RESUMO
BACKGROUND: Previous serological studies have indicated an association between viruses and atypical pathogens and Chronic Fatigue Syndrome (CFS). This study aims to investigate the correlation between infections from common pathogens, including typical bacteria, and the subsequent risk of developing CFS. The analysis is based on data from Taiwan's National Health Insurance Research Database. METHODS: From 2000 to 2017, we included a total of 395,811 cases aged 20 years or older newly diagnosed with infection. The cases were matched 1:1 with controls using a propensity score and were followed up until diagnoses of CFS were made. RESULTS: The Cox proportional hazards regression analysis was used to estimate the relationship between infection and the subsequent risk of CFS. The incidence density rates among non-infection and infection population were 3.67 and 5.40 per 1000 person-years, respectively (adjusted hazard ratio [HR] = 1.5, with a 95% confidence interval [CI] 1.47-1.54). Patients infected with Varicella-zoster virus, Mycobacterium tuberculosis, Escherichia coli, Candida, Salmonella, Staphylococcus aureus and influenza virus had a significantly higher risk of CFS than those without these pathogens (p < 0.05). Patients taking doxycycline, azithromycin, moxifloxacin, levofloxacin, or ciprofloxacin had a significantly lower risk of CFS than patients in the corresponding control group (p < 0.05). CONCLUSION: Our population-based retrospective cohort study found that infection with common pathogens, including bacteria, viruses, is associated with an increased risk of developing CFS.
Assuntos
Síndrome de Fadiga Crônica , Humanos , Síndrome de Fadiga Crônica/complicações , Síndrome de Fadiga Crônica/epidemiologia , Estudos Retrospectivos , Estudos de Coortes , Modelos de Riscos Proporcionais , Incidência , Escherichia coliRESUMO
OBJECTIVE: An increased prevalence of psychiatric comorbidities (including depression and anxiety disorder) has been observed among patients with chronic fatigue syndrome (CFS). However, few studies have examined the presence of depression and anxiety disorder before the diagnosis of CFS. This study aimed to clarify the preexisting comorbidities and treatments associated with patients with subsequent CFS diagnosis in a population-based cohort in Taiwan. METHODS: An analysis utilizing the National Health Insurance Research Database of Taiwan was conducted. Participants included were 6303 patients with CFS newly diagnosed between 2000 and 2010 and 6303 age-/sex-matched controls. RESULTS: Compared with the control group, the CFS group had a higher prevalence of depression and anxiety disorder before the diagnosis of CFS. Sampled patients who took specific types of antidepressants, namely, selective serotonin reuptake inhibitors (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI] 1.04-1.39), serotonin antagonists and reuptake inhibitors (SARI; aOR = 1.87, 95% CI 1.59-2.19), and tricyclic antidepressants (aOR = 1.46, 95% CI 1.09-1.95), had an increased risk of CFS. CFS risk was also higher among participants taking benzodiazepine, muscle relaxants, and analgesic drugs. A sub-group analysis revealed that SARI use was related to an increased risk of CFS in the depression, anxiety disorder, male, and female groups. In the depression and anxiety disorder groups, analgesic drug use was associated with an increased CFS risk. Nonpharmacological treatment administration differed between men and women. CONCLUSION: This population-based retrospective cohort study revealed an increased risk of CFS among populations with preexisting depression and anxiety disorder, especially those taking SARI and analgesic drugs.
Assuntos
Síndrome de Fadiga Crônica , Humanos , Masculino , Feminino , Síndrome de Fadiga Crônica/complicações , Síndrome de Fadiga Crônica/diagnóstico , Síndrome de Fadiga Crônica/tratamento farmacológico , Depressão/complicações , Depressão/diagnóstico , Depressão/tratamento farmacológico , Estudos Retrospectivos , Taiwan/epidemiologia , Transtornos de Ansiedade , AnsiedadeRESUMO
BACKGROUND: Blood shortage is a persistent problem affecting Taiwan's health-care system. The theory of planned behavior (TPB) has been commonly used in studies of health advocacy. The purpose of this study was to develop a questionnaire measuring clinicians' intention to prescribe transfusion based on the TPB. METHOD: A questionnaire comprising 15 items for assessing clinicians' intention to prescribe blood transfusion was developed, and it collected demographic characteristics, tested patient blood management (PBM) and perceived knowledge of PBM. Furthermore, the questionnaire contained four subscales related to the TPB. A total of 129 clinicians participated in this pilot study between July and December2020. Item analysis and exploratory factor analysis were conducted to examine the validity and reliability of this measurement instrument. RESULTS: The results indicated no statistically significant correlations between the demographic characteristics and PBM test scores. Regarding perceived knowledge, the results of a one-way analysis of variance revealed that the effect of age, hierarchy of doctors, and education level were significant. In terms of subjective norms, a significant effect on education level was noted [t (129) = 2.28, p < 0.05], with graduate school graduates receiving higher scores than college graduates. An analysis of variance demonstrated the effects of hierarchy, education level, and medical specialty on perceived behavioral control. The results of the regression analyses revealed that perceived knowledge (ß = 0.32, p < 0.01) and subjective norms (ß = 0.22, p < 0.05) were significantly related to clinicians' behavioral intentions. CONCLUSIONS: This study revealed that factors affecting clinicians' blood transfusion management can be explained using the TPB-based questionnaire. This study demonstrated that physicians' perceptions of whether most people approve of PBM and their self-assessment of their PBM knowledge affect their intentions to proceed with PBM. According to this finding, a support system among physicians must be established and maintained to increase physicians' confidence in promoting PBM.
Assuntos
Intenção , Médicos , Humanos , Projetos Piloto , Reprodutibilidade dos Testes , Teoria do Comportamento Planejado , Transfusão de SangueRESUMO
BACKGROUND: This study aims to provide 12-year nationwide epidemiology data to investigate the epidemiology and comorbidities of and therapeutic options for chronic fatigue syndrome (CFS) by analyzing the National Health Insurance Research Database. METHODS: 6306 patients identified as having CFS during the 2000-2012 period and 6306 controls (with similar distributions of age and sex) were analyzed. RESULT: The patients with CFS were predominantly female and aged 35-64 years in Taiwan and presented a higher proportion of depression, anxiety disorder, insomnia, Crohn's disease, ulcerative colitis, renal disease, type 2 diabetes, gout, dyslipidemia, rheumatoid arthritis, Sjogren syndrome, and herpes zoster. The use of selective serotonin receptor inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), Serotonin antagonist and reuptake inhibitors (SARIs), Tricyclic antidepressants (TCAs), benzodiazepine (BZD), Norepinephrine-dopamine reuptake inhibitors (NDRIs), muscle relaxants, analgesic drugs, psychotherapies, and exercise therapies was prescribed significantly more frequently in the CFS cohort than in the control group. CONCLUSION: This large national study shared the mainstream therapies of CFS in Taiwan, we noticed these treatments reported effective to relieve symptoms in previous studies. Furthermore, our findings indicate that clinicians should have a heightened awareness of the comorbidities of CFS, especially in psychiatric problems.
Assuntos
Diabetes Mellitus Tipo 2 , Síndrome de Fadiga Crônica , Antidepressivos Tricíclicos/farmacologia , Antidepressivos Tricíclicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Síndrome de Fadiga Crônica/tratamento farmacológico , Síndrome de Fadiga Crônica/epidemiologia , Feminino , Humanos , Masculino , Norepinefrina , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêuticoRESUMO
BACKGROUND: The circadian system is responsible for regulating various physiological activities and behaviors and has been gaining recognition. The circadian rhythm is adjusted in a 24-h cycle and has transcriptional-translational feedback loops. When the circadian rhythm is interrupted, affecting the expression of circadian genes, the phenotypes of diseases could amplify. For example, the importance of maintaining the internal temporal homeostasis conferred by the circadian system is revealed as mutations in genes coding for core components of the clock result in diseases. This study will investigate the association between circadian genes and metabolic syndromes in a Taiwanese population. METHODS: We performed analysis using whole-genome sequencing, read vcf files and set target circadian genes to determine if there were variants on target genes. In this study, we have investigated genetic contribution of circadian-related diseases using population-based next generation whole genome sequencing. We also used significant SNPs to create a metabolic syndrome prediction model. Logistic regression, random forest, adaboost, and neural network were used to predict metabolic syndrome. In addition, we used random forest model variables importance matrix to select 40 more significant SNPs, which were subsequently incorporated to create new prediction models and to compare with previous models. The data was then utilized for training set and testing set using five-fold cross validation. Each model was evaluated with the following criteria: area under the receiver operating characteristics curve (AUC), precision, F1 score, and average precision (the area under the precision recall curve). RESULTS: After searching significant variants, we used Chi-Square tests to find some variants. We found 186 significant SNPs, and four predicting models which used 186 SNPs (logistic regression, random forest, adaboost and neural network), AUC were 0.68, 0.8, 0.82, 0.81 respectively. The F1 scores were 0.412, 0.078, 0.295, 0.552, respectively. The other three models which used the 40 SNPs (logistic regression, adaboost and neural network), AUC were 0.82, 0.81, 0.81 respectively. The F1 scores were 0.584, 0.395, 0.574, respectively. CONCLUSIONS: Circadian gene defect may also contribute to metabolic syndrome. Our study found several related genes and building a simple model to predict metabolic syndrome.
Assuntos
Inteligência Artificial , Síndrome Metabólica , Ritmo Circadiano , Humanos , Síndrome Metabólica/genética , Redes Neurais de Computação , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Chronic fatigue syndrome (CFS) has been shown to be associated with infections. Tuberculosis (TB) is a highly prevalent infectious disease. Patients with chronic fatigue syndrome and post-tuberculosis experience similar symptoms. Furthermore, chronic fatigue syndrome and tuberculosis share similar plasma immunosignatures. This study aimed to clarify the risk of chronic fatigue syndrome following the diagnosis of Mycobacterium tuberculosis infection (MTI), by analyzing the National Health Insurance Research Database of Taiwan. METHODS: 7666 patients aged 20 years or older with newly diagnosed Mycobacterium tuberculosis infection during 2000-2011 and 30,663 participants without Mycobacterium tuberculosis infection were identified. Both groups were followed up until the diagnoses of chronic fatigue syndrome were made at the end of 2011. RESULTS: The relationship between Mycobacterium tuberculosis infection and the subsequent risk of chronic fatigue syndrome was estimated through Cox proportional hazards regression analysis, with the incidence density rates being 3.04 and 3.69 per 1000 person-years among the non-Mycobacterium tuberculosis infection and Mycobacterium tuberculosis infection populations, respectively (adjusted hazard ratio [HR] = 1.23, with 95% confidence interval [CI] 1.03-1.47). In the stratified analysis, the Mycobacterium tuberculosis infection group were consistently associated with a higher risk of chronic fatigue syndrome in the male sex (HR = 1.27, 95% CI 1.02-1.58) and age group of ≥ 65 years old (HR = 2.50, 95% CI 1.86-3.38). CONCLUSIONS: The data from this population-based retrospective cohort study revealed that Mycobacterium tuberculosis infection is associated with an elevated risk of subsequent chronic fatigue syndrome.
Assuntos
Síndrome de Fadiga Crônica , Tuberculose , Adulto , Idoso , Estudos de Coortes , Síndrome de Fadiga Crônica/complicações , Humanos , Incidência , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Tuberculose/complicações , Tuberculose/epidemiologia , Adulto JovemRESUMO
BACKGROUND: This study aims to provide 14-year nationwide epidemiology data to evaluate the incidence ratio of APS in Taiwan and the condition of comorbidities by analyzing the National Health Insurance Research Database. METHODS: Nineteen thousand one hundred sixty-three patients newly diagnosed as having APS during the 2000-2013 period and 76,652 controls (with similar distributions of age and sex) were analyzed. RESULTS: The incidence of APS increased from 4.87 to 6.49 per 10,000 person-years in the Taiwan population during 2000-2013. The incidence of APS increased with age after 20 years old, especially in the female population, and it rose rapidly after age over 60 years old. In addition, APS cohorts presented a higher proportion of diabetes mellitus, hypertension, hyperlipidemia, stroke, heart failure, atrial fibrillation, myocardial infarction, PAOD, chronic kidney disease, COPD, deep vein thrombosis, pulmonary embolism, SLE, rheumatoid arthritis, Sjogren's syndrome, and polymyositis. CONCLUSIONS: Our study indicated an increasing trend in APS incidence among the Taiwanese population and a relationship between APS and potential comorbidities. This large national study found that the APS risk is heavily influenced by sex and age. Thus, the distinctive sex and age patterns might be constructive given exploring potential causal mechanisms. Furthermore, our findings indicate that clinicians should have a heightened awareness of the probability of APS, especially in women in certain age groups presenting with symptoms of APS.
RESUMO
BACKGROUND: Influenza vaccine manufacturers traditionally use egg-derived candidate vaccine viruses (CVVs) to produce high-yield influenza viruses for seasonal or pandemic vaccines; however, these egg-derived CVVs need an adaptation process for the virus to grow in mammalian cells. The low yields of cell-based manufacturing systems using egg-derived CVVs remain an unsolved issue. This study aimed to develop high-growth cell-derived CVVs for MDCK cell-based vaccine manufacturing platforms. METHODS: Four H7N9 CVVs were generated in characterized Vero and adherent MDCK (aMDCK) cells. Furthermore, reassortant viruses were amplified in adherent MDCK (aMDCK) cells with certification, and their growth characteristics were detected in aMDCK cells and new suspension MDCK (sMDCK) cells. Finally, the plaque-forming ability, biosafety, and immunogenicity of H7N9 reassortant viruses were evaluated. RESULTS: The HA titers of these CVVs produced in proprietary suspension MDCK (sMDCK) cells and chicken embryos were 2- to 8-fold higher than those in aMDCK cells. All H7N9 CVVs showed attenuated characteristics by trypsin-dependent plaque assay and chicken embryo lethality test. The alum-adjuvanted NHRI-RG5 (derived from the fifth wave H7N9 virus A/Guangdong/SP440/2017) vaccine had the highest immunogenicity and cross-reactivity among the four H7N9 CVVs. Finally, we found that AddaVax adjuvant improved the cross-reactivity of low pathogenic H7N9 virus against highly pathogenic H7N9 viruses. CONCLUSIONS: Our study indicates that cell-derived H7N9 CVVs possessed high growth rate in new sMDCK cells and low pathogenicity in chicken embryo, and that CVVs generated by this platform are also suitable for both cell- and egg-based prepandemic vaccine production.
Assuntos
Imunização , Subtipo H7N9 do Vírus da Influenza A/imunologia , Vacinas contra Influenza/química , Influenza Humana/prevenção & controle , Vírus Reordenados/imunologia , Animais , Embrião de Galinha , Cães , Humanos , Subtipo H7N9 do Vírus da Influenza A/genética , Células Madin Darby de Rim Canino , Vírus Reordenados/genéticaRESUMO
BACKGROUND: The onset of chronic fatigue syndrome (CFS) has been shown to be associated with several immunological conditions such as infections or atopy. The aim of this study was to clarify the risk of chronic fatigue syndrome following the diagnosis of psoriasis, an immune-related dermatological disease, by analyzing the National Health Insurance Research Database of Taiwan. METHOD: 2616 patients aged 20 years or older with newly diagnosed psoriasis during 2004-2008 and 10,464 participants without psoriasis were identified. Both groups were followed up until the diagnoses of CFS were made at the end of 2011. RESULTS: The relationship between psoriasis and the subsequent risk of CFS was estimated through Cox proportional hazards regression analysis, with the incidence density rates being 2.27 and 3.58 per 1000 person-years among the non-psoriasis and psoriasis populations, respectively (adjusted hazard ratio [HR] = 1.48, with 95% confidence interval [CI] 1.07-2.06). In the stratified analysis, the psoriasis group were consistently associated with a higher risk of CFS in male sex (HR = 2.05, 95% CI 1.31-3.20) and age group of ≥ 60 years old (HR = 2.32, 95% CI 1.33-4.06). In addition, we discovered that the significantly increased risk of CFS among psoriasis patients is attenuated after they receive phototherapy and/or immunomodulatory drugs. CONCLUSIONS: The data from this population-based retrospective cohort study revealed that psoriasis is associated with an elevated risk of subsequent CFS, which is differentiated by sex and age.
Assuntos
Síndrome de Fadiga Crônica/epidemiologia , Síndrome de Fadiga Crônica/etiologia , Psoríase/complicações , Adulto , Estudos de Coortes , Comorbidade , Intervalos de Confiança , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Índice de Gravidade de Doença , Taiwan/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Similarities in the symptoms of chronic fatigue syndrome (CFS) and inflammatory bowel disease (IBD) have been observed as follows: severe disease activity in IBD correlates with severe fatigue, major psychiatric signs, the common use of medication, and bacterial translocation. One of several hypotheses for explaining the mechanisms underlying CFS suggests a similarity to the impaired intestinal mucosa of IBD. "This study investigated the risk of incident CFS among patients with IBD". METHODS: We conducted a population-based retrospective cohort study by using Taiwan's National Health Insurance Research Database to evaluate the subsequent risk of CFS in patients with IBD, according to demographic characteristics and comorbidities. The exposure cohort comprised 2163 patients with new diagnoses of IBD. Each patient was randomly selected and frequency matching according to gender and age with four participants from the general population who had no history of CFS at the index date (control cohort). Cox proportional hazards regression analysis was conducted to estimate the relationship between IBD and the subsequent risk of CFS. RESULTS: The exposure cohort had a significantly higher overall risk of subsequent CFS than that of the control group [adjusted hazard ratio (Christophi in Inflamm Bowel Dis 18(12):2342-2356, 2012) = 2.25, 95%, confidence interval (Aaron and Buchwald in Ann Intern Med 134(9 Pt 2):868-881, 2001; Farraye et al. in Am J Gastroenterol 112:241, 2017) 1.70-2.99]. Further analysis indicated a significantly higher risk of CFS in patients who were male (HR = 3.23, 95% CI 2.12-4.91), were older than 35 years, and had IBD but without comorbidity status, e.g. Cancers, diabetes, obesity, depression, anxiety, sleep disorder, renal disease (HR = 2.50, 95% CI 1.63-3.84) after adjustment. CONCLUSION: The findings from this population-based retrospective cohort study suggest that IBD, especially Crohn's disease, is associated with an increased risk of subsequent CFS.
Assuntos
Síndrome de Fadiga Crônica/complicações , Síndrome de Fadiga Crônica/epidemiologia , Doenças Inflamatórias Intestinais/complicações , Translocação Bacteriana , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologiaRESUMO
BACKGROUND: The overlapping symptoms and pathophysiological similarities between burn injury and chronic fatigue syndrome (CFS) are noteworthy. Thus, this study explores the possible association between burn injury and the subsequent risk of CFS. METHOD: We used data from the Taiwan National Health Insurance system to address the research topic. The exposure cohort comprised of 17,204 patients with new diagnoses of burn injury. Each patient was frequency matched according to age, sex, index year, and comorbidities with four participants from the general population who did not have a history of CFS (control cohort). Cox proportional hazards regression analysis was conducted to estimate the relationship between burn injury and the risk of subsequent CFS. RESULT: The incidence of CFS in the exposure and control cohorts was 1.61 and 0.86 per 1000 person-years, respectively. The exposure cohort had a significantly higher overall risk of subsequent CFS than did the control cohort (adjusted hazard ratio [HR] = 1.48, 95% confidence interval [CI] = 1.41-1.56). The risk of CFS in patients with burn injury in whichever stratification (including sex, age, and comorbidity) was also higher than that of the control cohort. CONCLUSION: The findings from this population-based retrospective cohort study suggest that thermal injury is associated with an increased risk of subsequent CFS and provided a point of view suggesting burn injuries in sun- exposed areas such as the face and limbs had greater impact on subsequent development of CFS compared with trunk areas. In addition, extensively burned areas and visible scars were predictors of greater physiological and psychosocial that are needed to follow-up in the long run.
Assuntos
Queimaduras/complicações , Síndrome de Fadiga Crônica/epidemiologia , Síndrome de Fadiga Crônica/etiologia , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) is a key conjugating enzyme of bilirubin and the anti-tumor medication irinotecan. Comprehensive analysis of UGT1A1 gene polymorphisms may provide benefit by predicting pharmacokinetics and outcomes of treatment with irinotecan and certain antiviral medications. METHODS: A high-resolution melting (HRM) analysis was designed to characterize the UGT1A1 gene. Genomic DNA from 110 healthy subjects was extracted from peripheral blood samples. The promoter and 11 exons from UGT1A1 were screened by HRM, and all results were subsequently confirmed by direct DNA sequencing. RESULTS: HRM analysis readily identified UGT1A1 gene mutations. We identified 5 different known variants of UGT1A1 including c.211 G > A; G71R, c.686 C > A; P229Q, c.1091 C > T; c.-3279 T > G; and c.-3156 G > A in 110 normal Taiwanese individuals. We also identified 8 new sequence variants, namely, c.-3296 C > T; c.43 C > A; c.45 G > A; c.234 G > A; c.577 G > A; c.614 C > T; c.1011 T > C; and c.1352 C > T. Each UGT1A1 variant was easily identifiable by differences in curves plotted from HRM data. CONCLUSIONS: HRM analysis was rapid, accurate, and economical for screening UGT1A1 gene mutations.
Assuntos
Glucuronosiltransferase/genética , Análise de Sequência de DNA/métodos , Éxons , Glucuronosiltransferase/química , Glucuronosiltransferase/metabolismo , Humanos , Mutação , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Temperatura de TransiçãoRESUMO
BACKGROUND: Chronic fatigue syndrome (CFS) has been linked to several conditions, including infections, immune system changes, or emotional stress. Our study aimed to assess the risk of CFS after a pneumonia diagnosis using data from National Health Insurance Research Database of Taiwan. METHODS: In this nested case-control study, we identified 2,000,000 adult patients from a nationwide population-based health insurance claims database spanning from January 1, 2000, to December 31, 2017. Each case diagnosed with a pathogenic infection was matched with a corresponding control using propensity scores. We excluded individuals under 20 years of age, those with a history of pathogenic infections before the index date, or those with more than one potential pathogen. To estimate hazard ratios (HR) and the adjusted hazard ratio (aHR) with their respective 95 % confidence intervals (CI), we applied univariable and multivariable Cox proportional hazard models. The multivariable analysis incorporated adjustments for age, sex, and comorbidity-related confounders. RESULTS: The relationship between infection and the subsequent risk of CFS was assessed using Cox proportional hazards regression analysis. The incidence density rates were 6.13 and 8.70 per 1000 person-years among the non-pulmonary infection and pulmonary infection populations, respectively (adjusted hazard ratio [HR] = 1.4, 95 % confidence interval [CI] 1.32-1.5). Patients infected with Pseudomonas, Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae, and influenza virus exhibited a significantly higher risk of CFS than those without these pathogens (p < 0.05). Additionally, patients with pneumonia had a significantly increased risk of thromboembolism compare with control group (p < 0.05).
Assuntos
Síndrome de Fadiga Crônica , Pneumonia , Modelos de Riscos Proporcionais , Humanos , Síndrome de Fadiga Crônica/epidemiologia , Masculino , Feminino , Taiwan/epidemiologia , Estudos de Casos e Controles , Adulto , Pessoa de Meia-Idade , Pneumonia/epidemiologia , Pneumonia/etiologia , Incidência , Fatores de Risco , Idoso , Adulto Jovem , Estudos de Coortes , Bases de Dados FactuaisRESUMO
In the last decade, great advances have been made in epidermal stem cell studies at the cellular and molecular level. These studies reported various subpopulations and differentiations existing in the epidermal stem cell. Although controversies and unknown issues remain, epidermal stem cells possess an immune-privileged property in transplantation together with easy accessibility, which is favorable for future clinical application. In this review, we will summarize the biological characteristics of epidermal stem cells, and their potential in orthopedic regenerative medicine. Epidermal stem cells play a critical role via cell replacement, and demonstrate significant translational potential in the treatment of orthopedic injuries and diseases, including treatment for wound healing, peripheral nerve and spinal cord injury, and even muscle and bone remodeling.
Assuntos
Células Epidérmicas , Ortopedia , Medicina Regenerativa/métodos , Células-Tronco/citologia , Animais , Humanos , Traumatismos da Medula Espinal/terapia , CicatrizaçãoRESUMO
Background The angiotensin receptor-neprilysin inhibitor (LCZ696) has emerged as a promising pharmacological intervention against renin-angiotensin system inhibitor in reduced ejection fraction heart failure (HFrEF). Whether the therapeutic benefits may vary among heterogeneous HFrEF subgroups remains unknown. Methods and Results This study comprised a pooled 2-center analysis including 1103 patients with symptomatic HFrEF with LCZ696 use and another 1103 independent HFrEF control cohort (with renin-angiotensin system inhibitor use) matched for age, sex, left ventricular ejection fraction, and comorbidity conditions. Three main distinct phenogroup clusterings were identified from unsupervised machine learning using 29 clinical variables: phenogroup 1 (youngest, relatively lower diabetes prevalence, highest glomerular filtration rate with largest left ventricular size and left ventricular wall stress); phenogroup 2 (oldest, lean, highest diabetes and vascular diseases prevalence, lowest highest glomerular filtration rate with smallest left ventricular size and mass), and phenogroup 3 (lowest clinical comorbidity with largest left ventricular mass and highest hypertrophy prevalence). During the median 1.74-year follow-up, phenogroup assignment provided improved prognostic discrimination beyond Meta-Analysis Global Group in Chronic Heart Failure risk score risk score (all net reclassification index P<0.05) with overall good calibrations. While phenogroup 1 showed overall best clinical outcomes, phenogroup 2 demonstrated highest cardiovascular death and worst renal end point, with phenogroup 3 having the highest all-cause death rate and HF hospitalization among groups, respectively. These findings were broadly consistent when compared with the renin-angiotensin system inhibitor control as reference group. Conclusions Phenomapping provided novel insights on unique characteristics and cardiac features among patients with HFrEF with sacubitril/valsartan treatment. These findings further showed potentiality in identifying potential sacubitril/valsartan responders and nonresponders with improved outcome discrimination among patients with HFrEF beyond clinical scoring.
Assuntos
Insuficiência Cardíaca , Humanos , Anti-Hipertensivos , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico , Valsartana/uso terapêutico , Função Ventricular Esquerda , Masculino , FemininoRESUMO
Background: Despite known sex differences in cardiac structure and function, little is known about how menopause and estrogen associate with atrioventricular mechanics and outcomes. Objective: To study how, sex differences, loss of estrogen in menopause and duration of menopause, relate to atrioventricular mechanics and outcomes. Methods: Among 4051 asymptomatic adults (49.8 ± 10.8 years, 35%women), left ventricular (LV) and left atrial (LA) mechanics were assessed using speckle-tracking. Results: Post-menopausal (vs. pre-menopausal) women had similar LV ejection fraction but reduced GLS, reduced PALS, increased LA stiffness, higher LV sphericity and LV torsion (all p < 0.001). Multivariable analysis showed menopause to be associated with greater LV sphericity (0.02, 95%CI 0.01, 0.03), higher indexed LV mass (LVMi), lower mitral e', lower LV GLS (0.37, 95%CI 0.04-0.70), higher LV torsion, larger LA volume, worse PALS (â¼2.4-fold) and greater LA stiffness (0.028, 95%CI 0.01-0.05). Increasing years of menopause was associated with further reduction in GLS, markedly worse LA mechanics despite greater LV sphericity and higher torsion. Lower estradiol levels correlated with more impaired LV diastolic function, impaired LV GLS, greater LA stiffness, and increased LV sphericity and LV torsion (all p < 0.05). Approximately 5.5% (37/669) of post-menopausal women incident HF over 2.9 years of follow-up. Greater LV sphericity [adjusted hazard ratio (aHR) 1.04, 95%CI 1.00-1.07], impaired GLS (aHR 0.87, 95%CI 0.78-0.97), reduced peak left atrial longitudinal strain (PALS, aHR 0.94, 95%CI 0.90-0.99) and higher LA stiffness (aHR 10.5, 95%CI 1.69-64.6) were independently associated with the primary outcome of HF hospitalizations in post-menopause. Both PALS < 23% (aHR:1.32, 95%CI 1.01-3.49) and GLS < 16% (aHR:5.80, 95%CI 1.79-18.8) remained prognostic for the incidence of HF in post-menopausal women in dichotomous analyses, even after adjusting for confounders. Results were consistent with composite outcomes of HF hospitalizations and 1-year all-cause mortality as well. Conclusion: Menopause was associated with greater LV/LA remodeling and reduced LV longitudinal and LA function in women. The cardiac functional deficit with menopause and lower estradiol levels, along with their independent prognostic value post-menopause, may elucidate sex differences in heart failure further.
RESUMO
Since iron is essential for neurotransmitter synthesis, decreased iron stores might lead to reduced production of biogenic amines which phenomenon was shown in Fibromyalgia (FM) patients. The aims are to investigate the association of iron deficiency anemia (IDA) and FM and to find the effects of different interventions. We conducted a study using the Taiwan National Health Insurance Research Database. The IDA cohort consisted of 13,381 patients with newly diagnosed IDA between 2000 and 2008. Each patient with IDA was frequency-matched with one people without IDA, by sex, age and index year. The Cox proportional hazards regression analysis was conducted to estimate the association between IDA and FM risk. The event was the occurrence of FM. The overall incidence density rate of FM in the IDA cohort was higher than in the non-IDA cohort with a multivariable Cox proportional hazards model measured adjusted hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.13-1.25). When using non-IDA group as reference, we compared with different therapies for IDA. The adjusted HRs of FM were 1.38 (95% CI = 1.30-1.47), 1.10 (95% CI = 1.03-1.16), 1.18 (95% CI = 0.98-1.43) and 0.73 (95% CI = 0.58-0.90) for IDA patient without therapy, iron supplement alone, blood transfusion alone and both iron supplement and blood transfusion respectively. Our results suggest IDA is associated with an increased risk of FM. All patients should have iron supplementation both to correct anemia and replenish body stores.
Assuntos
Anemia Ferropriva/complicações , Fibromialgia/complicações , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , TaiwanRESUMO
Chronic Fatigue Syndrome (CFS) has been defined as unexplained relapsing or persistent fatigue for at least 6 consecutive months. Immuno-inflammatory pathway, bacterial infection, and other causes play essential roles in CFS. Helicobacter pylori infection is one of the most common causes of foregut inflammation, leading to peptic ulcer disease (PUD). This study aimed to analyze the risk of CFS development between patients with and without PUD. Other related factors were also analyzed. We performed a retrospective, nationwide cohort study identifying patients with or without PUD respectively by analyzing the Longitudinal Health Insurance Database 2000 (LHID2000), Taiwan. The overall incidence of CFS was higher in the PUD cohort than in the non- PUD cohort (HR = 2.01, 95% CI = 1.75-2.30), with the same adjusted HR (aHR) when adjusting for age, sex, and comorbidities. The sex-specific PUD cohort to the non-PUD cohort relative risk of CFS was significant in both genders. The age-specific incidence of CFS showed incidence density increasing with age in both cohorts. There is an increased risk of developing CFS following PUD, especially in females and the aging population. Hopefully, these findings can prevent common infections from progressing to debilitating, chronic conditions such as CFS.
Assuntos
Síndrome de Fadiga Crônica/etiologia , Úlcera Péptica/complicações , Úlcera Péptica/epidemiologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Estudos de Coortes , Síndrome de Fadiga Crônica/fisiopatologia , Feminino , Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologiaRESUMO
Hemolytic anemia (HA) renders erythropoietic stress on the bone marrow and has been linked to osteoporosis. In this nationwide retrospective cohort study, we examined this correlation by utilizing the Taiwan National Health Insurance Research Database (NHIRD). We identified two cohorts, matching population with and without HA in a 1:4 ratio. A total of 2242 HA patients and 8968 non-HA patients were enrolled. Patients with HA had a significantly higher cumulative incidence (log-rank test p = 0.0073), higher incidence density (5.11 vs. 3.76 per 1000 persons-years), and a 1.31-fold risk of developing osteoporosis than non-HA patients (aHR = 1.31, 95% C.I. 1.04-1.63, p = 0.01). After adjusting for age, sex, and comorbidities, patients with factors including female (aHR = 2.57, 95% C.I. 2.05-3.22, p < 0.001), age > 65 (aHR = 9.25, 95% C.I. 7.46-11.50, p < 0.001), diagnosis of cholelithiasis (aHR = 1.76, 95% C.I. 1.20-2.58, p = 0.003) and peptic ulcer disease (aHR = 1.87, 95% C.I. 1.52-2.29, p < 0.001) had significantly higher risk of osteoporosis. We propose that this correlation may be related to increased hematopoietic stress, increased consumption of nitric oxide (NO) by hemolysis, and the inhibitory effects of iron supplements on osteogenesis through the receptor activator of nuclear factor κB ligand (RANKL)/Osteoprotegerin pathway and the Runt-related transcription factor 2 (RUNX2) factor. Our findings suggest that patients with hemolytic anemia are at a higher risk of developing osteoporosis, and it would be in the patient's best interest for physicians to be aware of this potential complication and offer preventative measures.