Enhancing pneumonia prognosis in the emergency department: a novel machine learning approach using complete blood count and differential leukocyte count combined with CURB-65 score.

BACKGROUND: Pneumonia poses a major global health challenge, necessitating accurate severity assessment tools. However, conventional scoring systems such as CURB-65 have inherent limitations. Machine learning (ML) offers a promising approach for prediction. We previously introduced the Blood Culture Prediction Index (BCPI) model, leveraging solely on complete blood count (CBC) and differential leukocyte count (DC), demonstrating its effectiveness in predicting bacteremia. Nevertheless, its potential in assessing pneumonia remains unexplored. Therefore, this study aims to compare the effectiveness of BCPI and CURB-65 in assessing pneumonia severity in an emergency department (ED) setting and develop an integrated ML model to enhance efficiency. METHODS: This retrospective study was conducted at a 3400-bed tertiary medical center in Taiwan. Data from 9,352 patients with pneumonia in the ED between 2019 and 2021 were analyzed in this study. We utilized the BCPI model, which was trained on CBC/DC data, and computed CURB-65 scores for each patient to compare their prognosis prediction capabilities. Subsequently, we developed a novel Cox regression model to predict in-hospital mortality, integrating the BCPI model and CURB-65 scores, aiming to assess whether this integration enhances predictive performance. RESULTS: The predictive performance of the BCPI model and CURB-65 score for the 30-day mortality rate in ED patients and the in-hospital mortality rate among admitted patients was comparable across all risk categories. However, the Cox regression model demonstrated an improved area under the ROC curve (AUC) of 0.713 than that of CURB-65 (0.668) for in-hospital mortality (p<0.001). In the lowest risk group (CURB-65=0), the Cox regression model outperformed CURB-65, with a significantly lower mortality rate (2.9% vs. 7.7%, p<0.001). CONCLUSIONS: The BCPI model, constructed using CBC/DC data and ML techniques, performs comparably to the widely utilized CURB-65 in predicting outcomes for patients with pneumonia in the ED. Furthermore, by integrating the CURB-65 score and BCPI model into a Cox regression model, we demonstrated improved prediction capabilities, particularly for low-risk patients. Given its simple parameters and easy training process, the Cox regression model may be a more effective prediction tool for classifying patients with pneumonia in the emergency room.

Patients with comorbid rheumatoid arthritis are predisposed to peritonsillar abscess: real-world evidence.

PURPOSE: The peritonsillar abscess (PTA)-rheumatoid arthritis (RA) association remains unclear. Here, the effects of RA on PTA incidence and prognosis are elucidated. METHODS: We compared PTA incidence and prognosis of 30,706 RFCIP-registered patients with RA (RA cohort) with matched individuals without RA from another database of 1 million randomly selected people representing Taiwan's population (non-RA cohort). RESULTS: The RA cohort had significantly higher PTA incidence [incidence rate ratio (IRR) (95% CI) 1.73 (1.10-2.71), P = 0.017) and cumulative incidence (P = 0.016, Kaplan-Meier curves). Cox regression analyses demonstrated RA cohort to have an estimated 1.72-fold increased PTA risk (95% CI 1.09-2.69, P = 0.019). PTA was more likely within the first 5 years of RA diagnosis (for < 1, 1-5, and ≥ 5 postdiagnosis years, IRRs: 2.67, 2.31, and 1.10, respectively, and P = 0.063, 0.021, and 0.794, respectively; average onset duration: 4.3 ± 3.3 years after RA diagnosis). PTA increased length of hospital stay significantly and risk of complication with deep neck infection nonsignificantly [6.5 ± 4.5 vs 4.6 ± 2.8 days (P = 0.045) and 18.52% vs 7.81% (P = 0.155), respectively]. Moreover, RA-cohort patients not receiving RA therapy exhibited 5.06-fold higher PTA risk than those receiving RA-related therapy (95% CI 1.75-14.62, P = 0.003). CONCLUSIONS: In patients with RA, PTA incidence is the highest within 5 years of RA diagnosis, and RA therapy is essential for reducing PTA risk. LEVEL OF EVIDENCE: 4.

Altered subgroups of regulatory T cells in patients with primary Sjögren's syndrome.

Primary Sjögren syndrome (pSS) is a systemic autoimmune inflammatory disease. Up to now, the role of regulatory T cells (Tregs) and their subgroups in pSS is still in controversial. In this study we tried to elucidate the roles of Tregs and its subgroups in pSS. Total 43 pSS patients and 23 health persons as control were enrolled in this study. We grouped the pSS patients according to the anti-SSa/SSb and the EULAR Sjögren's syndrome disease activity index (ESSDAI). Among the 43 pSS patients, 14 patients were followed after treatment. The percentage of rTregs (resting Treg cells) among Tregs was increased in the pSS group, and decreased after treatment. In the high disease activity subpopulation (ESSDAI ≥ 5), the percentage of rTregs among Tregs decreased after treatment. On the contrary, the percentage of aTregs (activated Treg cells) increased after treatment. It was in an inverse correlation between the percentage of aTreg and rTreg in pSS patients. The Tregs are co-cultured with responder T cells. Tregs from pSS patients showed poorer proliferation inhibitory function. Our results show that the percentages of Tregs and their subgroups altered in pSS patients. The percentage of aTreg and the percentage of rTreg have an inverse correlation in pSS patients. Compared to the control group, the percentage of rTregs among Tregs was increased in the pSS patients and decreased after the treatment. Our study also showed that The Tregs from pSS patients may have poorer inhibitory functions.

Danazol in Refractory Autoimmune Hemolytic Anemia or Immune Thrombocytopenia: A Case Series Report and Literature Review.

Danazol is a treatment option for autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Three patients with AIHA and eight patients with ITP between 2008 and 2022 were enrolled in the Rheumatology Outpatient Clinic of Chang Gung Memorial Hospital, Kaohsiung. Those patients were refractory or intolerant to conventional therapy and were treated with danazol. All the patients received an initial dose of danazol (200-400 mg). The observation period was 6 months. Three patients (100%) with AIHA and six (75%) with ITP achieved treatment response after 6 months of danazol therapy. The dose of glucocorticoid for responders could be reduced to ≤5 mg/day of prednisolone, and the immunosuppressants, except hydroxychloroquine and azathioprine for systemic lupus erythematosus, could be discontinued. Adverse events were acne in two (18.2%) patients and transient dose-related liver function impairment in one (9.1%) patient in the current series. Danazol therapy appears to be a favorable alternative for refractory AIHA and ITP by altering the erythrocyte membrane to resist osmotic lysis and protecting platelets against complement-mediated lysis. In this report, we also performed a literature review and searched the PubMed/Cochrane Library for articles published from 1984 to January 2022 on danazol therapy for patients with AIHA and ITP.

Epiglottitis in Patients With Preexisting Autoimmune Diseases: A Nationwide Case-Control Study in Taiwan.

OBJECTIVES: The role of autoimmune diseases on the risk for acute epiglottitis remains uncertain. This study aimed to delineate the association between epiglottitis and autoimmune diseases using population database. METHODS: A population-based retrospective study was conducted to analyze claims data from Taiwan National Health Insurance Research Database collected over January, 2000, to December, 2013. RESULTS: In total, 2339 patients with epiglottitis were matched with 9356 controls without epiglottitis by sex, age, socioeconomic status, and urbanization level. The correlation between autoimmune diseases and epiglottitis was analyzed by multivariate logistic regression. Compared with controls, patients with epiglottitis were much more likely to have preexisting Sjögren syndrome (adjusted odds ratio [aOR]: 2.37; 95% CI: 1.14-4.91; P = .021). In addition, polyautoimmunity was associated with increased risk of epiglottitis (aOR: 2.08; 95% CI: 1.14-3.80; P = .018), particularly in those aged >50 years (aOR: 2.61; 95% CI: 1.21-5.66; P = .015). CONCLUSIONS: Among autoimmune diseases, we verify the association between epiglottitis and Sjögren syndrome in Taiwan. Furthermore, we present the novel discovery that patients with epiglottitis have an increased risk of polyautoimmunity, particularly those aged >50 years.

Urban Particulate Matter Enhances ROS/IL-6/COX-II Production by Inhibiting MicroRNA-137 in Synovial Fibroblast of Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) has been associated with air pollution, possibly due to the augmentation of inflammatory effects. In this study, we aimed to determine the roles of inflammatory pathways and microRNA involved in the pathogenesis of RA fibroblast-like synoviocytes (FLS) inflammation induced by particulate matter. METHODS: The inflammatory mediators, messenger RNAs, microRNAs and their interrelationships were investigated using western blotting, QPCR, ELISA and immunohistochemistry. RESULTS: Particulate matter (PMs) induced an increase in the expression of interleukin-6 (IL-6) and cyclooxygenase-II (COX-II) in RA-FLS and microRNA-137 was found definitely to mediate the inflammatory pathways. PMs-induced generation of reactive oxygen species (ROS) in RA-FLS was attenuated by pretreatment with antioxidants. Nox-dependent ROS generation led to phosphorylation of ERK1/2, p38 and JNK, followed by downregulation of microRNA-137. In vivo studies, the joints of rats exposed to PMs revealed synovial fibroblast inflammation under pathologic examination and the expressions of IL-6 and COX-II were obviously increased. PMs exposure results in activated ROS-mediated mitogen-activated protein kinase (MAPK) signaling pathways and cause increased IL-6 and COX-II through downregulation of hsa-miRNA-137, which lead to inflammation and RA exacerbation. CONCLUSIONS: microRNA-137 plays an important role in PMs-induced RA acute exacerbation through MAPK signaling pathways and IL-6/COX-II activation. Targeting these mechanisms can potentially be used to develop new therapeutic strategies and prevention of RA inflammation in the future.

Real-world evidence for increased deep neck infection risk in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the association between rheumatoid arthritis (RA) and deep neck infection (DNI). STUDY DESIGN: Retrospective cohort study. METHODS: Patients newly diagnosed with RA between 2000 and 2011 were identified from the National Health Insurance Research Database in Taiwan. Moreover, patients without RA were randomly selected and matched at a 1:4 ratio by age, sex, urbanization level, income, and diabetes mellitus. The patients were followed up until death or the end of the study period (December 31, 2013). The primary outcome was the occurrence of DNI. RESULTS: In total, 30,207 patients with RA and 120,828 matched patients without RA were enrolled. Patients with RA had a significantly higher cumulative incidence of DNI than those without RA (P < 0.001). The adjusted Cox proportional hazard model demonstrated that RA was significantly associated with a higher incidence of DNI (hazard ratio: 2.80, 95% confidence interval: 2.26-3.46, P < 0.001). Therapeutic methods (surgical or nonsurgical) did not differ significantly between the patients with RA-DNI and with non-RA-DNI. Patients with RA-DNI had higher rates of tracheostomy, mediastinitis, mediastinitis-related mortality, and mortality than patients with non-RA-DNI, although these differences were without statistical significance. RA patients receiving no therapy experienced higher rates of DNI compared with those receiving methotrexate alone, disease-modifying antirheumatic drugs, or biologic therapies. CONCLUSION: This study is the first to investigate the association between RA and DNI. We conclude RA is an independent predisposing factor for DNI. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1402-1407, 2020.

Deep Neck Infection in Systemic Lupus Erythematosus Patients: Real-World Evidence.

Systemic lupus erythematosus (SLE) might increase deep neck infection (DNI) risk, but evidence supporting this hypothesis is limited. In this retrospective follow-up study, the SLE-DNI association was investigated using data from the Registry for Catastrophic Illness Patients, which is a subset of the Taiwan National Health Insurance Research Database. All patients newly diagnosed as having SLE in 1997-2011 were identified, and every SLE patient was individually matched to four patients without SLE according to sex, age, and socioeconomic status. The study outcome was DNI occurrence. DNI treatment modalities and prognoses in SLE and non-SLE patients, along with the association of steroid dose with DNI risk, were also studied. In total, 17,426 SLE and 69,704 non-SLE patients were enrolled. Cumulative DNI incidence was significantly higher in the SLE cohort than in the non-SLE cohort (p < 0.001). The Cox regression model demonstrated that SLE significantly increased DNI risk (hazard ratio: 4.70; 95% confidence interval: 3.50-6.32, p < 0.001). Moreover, in the sensitivity and subgroup analyses, the effect of SLE on DNI was stable. Relatively few SLE-DNI patients received surgical interventions (15.6% vs. 28.6%, p = 0.033). The between-group differences in tracheostomy use and hospitalisation duration were nonsignificant. In SLE patients, high steroid doses significantly increased DNI incidence (≥3 vs. <3 mg/day = 2.21% vs. 0.52%, p < 0.001). This is the first study demonstrating that SLE increases DNI risk by approximately five times and that high steroid dose increases DNI incidence in SLE patients.

Real-World Database Examining the Association between Sjögren's Syndrome and Chronic Rhinosinusitis.

OBJECTIVE: To investigate the risk of chronic rhinosinusitis (CRS) among patients with Sjögren's syndrome (SS). METHOD: A total of 18,723 patients diagnosed with SS between 1997 and 2011 were retrospectively analyzed. Moreover, 59,568 patients without SS were matched to patients with SS at a 1:4 ratio on the basis of sex, age, urbanization level, income level, and the comorbidities of rhinitis and nasal sepal deviation. Patients were followed up until death or the end of the study period (31 December, 2013). The primary outcome was the occurrence of CRS. RESULTS: The cumulative incidence of CRS was significantly higher in patients with SS than in those without SS (p < 0.001). The adjusted Cox proportional hazard model showed that patients with SS had a significantly higher incidence of CRS (hazard ratio, 2.51; 95% confidence interval, 2.22⁻2.84; p < 0.001). Sensitivity and subgroup analyses demonstrated SS was an independent risk factor for CRS. The dosage of intranasal corticosteroid spray used was not different between the SS and non-SS groups. Fewer patients with CRS in the SS group underwent sinus surgery (82/407 (20.2%)) than those in the non-SS group (179/667 (26.8%)) and this finding was statistically significant (p = 0.013). The number of operations did not differ significantly between patients with CRS in the SS and non-SS groups. CONCLUSIONS: SS is an independent risk factor for CRS. Our study extends the disease spectrum and prompts physicians to be aware of potential CRS occurrence after SS.

Prevalence and predictive value of high-positive rheumatoid factor and anti-citrullinated protein antibody levels in nonarthritic patients with chronic hepatitis C infection.

AIM: In order to increase diagnostic sensitivity for early disease in rheumatoid arthritis (RA), new classification criteria were approved in 2010 by the American College of Rheumatology and the European League Against Rheumatism. One of the criteria, a high-positive rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA) level, was given a high score of 3. However, the increased prevalence of RF in patients with chronic hepatitis C virus (HCV) infection markedly diminishes the diagnostic specificity of serum RF for RA in these patients. There are no published data on the prevalence and predictive value of high-positive RF and ACPA; thus, we investigated high-positive RF and ACPA levels in nonarthritic patients with chronic HCV infection. METHOD: Anti-citrullinated protein antibody and total RF were determined in serum from nonarthritic patients with chronic HCV infection (all had HCV RNA viremia). RESULT: In 271 HCV-infected patients, positive RF, positive ACPA, high-positive RF, and high-positive ACPA were detectable in 47.2%, 1.1%, 8.9% and 1.1%, respectively. In these patients, fatty liver was an independent factor for high-positive RF. CONCLUSION: In contrast to RF, ACPA is not increased in HCV infection. High-positive RF is not unusually present in nonarthritic patients with chronic HCV infection. ACPA may have improved value for the diagnosis of RA in this patient population. In patients with HCV infection, fatty liver may be a risk factor for high-positive RF.

Hypersensitivity and Cardiovascular Risks Related to Allopurinol and Febuxostat Therapy in Asians: A Population-Based Cohort Study and Meta-Analysis.

The safety of newer xanthine oxidase inhibitor febuxostat compared to allopurinol remains unclear. To compare the risks of allopurinol hypersensitivity and febuxostat hypersensitivity and cardiovascular diseases (CVDs) in Asians, we conducted a population-based cohort study enrolling patients receiving allopurinol or febuxostat from Chang Gung Memorial Hospital Health System across Taiwan during 2012-2016 and further performed a meta-analysis incorporating two recent studies. Among the 61,539 users, a corresponding 12,007 and 5,680 patients were identified as new users. The overall incidence of febuxostat hypersensitivity was significantly lower than allopurinol hypersensitivity (0.2 vs. 2.7 per 1,000 new users; P < 0.001). There were 33 allopurinol-hypersensitivity reactions (including 18 severe cutaneous adverse drug reactions), and only one patient developed febuxostat-maculopapular exanthema. Moreover, febuxostat did not statistically increase the risk of CVD (hazard ratio (HR), 1.16; P = 0.152) and related death (HR, 1.49; P = 0.496) compared to allopurinol. The result of the meta-analysis also showed a consistent result. In conclusion, the incidence and severity of febuxostat-hypersensitivity are lower than with allopurinol. Febuxostat did not show an increased risk of CVD and related death.

Ischemia heart disease and greater waist circumference are risk factors of renal function deterioration in male gout patients.

We examined the incidence of renal function deterioration (RFD) in a population of male gout patients and to identify associated risk factors. Subjects who had been regularly followed up for more than 2 years and had visited Chang Gung Memorial Hospital-Kaohsiung Medical Center Rheumatology Clinic between June 1, 2006 and January 31, 2007 were enrolled. Four subjects were excluded as secondary gout was suspected. Group I (Gr I) comprised subjects without RFD and group II (Gr II) comprised subjects with RFD during the follow-up period. RFD was defined as absolute increment in creatinine (Cr) levels over 0.4 mg/dl for subjects with baseline Cr levels 1.4 mg/dl. Clinical parameters were analyzed to study the potential risk factors of RFD. Of 318 male gout patients, 296 (93.1%) were categorized as Gr I, and 22 (6.9%) were categorized as Gr II. The observation periods for Gr I and Gr II were 81.20+/-53.29 and 92.41+/-46.72 months, respectively (p=0.338). Initial Cr levels are similar between the two groups (1.25+/-0.51 vs 1.25+/-0.61, p=0.963). Multiple logistic regression analysis revealed that current age, age at disease onset, disease duration, treatment duration, body weight, height, family history of gout, tophi, urolithiasis, tobacco use, alcohol consumption, history of cerebral vascular accident, hypertension, diabetes mellitus, dyslipidemia, base-line and final Cr, blood urea nitrogen level, serum uric acid level, and body-mass index were not independent risk factors. However, history of ischemic heart disease [IHD; odds ratio (OR) 7.68, 95% confidence interval (CI) 1.99-29.70] and greater waist circumference (WC; OR 1.06, 95% CI 1.01-1.11) were two independent risk factors of RFD. Additionally, the Cox multivariable analysis disclosed that IHD (p<0.001) and greater WC (p=0.011) deteriorated kidney function in these patients. The incidence of RFD in male gout patients is 6.9%. History of IHD and greater WC are two independent risk factors for developing RFD.

Cost-efficacy of biologic therapies for psoriatic arthritis from the perspective of the Taiwanese healthcare system.

BACKGROUND: Biologic therapies are more effective but more costly than conventional therapies in treating psoriatic arthritis. OBJECTIVES: To evaluate the cost-efficacy of etanercept, adalimumab and golimumab therapies in treating active psoriatic arthritis in a Taiwanese setting. METHODS: We conducted a meta-analysis of randomized placebo-controlled trials to calculate the incremental efficacy of etanercept, adalimumab and golimumab, respectively, in achieving Psoriatic Arthritis Response Criteria (PsARC) and a 20% improvement in the American College of Rheumatology score (ACR20). The base, best, and worst case incremental cost-effectiveness ratios (ICERs) for one subject to achieve PsARC and ACR20 were calculated. RESULTS: The annual ICER per PsARC responder were US$27 047 (best scenario US$16 619; worst scenario US$31 350), US$39 339 (best scenario US$31 846; worst scenario US$53 501) and US$27 085 (best scenario US$22 716; worst scenario US$33 534) for etanercept, adalimumab and golimumab, respectively. The annual ICER per ACR20 responder were US$27 588 (best scenario US$20 900; worst scenario US$41 800), US$39 339 (best scenario US$25 236; worst scenario US$83 595) and US$33 534 (best scenario US$27 616; worst scenario US$44 013) for etanercept, adalimumab and golimumab, respectively. CONCLUSIONS: In a Taiwanese setting, etanercept had the lowest annual costs per PsARC and ACR20 responder, while adalimumab had the highest annual costs per PsARC and ACR responder.

Tumor necrosis factor-α antagonist therapy for concomitant rheumatoid arthritis and hepatitis C virus infection: a case series study.

The aim of this study was to investigate treatment response and hepatic safety of anti-tumor necrosis factor-α therapy among patients with concomitant rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection. We reviewed the charts of 101 consecutive RA patients who were eligible for anti-TNF-α therapy in the Chiayi Branch of Chang Gung Memorial Hospital. Group A patients were sero-positive for anti-HCV antibodies and had HCV RNA but were negative for hepatitis B surface antigen (HBsAg). Group B (the control group) patients were sero-negative for both anti-HCV antibodies and HBsAg. Response to anti-TNF-α treatment was assessed by calculating disease activity score at 28 joints (DAS28) at baseline and 5, 8, and 11 months after the start of TNF-α antagonist therapy. Percentage change in DAS28 from baseline to month 5 was 21.36 ± 8.01 % in group A and 26.98 ± 10.43 % in group B (p = 0.011). However, there was no obvious difference in treatment response between groups at other time points. Anti-TNF-α therapy was discontinued within 1 year of starting treatment in two subjects in group A and 4 in group B. Response to anti-TNF-α was better in group B than in group A at 5 months, but there was no substantial difference in response at the 1-year evaluation. Although the study sample was small, our results suggest that the safety of anti-TNF-α therapy is similar in RA patients with and without concomitant HCV infection.

Rituximab-induced hepatitis C virus reactivation in rheumatoid arthritis.

The B-cell depletion agent rituximab (RTX) is used in lymphoma and rheumatoid arthritis (RA), and there have been several case reports of an RTX-induced reactivation of hepatitis C virus in patients with lymphoma. However, there have been no papers detailing hepatitis C virus reactivation after RTX therapy in a patient with RA. Here we report a case of RTX-induced hepatitis C virus reactivation in a patient with RA. Physicians should be aware that a close follow-up of liver function and viral load is mandatory after RTX therapy in patients with RA and concomitant hepatitis C.

Increased soluble CD4 in serum of rheumatoid arthritis patients is generated by matrix metalloproteinase (MMP)-like proteinases.

Higher soluble CD4 (sCD4) levels in serum have been detected in patients of infectious and chronic inflammatory diseases. However, how and why sCD4 is produced remains poorly understood. We establish sensitive ELISA and WB assays for sCD4 detection in conditioned medium of in vitro cell culture system and serum of chronic inflammatory patients. Serum samples from patients with systemic lupus erythematosus (SLE) (n = 79), rheumatoid arthritis (RA) (n = 59), ankylosing spondylitis (AS) (n = 25), gout (n = 31), and normal controls (n = 99) were analyzed using ELISA for sCD4 detection. Results from each assay were analyzed by the Kruskal-Wallis test. Dunn's multiple comparison post-test was then applied between groups. We confirm that cells expressing exogenous CD4 produce sCD4 in a constitutive and PMA-induced manner. Importantly, sCD4 production in a heterologous expression system is inhibited by GM6001 and TAPI-0, suggesting receptor shedding by matrix metalloproteinase (MMP)-like proteinases. Moreover, similar findings are recapitulated in human primary CD4(+) T cells. Finally, we show that serum sCD4 levels are increased in patients of chronic inflammatory diseases including RA and SLE, but not in those with gout. Intriguingly, sCD4 levels in RA patients are correlated positively with the disease activities and higher sCD4 levels seem to associate with poor prognosis. Taken together, we conclude that CD4 is shed from cell surface by a MMP-like sheddase and sCD4 level is closely related with the inflammatory condition in certain chronic diseases. Hence, sCD4 might be considered an important parameter for RA disease progression with potential diagnostic importance.