, we analyzed RTX refractory patients who did not respond to treatment at the time of B cell depletion. We identified, by single-cell RNA sequencing (scRNA-seq) analysis, a population of quiescent splenic memory B cells that present a unique, yet reversible, RTX-shaped phenotype characterized by down-modulation of B cell-specific factors and expression of prosurvival genes. Our results clearly demonstrate that these RTX-resistant autoreactive memory B cells reactivate as RTX is cleared and give rise to plasma cells and further germinal center reactions. Their continued surface expression of CD19 makes them efficient targets for current anti-CD19 therapies. This study thus identifies a pathogenic contributor to autoimmune diseases that can be targeted by available therapeutic agents.

Hepatic Sarcoidosis: Current Concepts and Treatments.

Hepatic sarcoidosis is a relatively common manifestation of extrapulmonary sarcoidosis. It occurs in 20 to 30% of cases and is rarely severe. However, a cluster of patients may develop severe complications such as cirrhosis and portal hypertension. In this review, we describe the current knowledge of clinical, biological, pathological, and radiological features of liver involvement in sarcoidosis and discuss essential clues for management and treatment.

Hypervirulent Klebsiella pneumoniae in Cryptogenic Liver Abscesses, Paris, France.

Liver abscesses containing hypervirulent Klebsiella pneumoniae have emerged during the past 2 decades, originally in Southeast Asia and then worldwide. We hypothesized that hypervirulent K. pneumoniae might also be emerging in France. In a retrospective, monocentric, cohort study, we analyzed characteristics and outcomes for 199 consecutive patients in Paris, France, with liver abscesses during 2010-2015. We focused on 31 patients with abscesses containing K. pneumoniae. This bacterium was present in most (14/27, 52%) cryptogenic liver abscesses. Cryptogenic K. pneumoniae abscesses were more frequently community-acquired (p<0.00001) and monomicrobial (p = 0.008), less likely to involve cancer patients (p<0.01), and relapsed less often (p<0.01) than did noncryptogenic K. pneumoniae liver abscesses. K. pneumoniae isolates from cryptogenic abscesses belonged to either the K1 or K2 serotypes and had more virulence factors than noncryptogenic K. pneumoniae isolates. Hypervirulent K. pneumoniae are emerging as the main pathogen isolated from cryptogenic liver abscesses in the study area.