Postpartum haemorrhage (PPH) can be exacerbated by haemostatic failure. We hypothesized that early fibrinogen replacement, guided by viscoelastometric testing, reduces blood product usage and bleed ...size.
Women with PPH 1000–1500 ml were enrolled. If Fibtem A5 was ≤15 mm and bleeding continued, subjects were randomized to fibrinogen concentrate or placebo. The primary outcome compared the number of units of red blood cells, plasma, cryoprecipitate and platelets transfused.
Of 663 women enrolled 55 were randomized. The adjusted incidence rate ratio (IRR) (95% CI) for the number of allogeneic units transfused in the fibrinogen group compared with placebo was 0.72 (0.3–1.7), P=0.45. In pre-specified subgroup analyses, subjects who had a Fibtem A5 ≤12 mm at the time of randomization and who received fibrinogen concentrate received a median (25th–75th centile) of 1 (0–4.5) unit of allogeneic blood products and had an additional 300 (100–350) ml blood loss whereas those who received placebo also received 3 (0–6) units of allogeneic blood products and had 700 (200–1550) ml additional blood loss; these differences were not statistically significantly different. There was one thrombotic event in each group.
Infusion of fibrinogen concentrate triggered by Fibtem A5 ≤15 mm did not improve outcomes in PPH. Pre-specified subgroup analyses suggest that fibrinogen replacement is not required if the Fibtem A5 is > 12 mm or Clauss fibrinogen >2 g litre−1, but an effect below these levels cannot be excluded. The raised fibrinogen at term appears to be a physiological buffer rather than required for haemostasis.
ISRCTN46295339 (http://www.isrctn.com/ISRCTN46295339, last accessed 5 July 2017), EudraCT 2012-005511-11 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=2012-005511-11, last accessed 5 July 2017).
Acute kidney injury (AKI) is a common complication following cardiac surgery performed on cardiopulmonary bypass (CPB) and has important implications for prognosis. The aetiology of cardiac ...surgery‐associated AKI is complex, but renal hypoxia, particularly in the medulla, is thought to play at least some role. There is strong evidence from studies in experimental animals, clinical observations and computational models that medullary ischaemia and hypoxia occur during CPB. There are no validated methods to monitor or improve renal oxygenation during CPB, and thus possibly decrease the risk of AKI. Attempts to reduce the incidence of AKI by early transfusion to ameliorate intra‐operative anaemia, refinement of protocols for cooling and rewarming on bypass, optimization of pump flow and arterial pressure, or the use of pulsatile flow, have not been successful to date. This may in part reflect the complexity of renal oxygenation, which may limit the effectiveness of individual interventions. We propose a multi‐disciplinary pathway for translation comprising three components. Firstly, large‐animal models of CPB to continuously monitor both whole kidney and regional kidney perfusion and oxygenation. Secondly, computational models to obtain information that can be used to interpret the data and develop rational interventions. Thirdly, clinically feasible non‐invasive methods to continuously monitor renal oxygenation in the operating theatre and to identify patients at risk of AKI. In this review, we outline the recent progress on each of these fronts.
We examined PrEP use, condomless anal sex (CAS), and PrEP adherence among men who have sex with men (MSM) attending sexual health clinics in Wales, UK. In addition, we explored the association ...between the introduction of measures to control transmission of SARS-CoV-2 on these outcomes. We conducted an ecological momentary assessment study of individuals in receipt of PrEP in Wales. Participants used an electronic medication cap to record PrEP use and completed weekly sexual behaviour surveys. We defined adherence to daily PrEP as the percentage of CAS episodes covered by daily PrEP (preceded by ≥ 3 days of PrEP and followed by ≥ 2 days). Sixty participants were recruited between September 2019 and January 2020. PrEP use data prior to the introduction of control measures were available over 5785 person-days (88%) and following their introduction 7537 person-days (80%). Data on CAS episodes were available for 5559 (85%) and 7354 (78%) person-days prior to and following control measures respectively. Prior to the introduction of control measures, PrEP was taken on 3791/5785 (66%) days, there were CAS episodes on 506/5559 (9%) days, and 207/406 (51%) of CAS episodes were covered by an adequate amount of daily PrEP. The introduction of pandemic-related control measures was associated with a reduction in PrEP use (OR 0.44, 95%CI 0.20–0.95), CAS (OR 0.35, 95%CI 0.17–0.69), and PrEP adherence (RR = 0.55, 95%CI 0.34–0.89) and this may have implications for the health and wellbeing of PrEP users and, in addition to disruption across sexual health services, may contribute to wider threats across the HIV prevention cascade.
Src kinase activity was found to protect endothelial cells from apoptosis during vascular endothelial growth factor (VEGF)–, but not basic fibroblast growth factor (bFGF)–, mediated angiogenesis in ...chick embryos and mice. In fact, retroviral targeting of kinase-deleted Src to tumor-associated blood vessels suppressed angiogenesis and the growth of a VEGF-producing tumor. Although mice lacking individual Src family kinases (SFKs) showed normal angiogenesis, mice deficient in pp60
c-src or pp62
c-yes showed no VEGF-induced vascular permeability (VP), yet fyn
−/− mice displayed normal VP. In contrast, inflammation-mediated VP appeared normal in Src-deficient mice. Therefore, VEGF-, but not bFGF-, mediated angiogenesis requires SFK activity in general, whereas the VP activity of VEGF specifically depends on the SFKs, Src, or Yes.
To investigate the prevalence of visual field defects in glaucomatous eyes, glaucoma suspects, and ocular hypertensives with 24-2 and 10-2 visual fields.
Prospective, cross-sectional study.
Patients ...with or suspected glaucoma tested with 24-2 and 10-2. Patients were classified into 3 groups on the basis of the presence of glaucomatous optic neuropathy (GON) and 24-2 visual field abnormalities: early glaucoma (GON and abnormal visual field, mean deviation >-6 decibels dB), glaucoma suspects (GON and normal visual field), and ocular hypertensives (normal disc, normal visual field, and intraocular pressure >22 mmHg). For the classification of visual field abnormalities, 24-2 and 10-2 tests performed on the same visit were analyzed.
Comparison of the prevalence of abnormal 24-2 versus 10-2 visual field results based on cluster criteria in each diagnostic group.
A total of 775 eyes (497 patients) were evaluated. A total of 364 eyes had early glaucoma, 303 eyes were glaucoma suspects, and 108 eyes were ocular hypertensives. In the glaucoma group, 16 of the 26 eyes (61.5%) classified as normal based on cluster criteria on 24-2 tests were classified as abnormal on 10-2 visual fields. In eyes with suspected glaucoma, 79 of the 200 eyes (39.5%) classified as normal on the 24-2 test were classified as abnormal on 10-2 visual fields. In ocular hypertensive eyes, 28 of the 79 eyes (35.4%) classified as normal on the 24-2 were classified as abnormal on the 10-2. Patients of African descent were more likely to have an abnormal 10-2 result (67.3 vs. 56.8%, P = 0.009).
Central visual field damage seen on the 10-2 test is often missed with the 24-2 strategy in all groups. This finding has implications for the diagnosis of glaucoma and classification of severity.
Summary
More than 50 interventions have been used to treat hidradenitis suppurativa (HS), and so therapy decisions can be challenging. Our objective was to summarize and appraise randomized ...controlled trial (RCT) evidence for HS interventions in adults. Searches were conducted in Medline, Embase, CENTRAL, LILACS, five trials registers and s from eight dermatology conferences until 13 August 2015. Two review authors independently assessed study eligibility, extracted data and assessed methodological quality. Primary outcomes were quality of life and adverse effects of the interventions. Twelve trials, from 1983 to 2015, investigating 15 different interventions met our inclusion criteria. The median trial duration was 16 weeks and the median number of participants was 27. Adalimumab 40 mg weekly improved the Dermatology Life Quality Index (DLQI) by 4·0 points, which equates to the minimal clinically important difference for the scale, compared with placebo (95% confidence interval −6·5 to −1·5 points). Evidence quality was reduced to ‘moderate’ because the results are based on only a single study. Adalimumab 40 mg every other week was ineffective in a meta‐analysis of two studies comprising 124 participants. Infliximab 5 mg kg−1 improved the DLQI score by 8·4 points after 8 weeks in a moderate‐quality study completed by 33 of 38 participants. Etanercept 50 mg twice weekly was ineffective. Inclusion of a gentamicin sponge prior to primary closure did not improve outcomes. Other interventions, including topical and oral antibiotics, were investigated by relatively small studies, preventing treatment recommendations due to imprecision. More, larger RCTs are required to investigate most HS interventions, particularly oral treatments and surgical therapy. Moderate‐quality evidence suggests that adalimumab given weekly and infliximab are effective, whereas adalimumab every other week is ineffective.
What's already known about this topic?
Many interventions have been tried for hidradenitis suppurativa (HS).
Evidence supporting the choice of intervention for HS is often limited.
What does this study add?
Moderate‐quality evidence suggests that adalimumab given weekly and infliximab are effective, whereas adalimumab every other week is ineffective.
There are very limited or no randomized controlled trial data in HS for antibiotic therapy, retinoids, oral immunomodulators or the timing and type of surgery to perform.
Linked Comment: Blok. Br J Dermatol 2016; 174: 953–954
Cardiac surgery requiring cardiopulmonary bypass is associated with postoperative acute kidney injury and neurocognitive disorders, including delirium. Intra-operative inflammation and/or impaired ...tissue perfusion/oxygenation are thought to be contributors to these outcomes. It has been hypothesised that these problems may be ameliorated by the highly selective α
-agonist, dexmedetomidine. We tested the effects of dexmedetomidine on renal and cerebral microcirculatory tissue perfusion, oxygenation and histology in a clinically relevant ovine model. Sixteen sheep were studied while conscious, after induction of anaesthesia and during 2 h of cardiopulmonary bypass. Eight sheep were allocated randomly to receive an intravenous infusion of dexmedetomidine (0.4-0.8 μg.kg
.h
) from induction of anaesthesia to the end of cardiopulmonary bypass, and eight to receive an equivalent volume of matched placebo (0.9% sodium chloride). Commencement of cardiopulmonary bypass decreased renal medullary tissue oxygenation in the placebo group (mean (95%CI) 5.96 (4.24-7.23) to 1.56 (0.84-2.09) kPa, p = 0.001), with similar hypoxic levels observed in the dexmedetomidine group (6.33 (5.33-7.07) to 1.51 (0.33-2.39) kPa, p = 0.002). While no differences in kidney function (i.e. reduced creatinine clearance) were evident, a greater incidence of histological renal tubular injury was observed in sheep receiving dexmedetomidine (7/8 sheep) compared with placebo (2/8 sheep), p = 0.041. Graded on a semi-quantitative scale (0-3), median (IQR range) severity of histological renal tubular injury was higher in the dexmedetomidine group compared with placebo (1.5 (1-2 0-3) vs. 0 (0-0.3 0-1) respectively, p = 0.013). There was no difference in cerebral tissue microglial activation (neuroinflammation) between the groups. Dexmedetomidine did not reduce renal medullary hypoxia or cerebral neuroinflammation in sheep undergoing cardiopulmonary bypass.
The hematopoietic system produces a large number of highly specialized cell types that are derived through a hierarchical differentiation process from a common stem cell population. miRNAs are ...critical players in orchestrating this differentiation. Here, we report the development and application of a high-throughput microfluidic real-time quantitative PCR (RT-qPCR) approach for generating global miRNA profiles for 27 phenotypically distinct cell populations isolated from normal adult mouse hematopoietic tissues. A total of 80,000 RT-qPCR assays were used to map the landscape of miRNA expression across the hematopoietic hierarchy, including rare progenitor and stem cell populations. We show that miRNA profiles allow for the direct inference of cell lineage relations and functional similarity. Our analysis reveals a close relatedness of the miRNA expression patterns in multipotent progenitors and stem cells, followed by a major reprogramming upon restriction of differentiation potential to a single lineage. The analysis of miRNA expression in single hematopoietic cells further demonstrates that miRNA expression is very tightly regulated within highly purified populations, underscoring the potential of single-cell miRNA profiling for assessing compartment heterogeneity.
As cancer cells undergo metastasis--invasion and migration of a new tissue--they penetrate and attach to the target tissue's basal matrix. This allows the cancer cell to pull itself forward into the ...tissue. The attachment is mediated by cell-surface receptors known as integrins, which bind to components of the extracellular matrix. Integrins are crucial for cell invasion and migration, not only for physically tethering cells to the matrix, but also for sending and receiving molecular signals that regulate these processes.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
One hundred six low‐altitude passes of magnetometer data from the last 2 months of the MErcury Surface, Space ENvironment, GEochemistry, and Ranging mission have been applied to produce a map of the ...crustal magnetic field at a constant altitude of 40 km covering latitudes of 35–75∘ N and longitudes of 270–90∘ E. Some anomalies correlate significantly with impact basins/craters (e.g., Rustaveli and Vyasa), while other basins/craters have no obvious anomalies. A possible interpretation that is consistent with lunar evidence is that some impactors delivered more ferromagnetic Fe–Ni metal to the interior subsurfaces and ejecta fields of the craters/basins that they produced. The amount of metallic iron that could plausibly be delivered is limited by the diameter and mass of an impactor that would yield a crater with observed diameters (e.g., 200 km for Rustaveli). This in turn limits the maximum amplitude of anomalies that could be induced by impactor‐added iron in the present‐day Mercury global field to relatively low values. It is therefore concluded that if impactor‐added iron is the source of the observed crater‐associated anomalies, then they must be almost entirely a consequence of ancient remanent magnetization. A broad magnetic anomaly occurs over the northern rise, a topographically high region with an associated strong free air gravity anomaly. A possible interpretation of the latter anomaly is that an early major impact preconditioned the region for a later mantle uplift event.
Plain Language Summary
The origin of crustal magnetic anomalies on heavily cratered, airless bodies like the Moon and Mercury remains uncertain. Mapping of MErcury Surface, Space ENvironment, GEochemistry, and Ranging magnetometer data at northern midlatitudes on Mercury shows that magnetic anomalies are concentrated near and within some impact basins and craters but not others. The association of anomalies with some craters but not others is consistent with the hypothesis that metallic iron in some impactors (either in an iron core or distributed in the body) was mixed into impact melt and ejecta which then became magnetized while cooling in a former core dynamo magnetic field. Other impactors containing little metallic iron (e.g., cometary nuclei) would have produced no magnetic anomalies. The amount of metallic iron that could plausibly have been delivered by impactors is too small to explain observed anomaly amplitudes as being induced by permeability in the present‐day Mercury global magnetic field. Permanent (remanent) magnetization originating in the early history of the planet is therefore required. One magnetic anomaly is found over the northern rise, a topographically high region with a strong gravity anomaly. This anomaly may indicate that an early major impact weakened the outer lithosphere, allowing a later mantle plume to uplift the region.
Key Points
Crustal magnetic anomalies correlate with some impact basins/craters on Mercury but not others
A possible explanation is that some impactors added more ferromagnetic material to the interiors and ejecta of the craters they produced
The metallic iron added by impactors is unlikely to explain the observed anomalies as being induced rather than remanent
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