Lessons learned: establishing a CLIA-equivalent laboratory for targeted mass spectrometry assays - navigating the transition from research to clinical practice.

Mass spectrometry (MS) assays offer exceptional capabilities in high multiplexity, specificity, and throughput. As proteomics technologies continue advancements to identify new disease biomarkers, transition of these innovations from research settings to clinical applications becomes imperative. To meet the rigorous regulatory standards of clinical laboratories, development of a clinical protein MS assay necessitates adherence to stringent criteria. To illustrate the process, this project focused on using thyroglobulin (Tg) as a biomarker and an immuno-multiple reaction monitoring (iMRM) MS-based assay as a model for establishing a Clinical Laboratory Improvement Amendments (CLIA) compliant laboratory within the Centers of Genomic and Precision Medicine, National Taiwan University. The chosen example also illustrates the clinical utility of MS assays to complement conventional immunoassay-based methods, particularly in cases where the presence of autoantibodies in 10-30% of patients hinders accuracy. The laboratory design entails a comprehensive coordination in spatial layout, workflow organization, equipment selection, ventilation systems, plumbing, electrical infrastructure, documentation procedures, and communication protocols. Practical aspects of the transformation process, including preparing laboratory facilities, testing environments, instrument validation, assay development and validation, quality management, sample testing, and personnel competency, are discussed. Finally, concordant results in proficiency testing demonstrate the harmonization with the University of Washington Medical Center and the quality assurance of the CLIA-equivalent Tg-iMRM MS assay established in Taiwan. The realization of this model protein MS assay in Taiwan highlights the feasibility of international joint development and provides a detailed reference map to expedite the implementation of more MS-based protein assays in clinical laboratories for patient care.

Predictors of Prolonged Euthyroidism After Radioactive Iodine Treatment for Graves' Disease: A Pilot Study.

OBJECTIVE: Patients with Graves' disease who remain hyperthyroid under the treatment of antithyroid drugs (ATD) or cannot tolerate ATD usually receive radioactive iodine (RAI) to control disease activity. This pilot study aimed to identify predictors of prolonged euthyroidism > 12 months after receiving RAI. METHODS: Demographic, clinical, and laboratory data from 117 patients receiving RAI were retrospectively collected, including age, gender, body surface area, smoking status, free thyroxine, thyrotropin, thyrotropin binding inhibiting immunoglobulin, microsomal antibody, thyroglobulin antibody, medication history, and thyroid volume. Only 85 patients without missing values were included in statistical analysis. The calculated RAI dose was the estimated thyroid volume × 0.4. The difference and ratio between the actual and calculated RAI doses were examined. A stepwise logistic regression analysis was conducted to identify important predictors of prolonged euthyroidism > 12 months. The cut-off values for discretizing continuous covariates were estimated by fitting generalized additive models. RESULTS: Among the 85 patients on RAI, 18 (21.2%) achieved prolonged euthyroidism > 12 months, 38 (44.7%) remained hyperthyroid with decreased ATD doses, but 29 (34.1%) suffered permanent hypothyroidism and needed long-term levothyroxine. Logistic regression analysis revealed that patients with age > 66 years, 33 < age ≤ 66 years, quitting smoking vs nonsmoking or current smoking, 600 < micorsomal antibody ≤ 1729 IU/mL, 47% < thyrotropin binding inhibiting immunoglobulin ≤ 81%, 7 < thyroglobulin antibody ≤ 162 IU/mL, 0.63 < ratio between actual and calculated RAI doses ≤ 1.96, or taking hydroxychloroquine would have a higher chance of reaching prolonged euthyroidism > 12 months after receiving RAI. Its area under the Receiver Operating Characteristic (ROC) curve was 0.932. CONCLUSION: Patients with Graves' disease who received an actual RAI dose close to the calculated RAI dose achieved prolonged euthyroidism > 12 months if they also took hydroxychloroquine during RAI treatment.

Immunotherapy in anaplastic thyroid cancer: Case series.

Unresectable anaplastic thyroid cancer (ATC) has a poor prognosis. Chemotherapy and radiotherapy have limited effects on it. Here, we present four cases who underwent immunotherapy for ATC. The patients were aged between 58 and 70 years. Two male patients with pulmonary metastases received pembrolizumab and lenvatinib. However, they died of septic shock and respiratory failure in 2.7 and 1 months, respectively, after the initiation of combination therapy. Another male patient with stage IVB disease was treated with spartalizumab. The tumor remained stable after surgical debulking but slightly progressed after 23 months. He survived for 45.5 months after spartalizumab initiation. A female patient with BRAF-mutant ATC and lung metastases was treated with a combination of pembrolizumab and lenvatinib, which was complicated with grade 4 transaminitis. The patient subsequently received dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor) treatment, which was continued for 10.2 months with a best response of partial remission. She died 18 months after the initial diagnosis (11.4 months after treatment with dabrafenib and trametinib). In conclusion, the treatment responses of immunotherapy, either alone or in combination with other therapies, were highly variable in patients with ATC and should be carefully monitored along with the side effects.

Different cutoffs of hypertension, risk of incident diabetes and progression of insulin resistance: A prospective cohort study.

BACKGROUND/PURPOSE: Hypertension is a risk factor of incident diabetes. In 2017, the ACC/AHA updated the definition of hypertension to above 130/80 mmHg, while the 2018 ESC/ESH guideline and the JNC7 criteria remained the cutoff of 140/90 mmHg. This study was aimed to investigate how different cutoffs of hypertension affect the association of hypertension to incident diabetes and the progression of insulin resistance. METHODS: A total of 1177 subjects without diabetes at baseline were followed for 4.5 years. Diabetes was diagnosed by the results of oral glucose tolerance tests and hemoglobin A1c, or if anti-diabetic agents were used. RESULTS: Hypertension by both criteria was associated with incident diabetes. Change of HOMA2-IR every 5 years (ΔHOMA2-IR/5 yr) was higher in subjects with hypertension than those without (adjusted p = 0.044). Subjects with treated hypertension had the highest risk of diabetes (HR 2.98, p < 0.001) and ΔHOMA2-IR/5 yr, compared with subjects with normal blood pressure. However, the associations of hypertension, HR of incident diabetes and ΔHOMA2-IR/5 yr were attenuated by the 2017 ACC/AHA criteria, as compared with that by the JNC7 and 2018 ESC/ESH criteria. CONCLUSION: Hypertension by both criteria is associated with incident diabetes and accelerated progression of insulin resistance, and the associations are attenuated by the 2017 ACC/AHA criteria.

Endoscopic ultrasound ablation in a patient with multiple metastatic pancreatic tumors from adrenocorticotropic hormone-producing thymic neuroendocrine neoplasm.

Adrenocorticotropic hormone (ACTH)-producing neuroendocrine neoplasm (NEN) of the thymus is rare. Lymph nodes and bones are the most common metastatic sites. Most cases present with florid Cushing's syndrome (CS). Here, we reported a 58-year-old woman, who presented with intermittent flush and weight loss. Imaging studies revealed tumors in the mediastinum, pancreas, and bones. Contrast-enhanced harmonic endoscopic ultrasound (EUS) of the pancreatic tumors showed heterogeneous and hyperenhancing characteristics. EUS elastography revealed a heterogeneous stiff pattern. EUS-fine needle biopsy to the pancreatic lesion confirmed the NEN nature. Serum ACTH and cortisol levels were abnormally high. Immunohistochemical staining of the thymic and pancreatic specimens was positive for ACTH. However, the patient did not have obvious CS appearance. The patient underwent surgery, radiation, EUS-guided ethanol injection, and anti-cancer medications, but the disease still progressed. The patient died from infection 16 months after NEN was diagnosed. In conclusion, the pancreas can be a metastatic site for ACTH-producing thymic NEN. EUS-associated procedures can help in the diagnosis and treatment of pancreatic metastatic NEN.

Immediate knowledge improvement and long-term teaching confidence after general medicine faculty training program.

BACKGROUND/PURPOSE: This study analyzed the effects of the General Medicine Faculty Training Program (GMFTP), which was implemented in 2009. The training program includes a 7-hour basic training (BT) to introduce ways of teaching and assessing the 6 core competencies identified by the Accreditation Council for Graduate Medical Education, and a 40-hour clinical training program. METHODS: Physicians from different hospitals attended the GMFTPs. Since 2010, we have been using quick tests to assess trainees' familiarity of core competencies. Knowledge improvement (KI) was defined as the difference between post-BT and pre-BT test scores. Since 2013, we have been annually mailing questionnaires to assess trainees' teaching confidence (TC) of core competencies. We analyzed the correlations between trainees' characteristics, KIs, and TCs. RESULTS: Between year 2009 and 2017, a total of 319 attending physicians (257 male, 62 female), with a mean age of 39.1 ± 6.2 years, completed the GMFTPs. Significant KI (32.6-55.4) was noted. There were no correlations between trainees' characteristics and KIs. The mean TCs for the 6 core competences were all above 4.0 (based on a 5-point Likert scale). TCs were positively correlated with age during GMFTP training, age when responding to the questionnaire, and duration between training and the last time responding to the questionnaire. TC showed no correlation with sex, hospitals, departments, or KI. CONCLUSION: Knowledge of teaching core competencies improved immediately after BT, but KIs did not correlate with TCs in long-term follow-up. After the training program, physicians' teaching confidence increased over time.

Immune checkpoint inhibitor therapy-induced hypophysitis ∼ a case series of Taiwanese patients.

Immune checkpoint blockade-based immunotherapy is a new modality of cancer treatment with a unique mechanism that has gained increased numbers of indication and is now used in several cancer types. However, immune-related adverse events (irAEs) emerge as a new entity of diseases involving one or multiple organ systems. irAEs could result in interruption of immunotherapy, morbidities or even death. Among various manifestations of irAEs, immune-mediated hypophysitis is rare but important, requiring prompt diagnosis and treatment to avoid life-threatening conditions. We report seven cases of immune-mediated hypophysitis in Taiwan. They suffered from various types of advanced cancer and received different regimens of immune checkpoint inhibitors. The time of onset after initiation of immunotherapy ranged from 5 to 36 weeks. All seven subjects were diagnosed of central adrenal insufficiency, while four of them had primary hypothyroidism. There was no typical finding of infiltrative hypophysitis on the pituitary MRI. There was no documented hormone recovery after diagnosis of hypophysitis, and the tumor responses to immunotherapy were variable in these seven patients. In conclusion, immune-mediated hypophysitis is often irreversible. Fortunately, it can be managed adequately with hormone replacements. Further investigations are warranted to unveil underlying mechanisms and ethnic differences to guide the solutions.

Extramedullary hematopoiesis involving the thyroid: A rare cytologic finding in otherwise healthy patients and review of literature.

BACKGROUND/PURPOSE: The thyroid gland is an uncommon site for the presence of extramedullary hematopoiesis (EMH). We report the cases of four Taiwanese women with hematopoietic elements on the smears of thyroid fine needle aspiration (FNA) samples and compare the findings with those of previously reported cases. METHODS: We retrieved the data of cases in which thyroid FNA performed between January 2000 and December 2016. The clinical manifestations, laboratory data, and image findings of cases with thyroid EMH were reported. A review of English literature was performed, and the reported cases were compared with our series. RESULTS: During the study period, 63,361 specimens of thyroid FNAs were identified. Four specimens contained hematopoietic elements from four women. Ultrasound study revealed calcifications in three patients. A review of English literature yielded 18 reports of thyroid EMH involving 29 patients. Twenty-six patients were women, and three were men. Nodule calcifications were found in 13 patients. Four patients had primary myelofibrosis, and one had chronic anemia. None had a thyroid malignancy. CONCLUSION: Four patients were noted to have bone marrow elements on the smears among 63,361 thyroid FNA samples. These four Taiwanese women presented with nodular goiter and foci of hematopoietic elements by thyroid FNA without any chronic disease of hematopoietic tissue or any evidence of a thyroid malignancy.

Improvement of Pituitary Function after Carotid Revascularization in Patients with Abnormal Cerebral Perfusion - A Pilot Study.

BACKGROUND: Brain ischemia may affect hypothalamic-pituitary axis function, which may influence the outcomes of patients with internal carotid artery (ICA) stenosis/occlusion. The objective of this study was to determine the influence of successful carotid revascularization on pituitary function in patients with severe ICA stenosis/occlusion. METHODS: This study was conducted from April 2009 to December 2014. Patients receiving successful endovascular interventions for severe ICA stenosis/occlusion were enrolled. The patients were divided into 2 groups: group 1 with abnormal ipsilateral cerebral perfusion, and group 2 without. Endocrine profiles were measured before and > 1 year after the procedure. Computed tomography perfusion studies were used to assess brain perfusion. RESULTS: Thirty-seven patients received successful interventions. Three patients were excluded due to re-stenosis before 1 year. There were 23 and 11 patients in group 1 and 2, with mean ages of 68 and 69 years, respectively. In the female patients, follicular stimulating hormone (FSH) and luteinizing hormone (LH) increased significantly (p = 0.043) after the interventions with a stable estradiol level in group 1. In contrast, FSH, LH and estradiol showed a decreasing trend in group 2. In the male patients, FSH and LH increased significantly (p < 0.01) after the interventions with a stable testosterone level in group 1, while testosterone showed a decreasing trend in group 2. Thyroid stimulating hormone increased significantly in the women in both groups, and in the men in group 1. CONCLUSIONS: Successful revascularization for severe ICA stenosis/occlusion may improve their pituitary function, especially FSH and LH levels.

Adrenocorticotropic hormone levels before treatment predict recurrence of Cushing's disease.

BACKGROUND/PURPOSE: Cushing's disease (CD) is the most common cause of endogenous Cushing's syndrome. Transsphenoidal surgery (TSS) is the first choice of treatment. Predicting prognosis after treatment can benefit further strategies of management, but currently there is no convenient predictor. This study aims to investigate characteristic changes after treatment and to identify potential prognostic predictors. METHODS: We retrospectively studied the records of CD patients presenting to the National Taiwan University Hospital, Taipei, Taiwan between 1992 and 2011. They were categorized according to treatment response. Clinical features and examination findings were compared between groups. RESULTS: Forty-one patients with CD were included. The follow-up time was 0.26-19.3 years. The time interval between the onset of symptoms and diagnosis was 2.1-120.0 months. The initial remission rate of CD after the first treatment was 82.9%. Mean body mass index (BMI) was 27.4 kg/m2 before treatment and 26.0 kg/m2 3 months after treatment. The patients in remission had a greater decrease in BMI after treatment and lower dehydroepiandrosterone sulfate (DHEAS) levels before treatment, compared with the recurrent group (both p < 0.05). Adrenocorticotropic hormone (ACTH) levels before treatment showed a significant positive correlation with recurrent diseases (p < 0.05). CONCLUSION: A larger decrease in BMI after treatment and lower DHEAS levels before treatment were noted for the patients who stayed in CD remission. Higher ACTH levels before treatment predicted a recurrence of CD. These are potentially simple and practical predictors of prognosis.

Characterization of FN1-FGFR1 and novel FN1-FGF1 fusion genes in a large series of phosphaturic mesenchymal tumors.

Phosphaturic mesenchymal tumors typically cause paraneoplastic osteomalacia, chiefly as a result of FGF23 secretion. In a prior study, we identified FN1-FGFR1 fusion in 9 of 15 phosphaturic mesenchymal tumors. In this study, a total of 66 phosphaturic mesenchymal tumors and 7 tumors resembling phosphaturic mesenchymal tumor but without known phosphaturia were studied. A novel FN1-FGF1 fusion gene was identified in two cases without FN1-FGFR1 fusion by RNA sequencing and cross-validated with direct sequencing and western blot. Fluorescence in situ hybridization analyses revealed FN1-FGFR1 fusion in 16 of 39 (41%) phosphaturic mesenchymal tumors and identified an additional case with FN1-FGF1 fusion. The two fusion genes were mutually exclusive. Combined with previous data, the overall prevalence of FN1-FGFR1 and FN1-FGF1 fusions was 42% (21/50) and 6% (3/50), respectively. FGFR1 immunohistochemistry was positive in 82% (45/55) of phosphaturic mesenchymal tumors regardless of fusion status. By contrast, 121 cases of potential morphologic mimics (belonging to 13 tumor types) rarely expressed FGFR1, the main exceptions being solitary fibrous tumors (positive in 40%), chondroblastomas (40%), and giant cell tumors of bone (38%), suggesting a possible role for FGFR1 immunohistochemistry in the diagnosis of phosphaturic mesenchymal tumor. With the exception of one case reported in our prior study, none of the remaining tumors resembling phosphaturic mesenchymal tumor had either fusion type or expressed significant FGFR1. Our findings provide insight into possible mechanisms underlying the pathogenesis of phosphaturic mesenchymal tumor and imply a central role of the FGF1-FGFR1 signaling pathway. The novel FN1-FGF1 protein is expected to be secreted and serves as a ligand that binds and activates FGFR1 to achieve an autocrine loop. Further study is required to determine the functions of these fusion proteins.

Identification of a novel FN1-FGFR1 genetic fusion as a frequent event in phosphaturic mesenchymal tumour.

Phosphaturic mesenchymal tumours (PMTs) are uncommon soft tissue and bone tumours that typically cause hypophosphataemia and tumour-induced osteomalacia (TIO) through secretion of phosphatonins including fibroblast growth factor 23 (FGF23). PMT has recently been accepted by the World Health Organization as a formal tumour entity. The genetic basis and oncogenic pathways underlying its tumourigenesis remain obscure. In this study, we identified a novel FN1-FGFR1 fusion gene in three out of four PMTs by next-generation RNA sequencing. The fusion transcripts and proteins were subsequently confirmed with RT-PCR and western blotting. Fluorescence in situ hybridization analysis showed six cases with FN1-FGFR1 fusion out of an additional 11 PMTs. Overall, nine out of 15 PMTs (60%) harboured this fusion. The FN1 gene possibly provides its constitutively active promoter and the encoded protein's oligomerization domains to overexpress and facilitate the activation of the FGFR1 kinase domain. Interestingly, unlike the prototypical leukaemia-inducing FGFR1 fusion genes, which are ligand-independent, the FN1-FGFR1 chimeric protein was predicted to preserve its ligand-binding domains, suggesting an advantage of the presence of its ligands (such as FGF23 secreted at high levels by the tumour) in the activation of the chimeric receptor tyrosine kinase, thus effecting an autocrine or a paracrine mechanism of tumourigenesis.

Perioperative growth hormone levels as an early predictor of new-onset secondary adrenal insufficiency following transsphenoidal pituitary tumor resection.

OBJECTIVE: This study aims to predict new-onset secondary adrenal insufficiency (NOSAI) after transsphenoidal pituitary tumor resection surgery using perioperative growth hormone (GH) and prolactin (PRL) levels, among other factors. METHODS: A cohort of 124 adult patients who underwent transsphenoidal resection for non-functioning pituitary adenoma, with routine perioperative glucocorticoid use, was used to develop the predictive regression model. An additional 46 patients served as the validation cohort. Generalized additive models were used to identify optimal cut-off points for the variables. RESULTS: The GH level on postoperative day one (POD1) can be a simple predictor by implementing a cut-off point of 0.41 ng/ml. A value ≤ 0.41 ng/mL predicted NOSAI with 0.6316 sensitivity and 0.7810 specificity for the original cohort and 1.0000 sensitivity and 0.7143 specificity for the validation cohort. The multiple logistic regression model included perioperative PRL level difference, perioperative GH level difference, intraoperative cerebrospinal fluid (CSF) leakage, tumor size, and the combined effect of diabetes insipidus (DI) and relative perioperative GH level difference. The areas under the receiver operating characteristic curves were 0.9410 (original cohort) and 0.9494 (validation cohort) for the regression model. CONCLUSION: Early morning GH level on POD1 can predict NOSAI with fair accuracy when perioperative stress dose glucocorticoid is administered. Prediction accuracy can be improved by considering CSF leakage, DI, and perioperative changes in GH and PRL in the final regression model.

Long-Term Changes of Urinary Exosomal Peptide Levels After Thyroidectomy in Patients with Thyroid Cancer: A Prospective Observational Study.

Background: The recurrence rate of thyroid cancer can be as high as 30%. The purpose of this study was to examine changes of urine exosomal peptide levels after thyroidectomy in patients with thyroid cancer to determine if levels can predict the risk of recurrence. Methods: Patients >20 years old as newly diagnosed with papillary thyroid cancer who had received a thyroidectomy were recruited. Urine samples were collected at 12 months after enrollment to the study, and 1 year later. Urine exosomes containing different peptides were identified and compared. Results: A total of 70 patients were enrolled in the study, and were classified by the interval between surgery and enrollment: 42 patients with < 5 years between surgery and enrollment, 14 patients between 5-10 years, and 14 patients longer than 10 years. No recurrence was observed in any patient during the 2 years after enrollment. No significant differences were found in the levels of serum proteins or urine exosomal peptides between groups, or between intervals. Known risk factors for high-risk thyroid cancer had only a mild correlation with serum protein levels and urine exosomal peptides. Conclusion: Our study revealed the long-term basal fluctuation ranges of serum proteins and urine exosomal peptides in patients with thyroid cancer who underwent thyroidectomy. For high-risk patients after thyroidectomy, concentrations of serum proteins or urine exosomal peptides within the ranges may indicate there is a lower risk of thyroid cancer recurrence during long-term follow-up. Trial Registration: ClinicalTrials.gov: NCT03488134.

An Appraisal of the Preventive Effect of Statins on the Development of Graves' Ophthalmopathy: A Hospital-Based Cohort Study.

INTRODUCTION: Graves' ophthalmopathy (GO) is an autoimmune inflammatory disorder observed in a substantial proportion of patients with Graves' disease (GD), with debilitating symptoms of disfiguring, periorbital pain, dry eyes, diplopia, and even visual disturbances. Previous studies involving Western populations have noted discrepancies in risk factors for GO. Therefore, this study aimed to determine the risk factors for GO development and the protective effect of statins in newly diagnosed patients with GD in Taiwan. METHODS: This retrospective case-control study was based on a tertiary center cohort involving patients with GD diagnosed between 2010 and 2019 at the National Taiwan University Hospital (n = 11,035). Patients who were diagnosed or treated elsewhere, had been followed up for less than 6 months or were with a diagnosis of orbital tumor were excluded. Overall, 3578 patients with GD met the inclusion criteria. Univariate and multivariate logistic regression analyses were used to ascertain the odds ratio (OR) of developing GO, with adjustment for sociodemographic factors, interventions for managing GD and thyroid hormone levels, to determine protective and risk factors for GO. RESULTS: In our multivariate model, the use of statins reduced the risk of GO development (OR 0.2; 95% confidence interval [CI] 0.08-0.50; p < 0.001). Thyroid dysfunction including hyperthyroidism (OR 4.2; 95% CI 2.97-5.88; p < 0.001) and hypothyroidism (OR 4.7; 95% CI 3.02-7.19; p < 0.001) was associated with an increased risk of developing GO. Smoking status and lipid profile were not risk factors in our cohort. CONCLUSION: In newly diagnosed patients with GD, the use of statins decreased the risk of developing GO by 80%, whereas serum lipid levels were not considered risk factors. Further nationwide population-based studies may help clarify the differences in risk factors between various ethnic groups. TRAIL REGISTRATION: This trial was approved by the Research Ethics Committee of National Taiwan University Hospital (202202066RINC), retrospectively registered from January 1, 2010 to December 31, 2019.

Hypogonadism among HIV-positive men who have sex with men in Taiwan: Prevalence and associated factors.

BACKGROUND: Male hypogonadism is not uncommon in people with HIV (PWH), with estimated prevalence ranging from 9% to 16%. Existing data are limited on the serum testosterone levels in PWH in Asian populations. METHODS: We enrolled HIV-positive men who have sex with men (MSM) and had been on stable antiretroviral therapy and MSM without HIV between February 2021 and November 2022. Serum free testosterone levels, sex hormone-binding globulins and other associated hormones were measured. Multiple linear regression analysis was performed to assess the association between serum free testosterone levels and clinical variables collected. RESULTS: A total of 447 MSM with HIV and 124 MSM without HIV were enrolled. Compared with MSM without HIV, MSM with HIV had a higher age (median, 41 versus 29.5 years) and prevalence of symptomatic hypogonadism (8.3% versus 1.6%). Among MSM who were aged <35 years, there were no significant differences in the serum free testosterone levels and prevalences of hypogonadism between the two groups. In multiple linear regression analysis, serum free testosterone level significantly decreased with advanced age (a decrease of 1.14 pg/mL per 1-year increase) and a higher body-mass index (BMI) (a decrease of 1.07 pg/mL per 1-kg/m2 increase), but was not associated with HIV serostatus. CONCLUSION: We found that MSM with HIV had a higher prevalence of symptomatic hypogonadism than MSM without HIV in Taiwan, which could be attributed to age difference. Serum free testosterone levels were negatively correlated with age and BMI, but did not show a significant correlation with HIV serostatus.

Serum vascular adhesion protein-1 level is higher in smokers than non-smokers.

BACKGROUND: Semicarbazide-sensitive amine oxidase (SSAO)/vascular adhesion protein-1 (VAP-1) is involved in the pathogenesis of both atherosclerosis and cancer. Because chemical components and metabolites of cigarettes are deaminated by SSAO, the relationship between smoking and serum SSAO/VAP-1 was studied in humans. METHODS: A total of 451 non-diabetic and normoalbuminuric Han Chinese subjects were recruited to participate in this study. Smoking history was obtained by using a questionnaire and those who smoked more than 100 cigarettes during a 6-month period were considered smokers. Serum VAP-1 concentration was measured by time-resolved immunofluorometric assay. Age, gender, waist circumference and estimated glomerular filtration rate (GFR) were adjusted in different statistical models. RESULTS: Smokers were mainly male (85.7% versus 26.3%) and were more obese than non-smokers (p < 0.05). Subjects with higher serum VAP-1 concentrations were older (p < 0.001) and tended to have larger waist circumferences and lower estimated GFR. Serum VAP-1 concentration was higher in smokers than in non-smokers (p < 0.05) after adjusting for age, gender, waist circumference, estimated GFR, liver biochemistry and lipid profile. CONCLUSIONS: Cigarette smoking is associated with elevated serum VAP-1 concentration. Whether VAP-1 and its SSAO activity link the relationship between cigarette smoking, atherosclerosis and cancer requires further investigation.

A 20-year study of autoimmune polyendocrine syndrome type II and III in Taiwan.

Purpose: Autoimmune polyendocrine syndrome (APS) is a rare immune-endocrinopathy characterized by the failure of at least two endocrine organs. Clinical characteristics have mainly been described in the Western population. This study comprehensively analyzed the demographic and clinical manifestations of APS II and APS III in Taiwan. Methods: Patients aged ≥20 years with a diagnosis of APS II or APS III in ten hospitals between 2001 and 2021 were enrolled. The clinical and serological characteristics of the patients were retrospectively reviewed. Results: Among the 187 enrolled patients (45 men and 142 women); only seven (3.7%) had APS II, while the others had APS III. Fifty-five patients developed hyperthyroidism and 44 patients developed hypothyroidism. Men were diagnosed with APS at a younger age than women (16.8 vs 27.8 years old, P = 0.007). Most patients were initially diagnosed with type 1 diabetes mellitus. There was a positive correlation between age at diagnosis and the likelihood of developing thyroid dysfunction. For every year older patients were diagnosed with APS III, the risk of developing hyperthyroidism increased by 3.6% (P = 0.002), and the risk of developing hypothyroidism increased by 3.7% (P = 0.035). Positive anti-parietal cell antibodies (APCA) were associated with a higher risk of anemia in patients with APS III (P < 0.001). Conclusion: This study provides the most comprehensive analysis of APS II and APS III in Asia. The percentage of patients with APS II was significantly lower than in the Western population. A second autoimmune endocrinopathy may develop several years after the first one. APCA examination is valuable when evaluating anemia in patients with APS.