Abstract
To assess the prophylactic effect of LipiFlow treatment in Meibomian gland dysfunction (MGD) patients exposed to an adverse environmental humidity. MGD patients were exposed to normal ...(23 °C; 50% relative humidity; 30 min) and adverse (23 °C; 10% relative humidity; 2 h) controlled environments consecutively during baseline and follow-up visits (3, 6, and 12 months) after a single LipiFlow treatment. Ocular Surface Disease Index (OSDI), lipid layer thickness (LLT), fluorescein tear break-up time (TBUT), corneal and conjunctival staining, change in dry eye symptoms questionnaire (CDES-Q), and Meibomian gland yielding liquid secretion (MGYLS), were assessed. Linear mixed-effects and cumulative logit mixed models were fitted to assess the effect of the LipiFlow treatment over time and within the controlled environments. Seventeen females and 4 males (59.6 ± 9.4 years) completed the study. LLT and TBUT did not vary significantly (
p
> 0.05) after LipiFlow treatment. OSDI, corneal and conjunctival staining, and MGYLS scores were improved (
p
≤ 0.01) 12 months after treatment. After the adverse exposure, corneal staining increased at all visits (
p
= 0.01), and there was no significant improvement in CDES-Q scores after LipiFlow treatment (
p
≥ 0.07). One LipiFlow treatment improved objective and subjective outcomes in MGD disease for at least one year. Further studies are needed to support that LipiFlow might also help as an adjuvant to avoid acute flares against an adverse environmental humidity.
Fishing is a major source of human impact, reducing density and size of a wide range of exploited species in comparison to areas exhibiting strong regulations (no-take and partially protected areas, ...including Territorial Use Rights for Fisheries, TURFs). Since size and density might have important consequences on reproduction, and therefore natural re-seeding, we monitored adult size, density and potential fecundity of the keyhole limpet (Fissurella latimarginata) and the red sea urchin (Loxechinus albus) in areas under two fishing regimes (TURFs and Open Access Areas, OAAs). Analyzing the distribution of suitable habitats, we predict spatial patterns of potential egg production, to identify reproductive hotspots along the central coast of Chile. The current system of TURFs in central Chile showed higher potential egg production of F. latimarginata and of L. albus than expected under a complete OAAs scenario (67 and 52% respectively). Potential egg production showed more than a twofold reduction when the complete TURFs scenario was compared against complete OAAs condition in both species. Individual size and density explained between 60% and 100% of the variability in potential egg production, suggesting the importance of the enhancement of both biological variables in TURFs in Chile. Potential egg production for both species in the northern part of the studied domain was higher due to the combined effect of (a) suitable habitat and (b) concentration of TURFs. Our results suggest that partially protected areas, such as TURFs can significantly enhance the production of propagules that could seed exploited areas.
Down syndrome (DS) is a genetic form of Alzheimer's disease (AD) with a high prevalence of obstructive sleep apnea (OSA). These characteristics place the DS population as an optimal model to study ...the relationship between sleep and AD and to design clinical trials of preventive sleep therapies for AD. Regrettably, OSA treatment with continuous positive airway pressure (CPAP) is often neglected in adults with DS. In both clinical practice and research trials, it is usually presumed that these patients will not adapt to or tolerate the therapy.
We aimed to evaluate the feasibility and long-term CPAP compliance in this population and their capacity to be enrolled in CPAP research studies.
We prospectively compared the CPAP compliance of 17 OSA patients with DS and 19 age and sex matched OSA euploid patients. CPAP management and follow-up schedules were prescribed according to the habitual clinical practice. We compared group differences in tolerance, objective, and subjective hours of nightly CPAP usage at the 1st, 3rd, 6th, 12th, 24th, and 36th month visits. Good compliance was defined as at least 4 h use per night. We also investigated predictive factors of long-term CPAP compliance.
The percentage of DS subjects with good CPAP compliance (81.2 vs. 78.9%) and the objective CPAP use (5 vs. 6 h,
= 0.92) did not differ from the control group (CG). Subjective CPAP compliance was significantly higher in OSA patients with DS than in controls in all the follow-up visits (8 vs. 6.75 h,
= 0.001). The DS group had a significantly higher number of visits (9 vs. 5;
= 0.021) and mask changes (2.5 vs. 2;
= 0.05) than controls. Objective hours of CPAP use at the first follow-up visit predicted long-term CPAP compliance (
< 0.005).
CPAP treatment is feasible and has good long-term compliance in OSA patients with DS. It should be recommended to improve health and prevent comorbidities. The DS population is indeed suitable to participate in longitudinal preventive sleep clinical trials for AD.
Introduction
To evaluate the short-term efficacy of cyclosporine A (CsA)-0.1% cationic emulsion (CE) in patients with dry eye disease (DED) and mitigation of the inflammatory flares triggered by ...desiccating stress environments.
Methods
A single-center non-randomized clinical trial was performed at a tertiary care setting. Twenty patients with DED treated with CsA 0.1% CE were exposed to a normal controlled environment (NCE) (23 °C, 50% relative humidity) and an adverse controlled environment (ACE) (23 °C, 10% relative humidity, 0.43 m/s localized airflow) during baseline and the 1- and 3-month visits. Patients underwent the following evaluations: conjunctival hyperemia and staining, corneal fluorescein staining (CFS) using the Oxford and Cornea and Contact Lens Research Unit (CCLRU) scale, meibomian gland (MG) secretion quality, Dry Eye Questionnaire-5, Symptom Assessment in Dry Eye (SANDE II), and Change in Dry Eye Symptoms Questionnaire. Multivariate models were adjusted for statistical analysis.
Results
Nineteen women and one man (mean age, 58.9 ± 12.3 years) completed the study. All symptom questionnaires, CFS, conjunctival hyperemia and staining, and MG secretion quality improved (
p
≤ 0.003) with 1 month of treatment; improvements were maintained after 3 months (
p
≤ 0.02), except for SANDE II (
p
≥ 0.07). The CFS worsening (total CCLRU) after baseline ACE exposure (from 8.6 to 10.1) was higher, although not significant (
p
= 0.64), compared with 1 month (from 5.4 to 5.8) and 3 months (from 5.0 to 5.9) after treatment.
Conclusion
Topical CsA-0.1% CE improved DED signs and symptoms after 1 month of treatment under controlled environmental conditions. Future studies should confirm the benefit of CsA-0.1% CE in desiccating stress environments.
Trial Registration
ClinicalTrials.gov identifier, NCT04492878.
Aims/Purpose: To characterize the Meibomian gland (MG) morphology in healthy subjects with an automatic software.
Methods: An automatic software was developed for image analysis in R code, consisting ...of 4 stages: (1) selection of the region of interest, (2) image preprocessing to obtain a binary and a skeleton image, (3) modelling of each MG to fit each MG to a piecewise linear model, and (4) quantification of the following MG features: tortuosity, MG shortening, number of MGs, deviation from a vertical line, and MG area. Meibography images of the upper eyelid were acquired using the Easy Tear View+®. A group of 156 healthy subjects were included, with a mean age and confidence interval (CI) of 43.88 (95% CI: 41.38–46.37) years, range 16–76 years. Reference intervals (RI) were calculated for each MG feature to be used as a diagnostic tool to classify a specific value as normal or non‐normal. Generalized Additive Models for Location, Scale and Shape were used to estimate the percentile curve for each morphologic feature of MG, considering the influence of age and sex.
Results: Age had an influence on tortuosity, mean = 0.3 (95% CI: 0.3–0.31), RI: 0.19–0.4 <20 years, and 0.24–0.39 at 50–60 years. Age and sex had an influence in the MG shortening, mean = 63% (95% CI: 62–64%), mean RI: 58–74% <20 years; 59–84% >75 years; women RI: 56–71% <20 years; 57–82% >75 years. The rest of the variables were not affected by age or sex: number of MGs = 16.05 (95% CI: 15.28–16.82), RI: 8–27; vertical deviation = 0.37 (95% CI: 0.36–0.38), RI: 0.29–0.45, and MG area = 14% (95% CI: 14–15%), RI: 8.17–19.81%.
Conclusions: Tortuosity variability decreases between 45 and 60 years of age. The MG shortening increases with age and is higher in men. These values could be useful to classify a meibography image as normal or non‐normal, helping to diagnose MG alterations in an objective way.
Background: The benefit of prophylactic implantable cardioverter defibrillators (ICDs) in patients with severe systolic dysfunction of non-ischemic origin is still unclear, and the identification of ...patients at risk for sudden cardiac death remains a major challenge. Aims/Methods: We retrospectively reviewed all consecutive patients with non-ischemic dilated cardiomyopathy (NICM) who underwent prophylactic ICD implantation between 2008 and 2020 in two tertiary centers. Our main goal was to identify the predictors of appropriate ICD therapies (anti-tachycardia pacing ATP and/or shocks) in this cohort of patients. Results: A total of 224 patients were included. After a median follow-up of 51 months, 61 patients (27.2%) required appropriate ICD therapies. Patients with appropriate ICD therapies were more frequently men (87% vs. 69%, p = 0.006), of younger age (59 years, (53–65) vs. 64 years, (57–70); p = 0.02), showed more right bundle branch blocks (RBBBs) (15% vs. 4%, p = 0.007) and less left bundle branch blocks (LBBBs) (26% vs. 47%, p = 0.005) in the ECG, and had higher left ventricular end-diastolic (100 mL/m2, (90–117) vs. 86, (71–110); p = 0.011) and systolic volumes (72 mL/m2, (59–87) vs. 61, (47–81), p = 0.05). In a multivariate competing-risks regression analysis, RBBB (HR 2.26, CI 95% 1.02–4.98, p = 0.043) was identified as an independent predictor of appropriate ICD therapies. Conclusion: RBBBs may help to identify patients with NICM at high risk of ventricular arrhythmias and requiring ICD intervention.
ABSTRACT Introduction and objectives: Endomyocardial biopsy (EMB) is an established diagnostic tool in myocardial disease. However, this technique may carry major complications. We present the ...diagnostic and safety results of our experience in EMB in the non-transplant setting. We also present the results after the implementation of a technical and safety protocol developed at our center. Methods: We retrospectively analyzed the data of all EMBs conducted in non-transplant patients from September 2004 through July 2018. We compared the diagnostic yield and rate of major complications of EMB in two different periods: before and after implementing the protocol. Results: We included 204 EMBs performed in 190 patients. The most frequent indications were the evaluation of ventricular dysfunction or suspected myocarditis (51.5%) and the evaluation of restrictive cardiomyopathy or suspected infiltrative disease (44.6%). One hundred and seventy-two EMBs were performed in the right cardiac chambers (84.3%) and 30 EMBs in the left cardiac chambers (14.7%). The specimens were taken from both ventricles on 2 cases only. Definite diagnosis was reached in 52% of the cases. After the implementation of the protocol, the diagnostic yield significantly improved (42.5% vs 58.1%; P = .030) and the rate of major complications decreased (from 7.5% to 3.2%; P = .167), with a statistically significant lower rate of cardiac perforation (6.3% vs 0.8%; P = .025). Conclusions: The EMB is a diagnostic tool with a great potential in patients with suspected cardiomyopathy. Our experience shows that a technical and safety protocol can help decrease the rate of complications and improve the diagnostic yield of EMB.
The purpose of this study was to analyze inflammation- and pain-related molecules in tears of patients suffering from chronic ocular pain associated with dry eye (DE) and/or a previous corneal ...refractive surgery (RS). Based on history, symptomatology, and clinical signs, the subjects (n = 180, 51.0 ± 14.7 years, 118 females, 62 males) in this cross-sectional study were assigned to one of five groups: DE and chronic ocular pain after RS (P/DE-RS, n = 52); asymptomatic subjects, i.e., without DE and chronic ocular pain, after RS (A-RS, n = 30); DE and chronic ocular pain without previous RS (P/DE-nonRS, n = 31); DE, no pain, and no previous RS (DE-nonRS, n = 35); and asymptomatic subjects with no previous RS (controls, n = 32). The tear concentrations of 20 cytokines and substance P (SP) were analyzed by immunobead-based assay and enzyme-linked immunosorbent assay, respectively. We found that tear levels of interleukin (IL)-10 and SP were increased in the RS groups. There were significant differences in IL-8/CXCL8 among the five groups. Nerve growth factor (NGF) tear levels were significantly higher in P/DE-RS than in DE-nonRS and controls. IL-9 had the highest percentage of detection in the P/DE-RS and P/DE-nonRS groups, while macrophage inflammatory protein (MIP)-1α, IL-2, and interferon (IFN)-γ were higher in the P/DE-RS, A-RS, and P/DE-nonRS groups. IL-17A was detected only in the A-RS group. Moderate correlations were observed in the A-RS, P/DE-nonRS, DE-nonRS and controls groups. A positive correlation was obtained between growth related oncogene concentration and tear break-up time (rho = 0.550; p = 0.012), while negative correlation was found between monocyte chemoattractant protein-3/CCL7 and conjunctival staining (rho = −0.560; p = 0.001), both in the A-RS group. IL-10 correlated positively with ocular pain intensity (rho = 0.513; p = 0.003) in the P/DE-nonRS group. Regulated on Activation Normal T Cell Expressed and Secreted/CCL5 correlated negatively with conjunctival staining (rho = −0.545; p = 0.001) in the DE-nonRS group. SP correlated negatively with corneal staining (rho = −0.559; p = 0.001) in the controls. In conclusion, chronic ocular pain was associated with higher IL-9 tear levels. IL-10, SP, MIP-1α/CCL3, IL-2, and IFN-γ were associated with previous RS. Higher levels of IL-8/CXCL8, MIP-1α/CCL3, IL-2, and IFN-γ were associated with DE-related inflammation, while NGF levels were related to chronic ocular pain and DE in RS patients. These findings suggest that improved knowledge of tear cytokines and neuromodulators will lead to a more nuanced understanding of how these molecules can serve as biomarkers of chronic ocular pain, leading to better therapeutic and disease management decisions.
•Inflammation- and pain-related molecules in patients with ocular pain and dry eye.•Cytokines and neuromodulators in tears differ in subjects with chronic ocular pain.•Molecular differences in tears related to dry eye inflammation.•Different molecular profile associated with previous corneal refractive surgery.
Desensitization allows the performance of human leukocyte antigen (HLA)-incompatible transplants. However, the incidence of acute rejection (AR) is high. This study aims to analyze the incidence of ...AR after transplantation with HLA-incompatible living donors in patients who underwent desensitization. Patients were immunosuppressed with tacrolimus, mycophenolic acid derivatives, and steroids after being desensitized with rituximab, plasma exchange, and/or immunoadsorption with specific cytomegalovirus immunoglobulins. A negative complement-dependent cytotoxicity or flow cytometry crossmatch and a donor-specific antibody titer < 1000 mean fluorescence intensity (MFI) were used to determine desensitization efficacy. A total of 36 patients underwent desensitization, and 27 (75%) were transplanted. After a follow-up of 58 ± 58 months (Min−Max: 0.13−169.5), five episodes of AR occurred: two antibody-mediated and three T-cell-mediated. No differences were found in baseline calculated panel-reactive antibodies (cPRA), class I or II MFI, number of antibodies, or Relative Intensity Scale (RIS) between AR and non-AR patients. Patients with antibody-mediated AR had higher cPRA (NS), MFI class I (p = 0.07) and class II (p = 0.006), and RIS (p = 0.01). The two patients with antibody-mediated AR and one patient with T-cell-mediated AR lost their grafts. In conclusion, the incidence of acute antibody-mediated rejection after desensitization was 7.4%, which occurred early post-transplantation in patients with high MFI and was associated with early graft loss.
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