To define and characterize a novel pre-Descemet's layer in the human cornea.
Clinical and experimental study.
We included 31 human donor sclerocorneal discs, including 6 controls (mean age, 77.7 ...years).
Air was injected into the stroma of donor whole globes (n = 4) and sclerocorneal discs (n = 21) as in the clinical deep anterior lamellar keratoplasty procedure with the big bubble (BB) technique. The following experiments were performed: (1) creation of BB followed by peeling of the Descemet's membrane (DM); (2) peeling off of the DM followed by creation of the BB, and (3) creation of the BB and continued inflation until the bubble popped to measure the popping pressure. Tissue obtained from these experiments was subjected to histologic examination.
Demonstration of a novel pre-Descemet's layer (Dua's layer) in the human cornea.
Three types of BB were obtained. Type-1, is a well-circumscribed, central dome-shaped elevation up to 8.5 mm in diameter (n = 14). Type-2, is a thin-walled, large BB of maximum 10.5 mm diameter, which always started at the periphery, enlarging centrally to form a large BB (n = 5), and a mixed type (n = 3). With type-1 BB, unlike type-2 BB, it was possible to peel off DM completely without deflating the BB, indicating the presence of an additional layer of tissue. A type-1 BB could be created after first peeling off the DM (n = 5), confirming that DM was not essential to create a type-1 BB. The popping pressure was 1.45 bar and 0.6 bar for type-1 BB and type-2 BB, respectively. Histology confirmed that the cleavage occurred beyond the last row of keratocytes. This layer was acellular, measured 10.15 ± 3.6 microns composed of 5 to 8 lamellae of predominantly type-1 collagen bundles arranged in transverse, longitudinal, and oblique directions.
There exists a novel, well-defined, acellular, strong layer in the pre-Descemet's cornea. This separates along the last row of keratocytes in most cases performed with the BB technique. Its recognition will have considerable impact on posterior corneal surgery and the understanding of corneal biomechanics and posterior corneal pathology such as acute hydrops, Descematocele and pre-Descemet's dystrophies.
The authors have no proprietary or commercial interest in any materials discussed in this article.
Direct oral anticoagulants (DOACs) account for most oral anticoagulant use. DOAC-associated bleeding events are commonly encountered in clinical practice and are associated with substantial morbidity ...and mortality. Both specific reversal agents and nonspecific hemostatic therapies, such as prothrombin complex concentrates, are used in the management of DOAC-associated bleeding. Measuring hemostatic efficacy and demonstrating a clinical impact from these therapies among studies of bleeding patients is challenging. Thrombin generation assays provide information on the total hemostatic potential of plasma, and have emerged as a promising modality to both measure the impact of DOACs on coagulation and to evaluate the effects of hemostatic therapies among patients with DOAC-associated bleeding. The mechanisms by which nonspecific hemostatic agents impact coagulation and thrombin generation in the context of DOAC therapy are unclear. As a result, we undertook a review of the literature using a systematic search strategy with the goal of summarizing the effects of DOACs on thrombin generation and the effects of both specific reversal agents and nonspecific hemostatic therapies on DOAC-altered thrombin generation parameters. We sought to identify clinical studies focusing on whether altered thrombin generation is associated with clinical bleeding and whether correction of altered thrombin generation parameters predicts improvements in clinical hemostasis. Lastly, we sought to outline future directions for the application of thrombin generation assays toward anticoagulation therapies and the question of anticoagulation reversal.
Direct oral anticoagulants (DOACs) have become the recommended first choice anticoagulant agent for treatment of acute venous thromboembolism (VTE) in non-cancer patients and are increasingly ...prescribed worldwide. They have not only intrinsic advantages, such as rapid onset of action and wide therapeutic windows, but also a lower risk of major, intracranial and fatal bleeding in VTE patients compared to vitamin K antagonists. Even though DOACs are often referred to as uniform drug class, there is growing evidence that each DOAC has a specific risk profile. Indirect comparisons and retrospective cohort studies suggest that apixaban may be associated with a lower risk of major bleeding than other DOACs, but there are no head-to-head trials with DOACs. Therefore, current guidelines do not recommend one DOAC over another and the choice of a specific DOAC is mainly based on physician and patient preferences, reimbursement and availability. Retrospective cohort studies and VTE registries are important to identify potential differences in efficacy and safety between DOACs; but they are methodologically too limited to inform the optimal choice of oral anticoagulant agent. Randomized controlled trials are crucial to inform sound treatment recommendations, because proper randomization is the key to unprejudiced treatment allocation and minimization of unmeasured and unknown confounding. Given increasing evidence of differences in safety profiles of DOACs from indirect comparisons and observational studies, it's time for head-to-head trials with DOACs.
•Direct oral anticoagulants (DOACs) are often referred to as uniform drug class.•Bleeding risk may differ between DOACs but there are no direct comparison trials.•Head-to-head DOAC trials are needed to inform the optimal anticoagulant therapy for acute VTE.
The potentially significant role of the biogenic trace gas dimethylsulfide (DMS) in determining the Earth's radiation budget makes it necessary to accurately reproduce seawater DMS distribution and ...quantify its global flux across the sea/air interface. Following a threefold increase of data (from 15,000 to over 47,000) in the global surface ocean DMS database over the last decade, new global monthly climatologies of surface ocean DMS concentration and sea‐to‐air emission flux are presented as updates of those constructed 10 years ago. Interpolation/extrapolation techniques were applied to project the discrete concentration data onto a first guess field based on Longhurst's biogeographic provinces. Further objective analysis allowed us to obtain the final monthly maps. The new climatology projects DMS concentrations typically in the range of 1–7 nM, with higher levels occurring in the high latitudes, and with a general trend toward increasing concentration in summer. The increased size and distribution of the observations in the DMS database have produced in the new climatology substantially lower DMS concentrations in the polar latitudes and generally higher DMS concentrations in regions that were severely undersampled 10 years ago, such as the southern Indian Ocean. Using the new DMS concentration climatology in conjunction with state‐of‐the‐art parameterizations for the sea/air gas transfer velocity and climatological wind fields, we estimate that 28.1 (17.6–34.4) Tg of sulfur are transferred from the oceans into the atmosphere annually in the form of DMS. This represents a global emission increase of 17% with respect to the equivalent calculation using the previous climatology. This new DMS climatology represents a valuable tool for atmospheric chemistry, climate, and Earth System models.
Neuromyelitis optica spectrum disorder (NMOSD) and anti-myelin oligodendrocyte glycoprotein (anti-MOG) syndromes are immune-mediated inflammatory conditions of the central nervous system that ...frequently involve the optic nerves and the spinal cord. Because of their similar clinical manifestations and habitual relapsing course they are frequently confounded with multiple sclerosis (MS). Early and accurate diagnosis of these distinct conditions is relevant as they have different treatments. Some agents used for MS treatment may be deleterious to NMOSD. NMOSD is frequently associated with antibodies which target aquaporin-4 (AQP4), the most abundant water channel in the CNS, located in the astrocytic processes at the blood-brain barrier (BBB). On the other hand, anti-MOG syndromes result from damage to myelin oligodendrocyte glycoprotein (MOG), expressed on surfaces of oligodendrocytes and myelin sheaths. Acute transverse myelitis with longitudinally extensive lesion on spinal MRI is the most frequent inaugural manifestation of NMOSD, usually followed by optic neuritis. Other core clinical characteristics include area postrema syndrome, brainstem, diencephalic and cerebral symptoms that may be associated with typical MRI abnormalities. Acute disseminated encephalomyelitis and bilateral or recurrent optic neuritis are the most frequent anti-MOG syndromes in children and adults, respectively. Attacks are usually treated with steroids, and relapses prevention with immunosuppressive drugs. Promising emerging therapies for NMOSD include monoclonal antibodies and tolerization.
In 2014, the Tele-ICU Committee of the Society of Critical Care Medicine published an article regarding the state of ICU telemedicine, one better defined today as tele-critical care. Given the rapid ...evolution in the field, the authors now provide an updated review.
We searched PubMed and OVID for peer-reviewed literature published between 2010 and 2018 related to significant developments in tele-critical care, including its prevalence, function, activity, and technologies. Search terms included electronic ICU, tele-ICU, critical care telemedicine, and ICU telemedicine with appropriate descriptors relevant to each sub-section. Additionally, information from surveys done by the Society of Critical Care Medicine was included given the relevance to the discussion and was referenced accordingly.
Tele-critical care continues to evolve in multiple domains, including organizational structure, technologies, expanded-use case scenarios, and novel applications. Insights have been gained in economic impact and human and organizational factors affecting tele-critical care delivery. Legislation and credentialing continue to significantly influence the pace of tele-critical care growth and adoption.
Tele-critical care is an established mechanism to leverage critical care expertise to ICUs and beyond, but systematic research comparing different models, approaches, and technologies is still needed.
AIMS: To evaluate the ability of Candida parapsilosis and Candida glabrata to develop phenotypic resistance to a benzophenone enriched fraction obtained from Brazilian red propolis (BZP‐BRP) as ...compared to fluconazole (FLC). To investigate possible synergy between BZP‐BRP and FLC and anidulafungin (AND). METHODS AND RESULTS: To analyse the development of resistance, isolates susceptible to these antifungals were cultured in increasing concentrations of FLC and BZP‐BRP. The increase in FLC minimum inhibitory concentration for all isolates was evident and the majority developed resistance, whereas none isolated became less susceptible to BZP‐BRP. Synergism was investigated by checkerboard method. BZP‐BRP demonstrated synergy with FLC and indifference with AND for most isolates. CONCLUSIONS: In conclusion, the synergism observed with FLC suggests that BZP‐BRP could be a possible therapeutic strategy for the treatment of infections related to FLC‐resistant Candida sp. SIGNIFICANCE AND IMPACT OF THE STUDY: The indiscriminate use of antifungals results in the emergence of drug‐resistant strains among previously susceptible populations. BZP‐BRP can become an alternative for the treatment of persistent infections caused by Candida sp.
Many anticoagulant strategies are available for the treatment of acute venous thromboembolism, yet little guidance exists regarding which drug is most effective and safe.
To summarize and compare the ...efficacy and safety outcomes associated with 8 anticoagulation options (unfractionated heparin UFH, low-molecular-weight heparin LMWH, or fondaparinux in combination with vitamin K antagonists); LMWH with dabigatran or edoxaban; rivaroxaban; apixaban; and LMWH alone) for treatment of venous thromboembolism.
A systematic literature search was conducted using MEDLINE, EMBASE, and the evidence-based medicine reviews from inception through February 28, 2014.
Eligible studies were randomized trials reporting rates of recurrent venous thromboembolism and major bleeding in patients with acute venous thromboembolism. Of the 1197 studies identified, 45 trials including 44,989 patients were included in the analyses.
Two reviewers independently extracted trial-level data including number of patients, duration of follow-up, and outcomes. The data were pooled using network meta-analysis.
The primary clinical and safety outcomes were recurrent venous thromboembolism and major bleeding, respectively.
Compared with the LMWH-vitamin K antagonist combination, a treatment strategy using the UFH-vitamin K antagonist combination was associated with an increased risk of recurrent venous thromboembolism (hazard ratio HR, 1.42; 95% credible interval CrI, 1.15-1.79). The proportion of patients experiencing recurrent venous thromboembolism during 3 months of treatment were 1.84% (95% CrI, 1.33%-2.51%) for the UFH-vitamin K antagonist combination and 1.30% (95% CrI, 1.02%-1.62%) for the LMWH-vitamin K antagonist combination. Rivaroxaban (HR, 0.55; 95% CrI, 0.35-0.89) and apixaban (HR, 0.31; 95% CrI, 0.15-0.62) were associated with a lower risk of bleeding than was the LMWH-vitamin K antagonist combination, with a lower proportion of patients experiencing a major bleeding event during 3 months of anticoagulation: 0.49% (95% CrI, 0.29%-0.85%) for rivaroxaban, 0.28% (95% CrI, 0.14%-0.50%) for apixaban, and 0.89% (95% CrI, 0.66%-1.16%) for the LMWH-vitamin K antagonist combination.
Using meta-analytic pooling, there were no statistically significant differences for efficacy and safety associated with most treatment strategies used to treat acute venous thromboembolism compared with the LMWH-vitamin K antagonist combination. However, findings suggest that the UFH-vitamin K antagonist combination is associated with the least effective strategy and that rivaroxaban and apixaban may be associated with the lowest risk for bleeding.
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