Objective
To compare
Pneumocystis jirovecii
pneumonia (PJP) risk between patients with autoimmune rheumatic diseases (ARD) and the general population
Methods
We identified patients with ARD recorded ...in the National Health Insurance Research Database of Taiwan from 2002 to 2015 and randomly selected a comparison cohort from the general population matched for age and sex. We analyzed PJP risk stratified by sex, age, comorbidities, and medications using Cox proportional hazard model.
Results
We enrolled 103,117 patients with ARD. PJP risk significantly increased in patients with any ARD and with each individual ARD like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren’s syndrome (SjS), polymyositis and dermatomyositis (PM/DM), systemic sclerosis (SSc), and systemic vasculitis. Patients with PM/DM showed prominent risk with incidence rate of 12.47/100,000 patient year (95% confidence interval (CI), 32.16–86.70). In a time-dependent Cox proportional hazard model with comorbidities and medications as covariates, PM/DM, SSc, SLE, and SjS significantly increased adjusted hazard ratios (aHR) of 5.40, 5.12, 4.09, and 3.64, respectively (95% CI of 2.82–10.35, 2.16–12.13, 2.41–6.95, and 2.06–6.42, respectively). AHR after adjusting for male sex, cancer, human immunodeficiency virus infection (HIV), and interstitial lung disease also significantly increased. Use of daily oral steroid dose of >10 mg conferred the highest risk followed by mycophenolate. Use of injected steroids, cyclophosphamide, biological agents, methotrexate, and cyclosporine conferred a significantly higher risk.
Conclusion
Underlying ARD significantly predisposes patients to PJP, with PM/DM posing the highest threat. In addition to underlying disease, comorbidities and concomitant immunosuppressants are major risks. The strongest risk is recent daily steroid dose of >10 mg. Mycophenolate seems to be a more prominent risk factor than cyclophosphamide.
Key Points
• Autoimmune rheumatic diseases (ARD) significantly increased the overall risk of PJP, and so did each individual ARD.
• Use of steroids, mycophenolate, cyclophosphamide, biological agents, methotrexate, and cyclosporine all significantly increased risk of PJP.
• Male, elderly, malignancy, HIV, and interstitial lung disease are also related to increased risk of PJP.
• Underlying ARD, comorbidities, and use of immunosuppressant should all be considered in determining the overall risk of PJP.
Answer Behçet’s disease, a type of vasculitis that most commonly affects people aged 20-40.2 The International Study Group diagnostic criteria3 include recurrent oral ulceration (more than three ...episodes in a year) plus two of four other characteristic findings: genital ulceration; eye lesions (uveitis/retinal vasculitis); skin lesions (erythema nodosum/pseudofolliculitis/papulopustules/acneiform nodules); or a positive pathergy test. Arthritis affects the medium and large joints (eg, wrists, hips, knees, and/or ankles) in approximately half of patients with Behçet’s disease.1 It is most prevalent in Turkey (80 to 370 cases per 100 000) with prevalence ranging from 13.5 to 35 cases per 100 000 in Japan, Korea, China, Iran, Iraq, and Saudi Arabia.2 In the US and Europe it is from 0.12 to 7.5 cases per 100 000.4 The cause of Behçet’s disease is still unknown, but herpes simplex virus, streptococcus, and gene sensitivity of HLA-B51 serotype are believed to be contributing factors.5 Owing to its varied clinical presentations, diagnosis and treatment of Behçet’s disease are sometimes delayed. Differentials of erythema nodosum include subcutaneous infections, erythema induratum, polyarteritis nodosa, subcutaneous cancers, pancreatic panniculitis, and α-1 antitrypsin deficiency.6 Learning points Raised temperature, ESR, and CRP could be caused by inflammation if infection is ruled out Consider erythema nodosum when acute tender erythematous nodules develop (especially on the legs) Search for underlying disease when erythema nodosum is present Consider Behçet’s disease in patients with recurrent oral ulcerations who have genital ulcerations, uveitis, retinal vasculitis, erythema nodosum, pseudofolliculitis, papulopustules, acneiform nodules, arthritis, and/or a positive pathergy test.
Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation ...potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan’s Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.
Apart from aging process, adult intervertebral disc (IVD) undergoes various degenerative processes. However, the nicotine has not been well identified as a contributing etiology. According to a few ...studies, nicotine ingestion through smoking, air or clothing may significantly accumulate in active as well as passive smokers. Since nicotine has been demonstrated to adversely impact various physiological processes, such as sympathetic nervous system, leading to impaired vasculature and cellular apoptosis, we aimed to investigate whether nicotine could induce IVD degeneration. In particular, we evaluated dose-dependent impact of nicotine in vitro to simulate its chronic accumulation, which was later treated by platelet-derived biomaterials (PDB). Further, during in vivo studies, mice were subcutaneously administered with nicotine to examine IVD-associated pathologic changes. The results revealed that nicotine could significantly reduce chondrocytes and chondrogenic indicators (Sox, Col II and aggrecan). Mice with nicotine treatment also exhibited malformed IVD structure with decreased Col II as well as proteoglycans, which was significantly increased after PDB administration for 4 weeks. Mechanistically, PDB significantly restored the levels of IGF-1 signaling proteins, particularly pIGF-1 R, pAKT, and IRS-1, modulating ECM synthesis by chondrocytes. Conclusively, the PDB impart reparative and tissue regenerative processes by inhibiting nicotine-initiated IVD degeneration, through regulating IGF-1/AKT/IRS-1 signaling axis.
Benign prostatic hyperplasia (BPH) is the most common urologic disease among elderly men. A well-established in vitro cell model is required to determine the therapeutic mechanism of BPH ...inflammation. In this study, we attempted to establish an immortalized human prostate stromal cell line by transfecting with HPV-16 E6/E7 and designated as ihPSC. No significant difference was found in fibroblast-like morphology between primary hPSC and ihPSC. The ihPSC possessed a significantly higher cell proliferation rate than primary hPSC. The prostate-specific markers and proteins including cytoskeleton (α-SMA and vimentin) and smooth muscle (calponin), especially the androgen receptor (AR) were also examined in ihPSC, almost identical to the primary hPSC. To create an in vitro model featuring chronic prostatic inflammation, ihPSC was stimulated with IFN-γ+IL-17 and then treated with the high molecular weight hyaluronic acid hylan G-F 20 as an alternative strategy for inhibiting BPH inflammation. Hylan G-F 20 could dose-dependently diminish the inflammation-induced proliferation in ihPSC. The enhanced expressions of inflammatory molecules including IL-1β, IL-6, IL-8, cyclooxygenase 2 (COX2), inducible nitrogen oxide synthase (iNOS), and Toll-like receptor 4 (TLR4) were all abolished by hylan G-F 20. For inflammatory signaling, hylan G-F 20 can also diminish the IFN-γ+IL-17-increased expression of iNOS and p65 in ihPSC. These findings suggest that ihPSC could provide a mechanism-based platform for investigating prostate inflammation. The hylan G-F 20 showed strong anti-inflammatory effects by decreasing inflammatory cytokines and signalings in the ihPSC, indicating its therapeutic potentials in BPH treatment in the future.
Osteoarthritis (OA) poses a major clinical challenges owing to limited regenerative ability of diseased or traumatized chondrocytes in articular cartilage. Previous studies have determined the ...individual therapeutic efficacies of hyaluronic acid (HA) and platelet-rich plasma (PRP) on OA; however, the underlying mechanism is still lacking. Therefore, we investigated mechanistic approach of HA+PRP therapy on chondrocyte apoptosis in IL-1β+TNF-α (I+T) treated
OA model, in addition to
anterior cruciate ligament transection-OA mice model. MTT assay showed an enhanced chondrocyte proliferation and viability in HA+PRP-treated group, compared to I+T, I+T/HA, I+T/PRP, I+T/HA+PRP groups. Further, HA+PRP also significantly suppressed ROS, apoptotic cleaved caspase-3 and PARP, p53 and p21 and MMP-1; whereas, cell cycle modulatory proteins including p-ERK, cyclin B1, D1, and E2 were upregulated. The sub-G1 population and TUNEL assay confirmed the higher abundance of healthy chondrocytes in HA+PRP group. A significantly decreased ARS staining in HA+PRP group was also noted, indicating reduced cartilaginous matrix mineralization compared to other groups. Conclusively, compared to HA or PRP, the combined HA+PRP might be a promising therapy for articular cartilage regeneration in osteoarthritic pathology, possibly via augmented anti-inflammatory, anti-oxidative chondrocyte proliferation and inhibited MMP-1 activity and matrix calcification.
The study was conducted to determine whether patients with rheumatoid arthritis (RA) are at increased risk of acute pancreatitis compared with those without RA and to determine if the risk of acute ...pancreatitis varied by anti-RA drug use. We used the large population-based dataset from the National Health Insurance (NHI) program in Taiwan to conduct a retrospective cohort study. Patients newly diagnosed with RA between 2000 and 2011 were referred to as the RA group. The comparator non-RA group was matched with propensity score, using age and sex, in the same time period. We presented the incidence density by 100,000 person-years. The propensity score and all variables were analyzed in fully adjusted Cox proportional hazard regression. The cumulative incidence of acute pancreatitis was assessed by Kaplan-Meier analysis, with significance based on the log-rank test. From claims data of one million enrollees randomly sampled from the Taiwan NHI database, 29,755 adults with RA were identified and 119,020 non-RA persons were matched as a comparison group. The RA cohort had higher incidence density of acute pancreatitis (185.7 versus 119.0 per 100,000 person-years) than the non-RA cohort. The adjusted hazard ratio (HR) was 1.62 (95% CI confidence interval 1.43-1.83) for patients with RA to develop acute pancreatitis. Oral corticosteroid use decreased the risk of acute pancreatitis (adjusted HR 0.83, 95% CI 0.73-0.94) but without a dose-dependent effect. Current use of disease modifying anti-rheumatic drugs or tumor necrosis factor blockers did not decrease the risk of acute pancreatitis. In conclusion, patients with RA are at an elevated risk of acute pancreatitis. Use of oral corticosteroids may reduce the risk of acute pancreatitis.
Our study presents a 319-gene panel targeting inherited retinal dystrophy (IRD) genes. Through a multi-center retrospective cohort study, we validated the assay's effectiveness and clinical utility ...and characterized the mutation spectrum of Taiwanese IRD patients. Between January 2018 and May 2022, 493 patients in 425 unrelated families, all initially suspected of having IRD without prior genetic diagnoses, underwent detailed ophthalmic and physical examinations (with extra-ocular features recorded) and genetic testing with our customized panel. Disease-causing variants were identified by segregation analysis and clinical interpretation, with validation via Sanger sequencing. We achieved a read depth of >200× for 94.2% of the targeted 1.2 Mb region. 68.5% (291/425) of the probands received molecular diagnoses, with 53.9% (229/425) resolved cases. Retinitis pigmentosa (RP) is the most prevalent initial clinical impression (64.2%), and 90.8% of the cohort have the five most prevalent phenotypes (RP, cone-rod syndrome, Usher's syndrome, Leber's congenital amaurosis, Bietti crystalline dystrophy). The most commonly mutated genes of probands that received molecular diagnosis are USH2A (13.7% of the cohort), EYS (11.3%), CYP4V2 (4.8%), ABCA4 (4.5%), RPGR (3.4%), and RP1 (3.1%), collectively accounted for 40.8% of diagnoses. We identify 87 unique unreported variants previously not associated with IRD and refine clinical diagnoses for 21 patients (7.22% of positive cases). We developed a customized gene panel and tested it on the largest Taiwanese cohort, showing that it provides excellent coverage for diverse IRD phenotypes.
The purpose of this study was to know the pathology associated with Baker's cyst (BC) in a rheumatology clinic and to evaluate the incidence, characteristics, and complications of BC. We reviewed the ...rheumatology ultrasound laboratory charts of patients with BC from Oct 2006 through Dec 2008. Demographic and disease data were also collected. Of the 1,120 patients who underwent ultrasound studies, 145 (12.9%) were found to have 180 BCs. The associated diseases were as follows: 91 (50.6%) osteoarthritis (OA) of the knee, 37 (20.6%) rheumatoid arthritis (RA), 25 (13.9%) gout, 14 (7.8%) seronegative spondyloarthropathy (SpA), and 13 (7.2%) pyrophosphate arthropathy. We found ruptured BCs in 12 patients, whose associated pathologies were in the following: four RA, four OA of the knee, two gout, one SpA, and one pyrophosphate arthropathy. The most frequent associated arthropathy of BCs was OA (50.6%), followed by RA (20.6%). However, in the cases of ruptured BC, the inflammatory pathology (66.7%) is more frequent than the degenerative one (33.3%).
Granular Co-rich Co-Pt nanograins having perpendicular coercivity (Hc ⊥ ) of 4.0 kOe and perpendicular squareness (S ⊥ ) of 0.75 can be achieved by depositing Co 80 Pt 20 (25 nm) film onto Ru (30 ...nm)/Ag (100 nm) bilayer films using an argon pressure of 5 mTorr to deposit an Ag underlayer at ambient temperature. However, it is found that the Co 80 Pt 20 film deposited directly onto an Ru layer without an Ag underlayer shows in-plane magnetic anisotropy. This is because an fcc Ag (111) underlayer can enhance the hcp Ru (0002) seed layer, inducing (0002) texture in the hexagonal Co 80 Pt 20 magnetic layer, leading to the perpendicular magnetic anisotropy of Co 80 Pt 20 films. TEM images show that granular nanograins with an average size of 8.0 nm can be observed in the Co 80 Pt 20 magnetic layer.
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