2023 Taiwan Society of Cardiology (TSOC) and Taiwan College of Rheumatology (TCR) Joint Consensus on Connective Tissue Disease-Associated Pulmonary Arterial Hypertension.

Background: Pulmonary arterial hypertension (PAH), defined as the presence of a mean pulmonary artery pressure > 20 mmHg, pulmonary artery wedge pressure ≤ 15 mmHg, and pulmonary vascular resistance (PVR) > 2 Wood units based on expert consensus, is characterized by a progressive and sustained increase in PVR, which may lead to right heart failure and death. PAH is a well-known complication of connective tissue diseases (CTDs), such as systemic sclerosis, systemic lupus erythematosus, Sjogren's syndrome, and other autoimmune conditions. In the past few years, tremendous progress in the understanding of PAH pathogenesis has been made, with various novel diagnostic and screening methods for the early detection of PAH proposed worldwide. Objectives: This study aimed to obtain a comprehensive understanding and provide recommendations for the management of CTD-PAH in Taiwan, focusing on its clinical importance, prognosis, risk stratification, diagnostic and screening algorithm, and pharmacological treatment. Methods: The members of the Taiwan Society of Cardiology (TSOC) and Taiwan College of Rheumatology (TCR) reviewed the related literature thoroughly and integrated clinical trial evidence and real-world clinical experience for the development of this consensus. Conclusions: Early detection by regularly screening at-risk patients with incorporations of relevant autoantibodies and biomarkers may lead to better outcomes of CTD-PAH. This consensus proposed specific screening flowcharts for different types of CTDs, the risk assessment tools applicable to the clinical scenario in Taiwan, and a recommendation of medications in the management of CTD-PAH.

Effects of biologics on reducing the risks of total knee replacement and total hip replacement in rheumatoid arthritis.

OBJECTIVES: RA damages the joints and increases the risks of total knee replacement (TKR) and total hip replacement (THR). However, the benefits of biologics in preventing TKR or THR remain unclear. METHODS: This retrospective nationwide study used the 2000-2013 claims-based National Health Insurance dataset. Biologics are reimbursed for refractory cases. The risks of TKR and THR in the biologic cohort were compared with those of an age- and sex-matched csDMARD cohort. A multivariate Cox regression model was used to investigate the benefits of bDMARDs for TKR and THR. RESULTS: TKR was performed in 5979 biologic cases and 11 958 matched controls, of which 249 (4.16%) and 871 (7.28%) cases received TKR, respectively. THR was performed in 6245 biologic cases and 12 490 matched controls, of which 159 (2.55%) and 516 (4.13%) cases had THR, respectively. The biologic cohort had significantly lower incidence rates of TKR (11.73 vs 16.33/1000 person-years, P < 0.001) and THR (7.09 vs 9.16/1000 person-years, P < 0.001). After adjustment for confounding factors, the regular bDMARD subgroup (average dose >0.95 defined daily dose/day) had significantly lower risks of TKR (aHR: 0.55, 95% CI: 0.38, 0.81) and THR (aHR: 0.63, 95% CI: 0.40, 0.98). Those without MTX use, with steroid use, with biologic switch, and overlapping antiphospholipid syndrome had significantly higher risks of TKR and THR. CONCLUSIONS: Compared with the csDMARD cohort, the risks of TKR and THR in the bDMARD cohort were the same as those in the low-to-moderate dose subgroups and significantly lower in those with regular bDMARD use.

Histone Deacetylase Inhibitors Downregulate Calcium Pyrophosphate Crystal Formation in Human Articular Chondrocytes.

Calcium pyrophosphate (CPP) deposition disease (CPPD) is a form of CPP crystal-induced arthritis. A high concentration of extracellular pyrophosphate (ePPi) in synovial fluid is positively correlated with the formation of CPP crystals, and ePPi can be upregulated by ankylosis human (ANKH) and ectonucleotide pyrophosphatase 1 (ENPP1) and downregulated by tissue non-specific alkaline phosphatase (TNAP). However, there is currently no drug that eliminates CPP crystals. We explored the effects of the histone deacetylase (HDAC) inhibitors (HDACis) trichostatin A (TSA) and vorinostat (SAHA) on CPP formation. Transforming growth factor (TGF)-ß1-treated human primary cultured articular chondrocytes (HC-a cells) were used to increase ePPi and CPP formation, which were determined by pyrophosphate assay and CPP crystal staining assay, respectively. Artificial substrates thymidine 5'-monophosphate p-nitrophenyl ester (p-NpTMP) and p-nitrophenyl phosphate (p-NPP) were used to estimate ENPP1 and TNAP activities, respectively. The HDACis TSA and SAHA significantly reduced mRNA and protein expressions of ANKH and ENPP1 but increased TNAP expression in a dose-dependent manner in HC-a cells. Further results demonstrated that TSA and SAHA decreased ENPP1 activity, increased TNAP activity, and limited levels of ePPi and CPP. As expected, both TSA and SAHA significantly increased the acetylation of histones 3 and 4 but failed to block Smad-2 phosphorylation induced by TGF-ß1. These results suggest that HDACis prevented the formation of CPP by regulating ANKH, ENPP1, and TNAP expressions and can possibly be developed as a potential drug to treat or prevent CPPD.

Office-based salivary gland ductal irrigation in patients with chronic sialoadenitis: A preliminary study.

BACKGROUND/PURPOSE: To evaluate the therapeutic responsiveness of office-based salivary gland ductal irrigation in patients with chronic sialoadenitis. METHODS: Between August 2017 and April 2019, 55 patients comprising the following three disease groups were enrolled: Sjogren's syndrome: 39 patients; postradiotherapy sialoadenitis: ten patients; and post-RAI sialoadenitis: six patients. Quantitative salivary scintigraphy was recorded, and a formulated questionnaire including the Summated Xerostomia Inventory was utilized to assess acute/chronic symptoms. All patients received at least three serial salivary gland ductal irrigations with a one-month interval in our outpatient department. RESULTS: The general response rates for each disease groups are as follows: Sjogren's syndrome: 61.5% (24/39); postradiotherapy: 60% (6/10); and post-RAI: 83.3% (5/6). Among the patients with Sjogren's syndrome, the parotid scintigraphic Tmin showed a significant positive correlation with the responsiveness of salivary irrigation (P = 0.046), whereas the treatment tended to be irresponsive in patients who previously took medicine for their related discomfort (P = 0.009). In the postradiotherapy and post-RAI groups, no significant factors were found to be associated with the responsiveness of irrigation. CONCLUSION: Simple salivary ductal irrigation without complex equipment can be performed as an outpatient procedure to alleviate glandular swelling or xerostomia in patients with Sjogren's syndrome, postradiotherapy sialoadenitis or post-RAI sialoadenitis, and it can be considered an alternative management approach for patients refractory to conventional strategies.

Risk of obstructive sleep apnea in patients with Sjögren syndrome and Behçet's disease: a nationwide, population-based cohort study.

PURPOSE: Patients with obstructive sleep apnea (OSA) have a higher risk of Behçet's disease (BD) and Sjögren syndrome (SS). However, the bidirectional relationship between these autoimmune diseases and OSA is unclear. We investigated the relationship between autoimmune diseases (SS and BD) and OSA. METHODS: SS and BD patients were identified through the Taiwan National Health Insurance Research Database from 2002 to 2012. Patients with SS or BD were matched according to age and sex with a control group in a ratio of 1:4. The study included 12,926 patients with SS and 51,704 non-SS controls. Similarly, 1221 patients with BD were matched with 4884 non-BD controls. We used a Cox regression model, stratified by age, gender, and comorbidities, to assess the risk of OSA. RESULTS: OSA was diagnosed in 0.61% of the SS cohort and 1.23% of the BD cohort. The higher overall risk for OSA was observed significantly in patients with SS than in controls (adjusted hazard ratio [HR] = 2.48, 95% confidence interval [CI] = 1.89-3.24). The higher risk was also observed significantly in BD patients than in controls (HR = 1.99, 95% CI = 1.06-3.72). Furthermore, men with SS or BD exhibited HR of 2.62 (95% CI 1.89 to 3.62) and 6.40 (95% CI 2.96 to 13.84) for developing OSA, respectively. CONCLUSION: Risk of OSA was significantly elevated in SS or BD patients compared with controls. Further study is warranted to elucidate underlying mechanisms.

Thymectomy in patients with myasthenia gravis increases the risk of autoimmune rheumatic diseases: a nationwide cohort study.

Objectives: Previous studies have shown myasthenia gravis (MG) and autoimmune rheumatic diseases (ARDs) share common pathogenetic mechanisms. Therefore, the present study investigated the possible relationship between MG and ARDs. Methods: We analysed Taiwanese medical data from the Registry of Catastrophic Illness and identified patients with MG. From the entire general population data of the National Health Insurance Research Database, we randomly selected a comparison cohort that was frequency-matched by age (in 5-year increments), sex, and index date. We analysed the risk of ARDs by using a Cox proportional hazards regression model stratified by sex, age and treatment. Results: In the present study, we enrolled 6478 patients with MG (58.03% women; mean age, 50.55 years) and 25 912 age- and sex-matched controls. The risk of total ARDs was 6.25 times higher in the MG cohort than in the non-MG cohort after adjustment for age and sex. Furthermore, the MG cohort was associated with a significantly higher risk of primary SS (pSS), SLE and other ARD types (adjusted hazard ratios: 15.84 [95% CI: 8.39, 23.91]; 11.32 [95% CI: 5.04, 25.429]; and 4.07 [95% CI: 1.31, 12.62], respectively). The MG cohort who underwent thymectomy had an increased risk of RA, pSS and SLE (adjusted hazard ratios: 4.41; 15.06; and 23.68, respectively). Conclusion: The present nationwide cohort study revealed an association between MG and incident ARDs. The MG cohort who underwent thymectomy had an increased risk of RA, pSS and SLE. Future studies are needed to elucidate the underlying pathogenesis and to translate this into clinical therapeutic options.

MCPIP3 as a Potential Metastasis Suppressor Gene in Human Colorectal Cancer.

Monocyte chemotactic protein induced protein 3 (MCPIP3) belongs to the Cys⁻Cys⁻Cys⁻His (CCCH)-zinc finger protein family and contains a highly conserved CCCH-zinc finger domain and a Nedd4-BP1 YacP nuclease (NYN) domain. Previous studies showed that MCPIP3 inhibits the expression of proinflammatory genes, such as vascular cell adhesion molecule (VCAM)-1, in human endothelial cells, but the roles and functions of MCPIP3 in cancer cells are still unknown. In human colorectal cancer specimens, we found that the messenger RNA expression of MCPIP3 was significantly downregulated in cancer tissues compared to adjacent normal tissues (18/25; average fold change of 8.18). Two cell models were used to demonstrate the anti-migration activity of MCPIP3. First, Tet-on T-REx-293/HA-MCPIP3 cells were used to examine whether MCPIP3 can change epithelial⁻mesenchymal transition (EMT)-related gene expressions. Second, we used two human colorectal cancer cell lines, SW620 and HCT116, to prove the role of MCPIP3 in regulating EMT-related gene expressions. We found that overexpression of MCPIP3 inhibited cell migration according to a wound-healing assay and Transwell invasion assay and vimentin expression, and increased E-cadherin expression in these two cell lines. These results suggest that MCPIP3 might play a negative role in cell migration of human colorectal cancer cells.

Nonsurgical periodontal treatment and prosthetic rehabilitation of a renal transplant patient with gingival enlargement: a case report with 2-year follow-up.

BACKGROUND: Drug-induced gingival enlargement is a common condition which can be observed in patients taking immunosuppressive medications following organ transplant surgery. The disfiguring excessive tissue often hinders proper oral hygiene practices, therefore accompanied by periodontitis, tooth mobility, and even pathological tooth migration in extreme cases. This case report presents a conservative treatment protocol for a patient with the aforementioned conditions involving neither surgical nor orthodontic intervention. Few related studies have reported such a noninvasive protocol for managing these kinds of conditions. CASE PRESENTATION: A 51-year-old woman presented with bleeding gingiva, mobile teeth and complained of chewing difficulties. She had undergone renal transplant surgery 16 years prior to this dental visit and had been taking immunosuppressive drugs including cyclosporine ever since. After clinical and radiographic examinations, the patient was diagnosed with drug-induced gingival enlargement, pathological tooth migration, severe periodontitis, and missing teeth. Through careful and meticulous nonsurgical debridement, oral hygiene instruction, tooth extraction, and occlusal adjustment, the patient's periodontium was restored to a healthy state without surgical intervention. Moreover, the patient's chewing function was restored by means of removable partial dentures. Good adaptation of prostheses and satisfaction with overall treatment outcomes were reported. CONCLUSIONS: Through proper diagnosis, treatment, and with good patient cooperation, complex systemic and dental problems can be managed conservatively without invasive surgeries to attain a stable periodontium and eventually, occlusal function could be restored.

Identification of susceptibility gene associated with female primary Sjögren's syndrome in Han Chinese by genome-wide association study.

Primary Sjögren's syndrome (PSS) is an autoimmune disease targeting exocrine glands. It ten times more dominantly affects women than men with an onset peak at menopause. The genetic factor predisposing women to PSS remains unclear. Therefore, we aimed to identify susceptibility loci for PSS in women. We performed genome-wide association study (GWAS) using 242 female PSS patients and 1444 female control in Han Chinese population residing in Taiwan. Replication was conducted in an independent cohort of 178 female PSS and 14,432 control subjects. We identified rs117026326 on GTF2I with GWAS significance (P = 1.10 × 10-15) and rs13079920 on RBMS3 with suggestive significance (P = 2.90 × 10-5) associating with PSS in women. The association of RBMS3 was further evidenced by imputation in which rs13072846 (P = 4.89 × 10-5) was identified and confirmed as female PSS associating SNP within the same LD with rs13079920. PSS pathogenesis involves both immune (effector) and exocrine (target) system. We suggested that while GTF2I is a previously reported associating gene which may function in immune system, RBMS3 is a novel susceptibility gene that predisposes women to PSS potentially through modulating acinar apoptosis and TGF-ß signaling in target exocrine system.

Calcium-containing crystals enhance receptor activator of nuclear factor κB ligand/macrophage colony-stimulating factor-mediated osteoclastogenesis via extracellular-signal-regulated kinase and p38 pathways.

OBJECTIVE: Diseases associated with calcium-containing crystal deposition can lead to local bone erosion. We aimed to determine whether calcium-containing crystal-hydroxyapatite, ß-tricalcium phosphate and CPPD enhanced osteoclastogenesis and to define underlying mechanisms of action. METHODS: Osteoclastogenesis was studied by culturing murine RAW 264.7 osteoclast precursor cells with RANK ligand (RANKL)/ M-CSF and/or calcium-containing crystals, and observing the tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and TRAP activity. Resorption pit formation was used to evaluate osteoclast activity. Real-time RT-PCR analysis revealed osteoclast marker genes, including TRAP, cathepsin K and calcitonin receptor (CTR). Western blotting was used to analyse the phosphorylation levels of signal transduction molecules. RESULTS: Three kinds of calcium-containing crystal significantly enhanced RANKL/M-CSF-induced osteoclastogenesis in RAW 264.7 cells, as evidenced by the increased number of TRAP-positive multinucleated cells, TRAP activity and resorption pit formation in a dose-dependent manner. Hydroxyapatite, ß-tricalcium phosphate and CPPD treatments significantly enhanced RANKL/M-CSF-induced mRNA expression of TRAP, cathepsin K and CTR. Moreover, the three kinds of calcium-containing crystal enhanced the phosphorylation of extracellular-signal-regulated kinase and p38 in RANKL/M-CSF-treated cells. CONCLUSION: We concluded that calcium-containing crystals can promote osteoclastogenesis and bone resorption through the extracellular-signal-regulated kinase and p38 pathways. Together with synovial activation, this mechanism may be important in the pathogenesis of destructive arthropathies triggered by calcium-containing crystals.

Three-dimensional information encryption and anticounterfeiting using digital holography.

In this work, arbitrary micro phase-step digital holography with optical interferometry and digital image processing is utilized to obtain information about an image of a three-dimensional object and encrypting keys. Then, a computer-generated hologram is used for the purpose of holographic encryption. All information about the keys is required to perform the decryption, comprising the amplitude and phase distribution of the encrypting key, the distance of image reconstruction, zero-order term elimination, and twin-image term suppression. In addition to using identifiable information on different image planes and linear superposition processing hidden within the encrypted information, not only can we convey an important message, but we can also achieve anticounterfeiting. This approach retains the strictness of traditional holographic encryption and the convenience of digital holographic processing without image distortion. Therefore, this method provides better solutions to earlier methods for the security of the transmission of holographic information.

Compensation of phase aberration by using a virtual confocal scheme in digital holographic microscopy.

This work presents cost-effective, simple arbitrary phase-step digital holographic microscopy to suppress both zero-order and twin-image terms. A virtual confocal offset lens under in-line configuration is also used to compensate for the introduced quadratic phase by using a microscope objective lens. In addition to reducing the difficulties of physical confocal configurations, the proposed method significantly increases the magnification power, ultimately achieving the purposes of an optical zoom. An attempt is also made to reduce the noise interference of a high magnification system by developing a long focal lens to reduce light detection size, subsequently gaining an approximately plane wave light source to illuminate the object within the effective depth of focus. Experimental results indicate that the proposed high magnification system can be elevated with low noise interference, and image reconstruction without quadratic phase terms.

Identification of tophi in ultrasound imaging based on transfer learning and clinical practice.

Gout is a common metabolic disorder characterized by deposits of monosodium urate monohydrate crystals (tophi) in soft tissue, triggering intense and acute arthritis with intolerable pain as well as articular and periarticular inflammation. Tophi can also promote chronic inflammatory and erosive arthritis. 2015 ACR/EULAR Gout Classification criteria include clinical, laboratory, and imaging findings, where cases of gout are indicated by a threshold score of ≥ 8. Some imaging-related findings, such as a double contour sign in ultrasound, urate in dual-energy computed tomography, or radiographic gout-related erosion, generate a score of up to 4. Clearly, the diagnosis of gout is largely assisted by imaging findings; however, dual-energy computed tomography is expensive and exposes the patient to high levels of radiation. Although musculoskeletal ultrasound is non-invasive and inexpensive, the reliability of the results depends on expert experience. In the current study, we applied transfer learning to train a convolutional neural network for the identification of tophi in ultrasound images. The accuracy of predictions varied with the convolutional neural network model, as follows: InceptionV3 (0.871 ± 0.020), ResNet101 (0.913 ± 0.015), and VGG19 (0.918 ± 0.020). The sensitivity was as follows: InceptionV3 (0.507 ± 0.060), ResNet101 (0.680 ± 0.056), and VGG19 (0.747 ± 0.056). The precision was as follows: InceptionV3 (0.767 ± 0.091), ResNet101 (0.863 ± 0.098), and VGG19 (0.825 ± 0.062). Our results demonstrate that it is possible to retrain deep convolutional neural networks to identify the patterns of tophi in ultrasound images with a high degree of accuracy.

Kinetics of Phenotype Modification Therapy with VISTA: A Retrospective Case Series Using 3D Digital Analysis

Phenotype modification therapy has emerged as one of the main treatment objectives of periodontal plastic surgery. However, long-term data on the stability of gingival thickness gains are not available. This study examined the kinetics of mucosal thickness gain as a measure of phenotype modification therapy following treatment of multiple gingival recession defects with vestibular incision subperiosteal tunnel access (VISTA). Six patients with 14 recession type (RT) II teeth were treated using VISTA and subepithelial connective tissue grafts (SCTG). Scanned images of study casts at pre- and postoperative periods (6 to 66 months) were digitally superimposed for quantitative evaluation of soft tissue dimensional changes. Mucosal thickness gains ranged from 1.0 ± 0.7 mm (1 mm apical to cement-enamel junction [CEJ]) to 1.4 ± 0.4 mm (5 mm apical to CEJ). The gingival thickness gains remained relatively stable, with thickness gains at 66 months of 0.5 ± 0.8, 0.9 ± 0.6, 1.1 ± 0.6, 1.0 ± 0.4, and 1.2 ± 0.6 mm at 1, 2, 3, 4 and 5 mm apical to the CEJ, respectively. Treatment of multiple gingival recession defects with VISTA and SCTG led to stable gingival thickness gains and shows promise as a strategy for phenotype modification therapy.

Multiple-hologram recording with one-beam encoding.

This research proposes a method that uses a single object beam to record multiple images in a photorefractive crystal medium without having to use any reference wave. The object beam in this study is modulated using a lenticular lens array sheet to produce a set of sub-object beams. These beams are then angularly separated on the recording plane and their scattered waves overlapped in an iron-doped photorefractive LiNbO3 crystal. This single-exposure, multiple-holographic-recording method is simple and proven successful via the experiments that recorded four holograms in a 30 x 1 mm³ LiNbO3:Fe crystal with single exposure.

A novel approach to assess volumetric bone loss at immediate implant sites and comparison to linear measurements: A pilot study.

OBJECTIVES: Studies have evaluated changes in hard tissue following immediate implant placement (IIP) through cone beam computed tomography (CBCT) imaging. This study compared the 3D volumetric changes of the alveolar bone at immediate implant sites with 2D linear measurement outcomes by using a novel image analysis workflow. METHODS: Preoperative and 6-month postoperative CBCT images of patients who underwent IIP and bone grafting in the maxillary esthetic area were acquired. Linear and volumetric measurements of buccal bone dimensions were taken using a specially designed workflow. The 2D and 3D measurements were compared, and their correlations were determined. RESULTS: Images from 13 patients (13 implants) were analyzed. Linear measurements revealed that the general linear buccal bone loss was less than 1mm in all segments. The 3D volumetric bone reduction (reported as median [first quantile, third quantile]) in the vertical, cervical, middle, and apical segments was 14.27 [11.33, 30.66] mm3 (51.30 [42.78, 66.91]%), 16.20 [10.35, 30.52] mm3 (18.20 [9.88, 24.74]%), 17.48 [8.42, 21.17] mm3 (24.05 [12.39, 28.22]%), and 6.87 [3.88, 9.45] mm3 (11.34 [5.14, 22.54]%), respectively. Significant positive correlations between 2D and 3D measurements were consistently identified in the cervical and middle segments, but no significant correlation was noted in the vertical segment. CONCLUSIONS: The results revealed that linear measurements could not fully represent volumetric bone dimensional changes. Performing volumetric measurements and 3D rendering could be valuable in presenting the actual amount and topography of peri-implant bone remodeling. CLINICAL SIGNIFICANCE: Linear measurements only partially represent the real-life event of 3D bone changes at immediate implant sites. Factors affecting hard tissue alterations following IIP should be reassessed using 3D volumetric measurement outcomes.

TLC599 in patients with osteoarthritis of the knee: a phase IIa, randomized, placebo-controlled, dose-finding study.

BACKGROUND: Corticosteroid injection for knee osteoarthritis is limited by its modest duration of treatment effect. The liposome formulation of dexamethasone sodium phosphate (TLC599) was developed for the sustained relief of osteoarthritis pain. This clinical study was conducted to evaluate the efficacy and safety of TLC599 at two dose levels in patients with knee osteoarthritis. METHODS: A randomized, double-blinded, placebo-controlled study was conducted in 75 patients with osteoarthritis of the knee from 13 study centers. Patients were randomized and administered a single intra-articular injection of TLC599 or placebo and assessed for efficacy and safety for 24 weeks. Patient-reported outcomes included the Western Ontario and McMaster Universities Arthritis (WOMAC) Index for pain and function and visual analog scale for pain. RESULTS: TLC599 at 12 mg demonstrated significantly greater reduction in WOMAC pain through 12 weeks (least squares (LS) mean difference = - 0.37, p = 0.0027) and through 24 weeks (LS mean difference = - 0.35, p = 0.0037) when compared to placebo. TLC599 12 mg also exhibited significantly greater improvement in function when compared to placebo at 24 weeks (LS mean difference = - 0.26, p = 0.0457). TLC599 18 mg did not significantly improve pain or function in comparison with placebo. The use of acetaminophen during the study was less in both TLC599 groups in comparison with placebo. No major or unexpected safety issues were reported. CONCLUSIONS: In participants with symptomatic knee osteoarthritis, TLC599 is a well-tolerated treatment that reduces pain and improves function for up to 24 weeks, a longer duration than that reported for existing IA treatments. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03005873 . Registered on 29 December 2016.

Association of interferon-based therapy with risk of autoimmune diseases in patients with chronic hepatitis C virus infection: A population-based Taiwanese cohort study.

Background: Interferon in combination with ribavirin has been the standard of care for chronic hepatitis C virus infection (HCV) for the past few decades. However, its effect on the risk of autoimmune diseases (ADs) among patients with HCV infection remains unclear. We assessed the potential association between interferon-based therapy (IBT) and AD risk in patients with HCV infection. Methods: This retrospective cohort study identified patients diagnosed with HCV infection between January 1, 2006, and December 31, 2015, from Taiwan's National Health Insurance Research Database. In total, 16,029 patients with HCV infection who received IBT and 141,214 patients with HCV infection who did not receive IBT were included. Both cohorts were followed up to assess the development of ADs. Hazard ratios (HRs) were calculated using the Cox proportional hazards regression model, which was adjusted for potential confounders. Results: The median follow-up period for IBT and non-IBT users was 4.53 and 3.34 years, respectively. No significant difference in the risk of overall ADs (adjusted HR [aHR]: 0.96, 95% confidence interval [CI]: 0.81-1.14) or systemic ADs (aHR: 0.88, 95% CI: 0.71-1.10) was noted during the study period. However, a slight increase in the risk of organ-specific ADs was noted among IBT users (incidence rate ratio: 1.33, 95% CI: 1.02-1.72). Furthermore, analysis of AD subgroups revealed a significant increase in the risks of Graves' disease (aHR: 6.06, 95% CI: 1.27-28.8) and Hashimoto's thyroiditis (aHR 1.49, 95% CI 1.01-2.21) among IBT users. Conclusions: IBT use increases the risk of autoimmune thyroid diseases (Hashimoto's thyroiditis and Graves' disease) in patients with HCV infection to a greater extent than non-IBT use.

H1-Antihistamines Reduce the Risk of Hepatocellular Carcinoma in Patients With Hepatitis B Virus, Hepatitis C Virus, or Dual Hepatitis B Virus-Hepatitis C Virus Infection.

PURPOSE: H1-antihistamines (AHs) may exert protective effects against cancer. This study investigated the association of AH use with the risk of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or dual HBV-HCV virus infection. MATERIALS AND METHODS: Patients with HBV, HCV, or dual HBV-HCV infection were enrolled from Taiwan's National Health Insurance Research Database and examined for the period from January 1, 2006, to December 31, 2015. We used the Kaplan-Meier method and Cox proportional hazards regression to evaluate the association between AH use and HCC risk. RESULTS: We included patients with HBV infection (n = 521,071), HCV (n = 169,159), and dual HBV-HCV (n = 39,016). Patients with HBV, HCV, or dual virus infection who used AHs exhibited significantly lower risk of HCC relative to patients who did not use AH, with their adjusted hazard ratio being 0.489 (95% CI, 0.455 to 0.524), 0.484 (95% CI, 0.450 to 0.522), and 0.469 (95% CI, 0.416 to 0.529), respectively. Furthermore, there was a dose-response relationship between AH use and the risk of HCC in the HBV cohort. The adjusted hazard ratios were 0.597 (95% CI, 0.530 to 0.674), 0.528 (0.465 to 0.600), 0.470 (0.416 to 0.531), and 0.407 (0.362 to 0.457) for AH use of 28-42, 43-63, 64-119, and ≥ 120 cumulative defined daily doses, respectively, relative to no AH use. Additionally, there was also a dose-response relationship between AH use and the risk of HCC in the HCV and dual HBV-HCV cohorts. CONCLUSION: AH use may reduce the risk for HCC among patients with HBV, HCV, or dual infection in a dose-dependent manner. Further mechanistic research is needed.