Krogsgaardennis0967
Abnormalities noted on EEG included diffuse slowing (n = 49), epileptiform discharges (n = 6), and nonconvulsive status epilepticus (n = 8). Although reversible, grade ≥3 ICANS was associated with significantly shorter progression-free (P = .02) and overall survival (progression being the most common cause of death; P = .001). Our results suggest that imaging and EEG abnormalities are common in patients with ICANS, and high-grade ICANS is associated with worse outcome after CAR T-cell therapy in LBCL patients.Serological classification of individuals as A, B, O, or AB is a mainstay of blood banking. ABO blood groups or ABH antigens, in addition to other surface glycans, act as unique red blood cell (RBC) signatures and direct immune responses. ABO subgroups present as weakened, mixed field, or unexpected reactivity with serological reagents, but specific designations remain complex. selleckchem Lectins detect glycan motifs with some recognizing ABH antigens. We evaluated a 45-probe lectin microarray to rapidly analyze ABO blood groups and associated unique glycan signatures within complex biological samples on RBC surface glycoproteins. RBC membrane glycoproteins were prepared from donor RBCs, n = 20 for each blood group. ABO blood group was distinguishable by lectin array, including variations in ABH antigen expression not observed with serology. Principal component analysis highlighted broad ABO blood group clusters with unexpected high and low antigen expression and variations were confirmed with ABH antibody immunoblotting. Using a subset of lectins provided an accurate method to predict an ABO serological phenotype. Lectin microarray highlighted the importance of ABO localization on glycoproteins and glycolipids and pointed to increased glycocalyx complexity associated with the expression of A and B antigens including high mannose and branched polylactosamine. Thus, lectins identified subtle surface ABO blood group glycoprotein density variations not detected by routine serological methods. Transfusion services observe alterations in ABH expression during malignancy, and ABO incompatible solid organ transplantation is not without risk of rejection. The presented methods may identify subtle but clinically significant ABO blood group differences for transfusion and transplantation.Proteasome inhibition is a standard of care for the primary treatment of patients with Waldenström macroglobulinemia (WM). We present the long-term follow-up of a prospective, phase II clinical trial that evaluated the combination of ixazomib, dexamethasone, and rituximab (IDR) in 26 treatment-naive patients with WM. IDR was administered as 6 monthly induction cycles followed by 6 every-2-month maintenance cycles. The MYD88 L265P mutation was detected in all patients, and CXCR4 mutations were detected in 15 patients (58%). The median time to response (TTR) and time to major response (TTMR) were 2 and 6 months, respectively. Patients with and without CXCR4 mutations had median TTR of 3 months and 1 month, respectively (P = .003), and median TTMR of 10 months and 3 months, respectively (P = .31). The overall, major, and very good partial response (VGPR) rates were 96%, 77%, and 19%, respectively. The rate of VGPR in patients with and without CXCR4 mutations were 7% and 36%, respectively (P = .06). The median progression-free survival (PFS) was 40 months, the median duration of response (DOR) was 38 months, and the median time to next treatment (TTNT) was 40 months. PFS, DOR, and TTNT were not affected by CXCR4 mutational status. The safety profile was excellent with no grade 4 adverse events or deaths to date. IDR provides a safe and effective frontline treatment option for symptomatic patients with WM. This study was registered at www.clinicaltrials.gov as #NCT02400437.
Despite increasing evidence that atopic dermatitis is common in older adults, it is unclear whether the evidence base for treating atopic dermatitis with systemic therapy is generalizable to that population. Older adults are most at risk for adverse events from medications, given age-related alterations in drug metabolism, increased comorbidity, and polypharmacy.
This systematic review examines the representation of older adults in randomized clinical trials (RCTs) of systemic immunomodulatory treatments for atopic dermatitis and whether safety and efficacy data are reported specifically for older individuals.
The Cochrane Central Register of Controlled Trials, Embase, MEDLINE databases, and the ClinicalTrials.gov trial register were searched from inception (MEDLINE via Ovid, 1946; Embase via Ovid, 1974) to November 7, 2019. RCTs investigating systemic immunomodulatory treatments for adults with atopic dermatitis were included. Titles, abstracts, and full-text papers were screened, and data were extract should be aware of this evidence gap when prescribing systemic therapy for atopic dermatitis. Randomized trials and observational studies that include older patients with atopic dermatitis are needed.
Study results suggest that older adults are underrepresented in RCTs of systemic treatment for atopic dermatitis, resulting in a lack of evidence supporting safe clinical use for older adults. Clinicians and patients should be aware of this evidence gap when prescribing systemic therapy for atopic dermatitis. Randomized trials and observational studies that include older patients with atopic dermatitis are needed.N-acyl-homoserine lactones (AHLs), a well-described group of quorum sensing molecules, may modulate plant defense responses and plant growth. However, there is limited knowledge regarding the defense responses of non-model crops to AHLs and the mechanism of action responsible for the modulation of defense responses against microbial pathogens. In the present study, long-chain N-3-oxo-tetradecanoyl-l-homoserine lactone (oxo-C14-HSL) was shown to have a distinct potential to prime cucumber for enhanced defense responses against the biotrophic oomycete pathogen Pseudoperonospora cubensis and the hemibiotrophic bacterium Pseudomonas syringae pv. lachrymans. We provide evidence that AHL-mediated enhanced defense against downy mildew disease is based on cell wall reinforcement by lignin and callose deposition, the activation of defense-related enzymes (peroxidase, β-1,3-glucanase, phenylalanine ammonia-lyase), and the accumulation of reactive oxygen species (hydrogen peroxide, superoxide) and phenolic compounds. Quantitative analysis of salicylic acid and jasmonic acid, and transcriptional analysis of several of genes associated with these phytohormones, revealed that defense priming with oxo-C14-HSL is commonly regulated by the salicylic acid signaling pathway. We also show that treatment with short- (N-hexanoyl-l-homoserine lactone) and medium-chain (N-3-oxo-decanoyl-l-homoserine lactone) AHLs promoted primary root elongation and modified root architecture, respectively, resulting in enhanced plant growth.Connexins (Cxs) oligomerise to form hexameric hemichannels in the plasma membrane that can further dock together on adjacent cells to form gap junctions and facilitate intercellular-trafficking of molecules. In this study, we report the expression and function of an 'orphan' connexin, Cx62, in human and mouse (Cx57, mouse homologue) platelets. A novel mimetic peptide (62Gap27) was developed to target the second extracellular loop of Cx62 and 3D structural models predicted its interference with gap junction and hemichannel function. The ability of 62Gap27 to regulate both gap junction and hemichannel-mediated intercellular communication was observed using FRAP analysis and flow cytometry. Cx62 inhibition by 62Gap27 suppressed a range of agonist-stimulated platelet functions and impaired thrombosis and haemostasis. This was associated with elevated PKA-dependent signalling in a cyclic adenosine monophosphate-independent manner, and was not observed in Cx57 deficient mouse platelets (in which the selectivity of 62Gap27 for this connexin was also confirmed). Notably, Cx62 hemichannels were observed to function independently of Cx37 and Cx40 hemichannels. Together, our data reveal a fundamental role for a hitherto uncharacterised connexin in the regulation of the function of circulating cells.
Stress imaging has been the standard for diagnosing functionally significant coronary artery disease. It is unknown whether novel, atherosclerotic plaque measures improve accuracy beyond coronary stenosis for diagnosing invasive fractional flow reserve (FFR) measurement.
To compare the diagnostic accuracy of comprehensive anatomic (obstructive and nonobstructive atherosclerotic plaque) vs functional imaging measures for estimating vessel-specific FFR.
Controlled clinical trial of diagnostic accuracy with a multicenter derivation-validation cohort of patients referred for nonemergent invasive coronary angiography. A total of 612 patients (64 [10] years; 30% women) with signs and symptoms suggestive of myocardial ischemia from 23 sites were included. Patients were recruited from 2014 to 2017. Data analysis began in August 2018.
Patients underwent invasive coronary angiography with measurement of invasive FFR, coronary computed tomographic angiography (CCTA) quantification of atherosclerotic plaque and Fyocardial perfusion imaging predictors were the summed rest and difference scores. In the validation cohort, the areas under the receiver operating characteristic curve were 0.81 for CCTA vs 0.67 for myocardial perfusion imaging (P < .001).
A comprehensive anatomic interpretation with CCTA, including quantification of obstructive and nonobstructive atherosclerotic plaque, was superior to functional imaging in the diagnosis of invasive FFR. Comprehensive CCTA measures improve prediction of vessel-specific coronary physiology more so than stress-induced alterations in myocardial perfusion.
ClinicalTrials.gov Identifier NCT02173275.
ClinicalTrials.gov Identifier NCT02173275.
Malaria is highly heterogeneous; its changing malaria micro-epidemiology needs to be addressed to support malaria elimination efforts at the regional level.
A three-year, population-based cohort study in two settings in the Peruvian Amazon (Lupuna, Cahuide) followed participants by passive and active case detection from January 2013 to December 2015. Incidence and prevalence rates were estimated using microscopy and PCR.
Lupuna registered 1,828 infections (1,708 P. vivax, 120 P. falciparum; incidence was 80.7 infections/100 person-years (95%CI [77.1-84.5]). Cahuide detected 1,046 infections (1,024 P. vivax, 20 P. falciparum, two mixed); incidence was 40.2 infections/100 person-years (95%CI [37.9-42.7]). Recurrent P. vivax infections predominated onwards from 2013. According to PCR data, submicroscopic predominated over microscopic infections, especially in periods of low transmission. The integration of parasitological, entomological and environmental observations evidenced an intense and seasonal transmission resilient to standard control measures in Lupuna, and a persistent residual transmission after severe outbreaks were intensively handled in Cahuide.
In two exemplars of complex local malaria transmission, standard control strategies failed to eliminate submicroscopic and hypnozoite reservoirs, enabling persistent transmission.
In two exemplars of complex local malaria transmission, standard control strategies failed to eliminate submicroscopic and hypnozoite reservoirs, enabling persistent transmission.
