Whole genome sequencing data used for surveillance of Campylobacter infections: detection of a large continuous outbreak,Denmark, 2019

Background Campylobacter is one of the most frequent causes of bacterial gastroenteritis. Campylobacter outbreaks are rarely reported, which could be a reflection of a surveillance without routine molecular typing. We have previously shown that numerous small outbreak-like clusters can be detected when whole genome sequencing (WGS) data of clinical Campylobacter isolates was applied.AimTyping-based surveillance of Campylobacter infections was initiated in 2019 to enable detection of large clusters of clinical isolates and to match them to concurrent retail chicken isolates in order to react on ongoing outbreaks.MethodsWe performed WGS continuously on isolates from cases (n = 701) and chicken meat (n = 164) throughout 2019. Core genome multilocus sequence typing was used to detect clusters of clinical isolates and match them to isolates from chicken meat.ResultsSeventy-two clusters were detected, 58 small clusters (2–4 cases) and 14 large clusters (5–91 cases). One third of the clinical isolates matched isolates from chicken meat. One large cluster persisted throughout the whole year and represented 12% of all studied Campylobacter cases. This cluster type was detected in several chicken samples and was traced back to one slaughterhouse, where interventions were implemented to control the outbreak.ConclusionOur WGS-based surveillance has contributed to an improved understanding of the dynamics of the occurrence of Campylobacter strains in chicken meat and the correlation to clusters of human cases.     

Glucocorticoid withdrawal schemes in chronic medical disorders. A systematic review.

This systematic review highlights the uncertainty about the safety and efficacy of glucocorticoid withdrawal in many chronic diseases, elucidating the need for further research in this area. The problem of glucocorticoid withdrawal seems to be good example for wide variation in physicians' approaches to weaning patients off glucocorticoids. This practice variation appears justified, given the well known extraordinary array of individual reactions to systemic glucocorticoid therapy [44], the obligation to individualize treatment, and scientific uncertainty. Moreover, only sparse information concerning health-related quality of life, well-being and symptoms, and socioeconomic sequelae after glucocorticoid withdrawal is available from published randomized trials. In conclusion, clinicians and patients need many more--and in a number of conditions, initial--high quality studies to assess the safety and efficacy of systemic glucocorticoid withdrawal schedules in chronic diseases.     

Anal Ultra Slow Waves (A Smooth Muscle Phenomenon Associated with Dyschezia)

Anal ultra slow waves (USWs) have been describedin a variety of anorectal disorders, all of which may beassociated with constipation. We investigated whetherthey represent a marker for dyschezia and whether their occurrence can be modified.Manometric and endosonographic studies were performed in25 patients with dyschezia, in 25 age- and sex-matchedcontrols, and in an equal number of patients with hemorrhoids. Patients exhibiting ultra slowwaves were repeatedly studied with and without localadministration of isosorbide dinitrate. In addition, wedetermined whether stimulatory maneuvers modify the occurrence of USWs. Anal USWs were persistentlyfound in 56% of patients with dyschezia, in 8% ofpatients with hemorrhoids, and in none of the healthycontrols. They were stimulated by anal squeeze and completely abolished by local administration ofisosorbide dinitrate. Ultra slow waves always occurredin conjunction with an increase in anal resting pressureand were tightly associated with a fluctuation in slow wave amplitude. Anal sphinctermorphology was similar in patients with dyschezia and incontrols. We conclude that anal USWs occur mostfrequently in patients with dyschezia and indicatesmooth muscle dysfunction. Treatment directed atabolishing this motor phenomenon may represent a novelapproach to the management of patients withdyschezia.     

Plasma homocysteine in 80-year-olds: relationships to medical, psychological and social variables

Plasma homocysteine concentrations in a group of 80-year-old persons were related to symptoms and signs. Plasma homocysteine concentrations higher than 15 mumol/l were associated with lower total life satisfaction (P<0.01), mood (P<0.05), zest for life (P<0.05), lower scores for reasoning (P<0.05), spatial ability (P<0.05), memory recognition (P<0.05), and subjective health (P<0.01). In an instrument comprising of 30 symptoms, plasma homocysteine concentrations higher than 15 mumol/l were associated with impaired concentration (P<0.05), restlessness (P<0.05), feeling cold (P<0.05), loss of weight (P<0.05), and feeling depressed (P<0.01). The above data indicate that plasma homocysteine values over 15 mumol/l could be relevant markers for clinical intervention.     

Endogenous aggregates of amyloidogenic cystatin C variant are removed by THP-1 cells in vitro and induce differentiation and a proinflammatory response

A mutation in the human cystatin C gene leads to familial cerebral amyloid angiopathy. This disease is known as “hereditary cerebral hemorrhage with amyloidosis-Icelandic type” or “hereditary cystatin C amyloid angiopathy.” The mutant cystatin C protein forms aggregates and amyloid, within the central nervous system almost exclusively in connection with the vascular system. It was not known whether immune cells could remove mutant cystatin C protein aggregates. Ex vivo mutant cystatin C protein aggregates, both in solution and dried onto a glass surface, induced adhesion to the substrate, differentiated the THP-1 monocyte cell line and led to a proinflammatory response. Aggregates were also taken up by both THP-1 cells and THP-1 derived macrophages. These are the same responses induced by other amyloidogenic protein species, such as amyloid β protein and amylin, supporting the model of all amyloidogenic proteins being toxic due to common structural motifs. Proinflammatory response induced by the ex vivo mutant cystatin C protein aggregates suggests that vascular inflammation plays an important role in hereditary cerebral hemorrhage with amyloidosis-Icelandic type. Ex vivo protein aggregates of cystatin C might better model cellular behavior than in vitro-generated aggregates or supplement in vitro material.     

Molecular Characterization of Enterotoxigenic Escherichia coli Isolates Recovered from Children with Diarrhea during a 4-Year Period (2007 to 2010) in Bolivia

Enterotoxigenic Escherichia coli (ETEC) is an important cause of childhood diarrhea. This study aimed to characterize ETEC strains isolated from Bolivian children aged <5 years according to enterotoxin profile, colonization factors (CFs), suggested virulence genes, and severity of disease. A total of 299 ETEC isolates recovered from children with diarrhea and 55 ETEC isolates from children without diarrhea (controls) were isolated over a period of 4 years. Strains expressing heat-labile toxin (LT) or heat-stable toxin (ST) alone were about equally common and twice as common as ETEC producing both toxins (20%). ETEC strains expressing human ST (STh) were more common in children aged <2 years, while ETEC strains expressing LT plus STh (LT/STh) were more frequent in 2- to 5-year-old children. Severity of disease was not related to the toxin profile of the strains. CF-positive isolates were more frequently identified in diarrheal samples than in control samples (P = 0.02). The most common CFs were CFA/I and CS14. CFA/I ETEC strains were more frequent in children aged <2 years than CS1+CS3 isolates and CS14 isolates, which were more prevalent in 2- to 5-year-old children. The presence of suggested ETEC virulence genes (clyA, eatA, tia, tibC, leoA, and east-1) was not associated with disease. However, east-1 was associated with LT/STh strains (P < 0.001), eatA with STh strains (P < 0.001), and tia with LT/STh strains (P < 0.001). A minor seasonal peak of ETEC infections was identified in May during the cold-dry season and coincided with the peak of rotavirus infections; this pattern is unusual for ETEC and may be important for vaccination strategies in Bolivia.     

Cardiac computed tomography in the contemporary evaluation of infective endocarditis

Increasing data have accumulated on the role of Cardiac Computed Tomography (CCT) in infective endocarditis (IE) with high accuracy for large vegetations, perivalvular complications and for exclusion of coronary artery disease to avoid invasive angiography. CCT can further help to clarify the etiology of infective prosthetic valve dysfunction (e.g. malposition, abscess, leak, vegetation or mass). Structural interventions have increased the relevance of CCT in valvular heart disease and have amplified its use. CCT may be ideally integrated into a multimodality approach that incorporates a central role of transesophageal echocardiography (TEE) with 18-FDG PET and/or cardiac magnetic resonance in individually selected cases, guided by the Heart Team. The coronavirus-19 (COVID-19) pandemic has resulted in renewed attention to CCT as a safe alternative or adjunct to TEE in selected patients. This review article provides a comprehensive, contemporary review on CCT in IE to include scan optimization, characteristics of common IE findings on CCT, published data on the diagnostic accuracy of CCT, multimodality imaging comparison, limitations and future technical advancements.