Reversal of Pulmonary Fibrosis: Human Umbilical Mesenchymal Stem Cells from Wharton's Jelly versus Human-Adipose-Derived Mesenchymal Stem Cells.

Pulmonary fibrosis (PF) is a progressive, non-reversible illness with various etiologies. Currently, effective treatments for fibrotic lungs are still lacking. Here, we compared the effectiveness of transplantation of human mesenchymal stem cells from umbilical cord Wharton's jelly (HUMSCs) versus those from adipose tissue (ADMSCs) in reversing pulmonary fibrosis in rats. Bleomycin 5 mg was intratracheally injected to establish a severe, stable, single left lung animal model with PF. On Day 21 post-BLM administration, one single transplantation of 2.5 × 107 HUMSCs or ADMSCs was performed. Lung function examination of Injury and Injury+ADMSCs rats displayed significantly decreased blood oxygen saturation and increased respiratory rates, while Injury+HUMSCs rats showed statistical amelioration in blood oxygen saturation and significant alleviation in respiratory rates. Reduced cell number in the bronchoalveolar lavage and lower myofibroblast activation appeared in the rats transplanted with either ADMSCs or HUMSCS than that in the Injury group. However, ADMSC transplantation stimulated more adipogenesis. Furthermore, matrix-metallopeptidase-9 over-expression for collagen degradation, and the elevation of Toll-like receptor-4 expression for alveolar regeneration were observed only in the Injury+HUMSCs. In comparison with the transplantation of ADMSCs, transplantation of HUMSCs exhibited a much more effective therapeutic effect on PF, with significantly better results in alveolar volume and lung function.

Mycoplasma pneumonia Infection Is Associated With an Increased Risk of Systemic Lupus Erythematosus: A Nationwide, Retrospective Cohort Study.

Background: Infections may play a role in the development of systemic lupus erythematosus (SLE). Objective: To assess the link between Mycoplasma pneumonia (M. pneumonia) infection and the incidence of SLE. Method: We conducted a retrospective cohort study, which identified 116,043 hospitalized patients with M. pneumoniae between 2000 and 2012 from the Taiwan National Health Insurance Research Database and compared them with 447,839 matched inpatients who had never been diagnosed with M. pneumonia infection (at a 1:4 ratio, matched by age, gender, and index year). Their comparative risk of developing SLE was evaluated. The follow-up period was defined as the time from the initial diagnosis of M. pneumonia infection to the date of SLE diagnosis, or December 31, 2013. The incidence rates of SLE were assessed in people with and without M. pneumoniae infection. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs), with the uninfected group used as the reference. Results: The adjusted HR of SLE for the M. pneumoniae group was 2.97 with 95% CI = 2.18-4.05 compared with the uninfected group. The risk was most significantly higher within 0.5 years after the M. pneumoniae infection with an adjusted HR of 6.18 (95% CI = 3.82-9.97, p < 0.01). The adjusted HR for SLE from 0.5 to 2 years and from 2 to 5 years after M. pneumoniae infection was 1.59 (95% CI = 0.70-3.59, p = 0.27) and 2.42 (95% CI = 1.22-4.81, p = 0.01), respectively. Conclusion: The incidence of SLE was significantly higher in subjects infected with M. pneumoniae.

Update on guidelines for the treatment of COPD in Taiwan using evidence and GRADE system-based recommendations.

Chronic obstructive pulmonary disease (COPD) has significant contributions to morbidity and mortality world-wide. Early symptoms of COPD are not readily distinguishable, resulting in a low rate of diagnosis and intervention. Different guidelines and recommendatations for the diagnosis and treatment of COPD exist globally. The first edition of clinical practice guidelines for COPD was published in 2016 by the Ministry of Health and Welfare in Taiwan in collaboration with the Taiwan evidence-based medicine association and Cochrane Taiwan, and was revised in 2019 in order to update recent diagnostic and therapeutic modalities for COPD and its acute exacerbation. This revised guideline covered a range of topics highlighted in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report, including strategies for the diagnosis, assessment, monitoring, and management of stable COPD and exacerbations, with particular focus on evidence from Taiwan. The recommendations included in the revised guideline were formed based on a comprehensive systematic review or meta-analysis of specific clinical issues identified by an expert panel that surveyed relevant scientific evidence in the literature and guidelines published by the clinical communities and organizations nationally and internationally. The guidelines and recommendations are applicable to the clinical settings in Taiwan. We expect this revised guideline to facilitate the diagnosis, treatment and management of patients with COPD by physicians and health care professionals in Taiwan. Adaptations of the materials included herein for educational and training purposes is encouraged.

Update on guidelines for the treatment of COPD in Taiwan using evidence and GRADE system-based recommendations

Chronic obstructive pulmonary disease (COPD) has significant contributions to morbidity and mortality world-wide. Early symptoms of COPD are not readily distinguishable, resulting in a low rate of diagnosis and intervention. Different guidelines and recommendatations for the diagnosis and treatment of COPD exist globally. The first edition of clinical practice guidelines for COPD was published in 2016 by the Ministry of Health and Welfare in Taiwan in collaboration with the Taiwan evidence-based medicine association and Cochrane Taiwan, and was revised in 2019 in order to update recent diagnostic and therapeutic modalities for COPD and its acute exacerbation. This revised guideline covered a range of topics highlighted in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report, including strategies for the diagnosis, assessment, monitoring, and management of stable COPD and exacerbations, with particular focus on evidence from Taiwan. The recommendations included in the revised guideline were formed based on a comprehensive systematic review or meta-analysis of specific clinical issues identified by an expert panel that surveyed relevant scientific evidence in the literature and guidelines published by the clinical communities and organizations nationally and internationally. The guidelines and recommendations are applicable to the clinical settings in Taiwan. We expect this revised guideline to facilitate the diagnosis, treatment and management of patients with COPD by physicians and health care professionals in Taiwan. Adaptations of the materials included herein for educational and training purposes is encouraged.

Increased risk of glaucoma amongst new-onset gout patients aged 20-39 years: A nationwide population-based cohort study in Taiwan.

OBJECTIVES: To provide epidemiologic evidence of whether gout increases the risk of new-onset glaucoma. METHODS: We conducted a 13-year nationwide, population-based, retrospective cohort study to examine the association between the history of gout and risk of glaucoma by using the Longitudinal Health Insurance Database (LHID) of Taiwan. The gout cohort included 52 943 patients with newly diagnosed gout who were recruited between 2000 and 2012. Each patient was propensity score matching with 1:1 person without gout from the LHID. To determine glaucoma occurrence, the study population was followed up until the end of 2013. Cumulative incidence, hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated after adjusting for age, sex, comorbidities, and ever ophthalmic visit. A Cox proportional hazard model was used to analyse the association between gout and incidence of glaucoma amongst patients with different potential risks. RESULTS: The adjusted HR for newly diagnosed glaucoma in the gout cohort was 1.00 (95% CI = 0.93-1.07, P = .931), compared with the non-gout cohort. Stratified subgroup analysis revealed that the HRs of glaucoma were 1.36 (95% CI = 1.09-1.70, P = .007), 0.99 (95% CI = 0.87-1.12, P = .871), and 0.95 (95% CI = 0.87-1.03, P = .235) in patients with gout aged 20-39, 40-54, and ≥55 years, respectively (P for interaction = .011). CONCLUSION: This nationwide population-based cohort study revealed that gout patients in the age group 20-39 years had a higher risk of glaucoma than non-gout controls.

Comparison of reversal of rat pulmonary fibrosis of nintedanib, pirfenidone, and human umbilical mesenchymal stem cells from Wharton's jelly.

BACKGROUND: The present study compared the effects of antifibrotic medications, pirfenidone, and nintedanib, with transplantation of human umbilical mesenchymal stem cells (HUMSCs) in restoring rat pulmonary fibrosis (PF). METHODS: A stable animal model was established via an intratracheal injection of 5 mg bleomycin (BLM). One single transplantation of 2.5× 107 HUMSCs or initiation of daily oral nintedanib/pirfenidone administration was performed on day 21 following BLM damage. RESULTS: Pulmonary function examination revealed that BLM rats exhibited a significant decrease in blood oxygen saturation and an increase in respiratory rates. While no significant improvements were found in BLM rats receiving nintedanib or pirfenidone, those who transplanted with HUMSCs showed a statistical amelioration in blood oxygen saturation and significant alleviation in respiratory rates. Quantification results revealed that a significant reduction in alveolar space and marked increases in substantial cell infiltration and collagen deposition in the left lungs of BLM rats. No significant alteration was observed in BLM rats administered nintedanib or pirfenidone. However, BLM rats transplanted with HUMSCs had a significant recovery in alveolar space and noticeable decreases in cell infiltration and collagen deposition. The inflammatory cell numbers in the bronchoalveolar lavage was increased in the BLM group. While the rats treated with nintedanib or pirfenidone had a lower cell number than the BLM group, a higher cell number was found as compared with the Normal group. In rats transplanted with HUMSCs, the cell number did not differ from the Normal group. CONCLUSIONS: Transplantation of HUMSCs could effectively treat PF as opposed to the administration of anti-fibrotic drugs with nintedanib or pirfenidone with a significant better result in lung volume, pathological changes, lung function, and blood oxygen saturation.

Prognostic nomogram for elderly patients with acute respiratory failure receiving invasive mechanical ventilation: a nationwide population-based cohort study in Taiwan.

Patients in critical care medicine are ageing. There is limited literature evaluating long-term outcomes and prognostic factors for the growing number of elderly patients with acute respiratory failure (ARF) receiving invasive mechanical ventilation (IMV). Data on elderly patients (≧ 65 years old) with ARF receiving intubation and IMV during 2003-2012 were retrospectively collected from the national health database in Taiwan. We included 7,095 elderly patients. The 28-day mortality was 33%, the 60-day mortality was 47.5%, and the 1-year mortality was 70.4%. Patients were divided into groups: young-old (65-74 years), middle-old (75-84 years), and oldest-old (≧ 85 years). Patients in the oldest-old and middle-old groups had higher 1-year mortality than the young-old group (p < 0.001). The multivariate logistic regression revealed 9 significant factors associated with 1-year mortality, and these factors were used to develop a prognostic nomogram. The present study showed that the long-term prognosis of elderly patients with ARF and IMV is very poor. This nomogram can help physicians estimate the 1-year mortality of elderly patients in the early stage of ARF and assist in clinical decision making.

LABA/LAMA fixed-dose combinations versus LAMA monotherapy in the prevention of COPD exacerbations: a systematic review and meta-analysis.

BACKGROUND: Long-acting muscarinic antagonist (LAMA) monotherapy is recommended for chronic obstructive pulmonary disease (COPD) patients with high risk of exacerbations. It is unclear whether long-acting ß2-agonist (LABA)/LAMA fixed-dose combinations (FDCs) are more effective than LAMAs alone in preventing exacerbations. The aim of this study was to systematically review the literature to investigate whether LABA/LAMA FDCs are more effective than LAMA monotherapy in preventing exacerbations. METHODS: We searched several databases and manufacturers' websites to identify relevant randomized clinical trials comparing LABA/LAMA FDC treatment with LAMAs alone ⩾24 weeks. Outcomes of interest were time to first exacerbation and rates of moderate to severe, severe and all exacerbations. RESULTS: We included 10 trials in 9 articles from 2013 to 2018 with a total of 19,369 patients for analysis in this study. Compared with LAMA monotherapy, LABA/LAMA FDCs demonstrated similar efficacy in terms of time to first exacerbation [hazard ratio, 0.96; 95% confidence interval (CI) 0.79-1.18; p = 0.71], moderate to severe exacerbations [risk ratio (RR), 0.96; 95% CI 0.90-1.03; p = 0.28], severe exacerbations (RR, 0.92; 95% CI 0.81-1.03; p = 0.15), and a marginal superiority in terms of all exacerbations (RR, 0.92; 95% CI 0.86-1.00; p = 0.04). The incidence of all exacerbation events was lower in the LABA/LAMA FDC group for the COPD patients with a history of previous exacerbations and those with a longer treatment period (52-64 weeks). CONCLUSION: This study provides evidence that LABA/LAMA FDCs are marginally superior in the prevention of all exacerbations compared with LAMA monotherapy in patients with COPD. The reviews of this paper are available via the supplemental material section.

Newly diagnosed iron deficiency anemia and subsequent autoimmune disease: a matched cohort study in Taiwan.

Objective: To explore whether newly diagnosed iron deficiency anemia (IDA) is associated with subsequent systemic autoimmune disease onset.Methods: The study identified 22,440 patients who received a diagnosis of IDA between 2000 and 2012 from a random sample of 1 million people from Taiwan's National Health Insurance Research Database. The patients with IDA were randomly matched with 89,528 patients with no IDA by age, gender, and index year. We followed the 2 groups until systemic autoimmune disease onset. Cox proportional hazards analysis was used to determine autoimmune disease risk by age, gender, and comorbidities, in terms of hazard ratios (HRs) and 95% confidence intervals (CIs).Results: Adjusted HR (95% CI) of autoimmune disease in the IDA group was 2.37 (1.92-2.92) compared with the non-IDA group. The subgroup analysis indicated that a patient with IDA had a significantly greater risk of autoimmune disease if they were female or had the comorbidities of hypertension, hyperlipidemia, cancer, allergic rhinitis, urticaria, chronic obstructive pulmonary disease, or chronic liver disease. The autoimmune disease was significantly more likely to occur within 2 years after a new diagnosis of IDA.Conclusions: IDA significantly increases autoimmune disease risk, particularly in female patients and patients with certain comorbidities. Clinicians should conduct further clinical evaluations and laboratory tests of autoimmune disease in patients with IDA.

The effect of emphysema on survival in patients with idiopathic pulmonary fibrosis: A retrospective study in Taiwan.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rare and chronic fibrosing interstitial lung disease. However, the clinical features and outcomes of IPF in Taiwan have not been well studied. In addition, the survival difference between patients with IPF alone and combined pulmonary fibrosis and emphysema (CPFE) remains controversial. METHODS: Patients diagnosed with IPF between 2006 and 2016 were retrospectively enrolled in this study. IPF was defined according to the 2011 American Thoracic Society/European Respiratory Society guideline. The clinical features, comorbidities, and outcomes of CPFE group and IPF-alone group were compared. The extents of emphysema and fibrosis were evaluated. RESULTS: In total, 114 patients with IPF were enrolled, and 86.8% of them were men with a mean age of 77.8 years. The median survival was 3.33 years in all patients with IPF. Moreover, 30 patients (26.3%) met the CPFE criteria. The CPFE group had a higher percentage of smokers (90% vs 50%, p < 0.001), higher forced vital capacity (82% vs 59%, p < 0.001), and lower fibrosis scores (8.5 ± 2.9 vs 10 ± 3.2, p = 0.022) than did the IPF-alone group. The baseline room air saturation and percentage of pulmonary hypertension were similar between the two groups. The survival time was not significantly different between the CPFE and IPF-alone groups (median survival, 3.58 vs 2.39 years, p = 0.163). In the multivariate analysis, higher fibrosis score, room air saturation < 90%, and lung cancer were significant factors associated with mortality. CONCLUSION: Our study showed that emphysema had no significant effect on the survival of patients with IPF. The outcome of IPF was mainly determined by the baseline disease severity and other comorbidities.

Reversal of bleomycin-induced rat pulmonary fibrosis by a xenograft of human umbilical mesenchymal stem cells from Wharton's jelly.

Pulmonary fibrosis (PF) is a progressive and irreversible condition with various causes, and no effective treatment has been found to rescue fibrotic lungs. Successful recovery from PF requires inhibiting inflammation, promoting collagen degradation and stimulating alveolar regeneration. Human umbilical mesenchymal stem cells (HUMSCs) not only regulate immune responses but also synthesize and release hyaluronan to improve lung regeneration. This study investigated the feasibility of HUMSC engraftment into rats with bleomycin (BLM)-induced PF to explore HUMSC therapeutic effects/outcomes. Methods: A unique BLM-induced left-lung-dominated PF animal model was established. Rats were transplanted with low-dose (5×106) or high-dose (2.5×107) HUMSCs on Day 21 after BLM injection. Combinations in co-culture of pulmonary macrophages, fibroblasts, HUMSCs treated with BLM and the same conditions on alveolar epithelia versus HUMSCs were evaluated. Results: Rats with high-dose HUMSC engraftment displayed significant recovery, including improved blood oxygen saturation levels and respiratory rates. High-dose HUMSC transplantation reversed alveolar injury, reduced cell infiltration and ameliorated collagen deposition. One month posttransplantation, HUMSCs in the rats' lungs remained viable and secreted cytokines without differentiating into alveolar or vascular epithelial cells. Moreover, HUMSCs decreased epithelial-mesenchymal transition in pulmonary inflammation, enhanced macrophage matrix-metallopeptidase-9 (MMP-9) expression for collagen degradation, and promoted toll-like receptor-4 (TLR-4) expression in the lung for alveolar regeneration. In coculture studies, HUMSCs elevated the MMP-9 level in pulmonary macrophages, released hyaluronan into the medium and stimulated the TLR-4 quantity in the alveolar epithelium. Principal Conclusions: Transplanted HUMSCs exhibit long-term viability in rat lungs and can effectively reverse rat PF.

Association of iron deficiency anemia with tuberculosis in Taiwan: A nationwide population-based study.

BACKGROUND: Iron deficiency is associated with decreased cellular immunity, which may predispose patients with iron deficiency anemia (IDA) to increased risk of developing tuberculosis (TB). This study investigated the relationship between newly diagnosed IDA and TB infection in Taiwan. METHODS: The study included data on 21,946 patients with incident IDA and 87,555 non-IDA controls from a national database covering the period 2000-2012. IDA and non-IDA subjects were matched 1:4 on age, gender, and index year. The follow-up period was defined as the time from the initial IDA diagnosis to the date of developing TB or 31 December 2013. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals, with the control group as the reference. RESULTS: The adjusted hazard ratio of TB for the IDA group was 1.99 (95% confidence interval, 1.77-2.25) compared with the control group. The subgroup analysis showed that for both genders, all age groups, and patients with diabetes mellitus, hyperlipidemia, hypertension, cancer, chronic obstructive pulmonary disease, and hepatitis B virus infection, the IDA group had significantly higher TB incidence. The association was significantly stronger within the 5 years after new IDA diagnosis for both genders and all age groups. CONCLUSIONS: Higher TB incidence was discovered in the IDA group, especially for patients with comorbidities.

Increased risk of ankylosing spondylitis after Mycoplasma pneumonia: A Nationwide population-based study.

This study aimed to investigate the relationship between Mycoplasma pneumonia (MP) infection and new development of ankylosing spondylitis (AS).Using data from the Taiwan National Health Insurance Research Database, we included a total of 116,084 patients with newly diagnosed MP between 2000 and 2012. The control cohort consisted of patients who did not have MP, matched 1:4 by age, sex, and index year. The follow-up period was defined as the time from the initial diagnosis of MP to the date of diagnosis of AS, censoring, or 31 December 2013. Cox proportional hazards regression analysis was used to analyze the risk of autoimmune diseases by sex, age, and comorbidities, with hazard ratios (HRs) and 95% confidence intervals (CIs).The eligible study participants included 116,084 patients in the MP group and 464,336 patients in the comparison group. The incidence rates of AS in the MP group and comparison groups were 1.49 and 0.74 per 1,000,000-person years, respectively. The adjusted HR of AS for the MP group was 2.45 (95% CI = 1.02-5.90) compared to the control group after adjustment for age, sex, and all covariates.MP remained an independent risk factor for developing AS in terms of sex, age, and comorbidities.

Association of Scrub Typhus With the Risk of Autoimmune Diseases: A Population-Based Cohort Study.

Infection plays a major role in the development of autoimmune diseases. In this study, we investigated the relationship between scrub typhus and systemic autoimmune diseases. We enrolled 6,928 hospitalized patients with scrub typhus between 2000 and 2012 from the Taiwan National Health Insurance Research Database, and we compared them with 27,712 selected inpatients who had never been diagnosed with scrub typhus (1:4 ratio, matched by age, sex, and index year) in relation to the risk of developing autoimmune diseases. Cox proportional hazards regression analysis was used to analyze the risk of autoimmune diseases by sex, age, and comorbidities, with hazard ratios and 95% confidence intervals. The adjusted hazard ratio for autoimmune diseases for the scrub typhus group was 2.4 (95% confidence interval: 1.66, 3.48, P < 0.0001) compared with the control group. Subgroup analysis showed that women aged <40 years had a significant higher risk of autoimmune diseases. The risk was significantly higher within 3 years after scrub typhus infection. In conclusion, a higher risk of autoimmune diseases was found among the scrub typhus group, especially for female patients, those aged <40 years, and within the first 3 years after getting scrub typhus.

Mortality and vertebral fracture risk associated with long-term oral steroid use in patients with chronic obstructive pulmonary disease: A systemic review and meta-analysis.

Short-term oral steroid use may improve lung function and respiratory symptoms in patients with stable chronic obstructive pulmonary disease (COPD). However, long-term oral steroid (LTOS) use is not recommended owing to its potential adverse effects. Our study aimed to investigate whether chronic use of oral steroids for more than 4 months would increase mortality and vertebral fracture risk in patients with stable COPD. A systemic search of the PubMed database was conducted, and meta-analysis was performed using Review Manager 5.3. Five studies with a total of 1795 patients showed there was an increased risk of mortality in patients using LTOS (relative risk, 1.63; 95% confidence interval (CI), 1.19-2.23; p < 0.0001; I2 = 86%). In addition, four studies with a total of 17,764 patients showed there was an increased risk of vertebral fracture in patients using LTOS (odds ratio, 2.31; 95% CI, 1.52-3.50; p = 0.03; I2 = 65%). Our meta-analysis showed LTOS was associated with increased mortality and vertebral fracture risk in patients with COPD, and this risk may be due to the adverse effects of LTOS and progression COPD.

Increased risk of rheumatoid arthritis among patients with Mycoplasma pneumonia: A nationwide population-based cohort study in Taiwan.

OBJECTIVE: An association between Mycoplasma pneumonia (MP) and rheumatoid arthritis (RA) had been reported in animal studies for decades. However, clinical evidence for this association is lacking. Therefore, this study aimed to provide epidemiologic evidence to clarify the relationship between MP and development of RA. METHODS: This 13-year nationwide, population-based, retrospective cohort study analyzed the risk of RA in a cohort of MP patients. We cross linked and compared the database of those with catastrophic illnesses to make sure the diagnoses of RA are correctly labeled. We selected 116,053 hospitalized patients diagnosed with MP between 2000 and 2012 from the Taiwan National Health Insurance Research Database and 464,212 matched controls at a 1:4 ratio by age, gender, and index year, in relation to the risk of developing RA. The follow-up period referred to the initial diagnosis of MP until the date of RA diagnosis, censoring of RA, or 31st December 2013. The Cox proportional hazard model was used to analyze the association between MP and incidence of RA among patients with different potential risks. RESULTS: The adjusted hazard ratio (HR) for incidental RA in the MP group was 1.37 (95% confidence interval CI = 0.87-2.16), compared to non-MP controls. Stratified analysis revealed that the adjusted HR was 3.05 (95% CI = 1.16-7.99, p = 0.02) in a subgroup of patients over the age of 65.The adjusted HR of RA for the MP group among aged ≦19 years and ≥ 65 years was 3.19 (95% CI = 1.04.9.76) and 4.14 (95% CI = 1.27,13.4) within the first 2 years of follow-up. CONCLUSION: This cohort study demonstrated that patients with MP had a higher risk of developing RA, especially in the first 2 years, in those aged younger than 19 and over 65.

Effective cardiac radiotherapy relieved life-threatening heart failure caused by advanced small cell lung cancer with cardiac metastasis: a case report.

Cardiac radiotherapy is rarely used in clinical practice because of concern of adverse effects on the heart. We present a case of a 64-year-old man with advanced small cell lung cancer (SCLC) treated with chemo-radiotherapy who attained partial remission initially but had disease progression to bulky cardiac metastasis and significant pericardial effusion. Severe heart failure with hepatic failure was found. Chemotherapy and pericardiocentesis were contraindicated because of the associated high risk and bleeding tendency. Emergent palliative cardiac radiotherapy resulted in rapid improvements of dyspnea, liver function, and urine output. Pericardiocentesis was performed 5 days later and effusion cytology confirmed metastatic SCLC. To our knowledge, this is the first case of effective cardiac radiotherapy for SCLC with life-threatening cardiac metastasis. Palliative cardiac radiotherapy may be an effective alternative treatment for radiosensitive malignancy with cardiac metastasis in cases of multiple organ dysfunction and unsuitability for chemotherapy and pericardiocentesis.

Xenograft of Human Umbilical Mesenchymal Stem Cells from Wharton's Jelly Differentiating into Osteocytes and Reducing Osteoclast Activity Reverses Osteoporosis in Ovariectomized Rats.

We examined the effects of human umbilical cord-derived mesenchymal stem cells (HUMSCs) in Wharton's jelly on ovariectomy (OVX)-induced osteoporosis by using in vitro and in vivo experiments. Two months after OVX, the rats gained weight and had a decreased serum estradiol level . Both micro-computed tomography (micro-CT) and histochemical analyses revealed a marked decrease in the bone volume (BV) and collagen content within the head, neck, and distal condyle of the femur, indicating that the osteoporosis animal model was successfully established 2 mo after bilateral OVX. Subsequently, 2.5 × 106 HUMSCs were injected into the bone marrow cavity of the left femurs 2 mo after OVX. The rats were divided into the following groups: normal + phosphate-buffered saline (PBS), normal + HUMSCs, OVX + PBS, and OVX + HUMSCs. Two months after transplantation, both micro-CT imaging and histochemical staining revealed that the normal + HUMSCs group had higher BV and collagen content in the epiphysis and metaphysis than did the normal + PBS group. In the OVX + HUMSCs group, a substantial increase in the rod-shaped trabecular bone and the abundant accumulation of collagen were observed around the site of HUMSC transplantation. Plenty of transplanted HUMSCs remained viable and differentiated into osteoblasts. In addition, HUMSC transplantation reduced the number of osteoclasts. Compared with HUMSCs cultured alone, HUMSCs cocultured with osteoblasts showed that the percentage of cells differentiating into osteoblasts significantly increased. Furthermore, osteoclasts cocultured with HUMSCs had significantly decreased cellular activity and differentiation capability. HUMSC transplantation into the distal femur of OVX rats could locally stimulate osteocalcin synthesis, increase the trabecular bone, and inhibit osteoclast activity.

IgG4-related lung disease presenting as interstitial lung disease with bronchiolitis: A case report.

RATIONALE: IgG4-related disease is a rare and novel disease entity that tends to involve multiple organs. The pulmonary manifestation of this disease is highly variable and may mimic lung cancer, pneumonia, interstitial lung disease (ILD), sarcoidosis, and so forth. Small airway disease is rarely reported in IgG4-related lung disease (IgG4-RLD). In the current study, we describe a rare case of IgG4-RLD with patterns of ILD and bronchiolitis. PATIENT CONCERN: A 43-year-old man had chronic cough and dyspnea on exertion for 4 years. Initial chest radiography showed diffuse interstitial infiltration. Follow-up chest computed tomography 4 years later revealed bilateral diffuse centrilobular nodules with tree-in-bud pattern, bronchial wall thickening, and mediastinal lymph nodes. Bilateral diffuse multifocal ground-glass opacities and mosaic attenuation were also observed. Pulmonary function test revealed mixed restrictive and obstructive ventilatory impairment. DIAGNOSES: Video-assisted thoracoscopic surgery (VATS) lung biopsy showed interstitial fibrosis with lymphoplasmacytic infiltration rich in IgG4-positive plasma cells. Serum IgG4 level also showed remarkable elevation. Therefore, IgG4-RLD is confirmed. INTERVENTION: VATS wedge resection of right upper lobe and mediastinal lymph node. OUTCOMES: The patient responded well to steroid and immunosuppression therapy, and was regular followed-up in outpatient clinic. LESSONS: IgG4-RLD should be considered not only in ILD, but also in small airway disease. Serum IgG4 level may be a useful tool for screening.

Long-acting beta2-agonists versus long-acting muscarinic antagonists in patients with stable COPD: A systematic review and meta-analysis of randomized controlled trials.

Several long-acting bronchodilators have been developed and are widely used as first-line treatment in patients with stable chronic obstructive pulmonary disease (COPD). However, the initial choice of therapy is still uncertain. The aim of this study was to examine the clinical efficacy and safety of long-acting muscarinic antagonist (LAMA) and long-acting beta2-agonist (LABA) in patients with stable COPD. We searched several databases and manufacturers' websites to identify relevant randomized clinical trials for meta-analysis. Outcomes of interest were trough forced expiratory volume in 1 s (FEV1 ), acute exacerbations, transitional dyspnoea index (TDI) score, St George's Respiratory Questionnaire (SGRQ) score and adverse events. Sixteen trials with a total of 22 872 patients were included in this study. Compared with LABA, LAMA were associated with a greater reduction in acute exacerbations (OR: 0.84, 95% CI: 0.74-0.94, P = 0.003) and fewer adverse events (OR: 0.92, 95% CI: 0.86-0.97, P = 0.005). There were no significant differences in trough FEV1 , TDI and SGRQ scores. In patients with stable COPD, LAMA were associated with a greater reduction in acute exacerbations and fewer adverse effects compared with LABA.