[Hepatitis B virus infection status and clinical characteristics in patients with rheumatoid arthritis].

Objective: To investigate the epidemiology of hepatitis B virus (HBV) infection in patients with rheumatoid arthritis (RA) in China and its association with RA disease characteristics. Methods: A cross-sectional study. A retrospective study was conducted on RA patients recruited from January 2001 to February 2023 in the Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital. Demographic and clinical data were collected including age, gender, disease duration, active smoking, RA disease activity, physical function, radiographic assessment, serological markers of HBV infection and liver function indicators. According to the status of HBV infection, RA patients were grouped as chronic HBV infection, resolved HBV infection and no HBV infection groups. The distribution of each group and the clinical characteristics of RA patients were analyzed. Results: Among 1 941 RA patients, 1 461 (75.3%) completed HBV screening, including 335 males (22.9%) and 1 126 females (77.1%), with a mean age of (55.4±13.1) years. The prevalence of chronic HBV infection was 10.1%(148/1 461), which was significantly higher in male patients than in females [14.6%(49/335) vs 8.8%(99/1 126), P<0.001], especially among those males born from 1970 to 1979[20.0%(7/35) vs 8.5%(17/201), P=0.037] and 1980-1989 [31.8%(7/22) vs 10.5%(14/133), P=0.007]. Among 148 RA patients with chronic HBV infection, there were 5 cases (3.4%) of chronic hepatitis B, 2 cases (1.4%) of HBV-associated cirrhosis and 1 case (0.7%) of hepatocellular carcinoma. The prevalence of resolved HBV infection was 57.6%(841/1 461). There were 472(32.3%) patients with no HBV infection and 267(56.6%) of them showed negative anti-HBs. Among all RA patients, 15 (1.0%) patients had abnormal liver function, of which 7 cases were drug-induced liver injury, 5 cases were chronic hepatitis B, 2 cases were non-alcoholic fatty liver disease, and 1 case was primary biliary cholangitis. Conclusion: Chronic HBV infection remains a common complication in RA patients in China, the infection rate is 10.1%, and the screening and management of HBV infection should be strengthened in clinical practice.

[Immune checkpoint inhibitor-induced eosinophilic fasciitis: a case report and literature review].

A 58-year-old male patient with angioimmunoblastic T-cell lymphoma developed a rash and skin tightness on the face, limbs, and trunk together with joint stiffness and dysfunction after 6 months of treatment with the programmed cell death protein-1 inhibitor camrelizumab. Laboratory tests revealed progressive eosinophilia over 6 months, with the eosinophil count increasing from 0.07×109/L to 3.3×109/L. Magnetic resonance imaging showed thickened skin of both forearms, while T2-weighted imaging showed markedly increased signal intensity within the myofascia. Skin biopsy of the right forearm showed thickened and fibrosed fascia and infiltration of inflammatory cells, including lymphocytes, plasma cells, and eosinophils. The patient was diagnosed with immune checkpoint inhibitor (ICI)-induced eosinophilic fasciitis (EF). After beginning treatment with methylprednisolone (40 mg daily), methotrexate (10 mg/week), and baricitinib (4 mg daily), his symptoms of skin tightness and joint dysfunction significantly improved within 1 month, and his peripheral blood eosinophil count decreased to 0.17×109/L. ICI-induced EF is a rare immune-related adverse reaction. To date, only 20 cases have been reported in published foreign literature, and their clinical characteristics are summarized here. The time from ICI treatment to EF was 12 (8,15) months, and the main clinical manifestations included skin involvement (n=19), joint dysfunction (n=11), myalgia/muscle weakness (n=9), and peripheral eosinophilia (n=16). After treatment, the clinical symptoms of EF improved in 17 patients, and eosinophil counts returned to normal after 3 (1,8) months. EF is a dysfunctional adverse response to ICI therapy. Tumor patients undergoing immunotherapy should be monitored for symptoms of EF. Early treatment is essential for preventing complications.

[Epidemiologic characteristics and drug resistance of isolated from blood culture escherichia coli in a hospital in Qinghai Province from 2016 to 2022].

Objective: To explore the drug resistance of Isolated From Blood Culture Escherichia coli (E. coli) in a hospital in Qinghai over the past seven years, to evaluate the ability of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to analyze the homologous origin of E. coli, and to establish a protein fingerprint library to match with it, adjuvant clinical experience medication so as to provide the basis for the prevention and control of hospital-acquired infections. Methods: Retrospective analysis of blood cultures sent to hospitals from January 2016 to December 2022. Drug resistance and resistance changes in E. coli.A total of 1 841 E. coli strains were isolated from Qinghai Provincial People's Hospital from January 2016 to December 2022; all strains were identified by MALDI-TOF MS, and the VITEK2.0 drug sensitivity analyzer was applied for drug sensitivity analysis of the strains, and the mass spectrometry homology analysis and self-constructed protein fingerprint library were carried out by MALDI-Biotyper software; the protein fingerprint library was built by using WHONET5.6 software was used to statistically analyze the drug sensitivity results, SPSS23.0 software was used to analyze the relationship between fingerprint typing and drug sensitivity, and the χ2 test was used for intergroup comparisons. Results: A total of 1 841 strains of E. coli were detected in 4 582 positive blood culture specimens from January 2016 to December 2022, with a detection rate of 40.17%; the resistance rate of E. coli from blood sources to piperacillin/tazobactam and ceftriaxone was on the rise, and it was slightly decreased to cefepime, amikacin, levofloxacin, and sulfamethoxazole, and there was not much change to the rest of the drugs; After MALDI-Biotyper clustering analysis, the 1841 E. coli strains from Isolated From Blood Culture were classified into two major clusters and five subtypes, of which type Ⅰa1 accounted for about 40%, type Ⅰa2 accounted for about 2.7%, type Ⅰb accounted for about 3.8, type Ⅱa accounted for about 46%, and type Ⅱb accounted for about 7.5%. The detection rate of type Ⅰa1 E. coli was higher in general surgery (50.45%) and emergency surgery (50.92%), and the detection rate of type Ⅰb E. coli was higher in emergency medicine(10.05%)than in other departments. The drug sensitivity results of different subtypes were compared with each other, the resistance rate of type Ⅰa1 E. coli to cefepime was 21.3% higher than that of the remaining four types, and the difference was statistically significant (χ2=37.74,P=0.000); the resistance rate of type Ⅱ E. coli(>60%) to sulfamethoxazole was higher than that of type Ⅰ (<60%) as a whole, and the difference was statistically significant (χ2=15.248,P=0.004); and a preliminary database of homologous protein fingerprints of E. coli has been established E. coli homologous protein fingerprint library and validated. The drug susceptibility results of 1 288 E. coli strains in the validation set were statistically analyzed and compared with those in the training set. There was no significant difference(P>0.05). Conclusion: In recent years, the resistance rate of E. coli isolated from a hospital in Qinghai province to piperacillin/Tazobactam, cefepime, amicacin and other antibiotics has changed greatly. A fingerprint database of E. coli homologous protein was established, and it was found that the drug sensitivity data of E. coli were different among different fingerprint types. According to drug sensitivity, drug use could assist clinical experience and provide evidence for prevention and control of hospital illness.

Muscle wasting, a neglected complication associated with physical dysfunction in elderly patients with rheumatoid arthritis: a cross-sectional observational study.

Objective: Little is known about muscle wasting in elderly patients with rheumatoid arthritis (RA). We examined muscle characteristics and their clinical significance in this group.Method: Consecutive RA patients were recruited and clinical data were collected. Muscle mass and distribution were assessed using bioelectric impedance analysis. Myopenia was defined as an appendicular skeletal muscle mass index (ASMI) ≤ 7.0 kg/m2 (men) and ≤ 5.7 kg/m2 (women).Results: Among the 643 RA patients recruited, 165 (25.7%) were elderly patients (age ≥ 60 years) with a mean age of 65.1 ± 4.5 years. Compared with young patients (age < 60 years), elderly RA patients had significantly higher Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP) (median 3.4 vs 3.2), Health Assessment Questionnaire Disability Index (HAQ-DI) (0.38 vs 0.13), and modified total Sharp score (mTSS) (16 vs 9), and a higher proportion of myopenia (54.5% vs 41.4%; all p < 0.01). Elderly RA patients with myopenia (n = 90, 14.0%) had significantly higher DAS28-CRP (3.6 vs 3.0), HAQ-DI (0.50 vs 0.12), and mTSS (21 vs 7) than young RA patients without myopenia (n = 280, 43.5%; all p < 0.0083). Multivariate logistic and linear regression analyses showed that myopenia, high HAQ-DI, active smoking, hypertension, diabetes, and coronary atherosclerotic heart disease were the main relevant characteristics of elderly RA patients. Age positively correlated with HAQ-DI, and ASMI negatively correlated with HAQ-DI (both p < 0.01). Further mediation analysis showed that ASMI partially mediated the association between age and HAQ-DI.Conclusion: Our data reveal that half of elderly RA patients manifest myopenia which aggravates physical dysfunction as a mediator of age. Myopenia, a neglected complication in elderly RA patients, should be recognized and further investigated.

FIT: Functional and imaging testing for patients with metastatic cancer.

BACKGROUND: Selecting study endpoints in prospective cancer cachexia trials remains poorly defined. The aim of this study was to further evaluate associations in changes in weight, body composition, functional outcomes, and patient-reported outcomes (PROs) in patients with metastatic cancer. METHODS: We completed a 2-year (2016-2018) observational study in patients with metastatic solid cancer and ECOG performance status 0 to 2 while receiving chemotherapy and/or immunotherapy. We completed assessments at study enrollment and 3 months from enrollment. We analyzed longitudinal changes in weight and body composition using validated methods. Functional assessments included the 6-Min Walk Test, Timed Up and Go Test, and Short Physical Performance Battery. PROs included the Functional Assessment of Anorexia/Cachexia Therapy and Functional Assessment of Cancer Therapy Fatigue. We analyzed changes in body composition and functional assessment using paired t tests. Additionally, we utilized linear regression models to assess relationships between changes in body composition and function outcomes and PROs, adjusting for age and sex. RESULTS: A total of 57 patients completed baseline assessments, but 19 patients did not complete 3-month assessments (5 died, 1 hospice, 13 withdrew). Of the 38 patients with complete data, the mean age was 61.8 years and 47% were female. Metastatic cancer types included 71% gastrointestinal, 13% lung, and 8% gynecologic. Half received chemotherapy, 16% immunotherapy, and 34% a combination. From enrollment to 3 months, we did not observe a change in weight or skeletal muscle but did find an increase in total adipose tissue (16.9 ± 52.4 cm2, 95% CI - 33.79-0.63; p = 0.059; ~ 1.5 pounds). We did not observe any association with changes in weight with any functional outcomes or PROs. However, greater losses in skeletal muscle were associated with greater declines in physical function (6-Min Walk Test [B = 0.04, p = 0.01], Short Physical Performance Battery [B = 2.44, p < 0.01]). CONCLUSIONS: Patients with metastatic cancer receiving cancer-directed therapy may not experience a change in body weight. However, we found an association between losses in skeletal muscle and greater declines in physical function. Therefore, when selecting study endpoints, prospective cancer cachexia studies may consider selecting changes in body composition over weight.

[Targeted therapy of pyogenic sterile arthritis, pyoderma gangrenosum, and acne syndrome (PAPA): a case report and literature review].

Objective: To analyze the clinical course and targeted therapy of pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. Methods: The clinical history of a 6-year-old boy with PAPA syndrome, who was admitted to Hong Kong University Shenzhen Hospital in September 2017, was reviewed. His genetic diagnosis was confirmed by whole exome sequencing. The response to targeted therapy was evaluated by comparing the inflammatory markers (erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) and serum cytokines (interleukin (IL)-1, IL-6 and tumor necrosis factor-α (TNF-α)) before and after biological agents treatment. For literature review, "PAPA syndrome" and"PSTPIP1 gene"were used as keywords to retrieve papers published from January 1997 to December 2019 from Pubmed, Wanfang and CNKI database. Results: The patient was a 6-year-old boy, admitted to the hospital due to recurrent joint swelling and pain for more than 4 years. Before treatment, the CRP (256 mg/L), ESR (105 mm/1 h) and cytokines including serum TNF-α (7.43 ng/L), IL-1 (<5 ng/L), IL-6 (301 ng/L) were significantly elevated. Culture of the joint effusion was negative, but the IL-6 level was above 1 000 ng/L. MRI showed osteomyelitis at the lower end of the right femur. Gene detection found a heterozygous variation of PSTPIP1 gene (c.748G>A, p.E250K). Arthralgia once alleviated after the initiation of tocilizumab and infliximab, but recurred after 1 year of treatment. Thereafter, the anti-IL-1 receptor antagonist (Anakinra) was commenced, followed by a significant improvement of the arthralgia, and a complete remission during the follow-up. Besides, the level of CRP, ESR, serum TNF-α, IL-1 and IL-6 were all decreased to normal on the last followed up in December 2019. Literature review found 29 articles and 87 patients in total. The initial symptoms included those of arthritis (n=58), pyoderma gangrenosum (n=33), and acne (n=24). Among all the cases, 13 genotypes were confirmed, and 47 variations involved amino acid p.E250. Steroid and/or biological agents were used in most patients. Conclusions: PAPA syndrome should be suspected in children with recurrent pyogenic sterile arthritis, and an early diagnosis could be achieved by genetic test. Targeted treatment with biological agent may control the symptoms effectively. Biological agents can control symptoms of this disorder effectively.

[Potential mechanism of transcription factor peroxisome proliferator-activated receptor-gamma coactivator-1 beta on promoting osteoclastogenesis].

Objective: To investigate the role of transcription factor peroxisome proliferator-activated receptor-gamma coactivator-1 beta (PGC-1ß) on osteoclastogenesis and related regulatory mechanism in the mouse monocyte-macrophage cell line (RAW264.7). Methods: PGC-1ß expression and location in RAW264.7 cells was detected by immunofluorescence, flow cytometry and western blot analysis with nuclear protein extraction. RAW264.7 cells were transfected with lentivirus for gene silencing or over-expression of PGC-1ß and cultured with macrophage colony-stimulating factor and receptor activator for nuclear factor-κB ligand. Cell viability was detected by cell counting kit-8. Cell apoptosis and cell cycle were detected by flow cytometry. Mature osteoclasts and their bone resorption activity were determined by tartrate-resistant acid phosphatase (TRAP) expression and toluidine blue staining. Western blot analysis was performed for detecting dendritic cell-specific transmembrane protein (DC-STAMP), cathepsin K, TRAP and matrix metalloproteinase (MMP)-9 expression, as well as cytoplasmic NF-κB-inducing kinase (NIK) and nuclear RelB. Results: PGC-1ß expression was observed in the nuclei of RAW264.7 cells. Down-regulation or overexpression of PGC-1ß in RAW264.7 cells did not affect cell viability, apoptosis or cell cycle. Down-regulation of PGC-1ß decreased the count of mature osteoclasts (49±21 cells vs. 147±42 cells, P=0.004) and the pit area of bone resorption lacunae (42.11µm(2)±11.30 µm(2) vs. 204.80µm(2)±31.09 µm(2), P<0.001), as well as the expression of cathepsin K, TRAP and MMP-9, but not DC-STAMP. Overexpression of PGC-1ß promoted osteoclast differentiation and bone resorption activity, as well as the expression of cathepsin K, TRAP and MMP-9. Down-regulation of PGC-1ß suppressed the protein expression of cytoplasmic NIK and nuclear RelB in RAW264.7 cells. Conclusion: PGC-1ß can promote the differentiation of RAW264.7 into osteoclasts and improve the bone resorption ability of the cells via activation of NIK/RelB pathway, which might be a promising therapeutic target for osteoporosis.