A System Out of Breath: How Hypoxia Possibly Contributes to the Pathogenesis of Systemic Sclerosis

Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular alterations and immunological disturbances and fibrosis, the order of which remains to be fully determined. Clinically, patients show clear signs of hypoxia in skin and internal organs. The low oxygen tension is potentially caused by a yet to be indentified circuitry involving the three features that typify SSc. In addition, once present, the hypoxia creates a vicious circle of ongoing pathology. In this paper, we provide an overview of the evidence that points towards the mechanisms causing hypoxia in SSc. In addition, data that suggest how hypoxia itself may orchestrate worsening of symptoms is presented. Altogether, it is clear that hypoxia is an important hallmark in SSc patients. By providing an overview of the mechanisms at play and the possible therapeutic avenues that have emerged, we hope to stimulate researchers to provide novel clues into the conundrum in SSc patients

Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter

In an effort to maximize outcomes, recent expert guidelines recommend more-intensive vancomycin dosing schedules to maintain vancomycin troughs between 15 and 20 mg/liter.The widespread use of these more-intensive regimens has been associated with an increase in vancomycin-induced nephrotoxicity reports.The purpose of this systematic literature review is to determine the nephrotoxicity potential of maintaining higher troughs in clinical practice.All studies pertaining to vancomycin-induced nephrotoxicity between 1996 and April 2012 were identified from PubMed, Embase, Cochrane Controlled Trial Registry, and Medline databases and analyzed according to Cochrane guidelines.Of the initial 240 studies identified, 38 were reviewed, and 15 studies met the inclusion criteria.Overall, higher troughs ( >15 mg/liter) were associated with increased odds of nephrotoxicity (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.95 to 3.65) relative to lower troughs of >15 mg/liter.The relationship between a trough of >15 mg/liter and nephrotoxicity persisted when the analysis was restricted to studies that examined only initial trough concentrations (OR, 3.12; 95% CI, 1.81 to 5.37).The relationship between troughs of >15 mg/liter and nephrotoxicity persisted after adjustment for covariates known to independently increase the risk of a nephrotoxicity event.An incremental increase in nephrotoxicity was also observed with longer durations of vancomycin administration.Vancomycin-induced nephrotoxicity was reversible in the majority of cases, with short-term dialysis required only in 3% of nephrotoxic episodes.The collective literature indicates that an exposure-nephrotoxicity relationship for vancomycin exists.The probability of a nephrotoxic event increased as a function of the trough concentration and duration of therapy

Monitoring en Evaluatie Pilot Zandmotor Fase 2: Datarapport groei juveniele vis Zandmotor voorjaar en zomer 2013

Dit rapport beschrijft de data die verzameld zijn tijdens het onderzoek naar juveniele vis en enkele epibenthos soorten in en rond de Zandmotor in het voorjaar en de zomer van 2013. De data is verzameld in 7 dagen verspreid over de periode mei tot en met augustus. De bemonstering is uitgevoerd met een rubberboot met een 2 meter boomkor tuig met maaswijdte van 10 mm en 20mm. Er zijn vistrekken uitgevoerd in de lagune en op 3 plekken rond de Zandmotor. Van iedere vistrek zijn alle vissen per soort gemeten en is al het epibenthos per soort geteld

The perceived waning of biologics in severe asthma

BACKGROUND: Biologics are highly effective in severe asthma and used at fixed dosing intervals. However, in clinical practice, dosing intervals are sometimes shortened if patients perceive a decreased biologic effect before the next administration. The occurrence and clinical relevance of this perceived waning of biological effect is unknown.OBJECTIVE: To explore (1) the frequency, severity and conditions, (2) associated symptoms and (3) relationship with clinical characteristics of the patient-perceived waning effect of biologics before the next administration.METHODS: Severe asthma patients receiving biological treatment ≥4 months were included. Based on 17 semi-structured patient interviews, we developed a questionnaire focusing on the waning effect of biologics before the next administration, which was distributed among 129 patients. Clinical characteristics, including asthma control (ACQ) and quality of life (AQLQ) scores, were collected from patient files.RESULTS: 65/101 patients who completed the questionnaire reported a waning of biological effect, graded as severe (median (IQR) 6.5 (5-7.5) on a 0-10 BORG-scale). Waning manifested in a broad spectrum of symptoms. Patients reporting waning had higher ACQ and lower AQLQ scores versus those without (p &lt; 0.05) and higher BORG-scores were associated with higher exacerbation rate (ρ = 0.309, p = 0.013). A third of all patients were in favor of extending or shortening their dosing interval.CONCLUSION: Two-thirds of severe asthma patients report waning of biologic effect at the end of the dosing interval, which is associated with poorer asthma control and quality of life. The diversity in observed waning of effect opens the way for research into more individualized dosing of biologics.</p

Coverage determinants of breast cancer screening in Flanders:an evaluation of the past decade

Background Breast cancer (BC) is the most common cancer in women in the developed world. In order to find developing cancers in an early stage, BC screening is commonly used. In Flanders, screening is performed in and outside an organized breast cancer screening program (BCSP). However, the determinants of BC screening coverage for both screening strategies are yet unknown. Objective To assess the determinants of BC screening coverage in Flanders. Methods Reimbursement data were used to attribute a screening status to each woman in the target population for the years 2008-2016. Yearly coverage data were categorized as screening inside or outside BCSP or no screening. Data were clustered by municipality level. A generalized linear equation model was used to assess the determinants of screening type. Results Over all years and municipalities, the median screening coverage rate inside and outside BCSP was 48.40% (IQR: 41.50-54.40%) and 14.10% (IQR: 9.80-19.80%) respectively. A higher coverage rate outside BSCP was statistically significantly (P < 0.001) associated with more crowded households (OR: 3.797, 95% CI: 3.199-4.508), younger age, higher population densities (OR: 2.528, 95% CI: 2.455-2.606), a lower proportion of unemployed job seekers (OR: 0.641, 95% CI: 0.624-0.658) and lower use of dental care (OR: 0.969, 95% CI: 0.967-0.972). Conclusion Coverage rate of BC screening is not optimal in Flanders. Women with low SES that are characterized by younger age, living in a high population density area, living in crowded households, or having low dental care are less likely to be screened for BC in Flanders. If screened, they are more likely to be screened outside the BCSP

Reply to "vancomycin-induced nephrotoxicity"

[No abstract available

Irregular screening participation increases advanced stage breast cancer at diagnosis:A population-based study

Objective: To evaluate the effect of irregular screening behaviour on the risk of advanced stage breast cancer at diagnosis in Flanders. Methods: All women aged 50–69 who were invited to the organized breast cancer screening and diagnosed with breast cancer before age 72 from 2001 to 2018 were included. All prevalent screen and interval cancers within 2 years of a prevalent screen were excluded. Screening behaviour was categorized based on the number of invitations and performed screenings. Four groups were defined: regular, irregular, only-once, and never attenders. Advanced stage cancer was defined as a stage III + breast cancer. The association between screening regularity and breast cancer stage at diagnosis was evaluated in multivariable logistic regression models, taking age of diagnosis and socio-economic status into account. Results: In total 13.5% of the 38,005 breast cancer cases were diagnosed at the advanced stage. Compared to the regular attenders, the risk of advanced stage breast cancer for the irregular attenders, women who participated only-once, and never attenders was significantly higher with ORadjusted:1.17 (95%CI:1.06–1.29) and ORadjusted:2.18 (95%CI:1.94–2.45), and ORadjusted:5.95 (95%CI:5.33–6.65), respectively. Conclusions: In our study, never attenders were nearly six times more likely to be diagnosed with advanced stage breast cancer than regular attenders, which was much higher than the estimates published thus far. An explanation for this is that the ever screened women is a heterogeneous group regarding the participation profiles which also includes irregular and only-once attenders. The benefit of regular screening should be informed to all women invited for screening

Vancomycin Heteroresistance Is Associated with Reduced Mortality in ST239 Methicillin-Resistant Staphylococcus aureus Blood Stream Infections

Background: Despite hVISA infections being associated with vancomycin treatment failure, no previous study has been able to detect a mortality difference between heteroresistant vancomycin intermediate Staphylococcus aureus (hVISA) and vancomycin susceptible Staphylococcus aureus (VSSA) bloodstream infections (BSI)

Au-Ag template stripped pattern for scanning probe investigations of DNA arrays produced by Dip Pen Nanolithography

We report on DNA arrays produced by Dip Pen Nanolithography (DPN) on a novel Au-Ag micro patterned template stripped surface. DNA arrays have been investigated by atomic force microscopy (AFM) and scanning tunnelling microscopy (STM) showing that the patterned template stripped substrate enables easy retrieval of the DPN-functionalized zone with a standard optical microscope permitting a multi-instrument and multi-technique local detection and analysis. Moreover the smooth surface of the Au squares (abput 5-10 angstrom roughness) allows to be sensitive to the hybridization of the oligonucleotide array with label-free target DNA. Our Au-Ag substrates, combining the retrieving capabilities of the patterned surface with the smoothness of the template stripped technique, are candidates for the investigation of DPN nanostructures and for the development of label free detection methods for DNA nanoarrays based on the use of scanning probes.Comment: Langmuir (accepted