Daviswilliams7792
New treatments are needed for patients with cutaneous T-cell lymphoma (CTCL), particularly for advanced mycosis fungoides (MF) and Sezary syndrome (SS). The immunopathology of MF and SS is complex, but recent advances in tumor microenvironment understanding have identified CCR4 as a promising therapeutic target. CCR4 is widely expressed on malignant T cells and Tregs in the skin and peripheral blood of patients with MF and SS. The interaction of CCR4 with its dominant ligands CCL17 and CCL22 plays a critical role in the development and progression of CTCL, facilitating the movement into, and accumulation of, CCR4-expressing T cells in the skin, and recruiting CCR4-expressing Tregs into the tumor microenvironment. Expression of CCR4 is upregulated at all stages of MF and in SS, increasing with advancing disease. Several CCR4-targeted therapies are being evaluated, including "chemotoxins" targeting CCR4 via CCL17, CCR4-directed chimeric antigen receptor-modified T-cell therapies, small-molecule CCR4 antagonists, and anti-CCR4 monoclonal antibodies. Only one is currently approved mogamulizumab, a defucosylated, fully humanized, anti-CCR4, monoclonal antibody for the treatment of relapsed/refractory MF and SS. Clinical trial da1ta confirm that mogamulizumab is an effective and well-tolerated treatment for relapsed/refractory MF or SS, demonstrating the clinical value of targeting CCR4.
To investigate neuroanatomic volume differences in tinnitus and hearing loss.
Cross-sectional.
Sixteen regions of interest (ROIs) in adults (43 male, 29 female) were examined using 3Tesla structural magnetic resonance imaging in four cohorts 1) tinnitus with moderate hearing loss (N = 31), 2) moderate hearing loss only (N = 15), 3) tinnitus with normal hearing (N = 17), and 4) normal hearing only (N = 13). ROI volumes were corrected for brain size, age, and sex variations. Analysis of covariance (ANCOVA) and post hoc Tukey's test were used to isolate the effects of tinnitus and hearing loss on volume differences. Effect sizes were calculated as the fraction of total variance (η
) in ANCOVA models and percent of mean volume difference relative to mean total volume.
The four cohort ANCOVA revealed tinnitus and hearing loss cohorts to have increased volume in the corona radiata (η
= 0.192; P = .0018) and decreased volume in the nucleus accumbens (η
= 0.252; P < .0001), caudate nucleus (η
= 0.188; P = .002), and inferior fronto-occipital fasciculus (η
= 0.250; P = .0001). Tinnitus with normal hearing showed decreased volume in the nucleus accumbens (22.0%; P = .001) and inferior fronto-occipital fasciculus (18.1%; P = .002), and hearing loss only showed increased volume in the corona radiata (10.7%; P = .01) and decreased volume in the nucleus accumbens (22.1%; P = .001), caudate nucleus (16.1%; P = .004), and inferior fronto-occipital fasciculus (18.3%; P = .003).
Tinnitus and hearing loss have overlapping effects on neurovolumetric alterations, especially impacting the nucleus accumbens and inferior fronto-occipital fasciculus. Neurovolumetric studies on tinnitus or hearing loss can be more complete by accounting for those two clinical dimensions separately and jointly.
3 Laryngoscope, 2021.
3 Laryngoscope, 2021.
Low-titer group O whole blood (LTOWB) is being increasingly transfused to injured patients. This study evaluated a range of clinical outcomes to determine if receipt of LTOWB predisposed recipients to worse outcomes compared to recipients of conventional component therapy (CCT).
A retrospective analysis of trauma patients who received at least 3 units of LTOWB (LTOWB group) versus those that received at least 3units of RBCs, 1 unit of plasma and 1 unit of platelets but no LTOWB (CCT group) during the first 24 h of their admission was performed. Causal treatment effects were explored using propensity score matching (PSM) and coarsened exact matching (CEM). Important clinical outcomes were evaluated.
There were 165 CCT and 155 LTOWB recipients eligible for matching. PSM and CEM reduced covariate imbalances between the CCT and LTOWB groups, with the exception that males remained over-represented in the LTOWB group due to the hospital's former resuscitation policy of not administering RhD-positive LTOWB to females <50. In both of the matched analyses, the LTOWB group received a median of 4 LTOWB units. There were no significant differences in 6-, 24-h mortality or 30-day mortality between groups, nor were there differences in the frequency of other clinical outcomes such as acute kidney injury, sepsis, venous/arterial thromboembolism; delta MODS was lower for the LTOWB recipients in the exact match group.
In both matched analyses, administration of a median of four LTOWB units did not result in a different frequency of major clinical outcomes including mortality.
In both matched analyses, administration of a median of four LTOWB units did not result in a different frequency of major clinical outcomes including mortality.
Gobally, Sub-Saharan Africa (SSA) has the largest maternal mortality burden, but the region lacks accurate data.
To review methods historically used to measure maternal mortality in SSA to inform future study methods.
We searched databases PubMed, Medline, WorldCat and CINHAL, using keywords "maternal mortality," "pregnancy-related death," "reproductive age mortality," "ratio," "rate," and "risk," using Boolean operators "OR" and "AND" to combine the search terms.
We searched for empirical and analytical studies that (1) measured maternal mortality levels, (2) were in SSA, (3) reported original results, and (4) were not duplicate studies. We included studies published in English since 1980.
We screened the studies using titles and abstracts, reading the full text of selected studies. We analyzed the estimates and strengths, and limitations of the methods.
We identified 96 studies that used nine methods demographic surveillance (n=4), health record reviews (n=18), confidential enquiries and maternal death surveillance and response (n=7), prospective cohort (n=9), reproductive age mortality survey (RAMOS) (n=6), sisterhood method (n=35), mixed methods (n=4), and mathematical modeling (n=13).
Sisterhood method studies and RAMOS studies that combined institutional records and community data produced maternal mortality ratios more comparable with WHO estimates.
Sisterhood method studies and RAMOS studies that combined institutional records and community data produced maternal mortality ratios more comparable with WHO estimates.
Extraversion and Conscientiousness are well-studied personality traits associated with reward processing and goal prioritization, respectively, and bear on individual differences in financial risk-taking. Using unique large datasets, we investigated the link between these traits and male online gamblers' actual betting participation and intensity.
We combined datasets containing online horse betting data (during 2015-2016) from the Finnish monopoly betting company, administrative registry data from Statistics Finland, and personality trait measures from the Finnish Defence Forces corresponding to Extraversion and Conscientiousness as defined in the five-factor model. selleck We modelled associations between these traits and betting participation (n=471,968) and intensity (n=11,217) among male horse bettors (age=36-53).
Controlling for demographics and IQ, individuals scoring high on Conscientiousness (or Extraversion) were less (or more) likely to bet and less (or more) intensive bettors-even when personality was measured 16-34years before betting occurred. One SD personality score increase represented an annual decrease (Conscientiousness) or increase (Extraversion) of €570-754 in spending.
Extraversion and Conscientiousness are implicated in real-life financial behavior with tangible consequences for individuals. These effects are stronger than for many known demographic variables used in gambling studies and persist up to 34years after personality has been measured.
Extraversion and Conscientiousness are implicated in real-life financial behavior with tangible consequences for individuals. These effects are stronger than for many known demographic variables used in gambling studies and persist up to 34 years after personality has been measured.
To examine the ability of a previously published risk score to predict incontinence at discharge in women with vesicovaginal fistulas (VVF) and to examine how the score correlates with an independent assessment of surgical skill.
This is a retrospective cohort study including cases from January to June 2018. We evaluated operative records for factors associated with incontinence at hospital discharge, as well as relationships between a risk score cut-point of 20 or more and surgical skill level. All women with VVF undergoing vaginal repair were included.
A total of 176 individuals underwent repair; 23 were performed by beginner, 85 by intermediate, 47 by advanced, and 21 by expert surgeons. Factors found significantly associated with incontinence at hospital discharge included Goh classification, fistula size, circumferential fistula, and vaginal scarring. A score of 20 or more predicted residual incontinence with a negative predictive value of 92% (odds ratio 7.75, 95% confidence interval 2.95-22.34). Applying the score cut-point of 20 or more, we found an increased proportion of "high-risk" cases allocated to surgeons with an increasing level of expertise.
The correlation we observed between a risk score cut-point of 20 or more, continence status, and an independent assessment of surgical skill is promising. Although the risk score is not meant to replace clinical judgment, it may provide a surgical trainee with an objective method of determining whether to operate or refer for optimal outcomes.
The correlation we observed between a risk score cut-point of 20 or more, continence status, and an independent assessment of surgical skill is promising. Although the risk score is not meant to replace clinical judgment, it may provide a surgical trainee with an objective method of determining whether to operate or refer for optimal outcomes.Individuals belonging to ethnic minority groups are more susceptible to depression and comorbid hypertension than European host populations. Yet, data on how depression is related to hypertension in ethnic groups in Europe are lacking. Therefore, we studied the association between significant depressed mood (SDM) and hypertension prevalence, awareness, treatment, and control among ethnic groups. Data from the HELIUS study included 22,165 adults (aged 18-70) from six ethnic backgrounds in the Netherlands. Logistic regression analysis was used to explore the association between SDM and hypertension prevalence, awareness, treatment, and control with adjustment for age, sex, and for sensitivity analysis purposes also for anti-depressants. After adjustment for age and sex, Dutch with SDM had an increased odds of hypertension (OR 95% CI 1.67; 1.08-2.59). Among Turkish, SDM was associated with higher odds of hypertension awareness (2.09; 1.41-3.09), treatment (1.92; 1.27-2.90) and control (1.72; 1.04-2.83). Among Moroccans, SMD was associated with an increased odds of hypertension awareness (1.