Activity

Furthermore, treatment with leptomycin B, a nuclear export inhibitor, inhibited both Ku70 translocation and IFN-λ1 induction, suggesting that Ku70 translocation is an essential and early event for its cytosolic DNA sensing. We further confirmed that enhancing the acetylation status of the cells promotes Ku70’s cytoplasmic accumulation, and therefore increases DNA-mediated IFN-λ1 induction. These findings provide insights into the molecular mechanism by which the versatile sensor detects pathogenic DNA in a localization-dependent manner.

Long-term lithium therapy (LTLT) has been associated with kidney insufficiency in bipolar disorder (BD). We aimed to investigate the risk factors of chronic kidney disease (CKD) development and progression among BD patients receiving LTLT.

We included adult patients with BD on LTLT (≥1year) who were enrolled in the Mayo Clinic Bipolar Biobank, Rochester, Minnesota. We reviewed electronic medical records to extract information related to lithium therapy and kidney-related data to assess changes in the estimated glomerular filtration rate (eGFR). CKD severity was assessed based on eGFR.

Among 154 patients who received LTLT, 41 patients (27%) developed CKD, of whom 20 (49%) patients continued lithium (continuers) and 19 (46%) discontinued it (discontinuers). The median time to stage 3 CKD development was 21.7years from the start of Li treatment. Type-2 diabetes mellitus and benzodiazepine use were independent predictors for CKD development in the survival analysis, after controlling for age. The subsequent CKD progression rate did not differ between continuers and discontinuers (mean GFR 48.6 vs. Vorinostat 44.1, p=0.13) at the end of follow-up duration (mean duration 3.5±4.4years for continuers and 4.9±5.3years for discontinuers).

CKD was observed in one fourth of patients with BD receiving LTLT. There was no significant difference in the progression of CKD among Li continuers versus discontinuers, at the mean follow-up duration of 4.2years, after the CKD diagnosis. Progression of CKD could be influenced by existing comorbidities and may not necessarily be due to lithium alone.

CKD was observed in one fourth of patients with BD receiving LTLT. There was no significant difference in the progression of CKD among Li continuers versus discontinuers, at the mean follow-up duration of 4.2 years, after the CKD diagnosis. Progression of CKD could be influenced by existing comorbidities and may not necessarily be due to lithium alone.

As cancer survivorship continues to improve, management of co-morbid diabetes has become an increasingly important determinant of health outcomes for people with cancer. This study aimed to compare indicators of diabetes quality of care between people with diabetes and without a history of cancer.

We used the Electronic Medical Record Administrative data Linked Database (EMRALD), a database of Ontario primary care EMR charts linked to administrative data, to identify people with diabetes and at least 1year follow-up. Persons with a history of cancer were matched 12 on age, sex and diabetes duration to those without cancer. We compared recommended diabetes quality of care indicators between persons with and without cancer using a matched cohort analysis.

Among 229,627 people with diabetes, we identified 2275 people with cancer and 4550 matched controls; 86.5% had diabetes diagnosed after cancer. Compared to controls, cancer people with diabetes were significantly less likely to receive ACE inhibitors or angiotensin receptor blockers (OR 0.75 [95% CI 0.64-0.89]), receive statin therapy if age 50-80years (OR 0.79 [95% CI 0.68-0.92]) and achieve an LDL cholesterol level <2.0mmol/L (OR 0.82 [95% CI 0.74-0.91]). There were no differences in recommended clinical testing or achieving A1C and blood pressure targets between groups.

Cancer survivors with diabetes are less likely to receive recommended cardiovascular risk-reducing therapies compared to people with diabetes without cancer of similar age, sex and diabetes duration. Further studies are warranted to determine if these associations are linked to worse survival, cardiovascular outcomes and quality of life.

Cancer survivors with diabetes are less likely to receive recommended cardiovascular risk-reducing therapies compared to people with diabetes without cancer of similar age, sex and diabetes duration. Further studies are warranted to determine if these associations are linked to worse survival, cardiovascular outcomes and quality of life.

The heterogeneous immune landscapes of intrahepatic cholangiocarcinoma (ICC) remain largely unknown. Here we aimed to investigate the implications of tissue-resident memory (TRM)-related features of tumour-infiltrating CD8

T cells (CD8

TILs) from ICC patients.

From ICC patients, we obtained blood samples and ICC surgical specimens (n=33). We performed multicolour flow cytometry, multiplexed immunohistochemistry and RNA sequencing.

When compared to peripheral CD8

T cells, the CD8

TILs included significantly higher proportions of the CD69

CD103

and CD69

CD103

TRM-like subsets (P<.001 for both). Relative to CD69

and CD69

CD103

cells, the CD69

CD103

CD8

TILs harboured higher levels of T-cell markers representing tumour specificity (ie CD39), proliferation (ie Ki-67) and T-cell activation (ie HLA-DR and CD38) (all P<.001). Moreover, compared to the stroma, the tumour margin and core density each had a significantly higher density of CD103

CD8

TILs (P<.001 for both). Idevelop future immunotherapeutic strategies such as maximizing TRM responses or inhibiting pathways contributing to immune evasion.

No data are available about whether Coronavirus disease 2019 (COVID-19) pandemic have led to changes in clinical profiles or results of exercise testing once the usual activity was reassumed, as well as if wearing a facemask has any impact on the tests. The aim of this study is to evaluate differences in the patients referred to exercise stress testing in the context of COVID-19 pandemic and analyse the feasibility and results of these tests wearing a facemask.

We included all patients referred for an exercise test from 1 June to 30 September 2020 and compared them with the patients attended within the same period in 2019 before and after propensity score matching. All patients referred in 2020 wore a facemask.

A total of 854 patients were included 398 in the 2020 group and 456 in 2019. No significant differences in baseline characteristics of the patients were observed, with the exception of dyspnoea, which was nearly twice as high in 2020 as compared with 2019. Regarding the results of the tests, no differences were observed, with almost 80% of maximal tests, similar functional capacity and over a 20% of positive exercise tests in both groups.