Viral clade is associated with severity of symptomatic genotype 3 hepatitis E virus infections in Belgium, 2010-2018.

BACKGROUND & AIMS: HEV genotype (gt) 3 infections are prevalent in high-income countries and display a wide spectrum of clinical presentations. Host - but not viral - factors are reported to be associated with worse clinical outcomes. METHODS: Demographic, clinical, and biochemical data laboratory-confirmed HEV infections (by PCR and/or a combination of IgM and IgG serology) at the Belgian National Reference Centre between January 2010 and June 2018 were collected using standardised case report forms. Genotyping was based on HEV open reading frame 2 sequences. Serum CXCL10 levels were measured by a magnetic bead-based assay. H&E staining was performed on liver biopsies. RESULTS: A total of 274 HEV-infected individuals were included. Subtype assignment was possible for 179/218 viraemic cases, confirming gt3 as dominant with an almost equal representation of clades abchijklm and efg. An increased hospitalisation rate and higher peak serum levels of alanine aminotransferase, bilirubin, and alkaline phosphatase were found in clade efg-infected individuals in univariate analyses. In multivariable analyses, clade efg infections remained more strongly associated with severe disease presentation than any of the previously identified host risk factors, being associated with a 2.1-fold higher risk of hospitalisation (95% CI 1.1-4.4, p = 0.034) and a 68.2% higher peak of bilirubin levels (95% CI 13.3-149.9, p = 0.010), independently of other factors included in the model. In addition, acute clade efg infections were characterised by higher serum CXCL10 levels (p = 0.0005) and a more pronounced liver necro-inflammatory activity (p = 0.022). CONCLUSIONS: In symptomatic HEV gt3 infections, clade efg is associated with a more severe disease presentation, higher serum CXCL10 levels, and liver necro-inflammatory activity, irrespective of known host risk factors. CLINICAL TRIAL REGISTRATION: The protocol was submitted to clinicaltrials.gov (NCT04670419). IMPACT AND IMPLICATIONS: HEV genotype (gt) 3 infections display a wide spectrum of clinical presentations currently ascribed to host factors. Here we examined the role of viral factors on liver disease outcomes by combining viral phylogeny with clinical, biochemical, cytokine, and histological data from 274 Belgian adults infected with HEV presenting between 2010 and 2018. HEV gt 3 clade efg infections were associated with a more severe disease presentation, higher serum CXCL10 levels and liver necro-inflammatory activity, irrespective of known host risk factors. HEV gt3 clade-dependent clinical outcomes call for broad HEV gt3 subtyping in clinical practice and research to help identify those at higher risk for worse outcomes and to further unravel underlying virus-host interactions.

Impact of Slim Linear Echoendoscope on the Practice of EUS.

BACKGROUND: Standard linear echoendoscopes have a large distal tip and bending radius, which can preclude adequate examination in some patients. OBJECTIVE: We examined the impact of having available slim linear echoendoscopes (SLE) on our endoscopic ultrasound (EUS) practice. MATERIALS AND METHODS: As a quality improvement measure, data on the need for the use of SLE were documented in 2000 consecutive procedures performed over a 10-month period from February to November 2022. When examination using a standard size echoendoscope failed due to technical limitations, the procedure was reattempted in the same session using a SLE. The main outcome was the impact of SLE, which was defined as the establishment of a new diagnosis or if findings altered treatment plan. RESULTS: A complete EUS examination failed in 23 of 2000 procedures (1.15%, 95% CI, 0.73-1.72%) performed using standard size echoendoscope (14 male, median age 73 y [IQR 66 to 79]). The examination was technically successful when using SLE in 22 of 23 (95.6%) patients. SLE impacted clinical management in all 22 patients (100%) by establishing tissue diagnosis in 19 and/or altering subsequent treatment plan in 5. Adverse event of transient hypoxia was observed in one patient (4.3%). CONCLUSIONS: A very experienced EUS team required SLE in 1.1% of consecutive examinations. Our findings suggest that when used, 95% of patients benefitted as it had a significant impact on their clinical management.

Bronchiolitis in COVID-19 times: a nearly absent disease?

Stay-at-home orders, physical distancing, face masks and other non-pharmaceutical interventions (NPIs) do not only impact COVID-19, but also the dynamics of various other infectious diseases. Bronchiolitis is a clinically diagnosed viral infection of the lower respiratory tract, and causes a yearly seasonal wave of admissions in paediatric wards worldwide. We counted 92,5% less bronchiolitis hospitalisations in Antwerp before the expected end of the peak this year (of which only 1 RSV positive), as compared to the last 3 years. Furthermore, there was a >99% reduction in the number of registered RSV cases in Belgium.Conslusion: The 2020 winter bronchiolitis peak is hitherto nonexistent, but we fear a 'delayed' spring/summer bronchiolitis peak when most NPIs will be relaxed and pre-pandemic life restarts. What is known? • Bronchiolitis causes a yearly seasonal wave of admissions in paediatric departments worldwide. • Non-pharmaceutical interventions (NPIs) do not only impact COVID-19, but also the dynamics of various other infectious diseases. What is new? • The 2020 winter bronchiolitis peak is hitherto nonexistent. • A 'delayed' spring or summer bronchiolitis peak could happen when most NPIs will be relaxed and pre-pandemic life restarts.

An international polypectomy practice survey.

Background and study aims: In recent years, cold snare polypectomy (CSP) has been recommended as the preferred approach for removal of small and diminutive colorectal polyps. We conducted an international survey among endoscopists to understand the uptake of CSP and changes in polypectomy practice during recent years.Patients and methods: Endoscopists were invited through gastroenterology, colorectal surgery and endoscopy societies to participate in an online survey. The primary outcome was to identify the predominant polypectomy approach used to remove 4‒10 mm colorectal polyps. Secondary outcomes included the uptake of CSP in the past 5 years, current polypectomy practice patterns for 1‒20 mm polyps, practice changes in recent years, and perceived benefits/concerns related to different polypectomy techniques.Results: The survey was distributed internationally by nine societies and completed by 808 endoscopists (response rate 3.7%). CSP was the predominant polypectomy technique for 4‒5 mm polyps (67.0%, 95% CI, 63.7-70.2%) and 6‒10 mm polyps (55.2%, 95% CI, 51.8-58.6%). For 1‒3 mm polyps, cold forceps remained the predominant technique (78.4%, 95% CI, 75.6-81.3%), whereas hot snare polypectomy (HSP) remained the predominant technique for 10‒20 mm polyps (92.5%, 95% CI, 90.7-94.3%). 87.5% (95% CI, 85.2-89.8%) of endoscopists reported an increase in CSP use during the past 5 years.Conclusions: This survey found a substantial increase in CSP use during recent years. CSP has become the predominant polypectomy approach for 4‒10 mm colorectal polyps, while HSP remained the predominant approach for larger (10‒20 mm) polyps. Clinical practice patterns are well aligned with recently issued guideline recommendations.

Screening for connective tissue disease-associated antibodies by automated immunoassay.

BACKGROUND: Antinuclear antibodies (ANAs) are useful for the diagnosis of ANA-associated systemic rheumatic disease (AASRD). The objective of this study was the evaluation of an immunoassay that detects antibodies to a mixture of 17 antigens as an alternative to indirect immunofluorescence (IIF). METHODS: Nine thousand eight hundred and fifty-six consecutive patients tested for ANAs were tested by IIF and EliA connective tissue disease screen (Thermo-Fisher). Medical records were reviewed for 2475 patients, including all patients that tested positive/equivocal by either test and a selection of 500 patients that tested negative. RESULTS: Concordance between IIF and EliA was 83.1%. AASRD was found in 12.8% of IIF-positive patients, 30.2% of EliA-positive patients and 0.4%, 46.6%, 5.8% and 3.0% of patients that tested, respectively, double negative, double positive, single positive for EliA and single positive for IIF. The association with AASRD increased with increasing antibody level. IIF and EliA were positive in, respectively, 90.4% and 69.9% of systemic lupus erythematosus (n=83), 100% and 84.1% of systemic sclerosis (n=63), 86.7% and 93.3% of Sjögren's syndrome (n=45), 88.2% and 52.9% of polymyositis/dermatomyositis (n=17), and in all cases of mixed connective tissue disease (n=8). The specificity was projected to be 94%-96% for EliA and 86% for IIF. When all AASRDs were taken together, the areas under the curve of receiver operator curves were similar between IIF and EliA. CONCLUSIONS: The positive predictive value for AASRD was higher for EliA than for IIF, but, depending on the disease, EliA might fail to detect antibodies that are detected by IIF. Combining immunoassay with IIF adds value.

Biological Variation of Chloride and Sodium in Sweat Obtained by Pilocarpine Iontophoresis in Adults: How Sure are You About Sweat Test Results?

INTRODUCTION: The measurement of chloride and sodium concentrations in sweat is an important test for the diagnosis of cystic fibrosis (CF). The aim of this study was to assess the analytical variation (CVA) and within-subject (CVI) and between-subject (CVG) biological variation of chloride and sodium concentrations in sweat, collected by pilocarpine iontophoresis and to determine their effect on the clinical interpretation of sweat test results. METHODS: Twelve Caucasian adults (six male and six female) without symptoms suggestive for CF and with a mean age of 41 years (range 28-59) were included in the study. At least eight samples of sweat were collected from each individual by pilocarpine iontophoresis. Chloride and sodium concentrations were measured in duplicate for each sample using ion selective electrodes. After the removal of outliers, the CVA, CVI, and CVG of chloride and sodium were determined, and their impact on measurement uncertainty and reference change value were calculated. RESULTS: The CVA, CVI, and CVG of chloride in sweat samples were 6.5, 17.7, and 47.2%, respectively. The CVA, CVI, and CVG of sodium sweat samples were 6.0, 17.5, and 42.6%, respectively. CONCLUSION: Our study indicates that sweat chloride and sodium concentration results must be interpreted with great care. Different components of variation, particularly the biological variations, have a considerable impact on the interpretation of these results. If no pre-analytical, analytical, or post-analytical errors are suspected, repeated sweat testing to confirm first-measurement results might not be desirable.

Safety and efficacy of early versus late removal of LAMS for pancreatic fluid collections.

Background and study aims Optimal timing for removal of lumen-apposing metal stents (LAMS) for effective drainage of pancreatic fluid collections (PFC) while minimizing adverse events (AE) is unknown. Outcomes of early (≤ 4 weeks) or delayed (> 4 weeks) LAMS removal on both clinical efficacy and the incidence of AE were assessed. Patients and methods This was a retrospective analysis of a prospectively maintained registry of PFC drainage between November 2016 and September 2021. Clinical success was defined as a 75% decrease in fluid collection volume with no need for reintervention at 6 months. AE were defined using the American Society for Gastrointestinal Endoscopy lexicon. Multiple logistic regression analysis was performed to determine variables associated with clinical success and AE. Results A total of 108 consecutive PFCs were included. LAMS deployment was technically successful in 103 of 108 cases (95.4%). Failure was associated with collection diameter ≤ 4 cm (odds ratio [OR] 24.0, P = 0.005) and presence of more than 50% necrotic material (OR 20.1, P = 0.01). Stents were left in place for a median of 48 days. Patients with early stent removal (< 4 weeks) had clinical success in 70.0% of cases, which was significantly less than in the group with delayed stent removal (96.4%, P = 0.03). On multiple regression analysis, clinical failure was associated with early stent removal (OR 25.5, P = 0.003). AEs occurred in 8.7% of cases (9/103). There were no predictors of AE. Notably, delayed stent removal did not predict the occurrence of AE. Conclusions Early LAMS removal (< 4 weeks) did not prevent AEs but did lead to increased clinical failure.

IL28B SNP screening and distribution in the French Canadian population using a rapid PCR-based test.

Single nucleotide polymorphisms (SNPs) in the proximity of the interleukin-28B (IL28B) gene can predict spontaneous resolution of hepatitis C virus (HCV) infection and response to interferon therapy. Screening for this polymorphism has become part of the standard criteria for the management of HCV-infected patients, hence the need for a rapid, cost-effective screening method. Here, we describe a rapid PCR-based test to screen for two IL28B SNPs (rs12979860 and rs8099917). We used this test to investigate IL28B polymorphism and prevalence in a cohort of French Canadian injection drug users who are part of a unique population known to have a strong genetic founder effect. This population had lower linkage disequilibrium between the two tested SNPs as compared to other cohorts (|d'| = 0.68, r = 0.59). The special genetic makeup should be considered in the management of HCV-infected patients within that population.

Endoscopic Ultrasound Guided Walled-off Necrosis Drainage.

Walled-off necrosis is a well-recognized complication of necrotizing pancreatitis that can cause sepsis, luminal or ductal obstruction, or persistent unwellness requiring multidisciplinary care. Recent data suggest that minimally invasive endoscopic treatment strategies are preferred over more invasive surgical approaches. Although endoscopic transmural drainage with or without necrosectomy is the primary approach for patients requiring an intervention, for collections not amenable to endoscopic approach, percutaneous drain placement followed by video-assisted retroperitoneal debridement or laparoscopic cystogastrostomy with internal debridement are other alternatives. More studies are required to optimize post-procedure care to shorten the length of stay and minimize resource utilization.

Primary leiomyosarcoma of the pancreas with metastasis to the spleen.

Video 1EUS evaluation of the pancreas and the spleen.

Value of pneumococcal PCR in respiratory samples for exclusion of pneumococcal pneumonia.

Background: Streptococcus pneumoniae is the main aetiological agent in bacterial pneumonia. Therefore pneumococcal PCR is often included in respiratory multiplex PCR panels, both commercial and in-house. But respiratory PCR results for S. pneumoniae are difficult to interpret due to frequent non-pathogenic colonization on the mucosal surface of the upper airways with pneumococci or to cross-reaction of the PCR target in non-pneumococcal streptococci. In this study we investigated the value of lytA gene pneumococcal PCR in patients presenting with pneumonia. Objectives: To assess the utility of lytA gene detection for S. pneumoniae in a respiratory multiplex quantitative PCR (qPCR) panel for patients presenting with pneumonia. Methods: A retrospective study was conducted for lytA gene results as target for S. pneumoniae in hospitalized patients who were diagnosed with pneumonia and for which a respiratory multiplex PCR panel was performed. Patients were classified as 'probable', 'possible' or 'unlikely' of having a pneumococcal pneumonia. Results: A sensitivity of 71.4% and specificity of 89.6% were found, corresponding to a negative predictive value and positive predictive value of 97.6% and 34.2%, respectively, when considering 'probable' versus 'possible/unlikely'. In the PCR-positive cases we found a statistically significant difference in semi-quantitative Ct values between the 'probable' and the 'possible/unlikely' groups. Conclusions: We conclude that a negative qPCR for the lytA gene in a respiratory sample is highly predictive of a negative S. pneumoniae culture and is possibly sufficient to exclude S. pneumoniae as a causative agent. Respiratory pneumococcal PCR has a high negative predictive value for pneumococcal disease but the positive predictive value is low.

Early life programming of nonalcoholic fatty liver disease in children.

BACKGROUND: Research is beginning to implicate early life characteristics in the development of pediatric nonalcoholic fatty liver disease, however the relationship with perinatal characteristics is poorly understood. AIMS: We evaluated the association between perinatal characteristics and nonalcoholic fatty liver disease in childhood. STUDY DESIGN: Nested case-control study. SUBJECTS: 5104 children born in Quebec, Canada between 2006 and 2019. Exposures included maternal diabetes, obesity, prematurity, and other birth complications. OUTCOME MEASURES: The outcome was nonalcoholic fatty liver disease diagnosed in hospital before 14 years of age. We calculated adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between birth characteristics and nonalcoholic fatty liver disease. RESULTS: A total of 104 children with nonalcoholic fatty liver disease were included. Gestational diabetes (OR 2.17, 95% CI 1.15-4.10), preexisting diabetes (OR 5.75, 95% CI 2.67-12.4), and maternal obesity (OR 3.06, 95% CI 1.71-5.45) were associated with childhood nonalcoholic fatty liver disease. Prematurity (OR 1.93, 95% CI 1.06-3.54) and neonatal intensive care unit admission (OR 2.18, 95% CI 1.10-4.33) were also associated with nonalcoholic fatty liver disease. However, there was no association with low birthweight, small-for-gestational age birth, and macrosomia. CONCLUSIONS: Maternal metabolic disorders and prematurity may initiate processes early in life that lead to the development of nonalcoholic fatty liver disease in childhood.

Long-Term Follow-Up into Adulthood of Pediatric-Onset Primary Sclerosing Cholangitis and Autoimmune Sclerosing Cholangitis.

Studies on pediatric patients with primary sclerosing cholangitis (PSC) have been limited by short follow-up and inconsistent classification of pediatric patients with autoimmune hepatitis-sclerosing cholangitis overlap (AIC). We conducted a retrospective study of patients diagnosed with AIC or PSC during childhood with extension of follow-up into adulthood. Methods: We reviewed records of patients followed for PSC or AIC between 1998 and 2019 at a pediatric referral center. Features at diagnosis, biochemical and liver-related outcomes (cholangitis, liver transplant, and cirrhosis) were compared. Results: Forty patients (27 PSC, 13 AIC) were followed for 92 months on average (standard deviation 79 months) with extension into adulthood in 52.5%; 70% had associated inflammatory bowel disease (IBD). The proportion of patients with significant fibrosis and abnormal baseline liver tests (serum bilirubin and transaminase levels) were similar in both groups. One year postdiagnosis, 55% (15/27) of PSC patients had normal liver tests versus only 15% (2/13) in the AIC group (P = 0.02). During follow-up, more liver-related events occurred in the AIC group (69% versus 27%, hazard ratio [HR] = 3.7 [95% confidence interval (CI): 1.4-10] P = 0.01). Baseline elevated serum bilirubin levels (HR = 5.3 [95% CI: 1.7-16.9] P = 0.005) and elevated transaminase levels at 1 year (HR = 9.09 [95% CI: 1.18-66.7) P = 0.03) were predictive of liver-related events, while having IBD was not (HR = 0.48 (95% CI: 0.15-1.5) P = 0.22). Conclusions: Pediatric patients with AIC and PSC presented at a similar fibrosis stage, however, with a more severe hepatitis in AIC. In this cohort, AIC was associated with more liver-related events, primarily driven by a higher rate of cirrhosis compared with PSC; transplant rates were similar.

The State of Microbiology Diagnostic of Prosthetic Joint Infection in Europe: An In-Depth Survey Among Clinical Microbiologists.

Background: This study aims to give an overview on how microbiology diagnosis tests of Prosthetic joint infections (PJI) is performed in Europe, and to explore whether any factor influences the decision on implementing a test. Methods: An extensive online survey of clinical microbiologists from seven European countries (Belgium, Estonia, Germany, Italy, Netherlands, Switzerland, and Spain). Following items were assessed: (i). general information on the laboratory, (ii) preference of the laboratory and clinical microbiologists regarding samples, (iii) transportation and (iv) processing of explanted foreign bodies and tissues and synovial fluid, (v) culture media and culture duration, (vi) reporting (identification and susceptibility testing), and (vii) use of molecular microbiology techniques. Results: Invited were 163 clinical microbiologists. The response rate from each country was above 50% (range 51-78%), except for Germany (36%). Frequent PJI diagnostics were the use of tissue pre-processing (58.1%), culturing synovial fluid in blood culture bottles (45.5%), use of sonication for processing explanted prosthesis (56.8%), reporting the presence of synovial leukocyte counts (67%), use of blood aerobic and anaerobic agar (97.7%), and enrichment media thioglycolate (69.3%). The most common incubation time of the culture media is 7-14 days (34.1-70.5%). The clinicians were called to report the culture results (80.7%), and to give antibiotic recommendation (67%). Conclusion: There are common practices in processing PJI samples and reporting results, which is promising for harmonization of PJI diagnostic in the future. However, variation in diagnostic tests should also be considered in interpreting and comparing clinical microbiology results.

A case of multisystem inflammatory syndrome (MIS-A) in an adult woman 18 days after COVID-19 vaccination.

We discuss a case of a young woman, presenting a constellation of clinical and biochemical features meeting the current case definition of multisystem inflammatory syndrome in adults (MIS-A), 18 days after receiving her first dose of the Oxford/AstraZeneca vaccine. Therapy by means of intravenous immunoglobulins was initiated, leading to clinical and biochemical recovery. Although a relationship between MIS-A and the preceding vaccination cannot be confirmed, it can also not be excluded, given the temporal association and the fact that there were no indicators of a preceding SARS-CoV-2 infection.