Distinct disease severity between children and older adults with COVID-19: Impacts of ACE2 expression, distribution, and lung progenitor cells

Abstract Background Children and older adults with coronavirus disease 2019 (COVID-19) display a distinct spectrum of disease severity yet the risk factors aren’t well understood. We sought to examine the expression pattern of angiotensin-converting enzyme 2 (ACE2), the cell-entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the role of lung progenitor cells in children and older patients. Methods We retrospectively analysed clinical features in a cohort of 299 patients with COVID-19. The expression and distribution of ACE2 and lung progenitor cells were systematically examined using a combination of public single-cell RNA-seq datasets, lung biopsies, and ex vivo infection of lung tissues with SARS-CoV-2 pseudovirus in children and older adults. We also followed up patients who had recovered from COVID-19. Results Compared with children, older patients (> 50 yrs.) were more likely to develop into serious pneumonia with reduced lymphocytes and aberrant inflammatory response (p = 0.001). The expression level of ACE2 and lung progenitor cell markers were generally decreased in older patients. Notably, ACE2 positive cells were mainly distributed in the alveolar region, including SFTPC positive cells, but rarely in airway regions in the older adults (p < 0.01). The follow-up of discharged patients revealed a prolonged recovery from pneumonia in the older (p < 0.025). Conclusion Compared to children, ACE2 positive cells are generally decreased in older adults and mainly presented in the lower pulmonary tract. The lung progenitor cells are also decreased. These risk factors may impact disease severity and recovery from pneumonia caused by SARS-Cov-2 infection in older patients.

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Clinical Characteristics, Risk Factors and Predictive Value of COVID-19 Pneumonia: A Retrospective Study of 173 Patients in Wuhan, China

10.21203/rs.3.rs-76134/v1 ◽

2020 ◽

Author(s):

Yang Zhang ◽

Jun Xue ◽

Mi Yan ◽

Jing Chen ◽

Hai Liu ◽

...

Keyword(s):

Risk Factors ◽

Predictive Model ◽

Disease Severity ◽

Roc Curve ◽

Predictive Value ◽

Older Patients ◽

Clinical Characteristics ◽

Lactic Dehydrogenase ◽

Older Age ◽

Hospital Outcome

Abstract Background: COVID-19 is a globally emerging infectious disease. As the global epidemic continues to spread, the risk of COVID-19 transmission and diffusion in the world will also remain. Currently, several studies describing its clinical characteristics have focused on the initial outbreak, but rarely to the later stage. Here we described clinical characteristics, risk factors for disease severity and in-hospital outcome in patients with COVID-19 pneumonia from Wuhan. Methods: Patients with COVID-19 pneumonia admitted to Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from February 13 to March 8, 2020, were retrospectively enrolled. Multivariable logistic regression analysis was used to identify risk factors for disease severity and in-hospital outcome and establish predictive models. Receiver operating characteristic (ROC) curve was used to assess the predictive value of above models.Results: 106 (61.3%) of the patients were female. The mean age of study populations was 62.0 years, of whom 73 (42.2%) had underlying comorbidities mainly including hypertension (24.9%). The most common symptoms on admission were fever (67.6%) and cough (60.1%), digestive symptoms (22.0%) was also very common. Older age (OR: 3.420; 95%Cl: 1.415-8.266; P=0.006), diarrhea (OR: 0.143; 95%Cl: 0.033-0.611; P=0.009) and lymphopenia (OR: 4.769; 95%Cl: 2.019-11.266; P=0.000) were associated with severe illness on admission; the area under the ROC curve (AUC) of predictive model were 0.860 (95%CI: 0.802-0.918; P=0.000). Older age (OR: 0.309; 95%Cl: 0.142-0.674; P=0.003), leucopenia (OR: 0.165; 95%Cl: 0.034-0.793; P=0.025), increased lactic dehydrogenase (OR: 0.257; 95%Cl: 0.100-0.659; P=0.005) and interleukins-6 levels (OR: 0.294; 95%Cl: 0.099-0.872; P=0.027) were associated with poor in-hospital outcome; AUC of predictive model were 0.752 (95%CI: 0.681-0.824; P=0.000).Conclusion: Older patients with diarrhea and lymphopenia need early identification and timely intervention to prevent the progression to severe COVID-19 pneumonia. However, older patients with leucopenia, increased lactic dehydrogenase and interleukins-6 levels are at a high risk for poor in-hospital outcome.Trial registration: ChiCTR2000029549

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Endothelial progenitor cells: novel biomarker and promising cell therapy for cardiovascular disease

Clinical Science ◽

10.1042/cs20100429 ◽

2010 ◽

Vol 120 (7) ◽

pp. 263-283 ◽

Cited By ~ 127

Author(s):

Shaundeep Sen ◽

Stephen P. McDonald ◽

P. Toby H. Coates ◽

Claudine S. Bonder

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Disease Risk ◽

Ex Vivo ◽

Individual Risk ◽

Vascular Risk ◽

Vascular Control ◽

Endothelial Progenitor

Bone-marrow-derived EPCs (endothelial progenitor cells) play an integral role in the regulation and protection of the endothelium, as well as new vessel formation. Peripheral circulating EPC number and function are robust biomarkers of vascular risk for a multitude of diseases, particularly CVD (cardiovascular disease). Importantly, using EPCs as a biomarker is independent of both traditional and non-traditional risk factors (e.g. hypertension, hypercholesterolaemia and C-reactive protein), with infused ex vivo-expanded EPCs showing potential for improved endothelial function and either reducing the risk of events or enhancing recovery from ischaemia. However, as the number of existing cardiovascular risk factors is variable between patients, simple EPC counts do not adequately describe vascular disease risk in all clinical conditions and, as such, the risk of CVD remains. It is likely that this limitation is attributable to variation in the definition of EPCs, as well as a difference in the interaction between EPCs and other cells involved in vascular control such as pericytes, smooth muscle cells and macrophages. For EPCs to be used regularly in clinical practice, agreement on definitions of EPC subtypes is needed, and recognition that function of EPCs (rather than number) may be a better marker of vascular risk in certain CVD risk states. The present review focuses on the identification of measures to improve individual risk stratification and, further, to potentially individualize patient care to address specific EPC functional abnormalities. Herein, we describe that future therapeutic use of EPCs will probably rely on a combination of strategies, including optimization of the function of adjunct cell types to prime tissues for the effect of EPCs.

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Roux-en-Y Reconstruction Following Distal Gastrectomy Reduced Endoscopic Reflux Esophagitis in Older Adults: Propensity Score–Matching Analysis

International Surgery ◽

10.9738/intsurg-d-20-00045.1 ◽

2021 ◽

Vol 105 (1-3) ◽

pp. 705-713

Author(s):

Mikito Inokuchi ◽

Taichi Ogo ◽

Shunsuke Kato ◽

Hiroto Nagano ◽

Takumi Irie ◽

...

Keyword(s):

Risk Factors ◽

Older Adults ◽

Reflux Esophagitis ◽

Older Patients ◽

Distal Gastrectomy ◽

Bile Reflux ◽

Clinical Findings ◽

Patients Âgés ◽

Billroth I ◽

Reconstruction Methods

Objective This study aimed to examine the functional outcomes of Roux-en-Y (RY) and Billroth I (BI) reconstruction methods following distal gastrectomy in patients ages ≥75 years with gastric cancer. Summary of background data RY and BI reconstructions are commonly performed after distal gastrectomy. However, no study has compared the 2 procedures in older adults. Methods We identified older patients who underwent RY (n = 103) or BI (n = 71) reconstruction following distal gastrectomy from 2011 to 2018 in our database. Patients in the RY and BI groups were matched by propensity scores, and each group included 62 patients. We compared short-term surgical outcomes and clinical findings at 1 year postoperatively. Additionally, risk factors for endoscopic reflux esophagitis following distal gastrectomy were evaluated. Results Reflux esophagitis, bile reflux, and remnant gastritis were significantly less frequent in RY reconstruction than in BI reconstruction. Moreover, both BI reconstruction and preoperative hiatus hernias were independent risk factors for postoperative endoscopic reflux esophagitis. Although the incidence of postoperative surgical complications following RY and BI was similar, RY was found to cause delayed gastric emptying more frequently than BI. Conclusion RY reconstruction is a favorable procedure to prevent reflux esophagitis in older patients, particularly in those with hiatal hernia.

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Telomere length and associated factors in older adults with hypertension

Journal of International Medical Research ◽

10.1177/0300060519882570 ◽

2019 ◽

Vol 47 (11) ◽

pp. 5465-5474 ◽

Cited By ~ 3

Author(s):

Pan Liu ◽

Yaxin Zhang ◽

Lina Ma

Keyword(s):

Risk Factors ◽

Older Adults ◽

Chronic Disease ◽

Telomere Length ◽

Psychological Factors ◽

Older Patients ◽

Associated Factors ◽

Molecular Mechanisms ◽

Telomerase Activity ◽

Pubmed Search

Telomeres and telomerase play important roles in the occurrence and development of hypertension. This review was performed to clarify the factors that influence telomere length and telomerase activity in older patients and elucidate the association of these factors with hypertension. A PubMed search and critical review of studies assessing the risk factors underlying the association of hypertension with telomere length and telomerase activity was performed. Telomere length and telomerase activity were found to be associated with hypertension. The factors that influence telomere length and telomerase activity in older patients with hypertension include genetics, demographics, social and environmental factors, chronic disease, psychological factors, and antihypertensive drug treatment. A better understanding of the molecular mechanisms underlying the association of hypertension with telomere length and telomerase activity may help to reduce the incidence of hypertension.

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Sarcopenia and Charlson Comorbidity Index are Risk Factors for Short-Term Postoperative Prognosis of Elderly Patients with Gastrointestinal Tumor: A Retrospective Study

10.21203/rs.3.rs-689510/v1 ◽

2021 ◽

Author(s):

Jiaqiu Wang ◽

Liqian Xu ◽

Shunmei Huang ◽

Quan Hui ◽

Xuexue Shi ◽

...

Keyword(s):

Risk Factors ◽

Older Adults ◽

Charlson Comorbidity Index ◽

Older Patients ◽

Gastrointestinal Tumor ◽

Short Term ◽

Postoperative Prognosis ◽

History Of ◽

Comorbidity Index ◽

Independent Risk Factors

Abstract Background Sarcopenia is one of the most common syndromes in the older adults. Gastrointestinal tumor is a malignant disease with high incidence. This study aimed to investigate the risk factors of sarcopenia in older adults with gastrointestinal tumor, the prognostic indicators of and short-term outcomes after resection for gastrointestinal tumor, and to explore the relationship between sarcopenia and short-term postoperative prognosis.Method A total of 247 older patients with gastrointestinal tumors who underwent radical resection in 2019 were included in this study. Relevant indexes were calculated using L3 slice image of computed tomography (CT) to evaluate sarcopenia. Short-term postoperative complications and length of stay were considered as short-term outcome of this study.Results Advanced age, lower higher body mass index (BMI), lower hemoglobin, having history of abdominal surgery and higher visceral fat index (VFI) were risk factors of sarcopenia, while higher BMI and lower subcutaneous fat index (SFI) were protective factors of sarcopenia. Further multivariate logistic regression analysis showed that having history of abdominal surgery, advanced age and lower BMI were independent risk factors. Sarcopenia and higher Charlson comorbidity index were independent risk factors of short-term postoperative complications in the elderly with gastrointestinal tumor. Higher Charlson comorbidity index gave rise to longer length of stay.ConclusionsSarcopenia and higher Charlson comorbidity index predict poor short-term prognosis of older patients undergoing gastrointestinal tumor resection.

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Risk factors for falls in older patients with cancer

BMJ Supportive & Palliative Care ◽

10.1136/bmjspcare-2017-001388 ◽

2017 ◽

Vol 8 (1) ◽

pp. 34-37 ◽

Cited By ~ 13

Author(s):

Xiaotao Zhang ◽

Ming Sun ◽

Suyu Liu ◽

Cheuk Hong Leung ◽

Linda Pang ◽

...

Keyword(s):

Risk Factors ◽

Social Support ◽

Older Adults ◽

Logistic Regression ◽

Major Depression ◽

Functional Impairment ◽

Older Patients ◽

Patients With Cancer ◽

Number Of Patients ◽

Risk Factors For Falls

ObjectivesA rising number of patients with cancer are older adults (65 years of age and older), and this proportion will increase to 70% by the year 2020. Falls are a common condition in older adults. We sought to assess the prevalence and risk factors for falls in older patients with cancer.MethodsThis is a single-site, retrospective cohort study. Patients who were receiving cancer care underwent a comprehensive geriatric assessments, including cognitive, functional, nutritional, physical, falls in the prior 6 months and comorbidity assessment. Vitamin D and bone densitometry were performed.AnalysisDescriptive statistics and multivariable logistic regression.ResultsA total of 304 patients aged 65 or above were enrolled in this study. The mean age was 78.4±6.9 years. They had haematological, gastrointestinal, urological, breast, lung and gynaecological cancers. A total of 215 patients with available information about falls within the past 6 months were included for final analysis. Seventy-seven (35.8%) patients had at least one fall in the preceding 6 months. Functional impairment (p=0.048), frailty (p<0.001), dementia (p=0.021), major depression (p=0.010) and low social support (p=0.045) were significantly associated with the fall status in the univariate analysis. Multivariate logistic regression analysis identified frailty and functional impairment to be independent risk factors for falls.ConclusionsFalls are common in older patients with cancer and lead to adverse clinical outcomes. Major depression, functional impairment, frailty, dementia and low social support were risk factors for falls. Heightened awareness and targeted interventions can prevent falls in older patients with cancer.

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Low muscle mass and Charlson comorbidity index are risk factors for short-term postoperative prognosis of elderly patients with gastrointestinal tumor: a cross-sectional study

BMC Geriatrics ◽

10.1186/s12877-021-02683-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jiaqiu Wang ◽

Liqian Xu ◽

Shunmei Huang ◽

Quan Hui ◽

Xuexue Shi ◽

...

Keyword(s):

Risk Factors ◽

Older Adults ◽

Muscle Mass ◽

Charlson Comorbidity Index ◽

Older Patients ◽

Gastrointestinal Tumor ◽

Short Term ◽

History Of ◽

Comorbidity Index ◽

Independent Risk Factors

Abstract Background Sarcopenia is one of the most frequent syndromes in older adults and one of its main characteristics is low muscle mass. Gastrointestinal tumor is a malignant disease with high incidence. This study aimed to investigate the risk factors of low muscle mass in older adults with gastrointestinal tumor, the prognostic indicators of and short-term outcomes after resection for gastrointestinal tumor, and to explore the relationship between low muscle mass and short-term postoperative prognosis. Method A total of 247 older patients with gastrointestinal tumors who underwent radical resection in 2019 were included in this study. Relevant indexes were calculated using L3 slice image of computed tomography (CT) to evaluate low muscle mass. Short-term postoperative complications and length of stay were considered as short-term outcomes of this study. Results Advanced age, lower higher body mass index (BMI), lower hemoglobin, having history of abdominal surgery and higher visceral fat index (VFI) were risk factors of low muscle mass, while higher BMI and lower subcutaneous fat index (SFI) were protective factors of low muscle mass. Further multivariate logistic regression analysis showed that having history of abdominal surgery, advanced age and lower BMI were independent risk factors. Low muscle mass and higher Charlson comorbidity index were independent risk factors of short-term postoperative complications in older adults with gastrointestinal tumor. Higher Charlson comorbidity index gave rise to longer length of stay. Conclusions Low muscle mass and higher Charlson comorbidity index predict poor short-term prognosis of older patients undergoing gastrointestinal tumor resection.

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Characteristics and Outcomes of Younger Adults with Embolic Stroke of Undetermined Source (ESUS): A Retrospective Study

Stroke Research and Treatment ◽

10.1155/2019/4360787 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6

Author(s):

Ali M. Al Khathaami ◽

Bayan Al Bdah ◽

Abdulmjeed Alnosair ◽

Abdulkarim Alturki ◽

Rayan Alrebdi ◽

...

Keyword(s):

Risk Factors ◽

Older Adults ◽

Retrospective Study ◽

Length Of Stay ◽

Older Patients ◽

Embolic Stroke ◽

Stroke Severity ◽

Median Length ◽

Younger Adults ◽

Significant Difference

Introduction. Embolic stroke of undetermined source (ESUS) in younger adults may have different risk factors compared with ESUS in elderly, and the approach to ESUS in young adults may require new therapies. We aimed to investigate the characteristics and outcomes in younger adults with ESUS at a single centre in Saudi Arabia. Patients and Methods. A retrospective study was conducted using the medical records of younger adults with ESUS according to the criteria of the Cryptogenic Stroke/ESUS International Working Group. Younger adults (aged ≤50 years) with ESUS were compared with older patients, on admission and discharge from hospital, using the modified Rankin scale (mRS) and the National Institute of Health Stroke Scale (NIHSS). Results. Among 147 patients with ESUS, 39 (26.5%) were younger adults. Younger adults compared with older adults with ESUS had fewer vascular risk factors, including lower rates of hypertension (43.6% vs. 70.3%; P=0.004), diabetes (35.9% vs. 57.4%; P=0.03), and dyslipidaemia (12.8% vs. 28.7%; P=0.05). There was no significant difference in poor outcome at discharge (defined as mRS > 2), which was observed in 17.9% of younger adults and 28.7% of older adults. Further, there were no significant differences in stroke severity at discharge (NIHSS score ≤5) or median length of stay. Discussion. Although the outcomes of ESUS do not differ between younger and older patients, younger patients have fewer identified risk factors. Conclusion. This study showed that 26.5% of patients with ESUS were aged ≤50 years. Although younger adults with ESUS had fewer risk factors, there were no significant differences in neurologic disability or mortality at discharge, stroke severity, or median length of stay.

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BACTERIAL PNEUMONIA IS A POSSIBLE RISK FACTOR FOR ORAL CANDIDIASIS IN OLDER ADULTS: A RETROSPECTIVE COHORT STUDY.

Innovation in Aging ◽

10.1093/geroni/igz038.3189 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S869-S869

Author(s):

Masato Nakajima ◽

Yojiro Umezaki ◽

Masahiro Yamaguchi ◽

Michiko Makino ◽

Nao suzuki ◽

...

Keyword(s):

Risk Factors ◽

Older Adults ◽

Pseudomonas Aeruginosa ◽

Risk Factor ◽

Klebsiella Pneumoniae ◽

Aspiration Pneumonia ◽

Older Patients ◽

Bacterial Pneumonia ◽

Oral Candidiasis ◽

Care Hospital

Abstract Both aspiration pneumonia and oral candidiasis are caused by opportunistic infection of intraoral commensals and have many similar risk factors linked to oral health in older adults. Candida albicans forms biofilms with respiratory bacteria such as Klebsiella pneumoniae and Pseudomonas aeruginosa. The aim of our study was to determine the relationship between bacterial pneumonia, including aspiration pneumonia, and oral candidiasis in older patients who were hospitalized with several systemic diseases in a community-based acute care hospital without a dental unit. We retrospectively analyzed 228 older patients (male: 105, female: 123) using multiple logistic regression. The mean age of the patients was 81.3 (SD: 11.1) years. Forty-four patients were oral candidiasis positive, and 78 patients suffered from bacterial pneumonia, including aspiration pneumonia. Results showed that bacterial pneumonia had the strongest statistical relationship with oral candidiasis (p=0.000, OR: 5.173, 95 % CI: 2.368–11.298). This was followed by poor oral hygiene (p=0.001, OR: 6.095, 95 % CI: 2.003–18.545) and severe dry mouth (p=0.043, OR: 2.507, 95 % CI: 1.031–6.098). Other conventional risk factors for oral candidiasis, such as diabetes mellitus, denture wearer, dysphagia, malnutrition, requiring care, use of inhalation steroids, were not statistically significant in this study. Fifteen species of bacteria, including Klebsiella pneumoniae and Pseudomonas aeruginosa, were detected by pharyngeal sputum culture in 24 of 31 patients who were diagnosed with both oral candidiasis and bacterial pneumonia. In conclusion, bacterial pneumonia is a possible new risk factor for oral candidiasis in older adults.

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Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

Clinical Science ◽

10.1042/cs20190999 ◽

2019 ◽

Vol 133 (22) ◽

pp. 2283-2299

Author(s):

Apabrita Ayan Das ◽

Devasmita Chakravarty ◽

Debmalya Bhunia ◽

Surajit Ghosh ◽

Prakash C. Mandal ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Chronic Inflammation ◽

Ex Vivo ◽

Human Subjects ◽

Critical Role ◽

Atherosclerotic Cardiovascular Disease ◽

Tnf Α ◽

Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

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