Schistosomiasis-associated pulmonary arterial hypertension: a systematic review.

Schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) is a life-threatening complication of chronic hepatosplenic schistosomiasis. It is suggested to be the leading cause of pulmonary arterial hypertension (PAH) worldwide. However, pathophysiological data on Sch-PAH are scarce. We examined the hypothesis that there are pronounced similarities in pathophysiology, haemodynamics, and survival of Sch-PAH and idiopathic PAH (iPAH).This systematic review and meta-analysis was registered in the PROSPERO database (identifier CRD42018104066). A systematic search and review of the literature was performed according to PRISMA guidelines for studies published between 01 January 1990 and 29 June 2018.For Sch-PAH, 18 studies evaluating pathophysiological mechanisms, eight studies on haemodynamics (n=277), and three studies on survival (n=191) were identified. 16 clinical registries reporting data on haemodynamics and survival including a total of 5792 patients with iPAH were included for comparison. Proinflammatory molecular pathways are involved in both Sch-PAH and iPAH. The transforming growth factor (TGF)-β signalling pathway is upregulated in Sch-PAH and iPAH. While there was no difference in mean pulmonary artery pressure (54±17 mmHg versus 55±15 mmHg, p=0.29), cardiac output (4.4±1.3 L·min-1 versus 4.1±1.4 L·min-1, p=0.046), and cardiac index (2.6±0.7 L·min-1·m-2 versus 2.3±0.8 L·min-1·m-2, p<0.001) were significantly higher in Sch-PAH compared to iPAH, resulting in a lower pulmonary vascular resistance in Sch-PAH (10±6 Woods units versus 13±7 Woods units, p<0.001). 1- and 3-year survival were significantly better in the Sch-PAH group (p<0.001).Sch-PAH and iPAH share common pathophysiological mechanisms related to inflammation and the TGF-β signalling pathway. Patients with Sch-PAH show a significantly better haemodynamic profile and survival than patients with iPAH

Course of chronic acral heel—ulcer.

<p>A: initial wound without PRF-treatment (diameter of wound 6 cm), B: PRF and amikacin applied to wound, C: 11 weeks after initiation of therapy and after 10 applications of PRF and amikacin (diameter of wound 0.75 cm).</p

Incubation of bacteria with PRF ± antimicrobial agent—Methods.

<p>Incubation of bacteria with PRF ± antimicrobial agent—Methods.</p

<i>In-vitro</i> release pharmacokinetics of amikacin, teicoplanin and polyhexanide in a platelet rich fibrin—layer (PRF)—a laboratory evaluation of a modern, autologous wound treatment - Fig 3

<p>Left: Mean zones of inhibition for MSSA and MRSA incubated with PRF and teicoplanin (MSSA σ = 0–5.5 mm; MRSA σ = 0–11.43 mm). Right: Release of teicoplanin out of a PRF-layer (σ = 7.5–42.8 mg/L; R square = 0.81).</p

Mean zones of inhibition for MSSA and <i>K</i>. <i>pneumoniae</i> with PRF and polyhexanide.

<p>Bacterial eradication occurred within the first 24 hours only.</p

Structural analysis of urinary light chains and proteomic analysis of hyaline tubular casts in light chain associated kidney disorders

Background Monoclonal overproduction of kappa and/or lambda light chains might result in renal light chain deposition disease. Light chain associated cast nephropathy and renal AL-amyloidosis represent two further pathologies going along with monoclonal gammopathy of renal significance and multiple myeloma. While cast nephropathy often manifests with acute kidney injury, AL-amyloidosis is rather accompanied with chronic kidney disease. Methods Urine samples were collected from 17 patients with multiple myeloma or monoclonal gammopathy. The urine sediment was stained for cast morphology by H/E and light chain immunofluorescence. Following micro-selection of casts under microscope, proteomic analysis of casts was performed by mass spectrometry. Sucrose gradient sedimentation was employed and light chain architecture examined by immunoblotting. Uromodulin was measured by ELISA in sucrose gradient fractions. Results Urinary casts were observed of about 30 µm in diameter by H/E staining and under immunofluorescence microscopy. Casts with a diameter of 20 µm were observed as a novel variant. Proteome analysis showed that in addition to the expected light chain variants produced by the malignant clone of plasma cells, also histones such as H2B and cathepsin B were contained. Uromodulin was not detectable in urinary casts of all patients. All eleven patients with lambda light chains showed predominant dimerized light chains in the urine immunoblot. Six patients with kappa light chains presented with predominantly monomeric forms of light chains in the immunoblot. The densitometric evaluated ratio of lambda dimers vs. monomers was significantly higher (2.12 ± 0.75) when compared with the ratio of kappa dimers vs. monomers (0.64 ± 0.47), p = 0.00001. Aggregates of light chains separated in part into denser sucrose fractions. Conclusion This work on urinary casts and light chains demonstrates that hyaline tubular casts represent a complex formation of protein-protein aggregates with histones and cathepsin B identified as novel cast components. Apart from the proteomic composition of the casts, also the formation of the light chains and aggregates is of relevance. Dimerized light chains, which are typical for lambda paraproteins, might be less dialyzable than monomeric forms and may therefore identify patients less responsive to high cut-off dialysis

PLOS ONE / The urine biomarker panel [IGFBP7]x[TIMP-2] (NephroCheck® parameter) does not correlate with IGFBP7 and TIMP-2 gene expression in urinary sediment

Background Acute kidney injury (AKI) is frequently observed in serious infections, following nephrotoxic medication, surgery and trauma. Here we tested whether the detection of two recently identified biomarkers for AKI, Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) and Insulin-Like Growth Factor Binding Protein 7 (IGFBP7), depends on the expression of these proteins in cells of the urinary sediment. Method We collected urine samples of 33 kidney transplant recipients and 14 non-transplanted patients who all had AKI (stages 13 according to KDIGO), and measured [IGFBP7]x[TIMP-2] using the NephroCheck® Astute1 40 meter. Concomitantly, we analyzed IGFBP7 and TIMP-2 mRNA expression by quantitative polymerase chain reaction (qPCR) from urinary sediment of the same patients, and correlated the results with [IGFBP7]x[TIMP-2] (protein), by linear regression analysis. We also determined the association between [IGFBP7]x[TIMP-2] and estimated glomerular filtration rate (eGFR), and between IGFBP7 and TIMP-2 mRNA expression and markers of inflammation. Light microscopy and confocal immunofluorescence served to illustrate changes in the urinary sediment over the time course of renal function improvement. Results Of the 47 analyzed AKI patients, 14 presented with ascending urinary tract infection. Serum creatinine (sCr), blood urea nitrogen (BUN) and eGFR in all patients were 3.92.28 mg/dL, 47.5923.1 mg/dL and 22.8816.0 mL/min/1.73m, respectively, on average standard deviation. [IGFBP7]x[TIMP-2] was 2.339.95 (ng/ml)/1000, and did not associate with IGFBP7 and TIMP-2 gene expression (r = -0.0220, p = 0.4216; respectively r = 0.0972, p = 0.1909). [IGFBP7]x[TIMP-2] did not associate with eGFR; IGFBP7 and TIMP-2 mRNA expression. Improvement of renal function went along with disappearance of casts, decrease in aquaporin1 positive renal epithelial cells and leukocytes from the urinary sediment. Conclusion The gene expression pattern of IGFBP7 and TIMP-2 from urinary sediment, which contains desquamated renal tubular epithelial cells, did not correlate with [IGFBP7]x[TIMP-2] protein, indicating that IGFBP7 and TIMP-2 measured in the NephroCheck® test originated predominantly from intact but stressed cells of the kidney itself.(VLID)488786

Dalbavancin reduces biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE)

Activity of dalbavancin against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) in biofilm was investigated and the microbicidal biofilm concentrations (MBC) were determined. Biofilms obtained from ten MRSA and ten MRSE bloodstream isolates, collected from patients in the General Hospital of Vienna between 2012 and 2015, were incubated with dalbavancin in trypticase soy broth (TSB) in serial dilution from 0.0625 mg/l to 256 mg/l using a microtiter plate biofilm model. The plates were incubated for 24 h at 37 C and 50% humidity. Biofilms were fixed with 2.5% glutaraldehyde and stained with crystal violet. Subsequently the optical density (OD620) was used to measure the MBC, defined as the concentration of dalbavancin leading to a 50% reduction of biofilm. MBC for MRSA was 1 mg/l4 mg/l (minimal inhibitory concentrations (MIC) 0.0312 mg/l0.064 mg/l). MBC for MRSE was 2 mg/l16 mg/l (MIC 0.023 mg/l0.0625 mg/l). Dalbavancin successfully reduced MRSA and MRSE in biofilms, and therefore provides a promising option for the treatment of biofilm-associated infections.(VLID)353192

Zika virus-induced itching rash in a returning traveller from Brazil

(VLID)485290

Hypoalbuminemia as predictor of recurrence of Clostridium difficile infection

Background Novel drugs for Clostridium difficile (C. difficile) infections have been proven to reduce recurrent infections. Because of their high financial costs, identification of patients at high risk for recurrence is essential to provide optimal treatment. The ATLAS scores ability to predict 90-day recurrence, disease complications and 1year all-cause mortality was evaluated. Methods 144 consecutive symptomatic patients with positive stool test for C. difficile were enrolled. The ATLAS score (consisting of the variables age, temperature, leukocyte count, albumin, systemic antibiotics, serum creatinine) was calculated and patients were stratified into 4 subgroups according to their scores. A Cox regression model was used to estimate the extent to which ATLAS was associated with 90-day recurrence. Furthermore, the score was correlated with disease complications and one-year all-cause mortality. Results ATLAS was unable to predict 90-day recurrence (p = 0.064, HR 1.134 [0.993;1.295]), but performed well for disease complications (D = 0.382, p < 0.001, HR 1.547 [1.266;1.889]) and mortality (p < 0.001, HR 1.374 [1.194;1.583]). Serum albumin was the only parameter able to predict 90-day recurrence (p = 0.016, HR 0.958 [0.926;0.992]) and was also a predictor of disease complications (p < 0.001, HR 0.865[0.809;0.924]) and one-year all-cause mortality (p < 0.001, HR 0.923 [0.896;0.950]). A threshold of 33.1g/L (sensitivity = 56%, specificity = 80%, AUC 0.683) and 29.2g/L (sensitivity = 75%, specificity = 70%, AUC 0.763) of serum albumin could be identified to be predictive for 90-day recurrence and one-year all-cause mortality, respectively. Conclusions Serum albumin and ATLAS are predictors of disease complications and mortality, while only serum albumin is significantly associated with 90-day disease recurrence.(VLID)364366