Diagnostic performance of computed tomography-digital subtraction angiography and conventional magnetic resonance imaging for evaluating the vascularity of osseous spinal tumors.

BACKGROUND AND PURPOSE: Patients with hypervascular spinal tumors may have severe blood loss during tumor resection, which increases the risks of perioperative morbidity and mortality. However, the preoperative evaluation of tumor vascularity may be challenging; moreover, the reliability of the data obtained in conventional preoperative noninvasive imaging is debatable. In this study, we compared conventional magnetic resonance imaging (MRI) and subtraction computed tomography angiography (CTA) in terms of their performance in vascularity evaluation. The catheter digital subtraction angiography (DSA) technique was used as a reference standard. METHODS: This study included 123 consecutive patients with spinal tumor who underwent subtraction CTA, catheter DSA, and subsequent surgery between October 2015 and October 2021. Data regarding qualitative and semiquantitative subtraction CTA parameters and conventional MRI signs were collected for comparison with tumor vascularity graded through catheter DSA. The diagnostic performance of qualitative CTA, quantitative CTA, and conventional MRI in assessing spinal tumor vascularity was analyzed. RESULTS: Qualitative subtraction CTA was the best noninvasive imaging modality in terms of diagnostic performance (area under the receiver operating characteristic curve [AUROC], 0.95). Quantitative CTA was relatively inferior (AUROC, 0.87). MRI results had low reliability (AUROC, 0.51 to 0.59). Intratumoral hemorrhage and prominent foraminal venous plexus were found to be the specific signs for hypervascularity (specificity 93.2%). CONCLUSIONS: Qualitative subtraction CTA offers the highest diagnostic value in evaluating spinal tumor vascularity, compared to quantitative CTA and MRI. Although conventional MRI may not be a reliable approach, certain MRI signs may have high specificity, which may be crucial for assessing spinal tumor vascularity.

Renal sympathetic denervation ameliorates the activated inflammatory response through JAK-STAT pathway in a chronic obstructive sleep apnea animal model.

OBJECTIVES: Obstructive sleep apnea (OSA) is known to increase the risk of cardiovascular disease and inflammation plays a significant role in this process. Renal denervation (RDN) is a novel approach aimed at reducing sympathetic nervous system activity. The role of RDN in the inflammatory response to chronic OSA (COSA) is currently unclear. The main objective was to study inflammatory mechanisms in the rabbit heart with COSA and the effects of RDN. METHODS: Eighteen rabbits were randomized into three groups: sham control, COSA, and COSA-RDN. COSA and COSA-RDN groups received liquid silicone injections, while the sham control group received normal saline. We performed combined surgical and chemical RDN through bilateral retroperitoneal flank incisions in the COSA-RDN group after silicone injections. The inflammatory mechanisms were assessed through immunoblotting, real-time PCR, and ELISA after the experiment. RESULTS: H&E staining showed immune cell infiltration in COSA, which decreased after RDN treatment. The level of α7nAChR was significantly reduced in COSA compared to the sham control but was restored to a similar level in the COSA-RDN group. Furthermore, the expressions of p-JAK2 and p-STAT3 were significantly reduced in COSA but showed an up-regulation following RDN treatment. Similarly, levels of the inflammatory markers IL-6, IL-1ß and TNF-α were markedly increased in COSA but decreased after RDN therapy. We observed NF-κB activation in the COSA rabbit model, which decreased after RDN treatment, as evidenced by decreased NF-κB expression. CONCLUSIONS: Our study suggests that RDN treatment may prevent COSA-associated heart inflammation via the JAK2-STAT3 signaling pathway.

A fixel-based analysis of white matter reductions early detects Parkinson disease with mild cognitive impairment.

BACKGROUND: White matter (WM) tract alterations are early signs of cognitive impairment in Parkinson disease (PD) patients. Fixel-based analysis (FBA) has advantages over traditional diffusion tensor imaging in managing complex and crossing fibers. We used FBA to measure fiber-specific changes in patients with PD mild cognitive impairment (PD-MCI) and PD normal cognition (PD-NC). METHODS: Seventy-one patients with PD without dementia were included: 39 PD-MCI and 32 PD-NC. All underwent diffusion-weighted imaging, clinical examinations, and tests to evaluate their cognitive function globally and in five cognitive domains. FBA was used to investigate fiber-tract alterations and compare PD-MCI with PD-NC subjects. Correlations with each cognitive test were analyzed. RESULTS: Patients with PD-MCI were significantly older (P = 0.044), had a higher male-to-female ratio (P = 0.006) and total Unified Parkinson's Disease Rating Scale score (P = 0.001). All fixel-based metrics were significantly reduced within the body of the corpus callosum and superior corona radiata in PD-MCI patients (family-wise error-corrected P value < 0.05) compared with PD-NC patients. The cingulum, superior longitudinal fasciculi, and thalamocortical circuit exhibited predominantly fiber-bundle cross-section (FC) changes. In regression analysis, reduced FC values in cerebellar circuits were associated with poor motor function in PD-MCI patients and poor picture-naming ability in PD-NC patients. CONCLUSIONS: PD-MCI patients have significant WM alterations compared with PD-NC patients. FBA revealed these changes in various bundle tracts, helping us to better understand specific WM changes that are functionally implicated in PD cognitive decline. FBA is potentially useful in detecting early cognitive decline in PD.

Aversive conditioning information transmission in Drosophila.

Animals rapidly acquire surrounding information to perform the appropriate behavior. Although social learning is more efficient and accessible than self-learning for animals, the detailed regulatory mechanism of social learning remains unknown, mainly because of the complicated information transfer between animals, especially for aversive conditioning information transmission. The current study revealed that, during social learning, the neural circuit in observer flies used to process acquired aversive conditioning information from demonstrator flies differs from the circuit used for self-learned classic aversive conditioning. This aversive information transfer is species dependent. Solitary flies cannot learn this information through social learning, suggesting that this ability is not an innate behavior. Neurons used to process and execute avoidance behavior to escape from electrically shocked flies are all in the same brain region, indicating that the fly brain has a common center for integrating external stimuli with internal states to generate flight behavior.

Fractal complexity alternations in paroxysmal atrial fibrillation patients with and without recurrence after pulmonary vein isolation.

BACKGROUND: Pulmonary vein isolation (PVI) is a cornerstone therapy for paroxysmal atrial fibrillation (PAF). The variations in nonlinear heart rate variability (HRV) between patients with and without recurrences remain unclear. We aimed to characterize the nonlinear HRV before and after PVI in patients with and without recurrence. METHODS: Twenty-five drug-refractory PAF patients (56.0 ± 9.1 years old, 20 males) who received PVI were enrolled. Holter electrocardiography were performed before, 1-3, and 6-12 months after PVI. After 8.2 ± 2.5 months of follow-ups after PVI, patients were divided into two groups: the recurrence (n = 8) and non-recurrence (n = 17) groups. Linear and nonlinear HRV variables were analyzed, including the Poincaré Plot analysis and the Detrended Fluctuation Analysis (DFA). RESULTS: The non-recurrence group, but not the recurrence group, had decreased high-frequency component (HF), the root mean square of successive RR interval differences (RMSSD), and the Poincaré Plot index SD1 1-3 months after PVI and increased DFAslope2 6-12 months after PVI. The non-recurrence group's LF/HF ratio and DFAslope1 decreased significantly 1-3 and 6-12 months after PVI, respectively, whereas there was no significant change in the recurrence group after PVI. CONCLUSIONS: Significantly reduced vagal tone 1-3 months after PVI, increased long-term fractal complexity 6-12 months after PVI, and decreased sympathetic tone as well as short-term fractal complexity 1-3 and 6-12 months after PVI led to a better AF-free survival after PVI. These findings suggest that neuromodulation and heart rate dynamics play crucial roles in AF recurrence following PVI.

Linking folding dynamics and function of SAM/SAH riboswitches at the single molecule level.

Riboswitches are regulatory elements found in bacterial mRNAs that control downstream gene expression through ligand-induced conformational changes. Here, we used single-molecule FRET to map the conformational landscape of the translational SAM/SAH riboswitch and probe how co-transcriptional ligand-induced conformational changes affect its translation regulation function. Riboswitch folding is highly heterogeneous, suggesting a rugged conformational landscape that allows for sampling of the ligand-bound conformation even in the absence of ligand. The addition of ligand shifts the landscape, favoring the ligand-bound conformation. Mutation studies identified a key structural element, the pseudoknot helix, that is crucial for determining ligand-free conformations and their ligand responsiveness. We also investigated ribosomal binding site accessibility under two scenarios: pre-folding and co-transcriptional folding. The regulatory function of the SAM/SAH riboswitch involves kinetically favoring ligand binding, but co-transcriptional folding reduces this preference with a less compact initial conformation that exposes the Shine-Dalgarno sequence and takes min to redistribute to more compact conformations of the pre-folded riboswitch. Such slow equilibration decreases the effective ligand affinity. Overall, our study provides a deeper understanding of the complex folding process and how the riboswitch adapts its folding pattern in response to ligand, modulates ribosome accessibility and the role of co-transcriptional folding in these processes.

Immune-mediated lung diseases: A narrative review.

The role of immunity in the pathogenesis of various pulmonary diseases, particularly interstitial lung diseases (ILDs), is being increasingly appreciated as mechanistic discoveries advance our knowledge in the field. Immune-mediated lung diseases demonstrate clinical and immunological heterogeneity and can be etiologically categorized into connective tissue disease (CTD)-associated, exposure-related, idiopathic, and other miscellaneous lung diseases including sarcoidosis, and post-lung transplant ILD. The immunopathogenesis of many of these diseases remains poorly defined and possibly involves either immune dysregulation, abnormal healing, chronic inflammation, or a combination of these, often in a background of genetic susceptibility. The heterogeneity and complex immunopathogenesis of ILDs complicate management, and thus a collaborative treatment team should work toward an individualized approach to address the unique needs of each patient. Current management of immune-mediated lung diseases is challenging; the choice of therapy is etiology-driven and includes corticosteroids, immunomodulatory drugs such as methotrexate, cyclophosphamide and mycophenolate mofetil, rituximab, or other measures such as discontinuation or avoidance of the inciting agent in exposure-related ILDs. Antifibrotic therapy is approved for some of the ILDs (e.g., idiopathic pulmonary fibrosis) and is being investigated for many others and has shown promising preliminary results. A dire need for advances in the management of immune-mediated lung disease persists in the absence of standardized management guidelines.

Dimensional Reduction for Single-Molecule Imaging of DNA and Nucleosome Condensation by Polyamines, HP1α and Ki-67.

Macromolecules organize themselves into discrete membrane-less compartments. Mounting evidence has suggested that nucleosomes as well as DNA itself can undergo clustering or condensation to regulate genomic activity. Current in vitro condensation studies provide insight into the physical properties of condensates, such as surface tension and diffusion. However, methods that provide the resolution needed for complex kinetic studies of multicomponent condensation are desired. Here, we use a supported lipid bilayer platform in tandem with total internal reflection microscopy to observe the two-dimensional movement of DNA and nucleosomes at the single-molecule resolution. This dimensional reduction from three-dimensional studies allows us to observe the initial condensation events and dissolution of these early condensates in the presence of physiological condensing agents. Using polyamines, we observed that the initial condensation happens on a time scale of minutes while dissolution occurs within seconds upon charge inversion. Polyamine valency, DNA length, and GC content affect the threshold polyamine concentration for condensation. Protein-based nucleosome condensing agents, HP1α and Ki-67, have much lower threshold concentrations for condensation than charge-based condensing agents, with Ki-67 being the most effective, requiring as low as 100 pM for nucleosome condensation. In addition, we did not observe condensate dissolution even at the highest concentrations of HP1α and Ki-67 tested. We also introduce a two-color imaging scheme where nucleosomes of high density labeled in one color are used to demarcate condensate boundaries and identical nucleosomes of another color at low density can be tracked relative to the boundaries after Ki-67-mediated condensation. Our platform should enable the ultimate resolution of single molecules in condensation dynamics studies of chromatin components under defined physicochemical conditions.

Toward Perfect Surfaces of Transition Metal Dichalcogenides with Ion Bombardment and Annealing Treatment.

Layered transition metal dichalcogenides (TMDs) are two-dimensional materials exhibiting a variety of unique features with great potential for electronic and optoelectronic applications. The performance of devices fabricated with mono or few-layer TMD materials, nevertheless, is significantly affected by surface defects in the TMD materials. Recent efforts have been focused on delicate control of growth conditions to reduce the defect density, whereas the preparation of a defect-free surface remains challenging. Here, we show a counterintuitive approach to decrease surface defects on layered TMDs: a two-step process including Ar ion bombardment and subsequent annealing. With this approach, the defects, mainly Te vacancies, on the as-cleaved PtTe2 and PdTe2 surfaces were decreased by more than 99%, giving a defect density <1.0 × 1010 cm-2, which cannot be achieved solely with annealing. We also attempt to propose a mechanism behind the processes.

Sacubitril/valsartan improves all-cause mortality in heart failure patients with reduced ejection fraction and chronic kidney disease.

BACKGROUND: Impaired renal function is frequently observed in patients with heart failure and reduced ejection fraction (HFrEF). The differential effect of sacubitril/valsartan and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEIs/ARBs) on the clinical and renal outcomes in patients with HFrEF and chronic kidney disease (CKD) remains unknown. AIMS: This study aimed to explore the differential effect of sacubitril/valsartan and ACEI/ARB on the clinical and renal outcomes as well as renal function over a 12-month follow-up period in HFrEF patients with and without CKD. METHODS: Patients with HfrEF (LVEF ≤35%) and NYHA class ≥II were enrolled from the Chang Gung Research Database between 2017 and 2020. Baseline characteristics were compared between patients prescribed sacubitril/valsartan and ACEI/ARB. After propensity score matching, the following clinical and renal outcomes were compared between the two groups in patients with and without CKD over a 12-month follow-up period: acute kidney injury (AKI), emergent dialysis/renal death, HF hospitalization, cardiovascular mortality, and all-cause mortality. RESULTS: This study enrolled 3735 HFrEF patients with a mean left ventricular EF of 27.56 ± 5.86%, who had been prescribed sacubitril/valsartan (N = 1708) or ACEI/ARB (N = 2027). After propensity score matching, the clinical and renal outcomes did not differ between the sacubitril/valsartan and ACEI/ARB groups in patients without CKD. In patients with CKD, the ACEI/ARB group had a significantly higher incidence of all-cause mortality than the sacubitril/valsartan group (14.89% vs. 10.50%; hazard ratio 1.46; 95% confidence interval 1.06-2.00; p = 0.02), and the incidence of AKI, HF hospitalization, and CV mortality did not differ between the two groups. CONCLUSIONS: Sacubitril/valsartan had a lower all-cause mortality compared to ACEI/ARB in symptomatic HFrEF patients with CKD. Further prospective randomized studies are warranted to confirm our findings.

Long-term Outcome of Seizure Control and Neurologic Performance After Limited Hippocampal Radiofrequency Thermocoagulation for Mesial Temporal Lobe Epilepsy.

OBJECTIVE: Limited hippocampal radiofrequency thermocoagulation (RFTC) for patients with mesial temporal lobe epilepsy was associated with good short-term seizure control and few complications. We aimed to demonstrate the neuropsychologic outcomes and assess the prognostic factors of long-term seizure control in these patients. METHODS: We included all patients with mesial temporal lobe epilepsy who underwent limited hippocampal RFTC from January 2016 to December 2020. Clinical data of age, sex, seizure control before and after operation were all corrected. Pre- and postoperative neuropsychologic function including full-scale intelligence quotient (FSIQ), memory quotient, and the Mini-Mental State Examination was used. RESULTS: Thirty-one patients (17 female and 14 male) with a mean epilepsy duration of 22.3 years and seizure frequency of 5.7 times per month were included. The intraoperative seizure rate was 19.3%, and a higher preoperative seizure frequency (P = 0.001) and longer duration of epilepsy (P = 0.042) were associated with the occurrence of intraoperative seizures. The postoperative FSIQ scores were significantly better than preoperative scores (mean 92.1 vs. 89.7, P = 0.014). Nine patients (29%) who underwent limited hippocampal RFTC were seizure-free at 1 year of follow-up. Responders represented 58% (n = 18) of patients at 1 year. The mean follow-up period was 34.7 ± 13.3 months. Five patients remained seizure free and 13 patients are still responders at the last follow-up visits. Long-term seizure frequency was 2.32 ± 2.86 times per month. CONCLUSIONS: Limited hippocampal RFTC is a safe stereotactic minimal invasive procedure with good neuropsychologic outcome and acceptable efficacy of seizure reduction in appropriately selected patients.

Clinical manifestations and outcomes of fungus-associated asthma: A multi-institution database study in Taiwan.

BACKGROUND: Differences in the clinical phenotypes and outcomes of fungus-associated asthma remain unclear. We aimed to investigate the presentation of asthmatics with fungal sensitization and/or positive fungal isolates. METHODS: Clinical characteristics, pulmonary function, microbiological data, allergy test reports, emergency department (ED) visits and hospitalizations were retrieved from the Chang Gung Research Database between 2010 and 2018; the largest electronic medical record-based database in Taiwan. Follow-up care was provided to each patient for 3 years. RESULTS: A total of 30,754 asthmatics were enrolled, and 7976 were eligible for analysis after applying the exclusion criteria. Of these patients, 694 had sputum examinations for fungi. The patients were divided into four groups: group 1, neither fungal sensitization nor fungal isolates in the sputum (n = 386); group 2, positive fungal sensitization (n = 58); group 3, positive fungal isolates (n = 217); and group 4, concomitant positive fungal sensitization and positive fungal isolates (n = 33). Asthmatic patients with fungal sensitization (groups 2 and 4) demonstrated significantly higher IgE levels compared with those without (groups 1 and 3). Group 4 patients had a higher frequency of hospitalization. Amongst patients under Global Initiative for Asthma (GINA) step 4-5 therapies, group 4 asthmatics possessed significantly higher incidence of respiratory failure. CONCLUSIONS: The prevalence of fungal sensitization and fungal isolates from sputum were even across asthmatic severities, but the clinical impact of fungi may be more significant among patients with more severe disease.

Long-term outcomes of very early treated infantile-onset Pompe disease with short-term steroid premedication: experiences from a nationwide newborn screening programme.

BACKGROUND: Starting enzyme replacement therapy (ERT) before severe irreversible muscular damage occurs is important in infantile-onset Pompe disease (IOPD). This long-term follow-up study demonstrates our diagnostic and treatment strategies for IOPD and compares our clinical outcomes with those of other medical centres. METHODS: In this long-term follow-up study, we analysed the outcomes of very early ERT with premedication hydrocortisone in patients with IOPD. Out of 1 228 539 infants screened between 1 January 2010 and 28 February 2021, 33 newborns had confirmed IOPD in Taipei Veterans General Hospital. Twenty-six were regularly treated and monitored at Taipei Veterans General Hospital. Echocardiographic parameters, biomarkers, IgG antibodies against alglucosidase alpha, pulmonary function variables and developmental status were all assessed regularly over an average follow-up duration of 6.18±3.14 years. We compared the long-term treatment outcomes of our patients with those of other research groups. RESULTS: The average age at ERT initiation was 9.75±3.17 days for patients with classic IOPD. The average of the latest antialglucosidase alpha IgG titre was 669.23±1159.23. All enrolled patients had normal heart sizes, motor milestones, cognitive function and pulmonary function that were near-normal to normal. Compared with patients in other studies, our patients had better outcomes in all aspects. CONCLUSION: Very early ERT using our rapid diagnostic and treatment strategy enabled our patients with IOPD to have better outcomes than patients in other medical centres.

UQCRC1 variants in early-onset and familial Parkinson's disease in a Taiwanese cohort.

Background: A recent Taiwanese study reported variants of the ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) gene linked to autosomal dominant parkinsonism with polyneuropathy. This study investigated the pathogenicity of UQCRC1 in a Taiwanese cohort of patients with Parkinson's disease (PD). Method: This study involved 107 participants (98 with early-onset PD and nine with familial PD). All UQCRC1 coding exons and exon-intron boundaries were sequenced. The rarity and pathogenicity of the identified variants were analyzed. The carrier frequencies of our cohort and the Taiwan Biobank were compared through a Pearson's χ2 or Fisher's exact test along with Bonferroni corrections. Results: Three missense variants (c.643G > C, p.D215H; c.800C > G, p.P267R, and c.923A > G, p.N308S) and seven rare variants were identified. No significant differences in the missense-variant carrier frequency were noted between our cohort and individuals in the Taiwan Biobank. Furthermore, no significant associations were noted between the variants and the risk of PD. Conclusions: Our study is not supporting a role of UQCRC1 variants in PD.

Novel mutation of IFT140 in an infant with Mainzer-Saldino syndrome presenting with retinal dystrophy.

A seven-month-old girl presented with bilateral roving nystagmus, hyperopia, and retinal dystrophy, and was brought to our ophthalmology clinic. Visual-evoked potentials (VEPs) were non-recordable in both the eyes. No other systemic symptoms or abnormalities were observed. Whole exome sequencing (WES) identified a compound heterozygous mutation in the IFT140 gene: c.1990G > A (p. Glu664Lys) and c.2214_2217del (p.Asp738GlufsTer47). The genetic results support a diagnosis of Mainzer-Saldino syndrome (MSS). Importantly, c.2214_2217del is a novel mutation in the IFT140 gene. Although the patient presents with isolated retinal dystrophy, it is crucial to monitor renal function overtime. Taken together, our results reinforce the role of IFT140 in syndromic ciliopathies. This report also highlights the role of combined WES approaches in identifying underlying mutations in infants presenting with isolated retinal dystrophy, considering MSS may present differently over time.

Impact of baseline renal function on the efficacy and safety of different Anticoagulants in Atrial Fibrillation Patients - A cohort study.

BACKGROUND: Vitamin K antagonists and different direct oral anticoagulants (DOACs) have different renal clearance rates. However, the impact of different stages of chronic renal impairment on the efficacy and safety of warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban in atrial fibrillation (AF) patients remains unclear. METHODS: This study enrolled AF patients from the Chang Gung Research Database. The study endpoints included thromboembolic events, major/fatal bleeding, gastrointestinal (GI) bleeding and intracranial hemorrhage (ICH). The risks of time to study endpoints between groups were compared using a Cox proportional hazards regression model with adjustment. RESULTS: This study enrolled 3525 patients with moderate renal impairment (30 ≤ creatinine clearance (CrCl) < 60 mL/min), 2846 patients with mild renal impairment (60 ≤ CrCl < 90 mL/min) and 1153 patients with CrCl ≥ 90 mL/min. Over the 3.3 ± 0.9 years follow-up period, the cumulative thromboembolic events rates and the cumulative event rates of major/fatal bleeding and ICH did not differ among the warfarin and different DOAC groups at different stages of chronic renal impairment. The annual incidences of thromboembolic events, major/fatal bleeding, GI bleeding, and ICH were similar among the warfarin and different DOAC groups at different stages of renal impairment. CONCLUSION: There did not appear to be major differences in bleeding or thromboembolic risk compared to warfarin in AF patients across a range of degree of renal failure when appropriate dose reductions of the DOACs are made.

Engineered helicase replaces thermocycler in DNA amplification while retaining desired PCR characteristics.

Polymerase Chain Reaction (PCR) is an essential method in molecular diagnostics and life sciences. PCR requires thermal cycling for heating the DNA for strand separation and cooling it for replication. The process uses a specialized hardware and exposes biomolecules to temperatures above 95 °C. Here, we engineer a PcrA M6 helicase with enhanced speed and processivity to replace the heating step by enzymatic DNA unwinding while retaining desired PCR characteristics. We name this isothermal amplification method SHARP (SSB-Helicase Assisted Rapid PCR) because it uses the engineered helicase and single-stranded DNA binding protein (SSB) in addition to standard PCR reagents. SHARP can generate amplicons with lengths of up to 6000 base pairs. SHARP can produce functional DNA, a plasmid that imparts cells with antibiotic resistance, and can amplify specific fragments from genomic DNA of human cells. We further use SHARP to assess the outcome of CRISPR-Cas9 editing at endogenous genomic sites.

Clinical outcomes and prognostic factors of bronchiectasis rheumatoid overlap syndrome: A multi-institution cohort study.

The information regarding bronchiectasis with RA (BROS) is limited in Asia. The objective of this study was to investigate the clinical characteristics and outcomes of BROS in Taiwan. This multi-institute cohort study included patients with BROS from January 2006 to December 2017. The clinical, functional and microbiological data of these patients were retrieved from the Chang Gung Research Database. Respiratory failure and mortality were the primary outcomes. Severe exacerbation was defined as bronchiectasis- related hospitalizations or emergency department visits. A total of 343 patients with BROS were identified. One hundred and eight patients had severe exacerbation and exhibited significantly more previous exacerbations, a lower FEV1 and higher BACI score (11.1 vs. 7.5) than patients without severe exacerbation. The most prevalent species in sputum were Non-tuberculous mycobacteria (NTM) (14.8 %), Pseudomonas aeruginosa (14.2 %), and fungus (5.9%). 68.8% of BROS patients used disease modifying antirheumatic drugs (DMARD), 7.9% used biological DMARD. NTM and tuberculosis infection rates were higher in bDMARD group compared with nbDMARD group and others. Overall, the 3-year respiratory failure rate and mortality rate were 14.6 and 25.7% respectively. Patients with RA diagnosed before bronchiectasis had a significantly higher cumulative incidence of mortality in a 3-year follow-up than those with RA diagnosed after bronchiectasis. In Cox regression, age, higher RF value and systemic steroid use were independent risk factors for mortality in BROS. BROS patients with severe exacerbation had a high mortality rate in Taiwan. bDMARD is associated with a trend of increased risk of NTM and TB infections.

Nonlinear Heart Rate Dynamics Before and After Paroxysmal Atrial Fibrillation Events.

Background: Heart rate complexity, derived from nonlinear heart rate variability (HRV), has been shown to help predict the outcomes of various diseases. Changes in heart rate complexity before and after paroxysmal atrial fibrillation (PAF) events are unclear. Objectives: To evaluate changes in heart rate complexity through nonlinear HRV before and after PAF events. Methods: We enrolled 65 patients (72 ± 12.34 years old, 31 females) with 99 PAF events who received 24-hour Holter recording, and analyzed nonlinear HRV variables including Poincaré plot analysis, sample entropy (SampEn), and multiscale entropy (MSE). HRV analyses were applied to a 20-minute window before the onset and after the termination of PAF events. HRV parameters were evaluated and compared based on eight different 5-minute time segments, as we divided each 20-minute window into four segments of 5 minutes each. Results: SampEn and MSE1~5 significantly decreased before the onset of PAF events, whereas SampEn, MSE1~5 and MSE6~20 significantly increased after the termination of PAF events. SD1 and SD2, which are nonlinear HRV parameters calculated via Poincaré plot analysis, did not significantly change before the PAF events, however they both decreased significantly after termination. Conclusions: Heart rate complexity significantly decreased before the initiation and increased after the termination of PAF events, which indicates the crucial role of nonlinear heart rate dynamics in the initiation and termination of PAF.

Dual versus Single Antiplatelet Therapy in Medically Treated Acute Myocardial Infarction Patients with Baseline Thrombocytopenia - Insights from a Multi-Institute Cohort Study.

Background: The safety and efficacy of dual antiplatelet therapy (DAPT) in medically treated acute myocardial infarction (AMI) patients with baseline thrombocytopenia (platelet count < 150 × 103/uL) are unclear. Methods: In this multi-institute retrospective cohort study, we included 468 patients with medically treated AMI with baseline thrombocytopenia and separated them into single antiplatelet therapy (SAPT) and DAPT groups according to the discharge anti-thrombotic strategy. The primary outcome was net clinical adverse events (NACEs), defined as a composite of death, ischemic events (myocardial infarction, ischemic stroke, and transient ischemic attack), and major bleeding within 30 days. Results: There were 168 patients in the SAPT group (100 taking aspirin and 68 taking clopidogrel) and 300 in the DAPT group. A primary outcome occurred in 35 (24.11 per 100 patient-months) patients in the SAPT group and 39 (14.26 per 100 patient-months) patients in the DAPT group [adjusted hazard ratio (HR): 0.67; 95% confidence interval (CI): 0.40-1.10; p = 0.1145]. Kaplan-Meier curves showed favorable results in the DAPT group (log-rank p = 0.0243). Bleeding events occurred in 18 (10.71 per 100 patient-months) patients in the SAPT group and 18 (6.40 per 100 patient-months) patients in the DAPT group (adjusted HR: 0.66; 95% CI: 0.32-1.36; p = 0.2573). Conclusions: DAPT versus SAPT as discharge anti-thrombotic strategy in thrombocytopenic patients with medically treated AMI did not significantly improve NACEs at 30 days. However, there was a trend towards favorable outcomes in the DAPT group. These results should be interpreted carefully with respect to the relatively limited trial population and study design.