The textures of sarcoidosis: quantifying lung disease through variograms.

Objective: Sarcoidosis is a granulomatous disease affecting the lungs in over 90% of patients. Qualitative assessment of chest CT by radiologists is standard clinical practice and reliable quantification of disease from CT would support ongoing efforts to identify sarcoidosis phenotypes. Standard imaging feature engineering techniques such as radiomics suffer from extreme sensitivity to image acquisition and processing, potentially impeding generalizability of research to clinical populations. In this work, we instead investigate approaches to engineering variogram-based features with the intent to identify a robust, generalizable pipeline for image quantification in the study of sarcoidosis. Approach: For a cohort of more than 300 individuals with sarcoidosis, we investigated 24 feature engineering pipelines differing by decisions for image registration to a template lung, empirical and model variogram estimation methods, and feature harmonization for CT scanner model, and subsequently 48 sets of phenotypes produced through unsupervised clustering. We then assessed sensitivity of engineered features, phenotypes produced through unsupervised clustering, and sarcoidosis disease signal strength to pipeline. Main results: We found that variogram features had low to mild association with scanner model and associations were reduced by image registration. For each feature type, features were also typically robust to all pipeline decisions except image registration. Strength of disease signal as measured by association with pulmonary function testing and some radiologist visual assessments was strong (optimistic AUC ≈ 0.9, p ≪ 0.0001 in models for architectural distortion, conglomerate mass, fibrotic abnormality, and traction bronchiectasis) and fairly consistent across engineering approaches regardless of registration and harmonization for CT scanner. Significance: Variogram-based features appear to be a suitable approach to image quantification in support of generalizable research in pulmonary sarcoidosis.

A Minimally Invasive Approach for Laparoscopic-Perineal Sigmoid Colpoplasty: Case Report and Innovations.

BACKGROUND Laparoscopic-perineal neovagina construction by sigmoid colpoplasty is a popular therapeutic approach for patients with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. The conventional approach requires an auxiliary abdominal incision to exteriorize the descending colon to fix the anvil for end-to-end colorectal anastomosis. We modified the natural orifice specimen extraction surgery (NOSES) approach by exteriorizing the descending colon through the artificial neovaginal tunnel to replace the anvil extracorporeally, without requiring an auxiliary abdominal incision. It was a more minimally invasive technique. CASE REPORT We performed this modified laparoscopic-perineal sigmoid colpoplasty in a 26-year-old woman with MRKH syndrome. We cut off a segment of the sigmoid colon with a vascular pedicle to make a new vagina out of it, the same as in the traditional laparoscopic-perineal sigmoid colpoplasty. What is new about this technique is that it has no need for abdominal incision and is more minimally invasive. The operating time was 315 min. No postoperative complications occurred. The postoperative hospital stay was 4 days. The modified laparoscopic-perineal approach, free from an auxiliary abdominal incision, demonstrated advantages, including a shorter hospital stay, expedited recovery, and comparable anatomical outcomes, when compared with the traditional approach. This innovation improves the surgical experience for patients with MRKH syndrome, addressing the physical and psychological aspects of their condition. CONCLUSIONS This refined laparoscopic-perineal neovagina construction by sigmoid colpoplasty represents a feasible and minimally invasive technique. It is an attractive option for MRKH syndrome patients in need of vaginal reconstruction, offering a streamlined procedure with reduced postoperative recovery time and enhanced patient outcomes.

Outcomes of different pulmonary rehabilitation protocols in patients under mechanical ventilation with difficult weaning: a retrospective cohort study.

BACKGROUND: The endeavor of liberating patients from ventilator dependence within respiratory care centers (RCCs) poses considerable challenges. Multiple factors contribute to this process, yet establishing an effective regimen for pulmonary rehabilitation (PR) remains uncertain. This retrospective study aimed to evaluate existing rehabilitation protocols, ascertain associations between clinical factors and patient outcomes, and explore the influence of these protocols on the outcomes of the patients to shape suitable rehabilitation programs. METHODS: Conducted at a medical center in northern Taiwan, the retrospective study examined 320 newly admitted RCC patients between January 1, 2015, and December 31, 2017. Each patient received a tailored PR protocol, following which researchers evaluated weaning rates, RCC survival, and 3-month survival as outcome variables. Analyses scrutinized differences in baseline characteristics and prognoses among three PR protocols: protocol 1 (routine care), protocol 2 (routine care plus breathing training), and protocol 3 (routine care plus breathing and limb muscle training). RESULTS: Among the patients, 28.75% followed protocol 1, 59.37% protocol 2, and 11.88% protocol 3. Variances in age, body-mass index, pneumonia diagnosis, do-not-resuscitate orders, Glasgow Coma Scale scores (≤ 14), and Acute Physiology and Chronic Health Evaluation II (APACHE) scores were notable across these protocols. Age, APACHE scores, and abnormal blood urea nitrogen levels (> 20 mg/dL) significantly correlated with outcomes-such as weaning, RCC survival, and 3-month survival. Elevated mean hemoglobin levels linked to increased weaning rates (p = 0.0065) and 3-month survival (p = 0.0102). Four adjusted models clarified the impact of rehabilitation protocols. Notably, the PR protocol 3 group exhibited significantly higher 3-month survival rates compared to protocol 1, with odds ratios (ORs) ranging from 3.87 to 3.97 across models. This association persisted when comparing with protocol 2, with ORs between 3.92 and 4.22. CONCLUSION: Our study showed that distinct PR protocols significantly affected the outcomes of ventilator-dependent patients within RCCs. The study underlines the importance of tailored rehabilitation programs and identifies key clinical factors influencing patient outcomes. Recommendations advocate prospective studies with larger cohorts to comprehensively assess PR effects on RCC patients.

Cost-effectiveness of diabetic retinopathy screening for newly diagnosed type 2 diabetic patients: A nationwide population-based propensity score-matched cohort study.

AIMS: This study investigated the association between the frequency of screening for diabetic retinopathy (DR) versus the development of DR and corresponding medical expenses among patients newly diagnosed with type 2 diabetes mellitus (T2DM). METHODS: This longitudinal, population-based study used the Taiwan National Health Insurance Research Database (2004 to 2020) as a data source. Propensity score matching (PSM) (sex, age, comorbidities and concurrent medication use) was employed in the grouping of T2DM patients according to different frequency of DR screening. Outcome measures included the proportion of patients who developed DR, who received DR treatment, and the associated medical expenses and hospitalizations. RESULTS: The 17-year cohort included 337,046 patients. After PSM, three groups each containing 35,739 patients were assembled and analyzed. Compared to low-frequency screening, high-frequency screening was more effective in detecting patients requiring treatment; however, the net cost for treatment was significantly lower. Standard-frequency screening appears to provide the best balance in terms of DR detection, diagnosis interval, the risk of DR-related hospitalization, and DR treatment costs. CONCLUSIONS: In this real-world cohort study covering all levels of the healthcare system, infrequent screening was associated with delayed diagnosis and elevated treatment costs, while a fundus screening interval of 1-2 years proved optimal in terms of detection and medical expenditures.

The role of lateral rectus muscle resection for severe esotropia after medial rectus muscle myectomy in Graves' ophthalmopathy.

PURPOSE: Persistent diplopia after rectus muscle myectomy is not uncommon but challenging in patients with Graves' ophthalmopathy. We investigated the role of lateral rectus muscle resection for patients after medial rectus muscle myectomy in Graves' ophthalmopathy. METHODS: We retrospectively reviewed and collected data from patients with persistent diplopia after medial rectus muscle myectomy for Graves' ophthalmopathy who underwent unilateral or bilateral lateral rectus muscle resection. The eyeball deviations in the primary and reading positions before and after the operation were measured. A successful surgical outcome was defined as having less than five prism diopters (PD) in the primary gaze and functional binocular vision in the central 30° field postoperatively. RESULTS: A total of fifteen patients were included (mean post-myectomy deviation: 35.9 PD, range: 14 to -75 PD). The lateral rectus muscle resection after medial rectus muscle myectomy achieved an 80.0% success rate, with one patient over-corrected and two patients under-corrected. CONCLUSIONS: The lateral rectus muscle resection is an effective and predictable procedure for managing residual esotropia in Graves' ophthalmopathy patients who have previously undergone medial rectus muscle myectomy.

An Appraisal of the Preventive Effect of Statins on the Development of Graves' Ophthalmopathy: A Hospital-Based Cohort Study.

INTRODUCTION: Graves' ophthalmopathy (GO) is an autoimmune inflammatory disorder observed in a substantial proportion of patients with Graves' disease (GD), with debilitating symptoms of disfiguring, periorbital pain, dry eyes, diplopia, and even visual disturbances. Previous studies involving Western populations have noted discrepancies in risk factors for GO. Therefore, this study aimed to determine the risk factors for GO development and the protective effect of statins in newly diagnosed patients with GD in Taiwan. METHODS: This retrospective case-control study was based on a tertiary center cohort involving patients with GD diagnosed between 2010 and 2019 at the National Taiwan University Hospital (n = 11,035). Patients who were diagnosed or treated elsewhere, had been followed up for less than 6 months or were with a diagnosis of orbital tumor were excluded. Overall, 3578 patients with GD met the inclusion criteria. Univariate and multivariate logistic regression analyses were used to ascertain the odds ratio (OR) of developing GO, with adjustment for sociodemographic factors, interventions for managing GD and thyroid hormone levels, to determine protective and risk factors for GO. RESULTS: In our multivariate model, the use of statins reduced the risk of GO development (OR 0.2; 95% confidence interval [CI] 0.08-0.50; p < 0.001). Thyroid dysfunction including hyperthyroidism (OR 4.2; 95% CI 2.97-5.88; p < 0.001) and hypothyroidism (OR 4.7; 95% CI 3.02-7.19; p < 0.001) was associated with an increased risk of developing GO. Smoking status and lipid profile were not risk factors in our cohort. CONCLUSION: In newly diagnosed patients with GD, the use of statins decreased the risk of developing GO by 80%, whereas serum lipid levels were not considered risk factors. Further nationwide population-based studies may help clarify the differences in risk factors between various ethnic groups. TRAIL REGISTRATION: This trial was approved by the Research Ethics Committee of National Taiwan University Hospital (202202066RINC), retrospectively registered from January 1, 2010 to December 31, 2019.

Impact of the geriatric nutritional risk index on long-term outcomes in patients undergoing hemodialysis: a meta-analysis of observational studies.

Background: This meta-analysis aimed to synthesize current evidence on the association between the Geriatric Nutritional Risk Index (GNRI) and long-term outcomes in patients undergoing hemodialysis. Methods: Electronic databases were systematically searched for relevant studies that investigated the association between GNRI and long-term outcomes in hemodialysis patients until November 2023. The primary outcome was the association between the GNRI (i.e., low versus high) and overall mortality risk, while the secondary outcome was the relationship between the GNRI and cardiovascular mortality risk. Results: Thirty cohort studies involving 55,864 patients were included. A low GNRI was found to be significantly associated with increased overall mortality (hazard ratio [HR]: 2.42, 95% confidence interval [CIs]: 2.10-2.79, p < 0.00001, I2 = 65%). Each unit increase in GNRI corresponded to a 5% reduction in mortality risk (HR: 0.95, 95% CI: 0.93-0.96, p < 0.00001, I2 = 79%). The association remained consistent across Asian (HR = 2.45, 95% CI: 2.08-2.88, p < 0.00001, I2 = 70%) and non-Asian subgroups (HR = 2.3, 95% CI: 1.72-3.06, p < 0.00001, I2 = 23%). Meta-regression analysis of patient age (coefficient: -0.002; p = 0.896), male proportion (coefficient: 0.002; p = 0.875), percentage of diabetes mellitus (coefficient: -0.003; p = 0.605), and follow-up duration (coefficient: -0.003; p = 0.431) revealed that these moderator variables did not significantly influence the association between GNRI and overall mortality risk. Cardiovascular mortality risk also increased with low GNRI (HR, 1.93; 95%CI: 1.51-2.45, p < 0.00001; I2 = 2%). Similarly, an inverse association was observed between the GNRI values and cardiovascular mortality risk (HR, 0.94; 95% CI: 0.91-0.97; p < 0.0001; I2 = 65%) (per unit increase). Conclusion: The GNRI is a simple nutritional screening tool that can be used to effectively stratify patients undergoing hemodialysis globally. Further studies are warranted to determine whether nutrition optimization based on the GNRI improves long-term outcomes. Systematic review registration: https://www.crd.york.ac.uk/prospero/, CRD42023483729.

The impact of perioperative ketamine or esketamine on the subjective quality of recovery after surgery: a meta-analysis of randomised controlled trials.

BACKGROUND: This meta-analysis aimed to evaluate the impact of ketamine/esketamine on postoperative subjective quality of recovery (QoR). METHODS: MEDLINE, Embase, Cochrane library, and Google Scholar were searched for randomised controlled trials (RCTs) that examined the impacts of perioperative ketamine/esketamine use and postoperative QoR. The primary outcome was subjective QoR (QoR-9, QoR-15, QoR-40) on postoperative day (POD) 1-3, whereas the secondary outcomes included pain severity, anxiety scores, depression scores, risk of adverse events (i.e. nausea, vomiting, dizziness, drowsiness), and length of stay. RESULTS: The analysis included 18 RCTs (1554 participants; ketamine: seven trials, esketamine: 11 trials), of which 15 were conducted in China. Ketamine/esketamine improved the QoR scores on PODs 1 and 2 compared with the control (standardised mean difference [SMD]: 0.63, P<0.0001 for POD 1; SMD: 0.56, P=0.04 for POD 2), without beneficial effect on POD 3. Subgroup analyses revealed significant differences in QoR scores on POD 1 by regimen (SMD: esketamine 1.14, ketamine 0.01) and country (SMD: China 0.82, other countries -0.21). The emotional domain of QoR was improved from PODs 1 to 3, whereas the other domains were only improved on POD 1. Lower postoperative anxiety (SMD: -0.48, P=0.003) and depression (SMD: -0.72, P=0.001) scores were also observed with ketamine/esketamine use. Furthermore, pain severity was reduced on PODs 1 and 2, with no difference in the risk of adverse events or length of stay. CONCLUSIONS: This meta-analysis demonstrated that ketamine/esketamine use in the perioperative period is associated with improved early subjective QoR, pain severity, and psychological symptoms without an increase in the likelihood of adverse events. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023477580).

Multi-omics Integration Identifies Genes Influencing Traits Associated with Cardiovascular Risks: The Long Life Family Study.

The Long Life Family Study (LLFS) enrolled 4,953 participants in 539 pedigrees displaying exceptional longevity. To identify genetic mechanisms that affect cardiovascular risks in the LLFS population, we developed a multi-omics integration pipeline and applied it to 11 traits associated with cardiovascular risks. Using our pipeline, we aggregated gene-level statistics from rare-variant analysis, GWAS, and gene expression-trait association by Correlated Meta-Analysis (CMA). Across all traits, CMA identified 64 significant genes after Bonferroni correction (p ≤ 2.8×10-7), 29 of which replicated in the Framingham Heart Study (FHS) cohort. Notably, 20 of the 29 replicated genes do not have a previously known trait-associated variant in the GWAS Catalog within 50 kb. Thirteen modules in Protein-Protein Interaction (PPI) networks are significantly enriched in genes with low meta-analysis p-values for at least one trait, three of which are replicated in the FHS cohort. The functional annotation of genes in these modules showed a significant over-representation of trait-related biological processes including sterol transport, protein-lipid complex remodeling, and immune response regulation. Among major findings, our results suggest a role of triglyceride-associated and mast-cell functional genes FCER1A, MS4A2, GATA2, HDC, and HRH4 in atherosclerosis risks. Our findings also suggest that lower expression of ATG2A, a gene we found to be associated with BMI, may be both a cause and consequence of obesity. Finally, our results suggest that ENPP3 may play an intermediary role in triglyceride-induced inflammation. Our pipeline is freely available and implemented in the Nextflow workflow language, making it easily runnable on any compute platform (https://nf-co.re/omicsgenetraitassociation).

Relationship between albumin-corrected anion gap and non-alcoholic fatty liver disease varied in different waist circumference groups: a cross-sectional study.

OBJECTIVES: To investigate the association of albumin-corrected anion gap (ACAG) with non-alcoholic fatty liver disease (NAFLD) and clinically significant fibrosis (CSF) defined by vibration-controlled transient elastography measurements. METHODS: This cross-sectional study including 4531 participants was conducted using the data from the NHANES database of cycles 2017-2018. The outcomes were set as NAFLD vs. non-NAFLD and NAFLD with CSF vs. NAFLD without CSF. The generalized additive model and restricted cubic spline analyses were used to assess the nonlinear relationship. The generalized linear models, logistic regression models, sensitivity analysis, P trend test, subgroup analysis, and mediation analysis were employed to analyze the association. Finally, an ACAG-based model was constructed and evaluated. RESULTS: A higher ACAG level was an independent risk factor for NAFLD (P < 0.05), but not for CSF (P > 0.05). The sensitivity analysis and P trend test results substantiated the significantly positive relationship between ACAG and NAFLD (P < 0.05). Interestingly, the obvious connection between ACAG and NAFLD varied in different waist circumference groups and played a central role in the central obesity group. In addition, alanine aminotransferase and waist circumference were the mediators in their relationship. Moreover, the ACAG-based model performed well in predicting NAFLD. CONCLUSIONS: ACAG level is independently associated with NAFLD but not CSF. ACAG might be a novel and reliable biomarker for predicting NAFLD clinically especially in the central obesity population.

Utilizing the National Early Warning Score 2 (NEWS2) to confirm the impact of emergency department management in sepsis patients: a cohort study from taiwan 1998-2020.

BACKGROUND: Most sepsis patients could potentially experience advantageous outcomes from targeted medical intervention, such as fluid resuscitation, antibiotic administration, respiratory support, and nursing care, promptly upon arrival at the emergency department (ED). Several scoring systems have been devised to predict hospital outcomes in sepsis patients, including the Sequential Organ Failure Assessment (SOFA) score. In contrast to prior research, our study introduces the novel approach of utilizing the National Early Warning Score 2 (NEWS2) as a means of assessing treatment efficacy and disease progression during an ED stay for sepsis. OBJECTIVES: To evaluate the sepsis prognosis and effectiveness of treatment administered during ED admission in reducing overall hospital mortality rates resulting from sepsis, as measured by the NEWS2. METHODS: The present investigation was conducted at a medical center from 1997 to 2020. The NEWS2 was calculated for patients with sepsis who were admitted to the ED in a consecutive manner. The computation was based on the initial and final parameters that were obtained during their stay in the ED. The alteration in the NEWS2 from the initial to the final measurements was utilized to evaluate the benefit of ED management to the hospital outcome of sepsis. Univariate and multivariate Cox regression analyses were performed, encompassing all clinically significant variables, to evaluate the adjusted hazard ratio (HR) for total hospital mortality in sepsis patients with reduced severity, measured by NEWS2 score difference, with a 95% confidence interval (adjusted HR with 95% CI). The study employed Kaplan-Meier analysis with a Log-rank test to assess variations in overall hospital mortality rates between two groups: the "improvement (reduced NEWS2)" and "non-improvement (no change or increased NEWS2)" groups. RESULTS: The present investigation recruited a cohort of 11,011 individuals who experienced the first occurrence of sepsis as the primary diagnosis while hospitalized. The mean age of the improvement and non-improvement groups were 69.57 (± 16.19) and 68.82 (± 16.63) years, respectively. The mean SOFA score of the improvement and non-improvement groups were of no remarkable difference, 9.7 (± 3.39) and 9.8 (± 3.38) years, respectively. The total hospital mortality for sepsis was 42.92% (4,727/11,011). Following treatment by the prevailing guidelines at that time, a total of 5,598 out of 11,011 patients (50.88%) demonstrated improvement in the NEWS2, while the remaining 5,403 patients (49.12%) did not. The improvement group had a total hospital mortality rate of 38.51%, while the non-improvement group had a higher rate of 47.58%. The non-improvement group exhibited a lower prevalence of comorbidities such as congestive heart failure, cerebral vascular disease, and renal disease. The non-improvement group exhibited a lower Charlson comorbidity index score [4.73 (± 3.34)] compared to the improvement group [4.82 (± 3.38)] The group that underwent improvement exhibited a comparatively lower incidence of septic shock development in contrast to the non-improvement group (51.13% versus 54.34%, P < 0.001). The improvement group saw a total of 2,150 patients, which represents 38.41% of the overall sample size of 5,598, transition from the higher-risk to the medium-risk category. A total of 2,741 individuals, representing 48.96% of the sample size of 5,598 patients, exhibited a reduction in severity score only without risk category alteration. Out of the 5,403 patients (the non-improvement group) included in the study, 78.57% (4,245) demonstrated no alteration in the NEWS2. Conversely, 21.43% (1,158) of patients exhibited an escalation in severity score. The Cox regression analysis demonstrated that the implementation of interventions aimed at reducing the NEWS2 during a patient's stay in the ED had a significant positive impact on the outcome, as evidenced by the adjusted HRs of 0.889 (95% CI = 0.808, 0.978) and 0.891 (95% CI = 0.810, 0.981), respectively. The results obtained from the Kaplan-Meier analysis indicated that the survival rate of the improvement group was significantly higher than that of the non-improvement group (P < 0.001) in the hospitalization period. CONCLUSION: The present study demonstrated that 50.88% of sepsis patients obtained improvement in ED, ascertained by means of the NEWS2 scoring system. The practical dynamics of NEWS2 could be utilized to depict such intricacies clearly. The findings also literally supported the importance of ED management in the comprehensive course of sepsis treatment in reducing the total hospital mortality rate.

Evaluation of Quality Properties of Brown Tigernut (Cyperus esculentus L.) Tubers from Six Major Growing Regions of China: A New Source of Vegetable Oil and Starch.

Tigernut has been recognized as a promising resource for edible oil and starch. However, the research on the quality characteristics of tigernut from different regions is lagging behind, which limits the application of tigernut in food industry. Tigernut tubers were obtained from six major growing regions in China, and the physicochemical properties of their main components, oil and starch, were characterized. Tigernut tubers from Baoshan contained the most oil (30.12%), which contained the most ß-carotene (130.4 µg/100 g oil) due to high average annual temperature. Gas chromatography analysis and fingerprint analysis results indicated that tigernut oil (TNO) consists of seven fatty acids, of which oleic acid is the major component. Changchun TNO contained the least total tocopherols (6.04 mg/100 g oil) due to low average annual temperature. Tigernut tubers from Chifeng (CF) contained the most starch (34.85%) due to the large diurnal temperature range. Xingtai starch contained the most amylose (28.4%). Shijiazhuang starch showed the highest crystallinity (19.5%). Anyang starch had the highest pasting temperature (76.0°C). CF starch demonstrated superior freeze-thaw stability (syneresis: 50%) due to low mean annual precipitation. The results could be further applied to support tigernut industries and relevant researchers that looks for geographical origin discrimination and improvements on tigernut quality, with unique physicochemical and technological properties.

Supraperiosteal fat repositioning with midface lift in lower eyelid blepharoplasty: an 18-year experience.

PURPOSE: To assess the clinical outcomes of fat repositioning via supraperiosteal dissection with midface lift for correction of tear trough deformity in a large Asian patient population. METHODS: Retrospectively review 1152 Asian patients who underwent fat repositioning to the supraperiosteal plane with a midface lift between 2005 and 2022. Surgical technique, postoperative course, and complications were recorded. At the 6-month postoperative follow-up, the degree of patient satisfaction was assessed. RESULTS: A total of 2304 eyes from 1152 patients with an average follow-up of 10 months. These procedures were performed using a transforniceal approach in 185 patients (16%) or a transcutaneous skin excision approach in 967 patients (84%). Among the patients who underwent the transcutaneous technique, seven individuals (0.6%) experienced effective treatment of lower lid ectropion through lateral tarsal strip procedures. Nine patients (0.7%) required revision surgery to address the remaining lateral fat pad due to inadequate lateral orbital fat excision during the initial procedure. At the 6-month follow-up, most patients reported a high level of satisfaction, with 800 patients (78%) expressing extreme satisfaction and 196 patients (19.1%) reporting satisfaction with the improvement in their appearance. No one reported facial numbness, lower eyelid or cheek paralysis, newly developed diplopia or granuloma formation. CONCLUSION: The procedure of fat repositioning involving supraperiosteal dissection and a midface lift, whether performed using a transforniceal approach or a transcutaneous skin excision approach, in lower eyelid blepharoplasty proves to be a secure and auspicious surgical technique for rectifying tear trough deformity and attaining a pleasing aesthetic outcome.

Long-term outcomes of inferomedial orbital wall decompression in Graves' ophthalmopathy in an Asian population: A 30-year retrospective study.

PURPOSE: This study aims to evaluate the long-term outcomes of inferomedial orbital wall decompression (IMOD) in Graves' ophthalmopathy (GO). METHODS: A retrospective review of 422 eyes of 226 patients with GO-related cosmetically disfiguring proptosis (COS), dysthyroid optic neuropathy (DON), or exposure keratopathy (EXP) who received IMOD from 1989 to 2020 was conducted. Hertel value (HE) and corrected visual acuity (CVA) were evaluated at baseline and regularly thereafter. Proptosis recurrence, diplopia, and adjuvant surgeries were assessed. Complete success was defined as proptosis reduction over 2 mm without recurrence and improved diplopia. Partial success was defined as proptosis reduction without recurrence but with persistent or new-onset diplopia, and failure as proptosis recurrence. RESULTS: After follow-up for 40.1 ± 39.6 months (range, 6-239 months), 236 eyes (55.9%) achieved complete success, 175 eyes (41.5%) achieved partial success, and 11 eyes (2.6%) had failure. Significant CVA improvement was observed in both DON and COS groups (P < 0.001 and P = 0.045, respectively). Average proptosis reduction was 5.2 ± 2.2 mm, with a significant increase of 0.5 mm after long-term follow-up (P < 0.001). Incidence of proptosis recurrence was 2.6%. Surgical success rate of COS group was positively correlated with preoperative HE. CONCLUSION: IMOD demonstrated excellent success rate in all three subgroups with a low proptosis recurrence rate and improved visual outcome in both DON and COS groups. Delayed proptosis reduction effect of IMOD may result in delayed-onset asymmetry, especially in the unilateral group.

COPD with elevated sputum group 2 innate lymphoid cells is characterized by severe disease.

Rationale: Pulmonary innate immune cells play a central role in the initiation and perpetuation of chronic obstructive pulmonary disease (COPD), however the precise mechanisms that orchestrate the development and severity of COPD are poorly understood. Objectives: We hypothesized that the recently described family of innate lymphoid cells (ILCs) play an important role in COPD. Methods: Subjects with COPD and healthy controls were clinically evaluated, and their sputum samples were assessed by flow cytometry. A mouse model of spontaneous COPD [genetically deficient in surfactant protein-D (SP-D -/- )] and ozone (O 3 ) exposure were used to examine the mechanism by which lack of functional SP-D may skew ILC2s to produce IL-17A in combination with IL-5 and IL-13, leading to a mixed inflammatory profile and more severe disease. Measurements and Main Results: COPD was characterized by poor spirometry, sputum inflammation, and the emergence of sputum GATA3 + ILCs (ILC2s), but not T-bet + ILCs (ILC1s) nor RORγt + ILCs (ILC3s). COPD subjects with elevated sputum ILC2s (the ILC2 high group) had worse spirometry and sputum neutrophilia and eosinophilia than healthy and ILC2 low subjects. This was associated with the presence of dual-positive IL-5 + IL-17A + and IL-13 + IL-17A + ILCs and nonfunctional SP-D in the sputum in ILC2 high subjects. SP-D -/- mice showed spontaneous airway neutrophilia. Lack of SP-D in the mouse lung licensed ILC2s to produce IL-17A, which was dose-dependently inhibited by recombinant SP-D. SP-D -/- mice showed enhanced susceptibility to O 3 -induced airway neutrophilia, which was associated with the emergence of inflammatory IL-13 + IL-17A + ILCs. Conclusions: We report that the presence of sputum ILC2s predicts the severity of COPD, and unravel a novel pathway of IL-17A plasticity in lung ILC2s, prevented by the immunomodulatory protein SP-D.

Different Anti-inflammatory Drugs on High-Sensitivity C-Reactive Protein in Patients After Percutaneous Coronary Intervention: A Pilot Randomized Clinical Trial.

ABSTRACT: Colchicine reduces atherothrombotic cardiovascular events in coronary artery disease because of its anti-inflammatory effect. However, the effects of the other anti-inflammatory drugs in coronary artery disease remain unclear. This study included 132 patients aged 18-80 years who completed the planned percutaneous coronary interventions and were treated with aggressive secondary prevention strategies for 4 weeks. The subjects were randomly assigned to 1 of the following treatment groups for 4 weeks: (1) control: no additional intervention; (2) colchicine: 0.5 mg once a day; (3) tranilast: 0.1 g thrice a day; or (4) oridonin: 0.5 g thrice a day. The primary outcome was the percentage change in high-sensitivity C-reactive protein (hsCRP) levels at the end of 4 weeks. In total, 109 patients completed the study. The mean age was 58.33 years, 81 (74.31%) were male, and 28 (25.69%) were female. The percentage changes in hsCRP after 4 weeks of treatment were -11.62%, -48.28%, -21.60%, and -7.81%, in the control, colchicine, tranilast, and the oridonin groups, respectively. Compared with the control group, only the colchicine group showed significantly greater reduction in hsCRP levels ( P = 0.022). In targeted proteomic analysis, proteins associated with neutrophil activation (azurocidin, myeloperoxidase, and myeloblastin), platelet aggregation (glycoprotein VI), and endothelial damage (galectin-3) were reduced with colchicine therapy. These results show that of 3 anti-inflammatory drugs only colchicine could reduce hsCRP in patients after percutaneous coronary interventions.

Cardiac and renal outcomes of direct oral anticoagulants in patients with atrial fibrillation.

BACKGROUND: Oral anticoagulation therapy with warfarin or direct oral anticoagulants (DOACs) is the mainstay for stroke prevention in patients with non-valvular atrial fibrillation (AF). The DOACs might have a lower risk of declining renal function than warfarin. This study aimed to compare renal outcomes among rivaroxaban, edoxaban, dabigatran, and warfarin. METHOD: This cohort study identified 2203 adults with AF who started anticoagulation therapy between 1 July 2013 and 31 December 2020, in a clinical database at a single centre. Inverse probability of treatment weighting was adopted to balance baseline characteristics among four anticoagulants treatment groups. The primary outcome was a composite of cardiac and renal outcomes, involving a ≥30% decline in estimated glomerular filtration rate (eGFR), renal failure and cardiovascular death. RESULTS: After propensity score weighting, dabigatran was associated with significantly lower risks of a ≥30% decline in eGFR (hazard ratio [HR]: .69, 95% confidence interval [CI]: .497-.951, p = .0237), doubling of the serum creatinine level (HR: .49, 95% CI: .259-.927, p = .0282) and the cardiac and renal outcome composite (HR: .67, 95% CI: .485-.913, p = .0115) than warfarin. Rivaroxaban and edoxaban did not show significant protective effects on renal outcomes compared to warfarin. CONCLUSION: In this study, patients treated with dabigatran had significantly reduced risks of declining renal function and composite cardiac and renal events than those treated with warfarin. However, rivaroxaban and edoxaban were not associated with lower risks of any renal outcomes than warfarin. More studies are warranted to investigate and compare the impact of renal function between different DOACs in patients with AF.