bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotyping empyema by pleural fluid culture results and macroscopic appearance: an 8-year retrospective study
Authors: Chan Ka Pang , Ng Susanna So Shan , Ling Kwun Cheung , Ng Ka Ching , Lo Lai Ping , Yip Wing Ho , Ngai Jenny Chun Li , To Kin Wang , Ko Fanny Wai San , Lee Yun Chor Gary , Hui David Shu Cheong
Published: January 2023

Background

The clinical impact of phenotyping empyema is poorly described. This study was designed to evaluate clinical characteristics and outcomes based on the two readily available parameters, pleural fluid culture status and macroscopic fluid appearance.

Methods

A retrospective study was conducted on patients with empyema hospitalised between 2013 and 2020. Empyema was classified into culture-positive empyema (CPE) or culture-negative empyema (CNE) and pus-appearing empyema (PAE) or non-pus-appearing empyema (non-PAE) based on the pleural fluid culture status and macroscopic fluid appearance, respectively.

Results

Altogether, 212 patients had confirmed empyema (CPE: n=188, CNE: n=24; PAE: n=118, non-PAE: n=94). The cohort was predominantly male (n=163, 76.9%) with a mean age of 65.0±13.6 years. Most patients (n=180, 84.9%) had at least one comorbidity. Patients with CPE had higher rates of in-hospital mortality (19.1%versus0.0%, p=0.017) and 90-day mortality (18.6%versus0.0%, p=0.017) and more extrapulmonary sources of infection (29.8%versus8.3%, p=0.026) when compared with patients with CNE. No significant difference in mortality rate was found between PAE and non-PAE during the in-hospital stay and at 30 days and 90 days. Patients with PAE had less extrapulmonary sources of infection (20.3%versus36.2%, p=0.010) and more anaerobic infection (40.9%versus24.5%, p=0.017) than those with non-PAE. The median RAPID (renal, age, purulence, infection source, and dietary factors) scores were higher in the CPE and non-PAE groups. After adjusting for covariates, culture positivity was not independently associated with mortality on multivariable analysis.

Conclusion

Empyema is a heterogeneous disease with different clinical characteristics. Phenotyping empyema into different subclasses based on pleural fluid microbiological results and macroscopic fluid appearance provides insight into the underlying bacteriology, source of infection and subsequent clinical outcomes.
Clinical response to benralizumab can be predicted by combining clinical outcomes at 3 months with baseline characteristics
Authors: Kroes Johannes A. , de Jong Kim , Hashimoto Simone , Zielhuis Sander W. , van Roon Eric N. , Sont Jacob K. , ten Brinke Anneke
Published: January 2023

Background

Benralizumab is highly effective in many, but not all, patients with severe asthma. Baseline characteristics alone are insufficient to predict an individual's probability of long-term benralizumab response. The objectives of the present study were to: 1) study whether parameters at 3 months, in addition to baseline characteristics, contribute to the prediction of benralizumab response at 1 year; and 2) develop an easy-to-use prediction tool to assess an individual's probability of long-term response.

Methods

We assessed the effect of benralizumab treatment in 192 patients from the Dutch severe asthma registry (RAPSODI). To investigate predictors of long-term benralizumab response (≥50% reduction in maintenance oral corticosteroid (OCS) dose or annual exacerbation frequency) we used logistic regression, including baseline characteristics and 3-month Asthma Control Questionnaire (ACQ-6) score and maintenance OCS dose.

Results

Benralizumab treatment significantly improved several clinical outcomes, and 144 (75%) patients were classified as long-term responders. Response prediction improved significantly when 3-month outcomes were added to a predictive model with baseline characteristics only (area under the receiver-operating characteristic (AUROC) 0.85versus0.72, p=0.001). Based on this model, a prediction tool using sex, prior biologic use, baseline blood eosinophils, forced expiratory volume in 1 s, and at 3 months OCS dose and ACQ-6 was developed which classified patients into three categories with increasing probability of long-term response (95% CI): 25% (3–65%), 67% (57–77%) and 97% (91–99%), respectively.

Conclusion

In addition to baseline characteristics, treatment outcomes at 3 months contribute to the prediction of benralizumab response at 1 year in patients with severe eosinophilic asthma. Prediction tools as proposed in this study may help physicians optimise the use of costly biologics.
Hyperoxia improves exercise capacity in cardiopulmonary disease: a series of randomised controlled trials
Authors: Müller Julian , Lichtblau Mona , Saxer Stéphanie , Schneider Simon R. , Appenzeller Paula , Bauer Meret , Hasler Elisabeth D. , Schwarz Esther I. , Bloch Konrad E. , Ulrich Silvia
Published: January 2023

Background

The aim of this study was to investigate the overall and differential effect of breathing hyperoxia (inspiratory oxygen fraction (
F

IO
2

) 0.5)
versus
placebo (ambient air,
F

IO
2

0.21) to enhance exercise performance in healthy people, patients with pulmonary vascular disease (PVD) with precapillary pulmonary hypertension (PH), COPD, PH due to heart failure with preserved ejection fraction (HFpEF) and cyanotic congenital heart disease (CHD) using data from five randomised controlled trials performed with identical protocols.

Methods

91 subjects (32 healthy, 22 with PVD with pulmonary arterial or distal chronic thromboembolic PH, 20 with COPD, 10 with PH in HFpEF and seven with CHD) performed two cycle incremental (IET) and two constant work-rate exercise tests (CWRET) at 75% of maximal load (W
max
), each with ambient air and hyperoxia in single-blinded, randomised, controlled, crossover trials. The main outcomes were differences in W
max
(IET) and cycling time (CWRET) with hyperoxia
versus
ambient air.

Results

Overall, hyperoxia increased W
max
by +12 W (95% CI: 9–16, p<0.001) and cycling time by +6:13 min (4:50–7:35, p<0.001), with improvements being highest in patients with PVD (W
max
/min: +18%/+118%
versus
COPD: +8%/+60%, healthy: +5%/+44%, HFpEF: +6%/+28%, CHD: +9%/+14%).

Conclusion

This large sample of healthy subjects and patients with various cardiopulmonary diseases confirms that hyperoxia significantly prolongs cycling exercise with improvements being highest in endurance CWRET and patients with PVD. These results call for studies investigating optimal oxygen levels to prolong exercise time and effects on training.
Early prediction of bronchopulmonary dysplasia: can noninvasive monitoring methods be essential?
Authors: Cui Xuewei , Fu Jianhua
Published: January 2023

Despite remarkable breakthroughs in diagnosis and treatment, the prevalence of bronchopulmonary dysplasia (BPD) in preterm infants and the consequent mortality have remained high over the last half-century. The pathophysiology of BPD is complicated, with several causes. In addition, infants with severe BPD are predisposed to a variety of complications that need multidisciplinary collaboration during hospitalisation and post-discharge home treatment. Consequently, early prediction, precise prevention and individualised management have become the cornerstones of therapeutic care of preterm infants with BPD, thereby improving patient survival and prognosis. BPD has an operational clinical description; however, it has various clinical phenotypes and endotypes, making accurate prediction challenging. Currently, most approaches for predicting BPD in preterm infants include invasive collection of biofluids, which is inappropriate in fragile neonates. Consequently, researchers and clinicians are becoming more interested in noninvasive monitoring for BPD prediction. Comprehensive assessments of pertinent research, however, remain scarce. In this review, we compared many noninvasive monitoring techniques that contribute to early prediction of BPD development in premature infants.
Adding a biologic to allergen immunotherapy increases treatment efficacy
Authors: Bożek Andrzej , Fischer Andreas , Bogacz-Piaseczynska Agnieszka , Canonica Giorgio Walter
Published: January 2023

Background

The application of allergen immunotherapy (AIT) in combination with biological agents has been found to increase both the safety and efficacy of the desensitisation procedure in patients with food and insect venom allergy. The aim of our study was to compare the effectiveness of AIT in patients with house dust mite (HDM)-driven asthma treated with and without omalizumab.

Materials and methods

The study was a placebo-controlled, three-armed, randomised, parallel-group, multicentre trial that included 52 patients with HDM-driven asthma. Only patients with monosensitisation to HDM were included. The study compared three patterns of therapy: omalizumab alone, HDM subcutaneous immunotherapy (SCIT-HDM)+ omalizumab, and SCIT alone. The main outcomes were evaluate the Asthma Control Questionnaire (ACQ) score, number of asthma exacerbations and reduction in the daily dose of inhaled steroids during 12 months of observation.

Results

All variants of therapy led to significantly improved ACQ scores and reduction of asthma exacerbations in all study groups after 12 months of treatment. A statistically significant reduction in the daily doses of inhaled corticosteroids in the group with omalizumab alone (650±150 µgversus500±50 µg for p=0.003) or SCIT-HDM+omalizumab (550±250 µgversus375±75 µg for p=0.001) was observed, favouring the latter group.

Conclusion

The efficacy of AIT for HDM-driven asthma is significantly increased by the combination of allergen vaccine with omalizumab.
Inhaled formoterol impairs aerobic exercise capacity in endurance-trained individuals: a randomised controlled trial
Authors: Jessen Søren , Lemminger Anders , Backer Vibeke , Fischer Mads , Di Credico Andrea , Breenfeldt Andersen Andreas , Bangsbo Jens , Hostrup Morten
Published: January 2023

Background

The 2022 Global Initiative for Asthma guidelines emphasise the inhaled long-acting β2-agonist formoterol as part of the first treatment step, and therefore formoterol use among athletes will probably increase. However, prolonged supratherapeutic use of inhaled β2-agonists impairs training outcomes in moderately trained men. We investigated whether inhaled formoterol, at therapeutic doses, imposes detrimental effects in endurance-trained individuals of both sexes.

Methods

51 endurance-trained participants (31 male, 20 female; mean±sdmaximal oxygen consumption (V̇O2max) 62±6 mL·min−1·kg bw−1and 52±5 mL·min−1·kg bw−1, respectively) inhaled formoterol (24 µg; n=26) or placebo (n=25) twice daily for 6 weeks. At baseline and follow-up, we assessedV̇O2maxand incremental exercise performance during a bike-ergometer ramp-test; body composition by dual-energy X-ray absorptiometry; muscle oxidative capacity by high-resolution mitochondrial respirometry, enzymatic activity assays and immunoblotting; intravascular volumes by carbon monoxide rebreathing; and cardiac left ventricle mass and function by echocardiography.

Results

Compared to placebo, formoterol increased lean body mass by 0.7 kg (95% CI 0.2–1.2 kg; treatment×trial p=0.022), but decreasedV̇O2maxby 5% (treatment×trial p=0.013) and incremental exercise performance by 3% (treatment×trial p<0.001). In addition, formoterol lowered muscle citrate synthase activity by 15% (treatment×trial p=0.063), mitochondrial complex II and III content (treatment×trial p=0.028 and p=0.007, respectively), and maximal mitochondrial respiration through complexes I and I+II by 14% and 16% (treatment×trial p=0.044 and p=0.017, respectively). No apparent changes were observed in cardiac parameters and intravascular blood volumes. All effects were sex-independent.

Conclusion

Our findings demonstrate that inhaled therapeutic doses of formoterol impair aerobic exercise capacity in endurance-trained individuals, which is in part related to impaired muscle mitochondrial oxidative capacity. Thus, if low-dose formoterol fails to control respiratory symptoms in asthmatic athletes, physicians may consider alternative treatment options.
Low-intensity pulsed ultrasound (LIPUS) enhances the anti-inflammatory effects of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles
Authors: Li Xueke , Zhong Yi , Zhou Wuqi , Song Yishu , Li Wenqu , Jin Qiaofeng , Gao Tang , Zhang Li , Xie Mingxing
Published: January 2023

Background

Bone marrow-derived mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs) have shown potent anti-inflammatory function in various pathological conditions, such as osteoarthritis and neurodegenerative diseases. Since the number of EVs naturally secreted by cells is finite and they usually bear specific repertoires of bioactive molecules to perform manifold cell–cell communication, but not one particular therapeutic function as expected, their practical application is still limited. Strategies are needed to increase the production of EVs and enhance their therapeutic function. Recent studies have suggested that low-intensity pulsed ultrasound (LIPUS) is a promising non-invasive method to increase the secretion of EVs and promote their anti-inflammatory effects. However, the effect of LIPUS stimulation of BMSCs on EVs derived from the cells remains unclear. The objective of this study was to investigate whether LIPUS stimulation on BMSCs could increase the secretion of EVs and enhance their anti-inflammatory effects.

Methods

BMSCs were exposed to LIPUS (300 mW/cm2) for 15 min and EVs were isolated by ultracentrifugation. Anti-inflammatory effects of EVs were investigated on RAW264.7 cells in vitro and in the allogeneic skin transplantation model. Small RNA-seq was utilized to identify components difference in EVs with/without LIPUS irradiation.

Results

In this study, we found that LIPUS stimulation could lead to a 3.66-fold increase in the EVs release from BMSCs. Moreover, both in vitro and in vivo experimental results suggested that EVs secreted from LIPUS-treated BMSCs (LIPUS-EVs) possessed stronger anti-inflammatory function than EVs secreted from BMSCs without LIPUS stimulation (C-EVs). RNA-seq analysis revealed that miR-328-5p and miR-487b-3p were significantly up-regulated in LIPUS-EVs compare with C-EVs. The suppression of MAPK signaling pathway by these two up-regulated miRNAs could be the potential mechanism of strengthened anti-inflammatory effects of LIPUS-EVs.

Conclusion

LIPUS stimulation on BMSCs could significantly increase the secretion of EVs. Moreover, EVs generated from LIPUS-treated BMSCs possessed much stronger anti-inflammatory function than C-EVs. Therefore, LIPUS could be a promising non-invasive strategy to promote the production of EVs from BMSCs and augment their anti-inflammatory effects.
Clinical relationship between dry eye disease and uveitis: a scoping review
Authors: Rojas-Carabali William , Mejía-Salgado Germán , Cifuentes-González Carlos , Villabona-Martínez Valeria , Barraquer-López Nicolás Doménico , Valdés-Arias David , de-la-Torre Alejandra
Published: January 2023

This scoping review examined the relationship between Dry Eye Disease (DED) and Uveitis. We searched Pubmed, Embase, and LILACS databases for articles in which at least one patient had DED and uveitis concomitantly. The search produced 2381 records, and 24 studies were included in the qualitative synthesis. We concluded that DED and uveitis of any etiology could appear concomitantly in patients of any age. However, both diseases seem to coexist more frequently in middle-aged women and cases of anterior uveitis. Therefore, it is crucial that ophthalmologists actively look for the coexistence of ocular surface abnormalities, especially in patients with these characteristics. Future studies should establish and quantify the risk factors and pathophysiological mechanisms of this coexistence to achieve an early diagnosis of both etiologies and comprehensive management of these patients.
Bradyrhizobium japonicum IRAT FA3 promotes salt tolerance through jasmonic acid priming in Arabidopsis thaliana
Authors: Gomez Melissa Y. , Schroeder Mercedes M. , Chieb Maha. , McLain Nathan K. , Gachomo Emma W.
Published: January 2023

Background

Plant growth promoting rhizobacteria (PGPR), such as Bradyrhizobium japonicum IRAT FA3, are able to improve seed germination and plant growth under various biotic and abiotic stress conditions, including high salinity stress. PGPR can affect plants’ responses to stress via multiple pathways which are often interconnected but were previously thought to be distinct. Although the overall impacts of PGPR on plant growth and stress tolerance have been well documented, the underlying mechanisms are not fully elucidated. This work contributes to understanding how PGPR promote abiotic stress by revealing major plant pathways triggered by B. japonicum under salt stress.

Results

The plant growth-promoting rhizobacterial (PGPR) strain Bradyrhizobium japonicum IRAT FA3 reduced the levels of sodium in Arabidopsis thaliana by 37.7%. B. japonicum primed plants as it stimulated an increase in jasmonates (JA) and modulated hydrogen peroxide production shortly after inoculation. B. japonicum-primed plants displayed enhanced shoot biomass, reduced lipid peroxidation and limited sodium accumulation under salt stress conditions. Q(RT)-PCR analysis of JA and abiotic stress-related gene expression in Arabidopsis plants pretreated with B. japonicum and followed by six hours of salt stress revealed differential gene expression compared to non-inoculated plants. Response to Desiccation (RD) gene RD20 and reactive oxygen species scavenging genes CAT3 and MDAR2 were up-regulated in shoots while CAT3 and RD22 were increased in roots by B. japonicum, suggesting roles for these genes in B. japonicum-mediated salt tolerance. B. japonicum also influenced reductions of RD22, MSD1, DHAR and MYC2 in shoots and DHAR, ADC2, RD20, RD29B, GTR1, ANAC055, VSP1 and VSP2 gene expression in roots under salt stress.

Conclusion

Our data showed that MYC2 and JAR1 are required for B. japonicum-induced shoot growth in both salt stressed and non-stressed plants. The observed microbially influenced reactions to salinity stress in inoculated plants underscore the complexity of the B. japonicum jasmonic acid-mediated plant response salt tolerance.
Analysis of related factors of portal vein thrombosis in liver cirrhosis
Authors: Xu Xiaotong , Jin Jinglan , Liu Yuwei , Li Hang
Published: January 2023

Background and aims

To investigate the usefulness of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), protein C (PC), and thromboelastography (TEG) to serve as a predictor of portal vein thrombosis (PVT) in patients with liver cirrhosis. Additionally, we examined the clinical significance of the above indicators in terms of disease progression.

Methods

A total of 123 patients with liver cirrhosis were recruited from May 2021 to December 2021, according to the imaging findings. They were divided into the PVT group (n = 52) and the non-PVT group (n = 71). Furthermore, patients with PVT were divided into plasma transfusion groups (n = 13) and non-plasma transfusion groups (n = 39). The basic general information, past medical history, laboratory, and imaging examination data were collected and analyzed.

Results

In univariate analysis, there was no significant difference between the two groups in IL-6, PC, reaction time (R), alpha angle (Angle), maximum amplitude, or coagulation index (CI) (P > 0.05). TNF-α in the PVT group was significantly lower than that in the non-PVT group (P = 0.001). K-time (K) in the PVT group was significantly higher than that in the non-PVT group (P = 0.031). There was no significant difference in IL-6, TNF-α, PC, or TEG between different Child–Pugh classification groups (P > 0.05). There were no significant differences in TEG between the plasma transfusion group and the non-plasma transfusion group. In Binary logistic regression analysis, TNF-α (OR = 0.9881, 95%CI = 0.971, 0.990, P < 0.001), K(OR = 1.28, 95% = 1.053, 1.569, P = 0.014), activate partial thromboplastin time (APTT) (OR = 0.753, 95%CI = 0.656, 0.865, P < 0.001), portal vein diameter (OR = 1.310, 95%CI = 1.108, 1.549, P = 0.002)and the history of splenectomy or embolism (OR = 7.565, 95%CI = 1.514, 37.799, P = 0.014)were related to the formation of PVT.

Conclusions

TNF-α, K, APTT, portal vein diameter, and splenectomy or embolism history were associated with PVT formation, but IL-6 was not.
The burden of disease-specific multimorbidity among older adults in India and its states: evidence from LASI
Authors: Patel Priyanka , Muhammad T. , Sahoo Harihar
Published: January 2023

Background

Around the world, advances in public health and changes in clinical interventions have resulted in increased life expectancy. Multimorbidity is becoming more of an issue, particularly in countries where the population is rapidly ageing. We aimed to determine the prevalence of multimorbidity and disease-specific multimorbidity and examine its association with demographic and socioeconomic characteristics among older adults in India and its states.

Methods

The individual data from the longitudinal ageing study in India (LASI) were used for this study, with 11 common chronic conditions among older adults aged 60 and above years (N = 31,464). Descriptive statistics were used to report the overall prevalence of multimorbidity and disease-specific burden of multimorbidity. Multinomial logistic regression has been used to explore the factors associated with multimorbidity.

Results

Prevalence of single morbidity was 30.3%, and multimorbidity was 32.1% among older people in India. Multimorbidity was higher among females and in urban areas and increased with age and among those living alone. Hypertension, arthritis and thyroid were highly prevalent among females and chronic lung diseases and stroke were highly prevalent among males. The older people in the state of Kerala had a high prevalence of multimorbidity (59.2%). Multimorbidity was found to be more likely in older age groups of 75–79 years (RR-1.69; CI: 1.53–1.87) and 80 years and above (RR-1.40; CI: 1.27–1.56) and in the Western (RR-2.16; CI: 1.90–2.44) and Southern regions (RR-2.89; CI: 2.57–3.24). Those who were living with a spouse (RR-1.60; CI: 1.15–2.23) were more likely to have multimorbidity. Disease-specific multimorbidity was high in chronic heart disease (91%) and low in angina (64.8%).

Conclusions

The findings suggest that multimorbidity has a positive relationship with advancing age, and disease-specific burden of multimorbidity is higher among chronic heart patients. Comorbidity, especially among those who already have chronic heart disease, stroke, cholesterol or thyroid disorder can have severe consequences on physical functioning, therefore, disease-specific health management needs to be enhanced.
Classification of benign and malignant subtypes of breast cancer histopathology imaging using hybrid CNN-LSTM based transfer learning
Authors: Srikantamurthy Mahati Munikoti , Rallabandi V. P. Subramanyam , Dudekula Dawood Babu , Natarajan Sathishkumar , Park Junhyung
Published: January 2023

Background

Grading of cancer histopathology slides requires more pathologists and expert clinicians as well as it is time consuming to look manually into whole-slide images. Hence, an automated classification of histopathological breast cancer sub-type is useful for clinical diagnosis and therapeutic responses. Recent deep learning methods for medical image analysis suggest the utility of automated radiologic imaging classification for relating disease characteristics or diagnosis and patient stratification.

Methods

To develop a hybrid model using the convolutional neural network (CNN) and the long short-term memory recurrent neural network (LSTM RNN) to classify four benign and four malignant breast cancer subtypes. The proposed CNN-LSTM leveraging on ImageNet uses a transfer learning approach in classifying and predicting four subtypes of each. The proposed model was evaluated on the BreakHis dataset comprises 2480 benign and 5429 malignant cancer images acquired at magnifications of 40×, 100×, 200× and 400×.

Results

The proposed hybrid CNN-LSTM model was compared with the existing CNN models used for breast histopathological image classification such as VGG-16, ResNet50, and Inception models. All the models were built using three different optimizers such as adaptive moment estimator (Adam), root mean square propagation (RMSProp), and stochastic gradient descent (SGD) optimizers by varying numbers of epochs. From the results, we noticed that the Adam optimizer was the best optimizer with maximum accuracy and minimum model loss for both the training and validation sets. The proposed hybrid CNN-LSTM model showed the highest overall accuracy of 99% for binary classification of benign and malignant cancer, and, whereas, 92.5% for multi-class classifier of benign and malignant cancer subtypes, respectively.

Conclusion

To conclude, the proposed transfer learning approach outperformed the state-of-the-art machine and deep learning models in classifying benign and malignant cancer subtypes. The proposed method is feasible in classification of other cancers as well as diseases.
The optimal minimum lymph node count for carcinoembryonic antigen elevated colon cancer: a population-based study in the SEER set and External set
Authors: Zhang Hao , Wang Chunlin , Liu Yunxiao , Hu Hanqing , Tang Qingchao , Huang Rui , Wang Meng , Wang Guiyu
Published: January 2023

Purpose

The aim of this paper was to clarify the optimal minimum number of lymph node for CEA-elevated (≥ 5 ng/ml) colon cancer patients.

Methods

Thirteen thousand two hundred thirty-nine patients from the SEER database and 238 patients from the Second Affiliated Hospital of Harbin Medical University (External set) were identified. For cancer-specific survival (CSS), Kaplan-Meier curves were drawn and data were analyzed using log-rank test. Using X-tile software, the optimal cut-off lymph node count was calculated by the maximal Chi-square value method. Cox regression model was applied to perform survival analysis.

Results

In CEA-elevated colon cancer, 18 nodes were defined as the optimal minimum node. The number of lymph node examined (< 12, 12-17 and ≥ 18) was an independent prognosticator in both SEER set (HR12-17 nodes = 1.329,P <  0.001; HR< 12 nodes = 1.985,P <  0.001) and External set (HR12-17 nodes = 1.774,P <  0.032; HR< 12 nodes = 2.741,P <  0.006). Moreover, the revised 18-node standard could identify more positive lymph nodes compared with the 12-node standard in this population.

Conclusions

With the purpose of favorable long-term survival and accurate nodal stage for CEA-elevated colon cancer patients, the 18-node standard could be regarded as an alternative to the 12-node standard advocated by the ASCO and NCCN guidelines.
Global burden of prostate cancer attributable to smoking among males in 204 countries and territories, 1990–2019
Authors: Zhang Hanfei , Huang Dingping , Zhang Yingfeng , Wang Xia , Wu Jiangtao , Hong Daqing
Published: January 2023

Introduction

Understanding the latest global spatio-temporal pattern of prostate cancer burden attributable to smoking can help guide effective global health policy. This study aims to elucidate the trends in smoking-related prostate cancer from 1990 to 2019 using Global Burden of Disease (GBD) 2019 study data.

Methods

Data on prostate cancer attributable to smoking were extracted from Global Burden of Disease Study (GBD) 2019. The numbers and age-standardized rates on smoking-related prostate cancer mortality (ASMR) and disability-adjusted life years (ASDR) were analyzed by year, age, region, country, and socio-demographic index (SDI) level. Estimated annual percentage change (EAPC) was calculated to evaluate the temporal trends of ASMR and ASDR from 1990 to 2019.

Results

Of all prostate cancer deaths and DALYs globally in 2019, 6% and 6.6% were attributable to smoking, which contributed to 29,298 (95% CI 12,789 to 46,609) deaths and 571,590 (95% CI 253,490 to 917,820) disability-adjusted life-years (DALYs) in 2019. The number of smoking-related deaths and DALYs showed an upward trend, increasing by half from 1990 to 2019, while ASMR and ASDR declined in five sociodemographic indexes (SDI) regions, with the fastest decline in high SDI regions. For geographical regions, Western Europe and East Asia were the high-risk areas of prostate cancer deaths and DALYs attributable to smoking, among which China and the United States were the countries with the heaviest burden. The ASMR has decreased in all age groups, with the fastest decrease occurring in 75–79 years old. The ASMR or ASDR tended to increase in countries with the lowest SDI, but declined in countries with the highest SDI. The EAPC in ASMR or ASDR was highly negatively correlated with Human Development Index (HDI) in 2019, with coefficients 0.46.

Conclusion

The number of smoking-related prostate cancer deaths and DALYs continued to increase globally, whereas its ASMR and ASDR have been decreasing. This substantial progress is particularly significant in developed regions and vary across geographic regions. Medical strategies to prevent and reduce the burden should be adjusted and implemented based on country-specific disease prevalence.
Multi-omics analyses of CD276 in pan-cancer reveals its clinical prognostic value in glioblastoma and other major cancer types
Authors: Dai Lirui , Guo Xuyang , Xing Zhe , Tao Yiran , Liang Wulong , Shi Zimin , Hu Weihua , Zhou Shaolong , Wang Xinjun
Published: January 2023

Background

CD276 (also known as B7-H3) is one of the most important immune checkpoints of the CD28 and B7 superfamily, and its abnormal expression is closely associated with various types of cancer. It has been shown that CD276 is able to inhibit the function of T cells, and that this gene may potentially be a promising immunotherapy target for different types of cancer.

Methods

Since few systematic studies have been published on the role of CD276 in cancer to date, the present study has employed single-cell sequencing and bioinformatics methods to analyze the expression patterns, clinical significance, prognostic value, epigenetic alterations, DNA methylation level, tumor immune cell infiltration and immune functions of CD276 in different types of cancer. In order to analyze the potential underlying mechanism of CD276 in glioblastoma (GBM) to assess its prognostic value, the LinkedOmics database was used to explore the biological function and co-expression pattern of CD276 in GBM, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. In addition, a simple validation of the above analyses was performed using reverse transcription-quantitative (RT-q)PCR assay.

Results

The results revealed that CD276 was highly expressed, and was often associated with poorer survival and prognosis, in the majority of different types of cancer. In addition, CD276 expression was found to be closely associated with T cell infiltration, immune checkpoint genes and immunoregulatory interactions between lymphoid and a non-lymphoid cell. It was also shown that the CD276 expression network exerts a wide influence on the immune activation of GBM. The expression of CD276 was found to be positively correlated with neutrophil-mediated immunity, although it was negatively correlated with the level of neurotransmitters, neurotransmitter transport and the regulation of neuropeptide signaling pathways in GBM. It is noteworthy that CD276 expression was found to be significantly higher in GBM compared with normal controls according to the RT-qPCR analysis, and the co-expression network, biological function and chemotherapeutic drug sensitivity of CD276 in GBM were further explored. In conclusion, the findings of the present study have revealed that CD276 is strongly expressed and associated with poor prognosis in most types of cancer, including GBM, and its expression is strongly associated with T-cell infiltration, immune checkpoint genes, and immunomodulatory interactions between lymphocytes and non-lymphoid cells.

Conclusions

Taken together, based on our systematic analysis, our findings have revealed important roles for CD276 in different types of cancers, especially GBM, and CD276 may potentially serve as a biomarker for cancer.
Novel cuproptosis-related long non-coding RNA signature to predict prognosis in prostate carcinoma
Authors: Cheng Xiaofeng , Zeng Zhenhao , Yang Heng , Chen Yujun , Liu Yifu , Zhou Xiaochen , Zhang Cheng , Wang Gongxian
Published: January 2023

Background

Cuproptosis, an emerging form of programmed cell death, has recently been identified. However, the association between cuproptosis-related long non-coding RNA (lncRNA) signature and the prognosis in prostate carcinoma remains elusive. This study aims to develop the novel cuproptosis-related lncRNA signature in prostate cancer and explore its latent molecular function.

Methods

RNA-seq data and clinical information were downloaded from the TCGA datasets. Then, cuproptosis-related gene was identified from the previous literature and further applied to screen the cuproptosis-related differentially expressed lncRNAs. Patients were randomly assigned to the training cohort or the validation cohort with a 1:1 ratio. Subsequently, the machine learning algorithms (Lasso and stepwise Cox (direction = both)) were used to construct a novel prognostic signature in the training cohorts, which was validated by the validation and the entire TCGA cohorts. The nomogram base on the lncRNA signature and several clinicopathological traits were constructed to predict the prognosis. Functional enrichment and immune analysis were performed to evaluate its potential mechanism. Furthermore, differences in the landscape of gene mutation, tumour mutational burden (TMB), microsatellite instability (MSI), drug sensitivity between both risk groups were also assessed to explicit their relationships.

Results

The cuproptosis-related lncRNA signature was constructed based on the differentially expressed cuproptosis-related lncRNAs, including AC005790.1, AC011472.4, AC099791.2, AC144450.1, LIPE-AS1, and STPG3-AS1. Kaplan–Meier survival and ROC curves demonstrate that the prognosis signature as an independent risk indicator had excellent potential to predict the prognosis in prostate cancer. The signature was closely associated with age, T stage, N stage, and the Gleason score. Immune analysis shows that the high-risk group was in an immunosuppressive microenvironment. Additionally, the significant difference in landscape of gene mutation, tumour mutational burden, microsatellite instability, and drug sensitivity between both risk groups was observed.

Conclusions

A novel cuproptosis-related lncRNA signature was constructed using machine learning algorithms to predict the prognosis of prostate cancer. It was closely with associated with several common clinical traits, immune cell infiltration, immune-related functions, immune checkpoints, gene mutation, TMB, MSI, and the drug sensitivity, which may be useful to improve the clinical outcome.
How severe would prioritization-induced bottlenecks need to be offset the benefits from prioritizing COVID-19 vaccination to those most at risk in New York City?
Authors: Kim Hae-Young , Bershteyn Anna , McGillen Jessica B. , Braithwaite R. Scott
Published: January 2023

Background

Prioritization of higher-risk people for COVID-19 vaccination could prevent more deaths, but could slow vaccination speed. We used mathematical modeling to examine the trade-off between vaccination speed and prioritization for individuals age 65+ and essential workers.

Methods

We used a stochastic, discrete-time susceptible-exposed-infected-recovered (SEIR) model with age- and comorbidity-adjusted COVID-19 outcomes (infections, hospitalizations, and deaths). The model was calibrated to COVID-19 hospitalizations, ICU census, and deaths in NYC. We assumed 10,000 vaccinations per day, initially restricted to healthcare workers and nursing home populations, and subsequently expanded to other populations at alternative times (4, 5, or 6 weeks after vaccine launch) and speeds (20,000, 50,000, 100,000, or 150,000 vaccinations per day), as well as prioritization options (+/− prioritization of people age 65+ and essential workers). In sensitivity analyses, we examined the effect of a SARS-COV-2 variant with greater transmissibility.

Results

To be beneficial, prioritization must not create a bottleneck that decreases vaccination speed by > 50% without a more transmissible variant, or by > 33% with the emergence of the more transmissible variant. More specifically, prioritizing people age 65+ and essential workers increased the number of lives saved per vaccine dose delivered: 3000 deaths could be averted by delivering 83,000 vaccinations per day without prioritization or 50,000 vaccinations per day with prioritization. Other tradeoffs involve vaccination speed and timing. Compared to the slowest-examined vaccination speed of 20,000 vaccinations per day, achieving the fastest-examined vaccination speed of 150,000 vaccinations per day would avert additional 313,700 (28.6%) infections and 1693 (24.1%) deaths. Emergence of a more transmissible variant would double COVID-19 infections, hospitalizations, and deaths over the first 6 months of vaccination. The fastest-examined vaccination speed could only offset the harm of the more transmissible variant if achieved within 5 weeks of vaccine launch.

Conclusions

Faster vaccination speed with sooner vaccination expansion would save more lives. Prioritization of COVID-19 vaccines to higher-risk populations would be more beneficial only if it does not create an excessive vaccine delivery bottleneck.
Deaths during the first year of the COVID-19 pandemic: insights from regional patterns in Germany and Poland
Authors: Myck Michał , Oczkowska Monika , Garten Claudius , Król Artur , Brandt Martina
Published: January 2023

Background

Given the nature of the spread of SARS-CoV-2, strong regional patterns in the fatal consequences of the COVID-19 pandemic related to local characteristics such as population and health care infrastructures were to be expected. In this paper we conduct a detailed examination of the spatial correlation of deaths in the first year of the pandemic in two neighbouring countries – Germany and Poland, which, among high income countries, seem particularly different in terms of the death toll associated with the COVID-19 pandemic. The analysis aims to yield evidence that spatial patterns of mortality can provide important clues as to the reasons behind significant differences in the consequences of the COVID-19 pandemic in these two countries.

Methods

Based on official health and population statistics on the level of counties, we explore the spatial nature of mortality in 2020 in the two countries – which, as we show, reflects important contextual differences. We investigate three different measures of deaths: the officially recorded COVID-19 deaths, the total values of excessive deaths and the difference between the two. We link them to important pre-pandemic regional characteristics such as population, health care and economic conditions in multivariate spatial autoregressive models. From the point of view of pandemic related fatalities we stress the distinction between direct and indirect consequences of COVID-19, separating the latter further into two types, the spatial nature of which is likely to differ.

Results

The COVID-19 pandemic led to much more excess deaths in Poland than in Germany. Detailed spatial analysis of deaths at the regional level shows a consistent pattern of deaths officially registered as related to COVID-19. For excess deaths, however, we find strong spatial correlation in Germany but little such evidence in Poland.

Conclusions

In contrast to Germany, for Poland we do not observe the expected spatial pattern of total excess deaths and the excess deaths over and above the official COVID-19 deaths. This difference cannot be explained by pre-pandemic regional factors such as economic and population structures or by healthcare infrastructure. The findings point to the need for alternative explanations related to the Polish policy reaction to the pandemic and failures in the areas of healthcare and public health, which resulted in a massive loss of life.
Illnesses and hardship financing in India: an evaluation of inpatient and outpatient cases, 2014-18
Authors: Thomas Arya Rachel , Dash Umakant , Sahu Santosh Kumar
Published: January 2023

Background

Progress towards universal health coverage requires strengthening the country's health system. In developing countries, the increasing disease burden puts a lot of stress on scarce household finances. However, this burden is not the same for everyone. The economic burden varies across the disease groups and care levels. Government intervention is vital in formulating policies in addressing financial distress at the household level. In India, even when outpatient care forms a significant proportion of out-of-pocket expenditure, government schemes focus on reducing household expenditure on inpatient care alone. Thus, people resort to hardship financing practices like informal borrowing or selling of assets in the event of health shocks. In this context, the present study aims to identify the disease(s) that correlates with maximum hardship financing for outpatients and inpatients and to understand the change in hardship financing over time.

Methods

We used two waves of National Sample Survey Organisation’s data on social consumption on health- the 71st and the 75th rounds. Descriptive statistics are reported, and logistic regression is carried out to explain the adjusted impact of illness on hardship financing. Pooled logistic regression of the two rounds is estimated for inpatients and outpatients. Marginal effects are reported to study the changes in hardship financing over time.

Results

The results suggest that cancer had the maximum likelihood of causing hardship financing in India for both inpatients (Odds ratio 2.41; 95% Confidence Interval (CI): 2.03 - 2.86 (71st round), 2.54; 95% CI: 2.21 - 2.93 (75th round)) and outpatients (Odds ratio 6.11; 95% CI: 2.95 - 12.64 (71st round), 3.07; 95% CI: 2.14 - 4.40 (75th round)). In 2018, for outpatients, the hardship financing for health care needs was higher at public health facilities, compared to private health facilities (Odds ratio 0.72; 95% CI: 0.62 - 0.83 (75th round). The marginal effects model of pooled cross-section analysis reveals that from 2014 to 2018, the hardship financing had decreased for inpatients (Odds ratio 0.747; 95% CI:0.80 - -0.70), whereas it had increased for outpatients (Odds ratio 0.0126; 95% CI: 0.01 - 0.02). Our results also show that the likelihood of resorting to hardship financing for illness among women was lesser than that of men.

Conclusion

Government intervention is quintessential to decrease the hardship financing caused by cancer. The intra-household inequalities play an important role in explaining their hardship financing strategies. We suggest the need for more financial risk protection for outpatient care to address hardship financing.
Impact of extracorporeal membrane oxygenation in immunocompetent children with severe adenovirus pneumonia
Authors: Shi Tingting , Chen Chen , Fan Huifeng , Yu Minghua , Li Ming , Yang Diyuan , Huang Li , Nie Zhiqiang , Lu Gen
Published: January 2023

Background

Severe adenovirus (Adv.) pneumonia can cause significant mortality in young children. There has been no worldwide consensus on the impact of extracorporeal membrane oxygenation (ECMO) in immunocompetent children with severe Adv. pneumonia. This study aimed to assess the impact of ECMO in immunocompetent children with severe Adv. pneumonia.

Methods

This study evaluated the medical records of 168 hospitalized children with severe Adv. pneumonia at the Guangzhou Women and Children’s Medical Center between 2019 and 2020.Nineteen patients in the ECMO group and 149 patients in the non-ECMO group were enrolled.

Results

Between these two groups, there were no differences in host factors such as sex, age (all P > 0.05). Significant differences were observed in shortness of breath/increased work of breathing; cyanosis; seizures; tachycardia; the partial pressure of oxygen in arterial blood (PO2); the ratio of PaO2 to the fraction concentration of oxygen in inspired air (FiO2; P/F); white blood cell, lymphocyte, monocytes, lactate dehydrogenase (LDH), serum albumin, and procalcitonin levels; and, pulmonary consolidation (all P < 0.05). There were significant differences in the parameters of mechanical ventilation (MV) therapy and complications such as respiratory failure, acute respiratory distress syndrome, septic shock, length of hospitalization, and death (all P < 0.05). The maximum axillary temperatures, respiratory rates, heart rates and LDH levels after receiving ECMO were significantly lower than those before ECMO (all P < 0.05). Additionally, SPO2, PO2, and P/F were significantly higher than those before ECMO (all P < 0.05). In MV therapy, FiO2, PIP, and PEEP were significantly lower than those before ECMO (all P < 0.05).

Conclusions

In our study, the clinical conditions of the patients in the ECMO group were much more severe than those in the non-ECMO group. Our study showed that ECMO might be beneficial for the patients with severe Adv. pneumonia.
Femoral neck fractures in non-geriatric patients: femoral neck system versus cannulated cancellous screw
Authors: Kenmegne Guy Romeo , Zou Chang , Fang Yue , He Xuanhong , Lin Yixiang , Yin Yijie
Published: January 2023

Background

The fractures of femoral neck account for 50% among hip fractures with around 3%-10% occurring in younger population of below 65 years. The newly introduced FNS as management approach appears to be a potential alternative to the traditional CCS. The aim of this study was to compare the clinical efficacy and outcome of the femoral neck system (FNS) and the cannulated cancellous screw (CCS) in the treatment of femoral neck fractures in adult below 65 years of age.

Methods

Data of 114 patients between 18–65 years, admitted in our department for femoral neck fracture from January 2019 to March 2021 were retrospectively studied and ranged into two groups based on the surgical methods: FNS group (56 patients) and CCS group (58 patients). The variables of interest including demographic and clinical variables (age, gender, fracture mechanism, injury side and classification), perioperative parameters(operation time, intraoperative bleeding, incision length and hospitalization time), postoperative outcomes and complications (fracture healing time, nonunion rate, femoral neck avascular necrosis, aseptic screw loosening and the Harris Hip Score), were analyzed and compared between the two groups.

Results

All 114 patients presented satisfactory reduction and were followed-up for a period of 12 to 36 months (mean 27 ± 2.07 months); there were no significant differences between both groups in terms of age, gender, fracture classification, side of injury, mechanism of injury, the operative time, intraoperative blood loss and the hospital length of stay. However, the fracture healing time between FNS group and CCS group was statistically significant (p < 0.05), respectively 2.86 ± 0.77 and 5.10 ± 0.81 months. The significant differences were also found in terms of numbers of fluoroscopies 8.34 ± 1.38 Vs 17.72 ± 2.19, the HHS 87.80 ± 1.92 Vs 84.28 ± 2.24, postoperative complications 8 (14.28%) Vs 26 (44.82) respectively in FNS and CCS group.

Conclusion

FNS presented satisfactory outcomes had significantly lower complications rate, therefore, can be one of the alternatives for internal implantation devices in treatment of femoral neck fracture in non-geriatric population.