Minimally invasive accessory splenectomy for recurrent gastric variceal bleeding due to left-sided portal hypertension: report of the first case.

Upper gastrointestinal bleeding from esophagogastric varices is a common scenario, especially in patients with portal hypertension induced by liver cirrhosis or other diseases with thrombosis of the splenic vein. However, accessory spleen as pathophysiological cause of a regional, left-sided portal hypertension and consecutive development of isolated gastric varices is rare. We report a case of recurrent gastric variceal bleeding resulting from sinistral portal hypertension associated with an accessory spleen in a patient who had traumatic splenectomy many decades before. The accessory spleen is an extremely rare cause for the development of regional, left-sided portal hypertension leading to isolated gastric varices. Minimally invasive splenectomy is a safe and efficient treatment option.

Ticking off diagnoses of abdominal pain: early neuroborreliosis with radiculopathy.

Lyme disease (LD) is the most common tick-borne illness. The diagnosis of LD is difficult because of the great variation in clinical manifestations. Although abdominal pain is generally not considered a sign of LD, in this case report we describe a patient with unexplained severe abdominal pain that eventually turned out to be LD due to radiculopathy. Since the incidence of LD is rising it is important to realise that severe abdominal pain could be the first clinical manifestation of early neuroborreliosis.

A multicentre verification study of the QuantiFERON®-TB Gold Plus assay.

OBJECTIVES: The aim of this verification study was to compare the QuantiFERON®-TB Gold Plus (QFT-Plus) to the QuantiFERON®-TB Gold In Tube (QFT-GIT). The new QFT-Plus test contains an extra antigen tube which, according to the manufacturer additionally elicits a CD8+ T-cell response above the CD4+ T-cell response. We assessed the value of this tube in detecting recent latent tuberculosis infections. METHODS: Between May 2015 and December 2016, 1031 subjects underwent QFT-Plus and QFT-GIT test. Overall agreement between both tests and performance for different test indications and/or immune states was assessed. A difference of >0.6 IU/mL interferon-γ release between the two antigen tubes of the QFT-Plus assay was considered a true difference and used as estimation for CD8+ T-cell response. RESULTS: Analysis of the QuantiFERON tests resulted in an overall agreement between assays of 95%. Subjects considered to be recently exposed to tuberculosis had significantly more often a true difference in interferon-γ release compared to all other subjects (p = 0.029). CONCLUSION: Results of QFT-Plus are highly comparable to QFT-GIT. Although there is an indication that a true difference in interferon-γ release between the antigen tubes is associated with recent latent tuberculosis infection, the QFT-Plus could not be used to exclude recent exposure.

The diagnostic accuracy of serological tests for Lyme borreliosis in Europe: a systematic review and meta-analysis.

BACKGROUND: Interpretation of serological assays in Lyme borreliosis requires an understanding of the clinical indications and the limitations of the currently available tests. We therefore systematically reviewed the accuracy of serological tests for the diagnosis of Lyme borreliosis in Europe. METHODS: We searched EMBASE en MEDLINE and contacted experts. Studies evaluating the diagnostic accuracy of serological assays for Lyme borreliosis in Europe were eligible. Study selection and data-extraction were done by two authors independently. We assessed study quality using the QUADAS-2 checklist. We used a hierarchical summary ROC meta-regression method for the meta-analyses. Potential sources of heterogeneity were test-type, commercial or in-house, Ig-type, antigen type and study quality. These were added as covariates to the model, to assess their effect on test accuracy. RESULTS: Seventy-eight studies evaluating an Enzyme-Linked ImmunoSorbent assay (ELISA) or an immunoblot assay against a reference standard of clinical criteria were included. None of the studies had low risk of bias for all QUADAS-2 domains. Sensitivity was highly heterogeneous, with summary estimates: erythema migrans 50% (95% CI 40% to 61%); neuroborreliosis 77% (95% CI 67% to 85%); acrodermatitis chronica atrophicans 97% (95% CI 94% to 99%); unspecified Lyme borreliosis 73% (95% CI 53% to 87%). Specificity was around 95% in studies with healthy controls, but around 80% in cross-sectional studies. Two-tiered algorithms or antibody indices did not outperform single test approaches. CONCLUSIONS: The observed heterogeneity and risk of bias complicate the extrapolation of our results to clinical practice. The usefulness of the serological tests for Lyme disease depends on the pre-test probability and subsequent predictive values in the setting where the tests are being used. Future diagnostic accuracy studies should be prospectively planned cross-sectional studies, done in settings where the test will be used in practice.

A Dutch nationwide evaluation of serological assays for detection of Borrelia antibodies in clinically well-defined patients.

Numerous tests for the detection of antibodies against Borrelia burgdorferi are commercially available. Manufacturer-derived data invariably report a high sensitivity and specificity, but comparative studies demonstrate large differences in clinical practice, especially with regard to specificity. We retrospectively collected data from validation studies for B. burgdorferi antibody assays from 8 laboratories in the Netherlands. The total number of samples was 809. Samples were selected based on clinical and laboratory parameters. We included samples from patients with erythema migrans, acrodermatitis chronicum atrophicans, and neuroborreliosis; cross-reactivity controls; and healthy controls. Data are presented from 10 enzyme-linked immunosorbent assays and 5 immunoblots. For manifestations of B. burgdorferi infection with short disease duration, the positivity rate of the assays varied significantly. In patients with long disease duration, the positivity rate differed only marginally. In cross-reactivity controls, there was significant variation in the reactivity rate. The majority of false-positive reactions are of the IgM isotype.

Infectivity of Borrelia burgdorferi sensu lato is unaltered in C3-deficient mice.

B. burgdorferi, B. afzelii, and B. bavariensis show resistance to mouse and human complement. B. garinii and B. valaisiana are sensitive to mouse and human complement. We evaluated whether the absence of C3 in mice influenced infectivity and pathogenicity of different Borrelia species. C3 knockout mice (C3-/-) and syngeneic C57Bl/6 wild-type (WT) mice were challenged with 5 different Borrelia species. After 2 weeks, quantitative PCR (qPCR), culture, histopathology, and immunofluorescence were performed on heart, joint, brain, bladder, and skin. Spirochaetes were detected by qPCR after infection with B. burgdorferi, B. afzelii, or B. bavariensis strains. In joints of C3-/-, but not WT mice challenged with B. burgdorferi, spirochaetes were detected by qPCR. No other significant differences between C3-/- and WT mice were seen. Histopathology demonstrated concordance between borrelia load and inflammation score. Only after B. burgdorferi and B. afzelii infection, spirochaetes were detected by immunofluorescence microscopy. B. burgdorferi was cultured from heart, joint, bladder, and skin from all mice within 2 weeks. B. afzelii and B. bavariensis grew only from heart tissue from both C3-/- and WT mice after 2-6 weeks. The infectivity and pathogenicity of complement-resistant Borrelia strains is unchanged in complement-deficient mice. Complement-susceptible strains do not become infectious in the absence of C3.

High sensitivity and specificity of the C6-peptide ELISA on cerebrospinal fluid in Lyme neuroborreliosis patients.

Lyme neuroborreliosis (LNB) is a serious but treatable disease. The diagnosis of LNB poses a challenge to clinicians, and improved tests are needed. The C6-peptide ELISA is frequently used on serum but not on cerebrospinal fluid (CSF). Data on the sensitivity of the C6-peptide ELISA in CSF in patients suffering from LNB have been conflicting. Serum-CSF pairs from 59 LNB patients, 36 Lyme non-neuroborreliosis cases, 69 infectious meningitis/encephalitis controls and 74 neurological controls were tested in a C6-peptide ELISA. With the optimal cut-off of 1.1, the sensitivity of the C6-peptide ELISA for LNB patients in CSF was 95%, and the specificity was 83% in the Lyme non-neuroborreliosis patients, 96% in the infectious controls, and 97% in the neurological controls. These results suggest that the C6-peptide ELISA has a high sensitivity and good specificity for the diagnosis of LNB patients in CSF. The C6-peptide ELISA can be used on CSF in a clinical setting to screen for LNB.

Discriminating Lyme neuroborreliosis from other neuroinflammatory diseases by levels of CXCL13 in cerebrospinal fluid.

CXCL13 in cerebrospinal fluid (CSF) could be an important component for diagnosing Lyme neuroborreliosis (LNB). Levels of intrathecal CXCL13 were determined for 58 LNB patients and 210 controls; sensitivity was 88% and specificity was 89% (cutoff, 250 pg of CXCL13/ml of CSF). Elevated levels of CXCL13 can aid in the diagnosis of LNB, but levels should be interpreted with care.

Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease.

BACKGROUND: Epithelial barrier function is impaired in Crohn's disease. AIM: To define the underlying cellular mechanisms with special attention to tight junctions. METHODS: Biopsy specimens from the sigmoid colon of patients with mild to moderately active or inactive Crohn's disease were studied in Ussing chambers, and barrier function was determined by impedance analysis and conductance scanning. Tight junction structure was analysed by freeze fracture electron microscopy, and tight junction proteins were investigated immunohistochemically by confocal laser scanning microscopy and quantified in immunoblots. Epithelial apoptosis was analysed in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling and 4',6-diamidino-2-phenylindole staining. RESULTS: Patients with active Crohn's disease showed an impaired intestinal barrier function as indicated by a distinct reduction in epithelial resistance. As distribution of conductivity was even, focal epithelial lesions (eg, microerosions) did not contribute to barrier dysfunction. Instead, freeze fracture electron microscopy analysis showed reduced and discontinuous tight junction strands. Occludin and the sealing tight junction proteins claudin 5 and claudin 8 were downregulated and redistributed off the tight junction, whereas the pore-forming tight junctions protein claudin 2 was strongly upregulated, which constitute the molecular basis of tight junction changes. Other claudins were unchanged (claudins 1, 4 and 7) or not detectable in sigmoid colon (claudins 11, 12, 14, 15 and 16). Claudin 2 upregulation was less pronounced in active Crohn's disease compared with active ulcerative colitis and was inducible by tumour necrosis factor alpha. As a second source of impaired barrier function, epithelial apoptosis was distinctly increased in active Crohn's disease (mean (SD) 5.2 (0.5)% v 1.9 (0.2)% in control). By contrast, barrier function, tight junction proteins and apoptosis were unaffected in Crohn's disease in remission. CONCLUSION: Upregulation of pore-forming claudin 2 and downregulation and redistribution of sealing claudins 5 and 8 lead to altered tight junction structure and pronounced barrier dysfunction already in mild to moderately active Crohn's disease.

[Angioarchitecture of the ulna and radius and their practical relevance]. / Angioarchitektur von Ulna und Radius und ihre praktische Relevanz.

The periosteal and endosteal blood supply of the human ulna and radius was investigated by anatomical dissection. The main artery concerned is the anterior interosseous artery. It supplies the diaphysis of ulna and radius; its branches feed the distal one-fourths of both the ulna and the radius. The proximal one-fourth of the ulna is supplied by the ulnar artery, the ulnar recurrent artery and the recurrent interosseous artery. Periosteal branches of the common interosseous artery, the ulnar artery and the recurrent interosseous artery supply the proximal one-fourth of the radius. In both bones the main branch of the nutrient artery has an ascending course. The anterior interosseous artery, as the main artery of the periosteal and endosteal supply of the human ulna and radius, is important in transplantation and reconstruction, especially with a view to reducing the rate of pseudarthrosis. When osteosynthesis is planned so-called LC-DC plates should be chosen to preserve the periosteal branches. When a vascularized bone graft is taken from the forearm the vascularization of the remaining bones has to be considered. The vascularity of this area allows various options in grafting.