Abstract This review analyzes the currently available literature on circadian rhythms of intraocular pressure (IOP), blood pressure, and calculated ocular perfusion pressure (OPP) in patients with ...open-angle glaucoma. Although adequately powered, prospective trials are not available. The existing evidence suggests that high 24-hour IOP and OPP fluctuations can have detrimental effects in eyes with glaucoma. The currently emerging continuous IOP monitoring technologies may soon offer important contributions to the study of IOP rhythms. Once telemetric technologies become validated and widely available for clinical use, they may provide an important tool towards a better understanding of long- and short-term IOP fluctuations during a patient's daily routine. Important issues that need to be investigated further include the identification of appropriate surrogate measures of IOP and OPP fluctuation for patients unable to undergo 24-hour measurements, the determination of formulae that best describe the relationship between systemic blood pressure and IOP with OPP, and the exact clinical relevance of IOP and OPP fluctuation in individual patients. Despite the unanswered questions, a significant body of literature suggests that OPP assessment may be clinically relevant in a significant number of glaucoma patients.
To investigate clinical and pathologic factors significant in predicting local response and time to further treatment after low-dose involved-field radiation therapy (LD-IFRT) for non-Hodgkin ...lymphoma (NHL).
Records of NHL patients treated at a single institution between April 2004 and September 2011 were retrospectively reviewed. Low-dose involved-field radiation therapy was given as 4 Gy in 2 fractions over 2 consecutive days. Treatment response and disease control were determined by radiographic studies and/or physical examination. A generalized estimating equation model was used to assess the effect of tumor and patient characteristics on disease response. A Cox proportional hazards regression model was used to assess time to further treatment.
We treated a total of 187 sites in 127 patients with LD-IFRT. Histologies included 66% follicular, 9% chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma, 10% marginal zone, 6% mantle cell lymphoma (MCL), and 8% other. Median follow-up time was 23.4 months (range, 0.03-92.2 months). The complete response, partial response, and overall response rates were 57%, 25%, and 82%, respectively. A CLL histology was associated with a lower response rate (odds ratio 0.2, 95% confidence interval 0.1-0.5, P=.02). Tumor size, site, age at diagnosis, and prior systemic therapy were not associated with response. The median time to first recurrence was 13.6 months. Those with CLL and age ≤ 50 years at diagnosis had a shorter time to further treatment for local failures (hazard ratio HR 3.63, P=.01 and HR 5.50, P=.02, respectively). Those with CLL and MCL had a shorter time to further treatment for distant failures (HR 11.1 and 16.3, respectively, P<.0001).
High local response rates were achieved with LD-IFRT across most histologies. Chronic lymphocytic leukemia and MCL histologies and age ≤ 50 years at diagnosis had a shorter time to further treatment after LD-IFRT.
Uveal melanoma (UM) is the most common primary intraocular cancer in adults. In the present study, we aimed to characterize the immunological features of primary UM cancer and to provide an ...association with prognostic markers and outcome. Also, we assessed the influence of the microenvironment on the expression of inhibitory immune checkpoints in UM. Genes of interest included MHC Class I and Class II molecules, as well as inhibitory immune-checkpoints, i.e. PDL1, PDL2, B7-H3, B7-H4, TBFRSF6B, CD47, CD155, GAL9, HVEM and CD200. We observed significant lower levels of MHC genes in UM cells as compared to normal uveal melanocytes. Unexpectedly however, the expression levels of most of the analyzed inhibitory immune-checkpoint genes were not different in cancer cells as compared to normal melanocytes, with the exception of CD200 and HVEM, that resulted significantly reduced. On the other hand, PDL1 inversely correlated with OS, PFS and thickness of the tumor. Also, PDL1, along with PDL2, expression significantly increased under inflammatory conditions. Finally, for the first time, we propose a possible role for CD47 in the immune evasive properties of UM. We show here that CD47 is significantly upregulated by UM cells following inflammatory stimuli and that it represents a good independent predictor of disease progression. The results from this study may propel advances in the development of immune-based therapies for UM patients.
...the American College of Cardiology’s Cardiovascular Disease in Women Committee sought to compare these findings in patients with AF to identify potential interventions that may help to rectify ...disparities of care. Whites have a higher incidence than blacks, and white men have a higher incidence than white women for all levels of risk factor burden, including smoking, alcohol consumption, body mass index, blood pressure, and diabetes (2,4). Registry data found women with AF were significantly less likely to receive oral anticoagulants at all stroke risk scores using the CHA2DS2-VASc algorithm (1 point for Congestive heart failure, Hypertension, Age >65 years, Diabetes, Female Sex, and Vascular disease, and 2 points for Stroke and Age >75 years) and less likely to receive oral anticoagulants than men (6). Compared with white men, women and certain ethnic groups with AF often experience longer lasting and more frequent symptomatic AF episodes, have worse quality of life, have more drug-related adverse events, have lower rates of anticoagulation, have less aggressive care in terms of rate versus rhythm management, and have a higher adjusted risk of death.
The comparative real-world outcomes of older patients with atrial fibrillation (AF) treated with anticoagulation compared with left atrial appendage occlusion (LAAO) may be different from those in ...clinical trials because of differences in anticoagulation strategies and patient demographics, including a greater proportion of women. We sought to compare real-world outcomes between older patients with AF treated with anticoagulation and those treated with LAAO by sex.
Using Medicare claims data from 2015 to 2019, we identified LAAO-eligible beneficiaries and divided them into sex subgroups. Patients receiving LAAO were matched 1:1 to those receiving anticoagulation alone through propensity score matching. The risks of mortality, stroke or systemic embolism, and bleeding were compared between matched groups with adjustment for potential confounding characteristics in Cox proportional hazards models.
Among women, 4085 LAAO recipients were matched 1:1 to those receiving anticoagulation; among men, 5378 LAAO recipients were similarly matched. LAAO was associated with a significant reduction in the risk of mortality for women and men (hazard ratio HR, 0.509 95% CI, 0.447-0.580; and HR, 0.541 95% CI, 0.487-0.601, respectively;
<0.0001), with a similar finding for stroke or systemic embolism (HR, 0.655 95% CI, 0.555-0.772; and HR, 0.649 95% CI, 0.552-0.762, respectively;
<0.0001). Bleeding risk was significantly greater in LAAO recipients early after implantation but lower after the 6-week periprocedural period for women and men (HR, 0.772 95% CI, 0.676-0.882; and HR, 0.881 95% CI, 0.784-0.989, respectively;
<0.05).
In a real-world population of older Medicare beneficiaries with AF, compared with anticoagulation, LAAO was associated with a reduction in the risk of death, stroke, and long-term bleeding among women and men. These findings should be incorporated into shared decision-making with patients considering strategies for reduction in AF-related stroke.
Abstract Objective In this study, we evaluate the impact of disability and multimorbidity on the risk of all-cause death in a population of frail older persons living in community. Study Design and ...Setting We analyzed data from the Aging and Longevity Study in the Sirente geographic area, a prospective cohort study that collected data on all subjects aged 80 years and older ( n = 364). The main outcome measure was all-cause mortality over 4-year follow-up. Results A total of 150 deaths occurred. Sixty-seven subjects (44.6%) died in the nondisabled group compared with 83 subjects (55.3%) in the disabled group ( P < 0.01). Thirty-nine subjects (31.7%) died among subjects without multimorbidity compared with 111 subjects (46.0%) with two or more diseases ( P < 0.01). When examining the combined effect of multimorbidity and disability, the effect of disability on the risk of death was higher than that of multimorbidity. After adjusting for potential confounders, relative to those without disability and multimorbidity, disabled subjects showed an increased risk of death when multimorbidity was associated (hazard ratio HR = 3.91; 95% confidence interval CI = 1.53–10.00) and in absence of multimorbidity (HR = 2.36; 95% CI = 0.63–8.83). Conclusion Our results show that disability exerts an important influence on mortality, independently of age and other clinical and functional variables.
We hypothesized patients implanted with ILRs for cryptogenic stroke in “real life” clinical practice will show an AF detection rate comparable to prior clinical studies, and that clinical or imaging ...features may help to identify those at higher risk of AF detection.
A retrospective chart review was conducted of all patients who presented with cryptogenic stroke and received an ILR at an academic medical center from 2015 to 2017 with an active inpatient stroke service. The electronic health record and remote monitoring were used to identify occurrence of AF.
A total of 178 patients who received ILRs for cryptogenic stroke were included. Overall, after a thorough evaluation for other etiologies of stroke, 35 (19.6%) were found to have AF detected. Mean follow-up was 365 days with a median time to detection of 131 days. Advanced age (p = 0.001), diastolic dysfunction on echo (p = 0.03), as well as ECG findings of premature atrial contractions (PACs) and p wave dispersion (PWD) > 40 ms were found to be predictive of AF detection (p = 0.04, p < 0.001, respectively). On multiple regression analysis, the only independent predictor of AF detection was PWD > 40 ms.
After a thorough evaluation to exclude other etiologies for stroke, approximately 20% of patients of our cryptogenic stroke population were found to have AF with ILR surveillance. Advanced age, diastolic dysfunction, as well as ECG findings of PACs and increased PWD may help to predict those at higher risk of AF detection, while PWD was the only independent predictor. This has important clinical implications, as better prediction of AF may help identify those at highest risk and might subsequently aid in guiding therapy.
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