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Background: As a disease characterized by chronic neutrophilic inflammation, various sputum biomarkers have been investigated in the association with the severity and prognosis of bronchiectasis. However, there is lack of data on the association between sputum interleukin-1beta (IL-1ß), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) levels at clinical stable state and the clinical, spirometric and blood inflammatory parameters, as well as prognostic scores. The purpose of the study is to assess the association between sputum IL-1ß, IL-8 and TNF-α levels at clinical stable state and various clinical and laboratory parameters in bronchiectasis. Methods: A prospective study was conducted in a major regional hospital and tertiary respiratory referral centre in Hong Kong, including 44 Chinese patients with bronchiectasis. The correlation between stable state sputum IL-1ß, IL-8 and TNF-α levels with various clinical, laboratory and spirometric parameters in bronchiectasis, as well as FACED [forced expiratory volume in one second (FEV1), age, chronic colonisation by Pseudomonas aeruginosa, radiological extension and dyspnoea]/E-FACED (FACED plus exacerbations) scores were assessed. Results: Baseline sputum IL-1ß level was found to have significant moderate positive correlation with baseline blood high sensitivity C-reactive protein (hs-CRP) level with Pearson correlation coefficient (r) of 0.529 (P=0.001). Baseline sputum IL-8 level was found to have significant moderate positive correlation with baseline FACED and E-FACED score with r of 0.574 (P<0.001) and 0.539 (P<0.001) respectively. Baseline sputum TNF-α level was found to have significant moderate positive correlation with baseline FACED score with r of 0.520 (P<0.001). Conclusions: Sputum IL-1ß and, IL-8 and TNF-α levels were shown to have significant correlation with various clinical, laboratory and spirometry parameters in bronchiectasis, as well as more severe disease as measured by FACED and E-FACED scores.
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BACKGROUND: Although bronchiectasis has been shown to be associated with cardiovascular disease, there is limited evidence of an association with subclinical atherosclerosis, especially carotid intima-media thickness (CIMT). METHODS: This prospective study compared CIMT among patients with and without bronchiectasis, and among bronchiectatic patients classified according to disease severity using the FACED score. The study was carried out at a major regional hospital and tertiary respiratory referral centre in Hong Kong. RESULTS: Total 155 Chinese patients with non-cystic fibrosis (CF) bronchiectasis and 512 controls were recruited. The mean CIMT was 0.58 ± 0.10 mm, 0.63 ± 0.11 mm and 0.66 ± 0.08 mm respectively among controls, patients with mild-to-moderate bronchiectasis and patients with severe bronchiectasis. There was no statistically significant difference in CIMT between patients with mild-to-moderate bronchiectasis and controls. Multivariate linear regression revealed that CIMT was significantly increased in patients with severe bronchiectasis relative to controls. The same phenomenon was observed among patients without a history of cardiovascular disease or cardiovascular risk factors. CONCLUSIONS: CIMT was significantly increased in patients with severe bronchiectasis compared with controls without bronchiectasis, but not among patients with mild-to-moderate bronchiectasis, which suggested the subclinical atherosclerosis to be more prevalent among patients with severe bronchiectasis.
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Bronquiectasia , Enfermedades de las Arterias Carótidas , Grosor Intima-Media Carotídeo , Índice de Severidad de la Enfermedad , Humanos , Bronquiectasia/diagnóstico por imagen , Bronquiectasia/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Hong Kong/epidemiología , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/epidemiología , Estudios de Casos y Controles , Anciano , Valor Predictivo de las Pruebas , Adulto , Factores de Riesgo , Medición de RiesgoRESUMEN
PURPOSE: Malignant and aggressive, small cell lung cancer (SCLC) constitutes about 15% of all diagnosed lung cancer cases. With primary therapeutic options such as chemotherapy accompanied by debilitating side effects, interest has been soaring in the therapeutic competencies of herbs. The pharmacological driving force behind the beneficial properties of Nigella sativa is the quinone, thymoquinone (TQ). The anti-cancer effects of TQ on different cancers have been extensively studied. Nonetheless, only one paper in the entire National Center for Biotechnology Information (NCBI) database describes its effects on SCLC. A more detailed investigation is required. METHODS: The current study examined the impact of TQ in vitro on five SCLC cell lines and in vivo in a nude mouse xenograft model. The following in vitro effects of TQ on SCLC were evaluated: (a) cell viability; (b) apoptosis; (c) cell cycle arrest; (d) intracellular reactive oxygen species (ROS) levels, and (e) protein expression in concomitant signaling pathways. For the in vivo effects of TQ on SCLC, (a) tumor volume was measured, and (b) selected protein expression in selected concomitant signaling pathways was determined by Western blotting. RESULT: In general, TQ reduced cell viability, induced apoptosis and cell cycle arrest, depleted ROS, and altered protein expression in associated signaling pathways. Furthermore, TQ exhibited a tumor-suppressive effect in an H446 SCLC xenograft model. CONCLUSION: The cytotoxic impact of TQ arising from anti-cancer mechanisms was elucidated. The positive results obtained in this study warrant further investigation.
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Apoptosis , Benzoquinonas , Neoplasias Pulmonares , Nigella sativa , Especies Reactivas de Oxígeno , Carcinoma Pulmonar de Células Pequeñas , Ensayos Antitumor por Modelo de Xenoinjerto , Benzoquinonas/farmacología , Benzoquinonas/uso terapéutico , Animales , Nigella sativa/química , Humanos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Ratones , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ratones Desnudos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: COVID-19 pandemic has disrupted tuberculosis (TB) services in many countries, but the impacts on sites of involvement, drug susceptibility, smear positivity and clinical outcomes, and clinical outcomes of co-infection with influenza and COVID-19 remain unclear. METHODS: Descriptive epidemiological study using episode-based and patient unique data of tuberculosis from Hospital Authority's territory-wide electronic medical record database, comparing baseline (January 2015-December 2019) and COVID-19 period (January 2020-December 2022), followed by univariate and multivariate analyses. Effects of co-infection with influenza and COVID-19 were investigated. RESULTS: The study included 10,473 episodes of laboratory-confirmed TB, with 6818 in baseline period and 3655 during COVID-19 period. During COVID-19 period, TB patients had a lower proportion of smear positivity (49.2 % vs 54.7 %, P < 0.001), and fewer cases of extrapulmonary TB (7.0 % vs 8.0 %, P = 0.078) and multidrug resistant TB (1.0 % vs 1.6 %, P = 0.020). Mortality was higher in TB patients with COVID-19 coinfection (OR 1.7, P = 0.003) and influenza coinfection (OR 2.6, P = 0.004). During COVID-19 period, there were higher rates of treatment delay (20.5 % vs 15.5 %, P < 0.001) and episodic death (15.1 % vs 13.3 %, P = 0.006). Factors associated with higher mortality included age ≥ 70 years (OR 7.24), treatment delay (OR 2.16), extrapulmonary TB (OR 2.13). smear positivity (OR 1.71) and Charlson comorbidity index score ≥ 3 (OR 1.37). Higher mortality was observed with co-infection by influenza (OR 1.18) and COVID-19 (OR 1.7). CONCLUSIONS: The epidemiology and outcomes of TB were changed during COVID-19 period. Mortality was higher during COVID-19 period and with co-infection by influenza and COVID-19.
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COVID-19 , Coinfección , Gripe Humana , Tuberculosis , Humanos , COVID-19/epidemiología , COVID-19/mortalidad , COVID-19/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Coinfección/epidemiología , Adulto , Anciano , Incidencia , Tuberculosis/epidemiología , Tuberculosis/mortalidad , Tuberculosis/complicaciones , Gripe Humana/epidemiología , Gripe Humana/mortalidad , Gripe Humana/complicaciones , SARS-CoV-2 , Adulto Joven , Adolescente , Pandemias , Anciano de 80 o más Años , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/mortalidad , NiñoRESUMEN
Influenza is an important respiratory viral pathogen in adults, with secondary bacterial pneumonia being a common complication. While pneumococcal vaccines can prevent pneumococcal pneumonia and invasive pneumococcal disease, whether they can also prevent the severe in-hospital outcomes among patients hospitalized for influenza has not been examined. A territory-wide retrospective study was conducted in Hong Kong, which included all adult patients having chronic airway diseases (asthma, bronchiectasis, and chronic obstructive pulmonary disease) hospitalized for influenza and who had received seasonal influenza vaccine. The occurrence of secondary bacterial pneumonia, mortality, and other severe in-hospital outcomes were compared among subjects with or without pneumococcal vaccination. There was a total of 3066 eligible patients who were hospitalized for influenza in public hospitals in Hong Kong from 1 January 2016 to 30 June 2023. Completed pneumococcal vaccination with PSV23/PCV13 conferred protection against secondary bacterial pneumonia, all-cause mortality, and respiratory cause of mortality with adjusted odds ratios of 0.74 (95% CI = 0.57-0.95, p = 0.019), 0.12 (95% CI = 0.03-0.53, p = 0.005), and 0.04 (95% CI = 0.00-0.527, p = 0.0038), respectively.
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Background: Bronchiectasis is a disease with predominantly neutrophilic inflammation. As a readily available biomarker, there is little evidence to support the use of blood neutrophil-to-lymphocyte ratio (NLR) to predict bronchiectasis exacerbation severe enough to warrant hospitalization. Methods: A registry-based retrospective cohort study was conducted at a in Hong Kong. Chinese patients with non-cystic fibrosis (CF) bronchiectasis were retrospectively reviewed and subsequently followed up to investigate the association of NLR and the need for hospitalization for bronchiectasis exacerbation. Data on the NLR for patients in a clinically stable state in 2018 were collected and patients followed up from 1 January 2019 to 31 December 2022. The primary outcome was the need for hospitalization due to bronchiectasis exacerbation over the next 4 years. Results: We reviewed 473 Chinese patients with non-CF bronchiectasis, of whom 94 required hospitalization for bronchiectasis exacerbation during the 4-year follow-up period. Multi-variable logistic regression adjusted for E-FACED score (Exacerbation, Forced expiratory volume in 1 s (FEV1), Age, Chronic colonization, Extension, and Dyspnea score), gender, age, smoking status, and presence of co-existing chronic obstructive pulmonary disease (COPD) was conducted to compare patients with highest and lowest quartile NLR. Results revealed that those with NLR at the highest quartile were at increased risk of hospitalization for bronchiectasis exacerbation with an adjusted odds ratio (aOR) of 2.02 (95% confidence interval = 1.00-4.12, p = 0.05). Conclusion: Blood NLR may serve as a marker to predict the need for hospitalization due to bronchiectasis exacerbation.
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Image-based cytometry faces challenges due to technical variations arising from different experimental batches and conditions, such as differences in instrument configurations or image acquisition protocols, impeding genuine biological interpretation of cell morphology. Existing solutions, often necessitating extensive pre-existing data knowledge or control samples across batches, have proved limited, especially with complex cell image data. To overcome this, "Cyto-Morphology Adversarial Distillation" (CytoMAD), a self-supervised multi-task learning strategy that distills biologically relevant cellular morphological information from batch variations, is introduced to enable integrated analysis across multiple data batches without complex data assumptions or extensive manual annotation. Unique to CytoMAD is its "morphology distillation", symbiotically paired with deep-learning image-contrast translation-offering additional interpretable insights into label-free cell morphology. The versatile efficacy of CytoMAD is demonstrated in augmenting the power of biophysical imaging cytometry. It allows integrated label-free classification of human lung cancer cell types and accurately recapitulates their progressive drug responses, even when trained without the drug concentration information. CytoMAD also allows joint analysis of tumor biophysical cellular heterogeneity, linked to epithelial-mesenchymal plasticity, that standard fluorescence markers overlook. CytoMAD can substantiate the wide adoption of biophysical cytometry for cost-effective diagnosis and screening.
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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Citometría de Flujo/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Aprendizaje Profundo , Línea Celular TumoralRESUMEN
While studies have suggested increased risks of severe COVID-19 infection in chronic obstructive pulmonary disease (COPD), the persistent and delayed consequences of COVID-19 infection on patients with COPD upon recovery remain unknown. A prospective clinical study was conducted in Hong Kong to investigate the persistent and delayed outcomes of patients with COPD who had COVID-19 infection of different severity (mild-moderate COVID-19 and severe COVID-19), compared with those who did not. Chinese patients with COPD ≥ 40 years old were recruited from March to September 2021. They were prospectively followed up for 24.9 ± 5.0 months until 31st August 2023. The primary outcome was the deterioration in COPD control defined as the change in mMRC dyspnea scale. The secondary outcomes included the change in exacerbation frequency and non-COVID-19 respiratory mortality (including death from COPD exacerbation or bacterial pneumonia). 328 patients were included in the analysis. Patients with mild-moderate and severe COVID-19 infection had statistically significant increased risks of worsening of mMRC dyspnoea scale by increase in 1 score from baseline to follow-up with adjusted odds ratios of 4.44 (95% CI = 1.95-10.15, p < 0.001) and 6.77 (95% CI = 2.08-22.00, p = 0.001) respectively. Patients with severe COVID-19 infection had significantly increased risks of increase in severe COPD exacerbation frequency with adjusted odds ratios of 4.73 (95% CI = 1.55-14.41, p = 0.006) non-COVID-19 respiratory mortality from COPD exacerbation or pneumonia with adjusted hazard ratio of 11.25 (95% CI = 2.98-42.45, p < 0.001). After recovery from COVID-19, worsening of COPD control from worsening of dyspnea, increase in severe exacerbation frequency to non-COVID-19 respiratory mortality (COPD exacerbation and pneumonia) was observed among patients with severe COVID-19. Mild to moderate COVID-19 was also associated with symptomatic deterioration.
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COVID-19 , Enfermedad Pulmonar Obstructiva Crónica , Índice de Severidad de la Enfermedad , Humanos , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , COVID-19/mortalidad , COVID-19/complicaciones , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios Prospectivos , Hong Kong/epidemiología , SARS-CoV-2/aislamiento & purificación , Disnea , Progresión de la EnfermedadRESUMEN
Background: Bronchiectasis is a common respiratory disease with neutrophilic inflammation being the predominant pathophysiology. Systemic immune-inflammation index (SII) is a simple and readily available biomarker being studied in various conditions including asthma, chronic obstructive pulmonary disease, and interstitial lung disease, but not in bronchiectasis. We aim to investigate the prognostic role of SII in bronchiectasis with this study. Methods: A retrospective cohort study in Chinese patients with non-cystic fibrosis (CF) bronchiectasis was conducted in Hong Kong, to investigate the association between baseline SII and of hospitalized bronchiectasis exacerbation risk over 4.5 years of follow-up, as well as correlating with disease severity in bronchiectasis. The baseline SII in 2018 was calculated based on stable-state complete blood count. Results: Among 473 Chinese patients with non-CF bronchiectasis were recruited, 94 of the patients had hospitalized bronchiectasis exacerbation during the follow-up period. Higher SII was associated with increased hospitalized bronchiectasis exacerbation risks with adjusted odds ratio (aOR) of 1.001 [95% confidence interval (CI): 1.000-1.001, P=0.003] for 1 unit (cells/µL) increase in SII count and aOR of 1.403 (95% CI: 1.126-1.748, P=0.003) for 1 standard deviation (SD) increase in SII. SII was found to have significant negative association with baseline forced expiratory volume in the first second (FEV1) (in litre and percentage predicted), forced vital capacity (FVC) in percentage; and significant positive correlation with the extent of bronchiectasis and baseline neutrophil to lymphocyte ratio (NLR). Conclusions: SII could serve as biomarker to predict the risks of hospitalized exacerbation in bronchiectasis patients, as well as correlating with the disease severity.
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PURPOSE: Cancer-related cognitive impairment is prevalent in metastatic lung cancer survivors. This study aimed to compare the effectiveness of aerobic exercise and Tai Chi on perceived cognitive function and the mediating role of psychoneurological symptoms with perceived cognitive impairment. METHODS: In a subgroup of a parent randomized clinical trial, participants who reported cognitive impairment underwent a 16-week aerobic exercise (n = 49), Tai Chi (n = 48), and control (n = 54) groups. Measures included perceived cognitive function and psychoneurological symptoms (sleep disturbance, fatigue, anxiety, and depression) assessed at baseline (T0), 16-week (T1), and 1 year (T2). RESULTS: Participants in Tai Chi showed significant improvements compared to aerobic exercise and control groups in perceived cognitive function at T1 (AE: between-group difference, 6.52; P < 0.001; CG: 8.34; P < 0.001) and T2 (AE: between-group difference, 3.55; P = 0.05; CG: 5.94; P < 0.001). Sleep disturbance, fatigue, anxiety, and depression at month 12 explained 24%, 31%, 32%, and 24% of the effect of the intervention on cognitive function at month 12, respectively. Only anxiety at month 4 explained 23% of the intervention effect at month 12. CONCLUSIONS: Tai Chi demonstrated beneficial effects on cognitive function in advanced lung cancer survivors with perceived cognitive impairment. Improvement in cognitive function was mediated by reducing sleep disturbance, fatigue, anxiety, and depression, highlighting the importance of addressing these symptoms in future interventions to improve cognitive function, with anxiety playing a significant role at an earlier stage. IMPLICATIONS FOR CANCER SURVIVORS: Tai Chi is a potentially safe complementary therapeutic option for managing cognitive impairment in this vulnerable population. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04119778; retrospectively registered on 8 October 2019.
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CONTEXT: Dyspnea, a prevalent and debilitating symptom in patients with advanced lung cancer, negatively affects symptom burden and prognosis. Physical activity has emerged as a promising non-pharmacological intervention for managing dyspnea. OBJECTIVES: This study compared the effectiveness of two widely-recognized physical activity modalities, namely Tai Chi (TC) and aerobic exercise (AE) for treating dyspnea in patients with advanced lung cancer. METHODS: Patients with advanced lung cancer (n=226) were randomized into TC, AE, or control groups. There was no baseline dyspnea requirement for patients. The AE group received two 60-minute supervised sessions and home-based exercises per month, the TC group received 60-minute sessions twice weekly, and the control group received exercise guidelines for 16 weeks. The primary outcome (sleep quality) of the study has been previously reported. In this secondary analysis, we focused on dyspnea outcomes, including overall and lung cancer-specific dyspnea. Assessments were conducted at baseline (T0), 16 weeks (T1), and one year (T2). RESULTS: Compared to the control group, TC significantly improved overall dyspnea at T1 (between-group difference, -8.69; P=0.03) and T2 (between-group difference, -11.45; P=0.01), but not AE. Both AE (between-group difference, -11.04; P=0.01) and TC (between-group difference, -14.19; P<0.001) significantly alleviated lung cancer-specific dyspnea at T2 compared with the control group. CONCLUSION: Both TC and AE alleviate dyspnea severity in patients with advanced lung cancer, and continuous exercise can yield substantial improvements. Due to its multi-component nature, Tai Chi has a greater effect on dyspnea.
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Disnea , Ejercicio Físico , Neoplasias Pulmonares , Taichi Chuan , Humanos , Disnea/terapia , Disnea/etiología , Neoplasias Pulmonares/complicaciones , Masculino , Femenino , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Terapia por Ejercicio/métodosRESUMEN
BACKGROUND: Although bronchiectasis is reported to be associated with cardiovascular disease, evidence for an association with cardiovascular events (CVEs) is lacking. METHODS: A territory-wide retrospective cohort study was conducted in Hong Kong involving all patients who had bronchiectasis diagnosed in public hospitals and clinics between 1 January 1993 and 31 December 2017 were included. Patients were allocated to be exacerbator or non-exacerbator group based on hospitalzied bronchiecsis history and CVEs over the next 5 years determined. Propensity score matching was used to balance baseline characteristics. RESULTS: 10 714 bronchiectasis patients (mean age 69.6±14.4 years, 38.9% men), including 1230 in exacerbator group and 9484 in non-exacerbator group, were analysed. At 5 years, 113 (9.2%) subjects in the exacerbator group and 87 (7.1%) in the non-exacerbator group developed composite CVEs. After adjustment for age, sex, smoking and risk factors for cardiovascular disease, bronchiectasis exacerbation was associated with increased risks for acute myocardial infarction (AMI), congestive heart failure (CHF) and CVE compared with those in the non-exacerbator group with adjusted HR of 1.602 (95% CI 1.006-2.552, p value=0.047), 1.371 (95% CI 1.016-1.851, p value=0.039) and 1.238 (95% CI 1.001-1.532, p=0.049) in the whole cohort. Findings were similar for the propensity score-matched cohort for AMI and CVE. CONCLUSION: Patients who were hospitalised for exacerbation of bronchiectasis were at significantly increased risk of AMI, CHF and CVE over a 5-year follow-up period.
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Bronquiectasia , Enfermedades Cardiovasculares , Insuficiencia Cardíaca , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Estudios Retrospectivos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Factores de Riesgo , Bronquiectasia/epidemiología , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/etiología , HospitalizaciónRESUMEN
BACKGROUND: Elevation of systemic inflammatory markers were found to correlate with increased disease extent, reduced lung function and higher risk of future severe exacerbations in patients with bronchiectasis. Although a significant correlation of circulating hs-CRP levels with HRCT scores and resting oxygen saturation in patients with stable-state non-cystic fibrosis (CF) bronchiectasis was suggested, there is little data on the relationship between hs-CRP and the prognosis of bronchiectasis and a lack of data on the role of hs-CRP in predicting bronchiectasis exacerbation. METHODS: A prospective study was conducted on Chinese patients with non- CF bronchiectasis from 1st October to 31st December 2021. Baseline serum hs-CRP were obtained at stable-state. The follow-up period lasted for one year. Co-primary endpoints were the development of any bronchiectasis exacerbation and hospitalized bronchiectasis exacerbation. RESULTS: Totally 123 patients were included. Higher hs-CRP was associated with increased risk to develop any bronchiectasis exacerbation, adjusted odds ratio (aOR) of 2.254 (95% CI = 1.040-4.885, p = 0.039), and borderline significantly increased hospitalized bronchiectasis exacerbation with aOR of 1.985 (95% CI = 0.922-4.277, p = 0.080). CONCLUSION: Baseline serum hs-CRP level at stable-state can predict risk of bronchiectasis exacerbation, which is reflecting chronic low-grade inflammation in bronchiectasis.
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Bronquiectasia , Fibrosis Quística , Humanos , Proteína C-Reactiva/metabolismo , Estudios Prospectivos , Pronóstico , InflamaciónRESUMEN
BACKGROUND: Digital subtraction angiography (DSA) yields high cumulative radiation dosages (RD) delivered to patients. We present a temporal interpolation of low frame rate angiograms as a method to reduce cumulative RDs. METHODS: Patients undergoing interventional evaluation and treatment of cerebrovascular vasospasm following subarachnoid hemorrhage were retrospectively identified. DSAs containing pre- and post-intervention runs capturing the full arterial, capillary, and venous phases with at least 16 frames each were selected. Frame rate reduction (FRR) of the original DSAs was performed to 50%, 66%, and 75% of the original frame rate. Missing frames were regenerated by sampling a gamma variate model (GVM) fit to the contrast response curves to the reduced data. A formal reader study was performed to assess the diagnostic accuracy of the "synthetic" studies (sDSA) compared to the original DSA. RESULTS: Thirty-eight studies met inclusion criteria (average RD 1,361.9 mGy). Seven were excluded for differing views, magnifications, or motion. GVMs fit to 50%, 66%, and 75% FRR studies demonstrated average voxel errors of 2.0 ± 2.5% (mean ± standard deviation), 6.5 ± 1.5%, and 27 ± 2%, respectively for anteroposterior projections, 2.0 ± 2.2%, 15.0 ± 3.1%, and 14.8 ± 13.0% for lateral projections, respectively. Reconstructions took 0.51 s/study. Reader studies demonstrated an average rating of 12.8 (95% CI 12.3-13.3) for 75% FRR, 12.7 (12.2-13.2) for 66% FRR and 12.0 (11.5-12.5) for 50% FRR using Subjective Image Grading Scale. Kendall's coefficient of concordance resulted in W = 0.506. CONCLUSION: FRR by 75% combined with GVM reconstruction does not compromise diagnostic quality for the assessment of cerebral vasculature. RELEVANCE STATEMENT: Using this novel algorithm, it is possible to reduce the frame rate of DSA by as much as 75%, with a proportional reduction in radiation exposure, without degrading imaging quality. KEY POINTS: ⢠DSA delivers some of the highest doses of radiation to patients. ⢠Frame rate reduction (FRR) was combined with bolus tracking to interpolate intermediate frames. ⢠This technique provided a 75% FRR with preservation of diagnostic utility as graded by a formal reader study for cerebral angiography performed for the evaluation of cerebral vasospasm. ⢠This approach can be applied to other types of angiography studies.
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Exposición a la Radiación , Humanos , Angiografía de Substracción Digital/métodos , Estudios Retrospectivos , Angiografía Cerebral/métodos , Dosis de RadiaciónRESUMEN
The proposal of improving reproducibility by lowering the significance threshold to 0.005 has been discussed, but the impact on conducting clinical trials has yet to be examined from a study design perspective. The impact on sample size and study duration was investigated using design setups from 125 phase II studies published between 2015 and 2022. The impact was assessed using percent increase in sample size and additional years of accrual with the medians being 110.97% higher and 2.65 years longer respectively. The results indicated that this proposal causes additional financial burdens that reduce the efficiency of conducting clinical trials.
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BACKGROUND AND OBJECTIVE: Respiratory viral infection is a common trigger of bronchiectasis exacerbation. Knowledge of the intermediate to long-term effect of COVID-19 on bronchiectasis is poor. METHODS: A retrospective cohort study of patient records was conducted to assess the frequency of bronchiectasis exacerbation following recovery from mild-to-moderate COVID-19. The exacerbation frequency at baseline, using 2019 and 2019-2021 data, was compared with that during the 1 year following recovery. RESULTS: A total of 234 adult patient records who had a confirmed diagnosis of bronchiectasis were identified, of whom 52 (22.2%) were classified as the COVID-19 group. Patients with COVID-19 had significantly more frequent annual exacerbations of bronchiectasis (total exacerbations and hospitalizations). Compared with 2019-2021 data, the total exacerbation frequency decreased by 0.1 ± 0.51 per year among non-COVID-19 patients but increased by 0.68 ± 1.09 per year among the COVID-19 group (p < 0.001). Compared with 2019 only data, exacerbation frequency decreased by 0.14 ± 0.79 per year among non-COVID-19 patients but increased by 0.76 ± 1.17 per year in the COVID-19 group, p < 0.001. The annual frequency of hospitalization for bronchiectasis increased by 0.01 ± 0.32 per year among non-COVID-19 patients and increased by 0.39 ± 1.06 per year in the COVID-19 group (p < 0.001) compared with 2019 to 2021 data. When compared with only 2019 data, it remained unchanged at 0 ± 0.43 per year among non-COVID-19 patients but increased to 0.38 ± 1.12 per year among COVID-19 patients (p < 0.001). CONCLUSION: Mild-to-moderate COVID-19 was associated with an increase in frequency of bronchiectasis exacerbation and frequency of hospitalizations following recovery.
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Bronquiectasia , COVID-19 , Adulto , Humanos , Antibacterianos/uso terapéutico , Estudios Retrospectivos , COVID-19/complicaciones , COVID-19/epidemiología , Bronquiectasia/diagnóstico , Fibrosis , Progresión de la EnfermedadRESUMEN
Phospholipid bilayers are dynamic cellular components that undergo constant changes in their topology, facilitating a broad diversity of physiological functions including endo- and exocytosis, cell division, and intracellular trafficking. These shape transformations consume energy, supplied invariably by the activity of proteins. Here, we show that cycles of oppositely directed osmotic stressesâunassisted by any protein activityâcan induce well-defined remodeling of giant unilamellar vesicles, minimally recapitulating the phenomenologies of surface area homeostasis and macropinocytosis. We find that a stress cycle consisting of deflationary hypertonic stress followed by an inflationary hypotonic one prompts an elaborate sequence of membrane shape changes ultimately transporting molecular cargo from the outside into the intravesicular milieu. The initial osmotic deflation produces microscopic spherical invaginations. During the subsequent inflation, the first subpopulation contributes area to the swelling membrane, thereby providing a means for surface area regulation and tensional homeostasis. The second subpopulation vesiculates into the lumens of the mother vesicles, producing pinocytic vesicles. Remarkably, the gradients of solute concentrations between the GUV and the daughter pinocytic vesicles create cascades of water current, inducing pulsatory transient poration that enable solute exchange between the buds and the GUV interior. This results in an efficient water-flux-mediated delivery of molecular cargo across the membrane boundary. Our findings suggest a primitive physical mechanism for communication and transport across protocellular compartments driven only by osmotic stresses. They also suggest plausible physical routes for intravesicular, and possibly intracellular, delivery of ions, solutes, and molecular cargo stimulated simply by cycles of osmotic currents of water.
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Fosfolípidos , Liposomas Unilamelares , Presión Osmótica , Liposomas Unilamelares/metabolismo , Ósmosis , AguaRESUMEN
Introduction: Nirmatrelvir-ritonavir (NMV-r) and molnupiravir (MOL) were developed as out-patient anti-viral for mild COVID-19. There was limited data on their role in treating COVID-19 for hospitalized patients, especially among adult patients who are unvaccinated and had chronic respiratory diseases. Methods: A territory-wide retrospective study was conducted in Hong Kong to compare the efficacy of NMV-r and MOL against COVID-19 in unvaccinated adult patients with asthma, chronic obstructive pulmonary disease, bronchiectasis and interstitial lung diseases presenting with moderate COVID-19 from 16th February 2022 to 15th March 2023. Results: A total of 1354 patients were included, 738 received NMV-r and 616 received MOL. NMV-r was more effective in reducing 90-day mortality with adjusted hazard ratios (aHR) of 0.508 (95% confidence interval [CI] = 0.314-0.822, p = 0.006). Patients who received NMV-r also had significantly shorter length of stay (LOS) than those receiving MOL, with median LOS of 4 (Interquartile range [IQR] = 2-7) for NMV-r and 6 (IQR = 3-10) for MOL (p-value < 0.001). There was no statistically significant difference in the development of respiratory failure and severe respiratory failure in the two groups. Discussion: NMV-r was more effective than MOL among unvaccinated adults with chronic respiratory diseases who were hospitalized for moderate COVID-19 without hypoxaemia on admission.
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COVID-19 , Citidina/análogos & derivados , Hidroxilaminas , Lactamas , Leucina , Nitrilos , Prolina , Enfermedad Pulmonar Obstructiva Crónica , Trastornos Respiratorios , Insuficiencia Respiratoria , Adulto , Humanos , Estudios Retrospectivos , Ritonavir/efectos adversos , Tratamiento Farmacológico de COVID-19 , Pacientes Ambulatorios , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/tratamiento farmacológico , Insuficiencia Respiratoria/etiología , Antivirales/efectos adversosRESUMEN
INTRODUCTION: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common and preventable event in patients with chronic obstructive pulmonary disease (COPD). Data regarding the impact of AECOPD on short- and long-term renal outcomes are lacking. METHODS: We included all COPD patients who were followed at Queen Mary Hospital (QMH) in year 2015 and reviewed their clinical/renal outcomes in subsequent five years. Relationships between AECOPD and adverse renal outcomes were evaluated. RESULTS: 371 COPD patients were included. 169 patients had hospitalized AECOPD in past one year (HAE group) while 202 patients did not (non-HAE group). 285 patients (76.8%) had renal progression/death and 102 (27.5%) patients developed acute kidney injury (AKI). HAE group showed a more rapid eGFR decline than non-HAE group (-4.64 mL/min/1.73m2/year vs. -2.40 mL/min/1.73m2/year, p = 0.025). HAE group had significantly higher risk for renal progression/death at 5 years [adjusted OR (aOR) 2.380 (95% CI = 1.144-4.954), p = 0.020]. The frequency of hospitalized AECOPD in past 3 years, any AECOPD in past 3 years, hospitalized AECOPD in past 3 years were also predictive of renal progression/death at 5 years [aOR were 1.176 (95% CI = 1.038- 1.331), 2.998 (95% CI = 1.438-6.250) and 2.887 (95% CI = 1.409-5.917) respectively; p = 0.011, 0.003 and 0.004]. HAE group also showed significantly higher risk of AKI [adjusted HR (aHR) 2.430; 95% CI = 1.306-4.519, p = 0.005]. CONCLUSIONS: AECOPD, in particular HAE, was associated with increased risk of renal progression/death and AKI. Prevention of AECOPD, especially HAE, may potentially improve short- and long-term renal outcomes in COPD patients.