Machine learning-based extrachromosomal DNA identification in large-scale cohorts reveals its clinical implications in cancer.

The clinical implications of extrachromosomal DNA (ecDNA) in cancer therapy remain largely elusive. Here, we present a comprehensive analysis of ecDNA amplification spectra and their association with clinical and molecular features in multiple cohorts comprising over 13,000 pan-cancer patients. Using our developed computational framework, GCAP, and validating it with multifaceted approaches, we reveal a consistent pan-cancer pattern of mutual exclusivity between ecDNA amplification and microsatellite instability (MSI). In addition, we establish the role of ecDNA amplification as a risk factor and refine genomic subtypes in a cohort from 1015 colorectal cancer patients. Importantly, our investigation incorporates data from four clinical trials focused on anti-PD-1 immunotherapy, demonstrating the pivotal role of ecDNA amplification as a biomarker for guiding checkpoint blockade immunotherapy in gastrointestinal cancer. This finding represents clinical evidence linking ecDNA amplification to the effectiveness of immunotherapeutic interventions. Overall, our study provides a proof-of-concept of identifying ecDNA amplification from cancer whole-exome sequencing (WES) data, highlighting the potential of ecDNA amplification as a valuable biomarker for facilitating personalized cancer treatment.

Impact of Low Muscle Mass on Hepatocellular Carcinoma Patients Undergoing Transcatheter Liver-Directed Therapies: Systematic Review & Meta-Analysis.

BACKGROUND AND AIM: Transcatheter liver-directed intra-arterial therapies are mainstream treatment options for intermediate-stage hepatocellular carcinoma (HCC). However, the effect of low skeletal muscle mass (LSMM) on overall survival (OS) in these patients remains uncertain. We aimed to ascertain the prevalence and prognostic effect of LSMM in this population. METHOD: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive search was performed in the PubMed and Embase databases until Oct 2023. Random-effects meta-analysis was performed to determine the pooled prevalence of LSMM and calculate the hazard ratio (HR) for OS with a 95% confidence interval (CI) in patients with intermediate-stage HCC undergoing various transarterial therapies, comparing those with and without LSMM. RESULTS: Twelve studies involving 2450 patients were included. The pooled prevalence of LSMM was 46% (95% CI, 38-55%), and the results were consistent across different treatments, regions, and age subgroups. The meta-analysis indicated that LSMM was significantly associated with decreased OS (HR, 1.78; 95% CI, 1.36-2.33; I2, 75%). Subgroup analyses reassured the main findings across various therapies, including transarterial chemoembolization (TACE) (HR, 1.68; 95% CI, 1.23-2.30; I2, 81%), transarterial embolization (TAE) (HR, 2.45; 95% CI, 1.42-4.22; I2, 0%), and transarterial radioembolization (TARE) (HR, 1.94; 95% CI, 1.01-3.73; I2, 0%). CONCLUSIONS: In intermediate-stage HCC, LSMM is common and associated with reduced OS. To achieve an optimal prognosis, clinicians should incorporate routine LSMM measurement into practice, while caring for patients with intermediate-stage HCC, irrespective of TACE, TAE, and TARE.

Deep convolutional neural network with fusion strategy for skin cancer recognition: model development and validation.

We aimed to develop an accurate and efficient skin cancer classification system using deep-learning technology with a relatively small dataset of clinical images. We proposed a novel skin cancer classification method, SkinFLNet, which utilizes model fusion and lifelong learning technologies. The SkinFLNet's deep convolutional neural networks were trained using a dataset of 1215 clinical images of skin tumors diagnosed at Taichung and Taipei Veterans General Hospital between 2015 and 2020. The dataset comprised five categories: benign nevus, seborrheic keratosis, basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. The SkinFLNet's performance was evaluated using 463 clinical images between January and December 2021. SkinFLNet achieved an overall classification accuracy of 85%, precision of 85%, recall of 82%, F-score of 82%, sensitivity of 82%, and specificity of 93%, outperforming other deep convolutional neural network models. We also compared SkinFLNet's performance with that of three board-certified dermatologists, and the average overall performance of SkinFLNet was comparable to, or even better than, the dermatologists. Our study presents an efficient skin cancer classification system utilizing model fusion and lifelong learning technologies that can be trained on a relatively small dataset. This system can potentially improve skin cancer screening accuracy in clinical practice.

Violaceous Plaque With Blackish Papules and Nodules in an Elderly Man.

A man in his 80s presents with a 3-month history of a violaceous plaque with blackish papules and nodules on his left cheek, neck, and chest. What is your diagnosis?

Prevalence and Effect of Low Skeletal Muscle Mass among Hepatocellular Carcinoma Patients Undergoing Systemic Therapy: A Systematic Review and Meta-Analysis.

Low skeletal muscle mass (LSMM) is associated with poor outcomes in hepatocellular carcinoma (HCC) patients. With the emergence of new systemic therapeutics, understanding the effect of LSMM on HCC treatment outcomes is critically important. This systematic review and meta-analysis investigates the prevalence and effect of LSMM among HCC patients undergoing systemic therapy as reported in studies identified in searches of the PubMed and Embase databases published through 5 April 2023. The included studies (n = 20; 2377 HCC patients undergoing systemic therapy) reported the prevalence of LSMM assessed by computer tomography (CT) and compared the survival outcomes [overall survival (OS) or progression-free survival (PFS)] between HCC patients with and without LSMM. The pooled prevalence of LSMM was 43.4% (95% CI, 37.0-50.0%). A random-effects meta-analysis showed that HCC patients receiving systemic therapy with comorbid LSMM had a lower OS (HR, 1.70; 95% CI, 1.46-1.97) and PFS (HR, 1.32; 95% CI, 1.16-1.51) than did those without. Subgroup analysis according to systemic therapy type (sorafenib, lenvatinib, or immunotherapy) yielded similar results. In conclusion, LSMM is prevalent among HCC patients undergoing systemic therapy and is associated with poorer survival. Early intervention or prevention strategies to improve muscle mass may be necessary for this patient population.

Risk of malignancy in patients with psoriasis receiving systemic medications: A nested case-control study.

Large-scale, real-world studies on the side effects of systemic therapies (including biologics) in patients with psoriasis are limited. We aimed to calculate the risk of malignancy in patients with psoriasis who were treated with systemic medications. Nested case-control analyses were performed among psoriasis patients without a history of malignancy. We recruited 4188 patients with newly diagnosed psoriasis and successive malignancies, and 8376 matched controls from the National Health Insurance Research Database in Taiwan. The therapy duration was within 5 years before malignancy onset and further stratified into two groups according to the duration of medication usage. Multivariate conditional logistic regression adjusted for potential confounders was used to estimate malignancy risk associated with systemic treatments. Among psoriasis patients, long-term (> 12 months) treatment with cyclosporine increased the risk of malignancy compared with no exposure (odds ratio, 1.57; p = 0.01). Short-term (≤ 12 months) or long-term (> 12 months) use of other systemic treatments, including methotrexate, azathioprine, systemic retinoids, mycophenolate mofetil, sulfasalazine, etanercept, adalimumab, and ustekinumab, was not associated with an increased risk of malignancy in patients with psoriasis. Long-term treatment with cyclosporine increased the risk of malignancy in patients with psoriasis by 1.57-fold.

Association between bullous pemphigoid and risk of venous thromboembolism: A nationwide population-based cohort study.

Bullous pemphigoid (BP) has been reported to be associated with an increased risk of venous thromboembolism (VTE). However, the exact time course is unclear, and no previous studies have been reported in the Asian population. This nationwide population-based cohort study examined the risk of VTE among BP patients in Taiwan between 2007 and 2018. A total of 12 692 BP patients were 1:2 matched with non-BP patients by age, sex, and propensity score of comorbidities. Cumulative incidence and Cox proportional hazards models were used to investigate the risk of VTE. The BP cohort had a significantly higher VTE rate than the non-BP cohort (0.17% vs. 0.08%, p = 0.015) in 1 year; the finding was more prominent within the first 6 months after diagnosis. BP was a significant risk factor for VTE (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.01-4.06); the association mildly diminished but remained significant after extending the follow-up period to 2 years (HR, 1.73; 95% CI, 1.06-2.81). Other significant risk factors for VTE included cancer, chronic liver disease and cirrhosis, and female sex. In conclusion, this study revealed a 2.02-fold increased risk of VTE in patients with BP in Taiwan.

Comprehensive profiling of 1015 patients' exomes reveals genomic-clinical associations in colorectal cancer.

The genetic basis of colorectal cancer (CRC) and its clinical associations remain poorly understood due to limited samples or targeted genes in current studies. Here, we perform ultradeep whole-exome sequencing on 1015 patients with CRC as part of the ChangKang Project. We identify 46 high-confident significantly mutated genes, 8 of which mutate in 14.9% of patients: LYST, DAPK1, CR2, KIF16B, NPIPB15, SYTL2, ZNF91, and KIAA0586. With an unsupervised clustering algorithm, we propose a subtyping strategy that classisfies CRC patients into four genomic subtypes with distinct clinical characteristics, including hypermutated, chromosome instability with high risk, chromosome instability with low risk, and genome stability. Analysis of immunogenicity uncover the association of immunogenicity reduction with genomic subtypes and poor prognosis in CRC. Moreover, we find that mitochondrial DNA copy number is an independent factor for predicting the survival outcome of CRCs. Overall, our results provide CRC-related molecular features for clinical practice and a valuable resource for translational research.

Anti-PD-1 antibody SHR-1210 plus apatinib for metastatic colorectal cancer: a prospective, single-arm, open-label, phase II trial.

In the REGONIVO study, regorafenib combined with nivolumab was effective in the treatment of microsatellite stable (MSS) metastatic colorectal cancer (mCRC), which indicated anti-angiogenic drugs may enhance the efficacy of immune checkpoint inhibitors. Therefore, we designed a single-arm, single-center, open-label, phase II trial to determine the toxicity and efficacy of SHR-1210 (an anti-PD-1 antibody) plus apatinib in MSS mCRC. The sample size was estimated using a Simon Optimum two-stage design. 10 patients were included at the first stage and if one effective patient observed, an additional 19 patients would be added. Patients with MSS mCRC who refractory to second-line treatment or intolerant to standard treatment were given SHR-1210 200 mg every 2 weeks and apatinib 250-375 mg once daily until unacceptable toxicity or disease progression occurred. In our study, the objective response rate was 0% and the disease control rate was 22.2%. The median progression-free survival was 1.83 months (95% confidence interval (CI) 1.80-1.86 months), and the median overall survival was 7.80 months (95% CI 0-17.07). Treatment-related adverse events (AEs) occurred in all patients (100%). The most common treatment-related AEs were hypertension and proteinuria (70% each). Grade 3 AEs were observed in nine patients (9/10, 90%), and the commonest was hypertension (30%). In conclusion, SHR-1210 combined with apatinib has failed to improve the efficacy of treatment of MSS mCRC, and the intolerable toxicity may be the leading cause.

Cigarette Smoking, Alcohol Consumption, and Risk of Alopecia Areata: A Population-Based Cohort Study in Taiwan.

BACKGROUND: The effects of cigarette smoking and alcohol consumption on the risk of alopecia areata (AA) are unclear. OBJECTIVE: The aim was to examine the association of cigarette smoking and alcohol consumption with AA. METHODS: We collected participants from four rounds (2001, 2005, 2009, and 2013) of the Taiwan National Health Interview Survey. Incident AA cases were identified from the National Health Insurance database. RESULTS: Of the 60,055 participants, 154 developed AA during the 647,902 person-years of follow-up. After controlling for confounders, current smokers had a higher risk of incident AA than never smokers [adjusted hazard ratio (aHR) 1.88; 95% confidence interval (CI) 1.22-2.88]. There was a trend toward an increased risk of AA with increasing numbers of years of smoking and cumulative pack-years of smoking among current smokers. The aHRs (95% CIs) of current smokers of > 5 and ≤ 15 cigarettes per day, > 10 and ≤ 20 years of smoking, ≤ 10, and > 10 and ≤ 20 pack-years of smoking were 2.03 (1.17-3.51), 2.25 (1.21-4.18), 1.86 (1.12-3.09), and 2.04 (1.04-4.01), respectively. Conversely, social and regular drinkers had significantly lower risks of AA than never drinkers [aHRs (95% CIs) 0.65 (0.43-0.98) and 0.49 (0.26-0.93), respectively]. CONCLUSION: Current smokers had an increased risk of developing AA, while alcohol consumption was associated with a decreased risk of AA.

Neurological Cancer is a Risk Factor for Bullous Pemphigoid: 11-Year Population-Based Cohort Study.

BACKGROUND: There is evidence suggesting an association between bullous pemphigoid (BP) and a range of neurological diseases. Whether neurological cancer is a risk factor for BP remains unknown. OBJECTIVE: The aim of the study was to investigate the risk of subsequent BP among patients with neurological cancer. METHODS: This nationwide population-based cohort study was based on data obtained from the Taiwan National Health Insurance Research Database between 2000 and 2012. A total of 8313 patients with neurological cancer and 33,252 age-, sex-, and index-date-matched controls were recruited. The hazard ratio (HR) for subsequent BP in patients with neurological cancer was analyzed using a Cox model and Fine-Gray competing risk model, with mortality as the competing event. RESULTS: The incidence rates of BP per 100,000 person-years were 37.2 for patients with neurological cancer and 6.8 for controls. The crude incidence rate ratio was 5.49 (95% confidence interval [CI] 2.18-13.30). The mean time to occurrence of BP was 4.48 ± 3.40 years for patients with neurological cancer. Neurological cancer (HR 9.65, 95% CI 3.76-24.77 for the Cox model; HR 2.41, 95% CI 1.14-5.14 for the competing risk model), age per year (HR 1.10, 95% CI 1.05-1.15 for the Cox model; HR 1.06, 95% CI 1.02-1.09 for the competing risk model), and dementia (HR 6.31, 95% CI 2.49-15.99 for the Cox model; HR 7.50, 95% CI 2.84-19.85 for the competing risk model) significantly increased the risk of BP. CONCLUSIONS: Neurological cancer increased the risk for subsequent BP by 2.4-fold, with a relatively short gap of 4.5 years.

Effect of energy per atom (E/n) on the Ar gas cluster ion beam (Ar-GCIB) and O2+ cosputter process.

Gas cluster ion beam (GCIB) is a promising technique for preserving molecular structures during ion sputtering and successfully profiling biological and soft materials. However, although GCIB yields lower damage accumulation compared with C60+ and monoatomic ion beams, the inevitable alteration of the chemical structure can introduce artifacts into the resulting depth profile. To enhance the ionization yield and further mask damage, a low-energy O2+ (200-500 V) cosputter can be applied. While the energy per atom (E/n) of GCIB is known to be an important factor influencing the sputter process, the manner through which E/n affects the GCIB-O2+ cosputter process remains unclear. In this study, poly(ethylene terephthalate) (PET) was used as a model material to investigate the sputter process of 10-20 kV Ar1000-4000+ (E/n = 2.5-20 eV per atom) with and without O2+ cosputter at different energies and currents. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) with Bi32+ as the primary ion was used to examine surfaces sputtered at different fluences. The sputter craters were also measured by alpha-step and atomic force microscopy in quantitative imaging mode. The SIMS results showed that the steady-state cannot be obtained with E/n values of less than 5 eV per atom due to damage accumulation using single GCIB sputtering. With a moderate E/n value of 5-15 eV per atom, the steady-state can be obtained, but the ∼50% decay in intensity indicated that damage cannot be masked completely despite the higher sputter yield. Furthermore, the surface Young's modulus decreased with increasing E/n, suggesting that depolymerization occurred. At an E/n value of 20 eV per atom, a failed profile was obtained with rapidly decreased sputter rate and secondary ion intensity due to the ion-induced crosslink. With O2+ cosputtering and a moderate E/n value, the oxidized species generated by O2+ enhanced the ionization yield, which led to a higher ion intensity at steady-state in general. Because higher kinetic energy or current density of O2+ led to a larger interaction volume and more structural damage that suppressed molecular ion intensity, the enhancement from O2+ was most apparent with low-energy-high-current (200 V, 80 µA cm-2) or high-energy-low-current (500 V, 5 µA cm-2) O2+ cosputtering with 0.5 µA cm-2 GCIBs. In these cases, little or no intensity drop was observed at the steady-state.

Smoking, but not alcohol, is associated with risk of psoriasis in a Taiwanese population-based cohort study.

BACKGROUND: Alcohol consumption and smoking have long been suspected of increasing the risk of developing psoriasis. Most evidence to date has derived from cross-sectional or case-control studies. OBJECTIVE: We sought to investigate the effects of alcohol and smoking on incident psoriasis. METHODS: Alcohol consumption, smoking status, and other covariates were collected from four rounds (2001, 2005, 2009, and 2013) of the Taiwan National Health Interview Survey. Incident psoriasis was identified from the National Health Insurance database. Cox regression model was used for the analysis. RESULTS: Of 60,136 subjects, 242 (0.40%) developed psoriasis. After controlling for demographics and comorbidities, alcohol consumption was not significantly associated with psoriasis risk. Conversely, psoriasis risk was higher for current smokers than never smokers (adjusted hazard ratio 1.47 [95% confidence interval 1.04-2.07]). The risks were higher among subjects who smoked >25 cigarettes per day and for >20 pack-years. In subgroup analysis, current smoking was significantly associated with risk of psoriasis without psoriatic arthritis but not psoriatic arthritis alone. LIMITATIONS: Alcohol consumption was not assessed based on the number of drinks consumed. CONCLUSION: Current smoking increased the risk of psoriasis, particularly augmented for individuals who smoked >25 cigarettes per day and for >20 pack-years, while alcohol consumption was not significantly associated with psoriasis development.

The Risk of Mortality among Psoriatic Patients with Varying Severity: A Nationwide Population-Based Cohort Study in Taiwan.

Background: Previous studies showed conflicting results regarding the mortality risk in psoriasis patients with respect to disease severity and presence of psoriatic arthritis. This study aimed to determine the mortality risk in patients with mild and severe psoriasis and patients with psoriatic arthritis (PsA). Methods: A nationwide population-based cohort study was conducted based on data from the Taiwan National Health Insurance Research Database between 2002 and 2012. Incident psoriasis subjects were classified into two groups: psoriasis without arthritis and psoriasis with arthritis. Patients who had received systemic therapy and/or phototherapy were classified as having severe psoriasis; otherwise, patients were classified as having mild psoriasis. Control subjects without psoriasis were selected to match each psoriasis patient from the database within the same observational period. Cox proportional hazards analysis was used to compare the hazard ratio (HR) of time to death. Results: A total of 106,701 patients with psoriasis were included in this study. After controlling for demographics and comorbidities, psoriasis patients had a higher mortality risk compared with the control group (HR 1.41; 95% confidence interval (CI) 1.36 to 1.46). Compared with psoriasis alone, the mortality risk was not increased for PsA (HR = 1.01; 95% CI 0.93 to 1.10). Besides, severe psoriasis did not increase mortality risk compared with mild psoriasis (HR = 1.0; 95% CI 0.95 to 1.06). Conclusions: Patients with psoriasis had a higher mortality risk compared with control subjects, whereas psoriasis severity and presence of PsA had no impact on mortality risk in psoriasis patients.

Cancer Risks in Vitiligo Patients: A Nationwide Population-Based Study in Taiwan.

Vitiligo is an autoimmune disease characterized by destruction of melanocytes and associated with other autoimmune disease. Whether the dysregulation of immune system enhances oncogenesis or not remains obscure. Until now, no nationwide population-based study has been conducted regarding this. As such, this paper aims to clarify cancer risk in vitiligo patients. A retrospective nationwide population-based cohort study between 2000 and 2010 was performed based on data from the National Health Insurance Research Database of Taiwan. Standardized incidence ratios (SIRs) of cancers were analyzed. Among the 12,391 vitiligo patients (5364 males and 7027 females) and 48,531.09 person-years of observation, a total of 345 cancers were identified. Significantly increased SIRs were observed for prostate cancer in male patients, thyroid cancer and breast cancer in female patients and bladder cancers in both male and female patients. Unfortunately, the low incidence rate of certain cancers limited the power of our statistical analyses. This study demonstrated the patterns of malignancies in vitiligo patients of Taiwan. Compared with the general population, male patients had higher risks of prostate cancer and female patients had higher risks of thyroid cancer and breast cancer. The risks of bladder cancer were also increased in both male and female patients.

Albumin levels and cause-specific mortality in community-dwelling older adults.

To investigate the association between serum albumin levels and cause-specific mortality among community-dwelling older adults. This cohort study was based on data obtained from the government-sponsored Annual Geriatric Health Examination Program for the older adults in Taipei City between 2006 and 2010. The study sample consisted of 77,531 community-dwelling Taipei citizens (≥65 years old). Mortality was determined by matching the participants' medical records with national death files. Serum albumin levels were categorized into <3.6, 3.6-3.7, 3.8-3.9, 4.0-4.1, 4.2-4.3, and ≥4.4 g/dL. Cox proportional hazards regression models were used to evaluate the association between albumin levels and cause-specific mortality. Spline regression was used to calculate the risk of mortality associated with albumin levels, modeled as continuous variables. Community-dwelling older adults had a mean albumin level of 4.3 g/dL, which significantly reduced by age. Compared to albumin levels ≥4.4 g/dL, mildly low albumin levels (4.2-4.3 g/dL) were associated with an increased mortality risk (hazard ratio [HR]: 1.16, 95% confidence interval [CI]: 1.05-1.28 for all-cause mortality), and albumin levels <4.2 g/dL were associated with significantly higher rates of all-cause, cancer, cardiovascular, and respiratory mortalities. In the spline regression, the curve of mortality risk was relatively flat at an albumin level ≥4.4 g/dL, and the mortality risk gradually increased as the albumin level declined. Albumin levels ≥4.4 g/dL were associated with better survival among community-dwelling older adults, and mortality risk increased as the albumin level decreased.

Integration of paper-based microarray and time-of-flight secondary ion mass spectrometry (ToF-SIMS) for parallel detection and quantification of molecules in multiple samples automatically.

With its low-cost fabrication and ease of modification, paper-based analytical devices have developed rapidly in recent years. Microarrays allow automatic analysis of multiple samples or multiple reactions with minimal sample consumption. While cellulose paper is generally used, its high backgrounds in spectrometry outside of the visible range has limited its application to be mostly colorimetric analysis. In this work, glass-microfiber paper is used as the substrate for a microarray. The glass-microfiber is essentially chemically inert SiOx, and the lower background from this inorganic microfiber can avoid interference from organic analytes in various spectrometers. However, generally used wax printing fails to wet glass microfibers to form hydrophobic barriers. Therefore, to prepare the hydrophobic-hydrophilic pattern, the glass-microfiber paper was first modified with an octadecyltrichlorosilane (OTS) self-assembled monolayer (SAM) to make the paper hydrophobic. A hydrophilic microarray was then prepared using a CO2 laser scriber that selectively removed the OTS layer with a designed pattern. One microliter of aqueous drops of peptides at various concentrations were then dispensed inside the round patterns where OTS SAM was removed while the surrounding area with OTS layer served as a barrier to separate each drop. The resulting specimen of multiple spots was automatically analyzed with a time-of-flight secondary ion mass spectrometer (ToF-SIMS), and all of the secondary ions were collected. Among the various cluster ions that have developed over the past decade, pulsed C60+ was selected as the primary ion because of its high secondary ion intensity in the high mass region, its minimal alteration of the surface when operating within the static-limit and spatial resolution at the ∼µm level. In the resulting spectra, parent ions of various peptides (in the forms [M+H]+ and [M+Na]+) were readily identified for parallel detection of molecules in a mixture. By normalizing the ion intensity of peptides with respect to the glass-microfiber matrix ([SiOH]+), a linear calibration curve for each peptide was generated to quantify these components in a mixture.

Comorbid autoimmune diseases in patients with sarcoidosis: A nationwide case-control study in Taiwan.

The association between sarcoidosis and autoimmune comorbidities has been reported, however, it has seldom been confirmed by a large nationwide study. Our study aimed to clarify the association between sarcoidosis and autoimmune comorbidities in the Taiwanese. A total of 1237 patients with sarcoidosis and 4948 age- and sex-matched control subjects were selected from the National Health Insurance Research Database of Taiwan from 1997 to 2010. Multiple logistic regressions were performed to calculate the odds of comorbidities between the two groups. The prevalence of sarcoidosis was 2.17/100 000 individuals in Taiwan. Sarcoidosis patients tended to run a higher risk of autoimmune comorbidities than the control group (17.6% vs 9.4%, P < 0.05). Autoimmune thyroid disease (adjusted odd ratio [aOR], 1.32; 95% confidence interval [CI], 1.05-1.64), Sjögren's syndrome (aOR, 11.6; 95% CI, 4.36-31.0) and ankylosing spondylitis (aOR, 3.80; 95% CI, 2.42-5.97) were significantly associated with sarcoidosis. The sex-stratified analyses were carried out to demonstrate a significant association of sarcoidosis with ankylosing spondylitis in both sexes, but with autoimmune thyroid disease in male patients and with Sjögren's syndrome female patients, respectively. Besides, the diagnosis of the autoimmune comorbidities strongly associated with sarcoidosis tended to be established after that of sarcoidosis. This study demonstrated that patients with sarcoidosis tended to have autoimmune thyroid disease, Sjögren's syndrome and ankylosing spondylitis, and the diagnosis of sarcoidosis usually preceded that of associated comorbidities. Clinicians should be alert to autoimmune comorbidities in patients with sarcoidosis.

What Constitutes Normal Hemoglobin Concentrations in Community-Dwelling Older Adults?

OBJECTIVES: To assess the relationship between hemoglobin concentration and cause-specific mortality. DESIGN: Cohort study. SETTING: Data from the government-sponsored Annual Geriatric Health Examination Program. PARTICIPANTS: Community-dwelling Taipei citizens aged 65 and older followed up between 2006 and 2010 (N = 77,532). MEASUREMENTS: Mortality was determined by matching participants' medical records with national death files. Cox proportional hazards regression models were used to evaluate the relationship between hemoglobin concentration (World Health Organization (WHO)-defined anemia and 7 hemoglobin concentrations) and cause-specific mortality. RESULTS: The mortality risk of WHO-defined anemia increased substantially in both sexes for all-cause and cancer mortalities (men, hazard ratio (HR) = 1.86, 95% confidence interval (CI) = 1.71-2.02 for all-cause mortality; HR = 1.94, 95% CI = 1.69-2.22 for cancer mortality; for women, HR = 1.63, 95% CI = 1.43-1.86 for all-cause mortality; HR = 1.74, 95% CI = 1.38-2.19 for cancer mortality). Men with hemoglobin concentrations of 15.0 to 15.9 g/dL and women with hemoglobin concentrations of 13.0 to 13.9 g/dL had the lowest risks of all-cause, cardiovascular, and cancer mortality. Risks of all-cause and cancer mortality increased significantly when hemoglobin concentrations were less than 14 g/dL in men and less than 12 g/dL in women. Even mild anemia (11.0-11.9 g/dL) was associated with greater mortality risk. Stratification according to age, body mass index, estimated glomerular filtration rate, and presence of comorbidities did not lead to any substantial changes. CONCLUSION: Hemoglobin concentrations associated with optimal survival in older adults were identified and additional data provided regarding the relationship between hemoglobin concentrations and cause-specific mortality risks in older adults.