CD169+ Macrophages Capture and Dendritic Cells Instruct: The Interplay of the Gatekeeper and the General of the Immune System

Since the seminal discovery of dendritic cells (DCs) by Steinman and Cohn in 1973, there has been an ongoing debate to what extent macrophages and DCs are related and perform different functions. The current view is that macrophages and DCs originate from different lineages and that only DCs have the capacity to initiate adaptive immunity. Nevertheless, as we will discuss in this review, lymphoid tissue resident CD169+ macrophages have been shown to act in concert with DCs to promote or suppress adaptive immune responses for pathogens and self-antigens, respectively. Accordingly, we propose a functional alliance between CD169+ macrophages and DCs in which a division of tasks is established. CD169+ macrophages are responsible for the capture of pathogens and are frequently the first cell type infected and thereby provide a confined source of antigen. Subsequently, cross-presenting DCs interact with these antigen-containing CD169+ macrophages, pick up antigens and activate T cells. The cross-priming of T cells by DCs is enhanced by the localized production of type I interferons (IFN-I) derived from CD169+ macrophages and plasmacytoid DCs (pDCs) that induces DC maturation. The interaction between CD169+ macrophages and DCs appears not only to be essential for immune responses against pathogens, but also plays a role in the induction of self-tolerance and immune responses against cancer. In this review we will discuss the studies that demonstrate the collaboration between CD169+ macrophages and DCs in adaptive immunity

Urogenital tuberculosis: patient classification in seven different groups according to clinical and radiological presentation

PURPOSE: To describe and classify 80 cases of urogenital tuberculosis in seven groups of similar clinical and radiological presentation. MATERIALS AND METHODS: 80 patients (56 males, 70%; median age 34 years; age range 12 to 75) with urogenital tuberculosis were retrospectively reviewed. The patients were divided in seven groups: 1) Bilateral parenchymatous renal lesions; 2) No or minimal changes on radiographic examination; 3) Unilateral renal tuberculosis; 4) Contracted bladder; 5) Contracted bladder with renal failure; 6) Tuberculosis on a transplanted kidney; 7) Isolated genital tuberculosis. RESULTS: 1) Seven (8.8%) patients had multiple bilateral parenchymatous renal lesions with fever and malaise, characteristic of miliary tuberculosis. Three of these patients had AIDS. 2) Six (7.5%) cases had an early diagnosis, with minimal or no radiographic lesions. Two did not have any urologic symptoms. 3) Twelve (15%) patients had unilateral renal tuberculosis with partial (1 case) or total non-function kidney. 4) Thirty-seven (46.3%) patients had contracted bladder associated with unilateral partial (1 case) or total non-function kidney. 5) Ten (12.5%) patients had end stage renal disease due to tuberculosis with contracted bladder. 6) Four (5.0%) patients had tuberculosis on a transplanted kidney, with graft loss in half the cases. 7) Four (5.0%) patients had prostate or epididymis tuberculosis without associated renal lesion. CONCLUSIONS: Urogenital tuberculosis is a destructive disease of the urogenital tract with variable clinical and radiographic presentation. A classification according to similar patterns correlating with disease stage is feasible although early diagnosis is the only prevention of the most severe forms

Association of acculturation with drinking games among Hispanic college students

Objective: This cross-sectional study was conducted to investigate which components of acculturation relate to drinking games participation among Hispanic college students. We also sought to examine whether the relationships between acculturation and drinking games would differ from the associations between acculturation and other alcohol-related outcomes. Method: A sample of 1,397 Hispanic students aged 18-25 (75% women; 77% US-born) from 30 US colleges and universities completed a confidential online survey. Results: Associations among acculturative processes, drinking games participation, general alcohol consumption, and negative drinking consequences differed across gender. Most significant findings emerged in the domain of cultural practices. For women, US cultural practices were associated with greater general alcohol consumption, drinking games frequency, and amount of alcohol consumed while gaming, whereas for men, US cultural practices were associated with general alcohol consumption and negative drinking consequences. Conclusions: Hispanic and US cultural practices, values, and identifications were differentially associated with drinking games participation, and these associations differed by gender. It is therefore essential for college student alcohol research to examine US culture acquisition and Hispanic culture retention separately and within the domains of cultural practices, values, and identifications

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus.METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis.RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (<45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]).CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791

Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting & Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (<60, 60-69, and >_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 & PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages <60, 60-69, and >_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791