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BMC Surgery Jun 2024Patients with gout are at risk for increased serum uric acid (SUA) levels and gout attacks in the short term after undergoing bariatric surgery, and the purpose of this...
BACKGROUND/PURPOSE
Patients with gout are at risk for increased serum uric acid (SUA) levels and gout attacks in the short term after undergoing bariatric surgery, and the purpose of this study was to evaluate the benefits of short-term treatment with uric acid-lowering medication after bariatric surgery for the control of gout attacks and SUA levels in patients with gout.
METHODS
71 patients who underwent SG from January 2020 to December 2022 were prospectively included. These patients were diagnosed with hyperuricemia before surgery and had a history of gout attacks. Patients were classified into a drug-treatment group (DTG, n = 32) and a non-drug-treatment group (NDTG, n = 39) according to whether they took uric acid-lowering medication after surgery. Changes in the number of gout attacks, body mass index (BMI), and SUA levels at 1 week, 1 month, 3 months, and 6 months after bariatric surgery were measured in both groups.
RESULTS
In the DTG, 22 patients (68.8%) experienced an increase in SUA within 1 week, 3 patients (9.4%) had an acute attack of gout within the first month, and no patients had a gout attack thereafter. In the NDTG, 35 patients (89.7%) experienced an increase in SUA within 1 week, 7 patients (17.9%) had an acute gout attack within the first month, and 4 patients (10.3%) experienced gout attacks between month 1 and month 3 postoperatively. Both groups were free of gout attacks between the 3rd and 6th postoperative month and showed a significant decrease in SUA and BMI by the sixth month.
CONCLUSION
In patients with gout, continued use of uric acid-lowering medication after bariatric surgery is beneficial in reducing the number of gout attacks and the risk of rising SUA.
Topics: Humans; Gout; Bariatric Surgery; Male; Female; Middle Aged; Uric Acid; Gout Suppressants; Adult; Prospective Studies; Hyperuricemia; Body Mass Index; Postoperative Complications; Treatment Outcome
PubMed: 38877436
DOI: 10.1186/s12893-024-02472-6 -
International Journal of... 2024TYK2 inhibitors and traditional natural drugs as promising drugs for psoriasis therapy are receiving increasing attention. They both affect different molecules of...
INTRODUCTION
TYK2 inhibitors and traditional natural drugs as promising drugs for psoriasis therapy are receiving increasing attention. They both affect different molecules of JAK/STAT pathway, but it is currently unclear whether their combination will enhance the effect on psoriasis. In this study, we used imiquimod (IMQ)-induced psoriasis mouse model to investigate the therapeutic effects of the combined administration of deucravacitinib (TYK2 inhibitor) and shikonin.
METHODS
Aldara cream containing 5% IMQ was used to topically treat the dorsal skin of each mouse for a total of six consecutive days to induce psoriasis. The psoriasis area and severity index (PASI) scores were recorded every day. On the 7 day, skin tissues were taken for histopathological examination and the content of cytokines in skin were evaluated. The frequency of immune cells in peripheral blood, spleen and skin were detected through flow cytometry.
RESULTS
Compared to the vehicle control group, the psoriasis symptoms and immune disorder improved significantly in the combination therapy group and deucravacitinib treatment group on the 7th day, and the expressions of p-STAT3 and Ki67 in skin were reduced as well. Moreover, the combined treatment of deucravacitinib and shikonin for psoriasis was superior to the monotherapy group, especially in inhibiting abnormal capillaries proliferation, reducing immune cells infiltration and decreasing the concentration of IL-12p70 in skin.
CONCLUSION
The combination of deucravacitinib and shikonin is a promising clinical application.
Topics: Animals; Psoriasis; Imiquimod; Naphthoquinones; Drug Therapy, Combination; Mice; Skin; Disease Models, Animal; Cytokines; Mice, Inbred BALB C; Male; Female; Benzimidazoles; Quinolones
PubMed: 38876119
DOI: 10.1177/03946320241260262 -
Medicine Jun 2024Pleural effusion, especially bilateral bloody pleural effusion, is a rare complication of Waldenström macroglobulinemia (WM). Pleural effusion in patients with WM has...
RATIONALE
Pleural effusion, especially bilateral bloody pleural effusion, is a rare complication of Waldenström macroglobulinemia (WM). Pleural effusion in patients with WM has many causes, such as infection, tumor invasion of the pleura, and rupture of the thoracic duct or its branches. Patients with WM presenting to the respiratory department with chest tightness and shortness of breath need more differential diagnosis by respiratory physicians, which is helpful for effective treatment. Herein, we present a case of MV diagnosis in a patient with bilateral bloody pleural effusion.
PATIENT CONCERN
Our patient is a 59-year-old man with WM presenting as having bilateral bloody pleural effusion.
INTERVENTIONS
The patient was treated with pleural effusion drainage. After confirming the diagnosis, the patient was treated with rituximab, cyclophosphamide, and dexamethasone.
OUTCOMES
Following these treatments, the patient's symptoms improved, and ultrasound showed a decrease in pleural effusion.
LESSONS
Despite its favorable prognosis, the cause of pleural effusion in a patient with WM can be challenging to diagnose. The cause of pleural effusion should be considered a differential diagnosis when diagnosing patients diagnosed with WM.
Topics: Humans; Waldenstrom Macroglobulinemia; Male; Middle Aged; Pleural Effusion; Diagnosis, Differential; Rituximab; Cyclophosphamide; Dexamethasone
PubMed: 38875392
DOI: 10.1097/MD.0000000000038406 -
PloS One 2024Emulation of the "target trial" (TT), a hypothetical pragmatic randomized controlled trial (RCT), using observational data can be used to mitigate issues commonly...
Designing target trials using electronic health records: A case study of second-line disease-modifying anti-rheumatic drugs and cardiovascular disease outcomes in patients with rheumatoid arthritis.
BACKGROUND
Emulation of the "target trial" (TT), a hypothetical pragmatic randomized controlled trial (RCT), using observational data can be used to mitigate issues commonly encountered in comparative effectiveness research (CER) when randomized trials are not logistically, ethically, or financially feasible. However, cardiovascular (CV) health research has been slow to adopt TT emulation. Here, we demonstrate the design and analysis of a TT emulation using electronic health records to study the comparative effectiveness of the addition of a disease-modifying anti-rheumatic drug (DMARD) to a regimen of methotrexate on CV events among rheumatoid arthritis (RA) patients.
METHODS
We used data from an electronic medical records-based cohort of RA patients from Northwestern Medicine to emulate the TT. Follow-up began 3 months after initial prescription of MTX (2000-2020) and included all available follow-up through June 30, 2020. Weighted pooled logistic regression was used to estimate differences in CVD risk and survival. Cloning was used to handle immortal time bias and weights to improve baseline and time-varying covariate imbalance.
RESULTS
We identified 659 eligible people with RA with average follow-up of 46 months and 31 MACE events. The month 24 adjusted risk difference for MACE comparing initiation vs non-initiation of a DMARD was -1.47% (95% confidence interval [CI]: -4.74, 1.95%), and the marginal hazard ratio (HR) was 0.72 (95% CI: 0.71, 1.23). In analyses subject to immortal time bias, the HR was 0.62 (95% CI: 0.29-1.44).
CONCLUSION
In this sample, we did not observe evidence of differences in risk of MACE, a finding that is compatible with previously published meta-analyses of RCTs. Thoughtful application of the TT framework provides opportunities to conduct CER in observational data. Benchmarking results of observational analyses to previously published RCTs can lend credibility to interpretation.
Topics: Humans; Arthritis, Rheumatoid; Antirheumatic Agents; Electronic Health Records; Cardiovascular Diseases; Female; Male; Middle Aged; Methotrexate; Aged; Treatment Outcome; Randomized Controlled Trials as Topic; Comparative Effectiveness Research; Adult
PubMed: 38875273
DOI: 10.1371/journal.pone.0305467 -
Antiviral Therapy Jun 2024Angiotensin-converting enzyme 2 (ACE2) is the receptor that enables SARS-CoV-2 to invade host cells. Previous studies have reported that reducing ACE2 expression may...
Angiotensin-converting enzyme 2 (ACE2) is the receptor that enables SARS-CoV-2 to invade host cells. Previous studies have reported that reducing ACE2 expression may have an anti-SARS-CoV-2 effect. In this study, we constructed a pGL4.10-F2-ACE2 vector with double luciferase genes (firefly and Renilla luciferase) under the control of the ACE2 promoter and used it to screen compounds from Chinese traditional medicinal herbs (CTMHs) that can inhibit ACE2 transcription in human cells. We transfected HEK293T cells with pGL4.10-F2-ACE2 and treated them with CTMH compounds and then measured fluorescence to evaluate the indirect inhibition of ACE2 transcription. Out of 37 compounds tested, andrographolide demonstrated a dose-dependent inhibition of ACE2 transcription. We further confirmed by RT-qPCR and Western blot assays that andrographolide also reduced ACE2 expression in BEAS-2B cells in a dose-dependent manner. Moreover, pseudovirus infection assays in BEAS-2B cells demonstrated that andrographolide can inhibit SARS-CoV-2 infection in a dose-dependent manner. These results suggest that andrographolide has potential anti-SARS-CoV-2 activity and could be a candidate drug for COVID-19 prevention and treatment.
Topics: Humans; Diterpenes; Angiotensin-Converting Enzyme 2; SARS-CoV-2; HEK293 Cells; Down-Regulation; COVID-19 Drug Treatment; COVID-19; Antiviral Agents; Drugs, Chinese Herbal
PubMed: 38873947
DOI: 10.1177/13596535241259952 -
Clinical Cardiology Jun 2024Elevated serum uric acid (sUA) is associated with heart failure (HF).
BACKGROUND
Elevated serum uric acid (sUA) is associated with heart failure (HF).
HYPOTHESIS
Urate-lowering therapy (ULT) in HF is associated with lower risk of HF hospitalization (hHF) and mortality.
METHODS
Data on patients with HF and gout or hyperuricemia in the Clinical Practice Research Datalink database linked to the Hospital Episode Statistics and the Office for National Statistics in the United Kingdom were analyzed. Risks of hHF and all-cause mortality or cardiovascular-related mortality by ULT exposure (ULT initiated within ≤6 months of gout or hyperuricemia diagnosis) were analyzed in a propensity score-matched cohort using adjusted Cox proportional hazards regression models.
RESULTS
Of 2174 propensity score-matched pairs, patients were predominantly male, aged >70 years, with mean ± standard deviation sUA 9.3 ± 1.8 (ULT-exposed) and 9.4 ± 1.9 mg/dL (ULT-unexposed). At 5 years, ULT-exposed patients had a 43% lower risk of hHF or all-cause mortality (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.51-0.65) and a 19% lower risk of hHF or cardiovascular-related mortality (adjusted HR: 0.81; 95% CI: 0.71-0.92) versus no ULT exposure.
CONCLUSION
ULT was associated with reduced risk of adverse clinical outcomes in patients with HF and gout or hyperuricemia over 5 years.
Topics: Humans; Hyperuricemia; Male; Heart Failure; Female; Aged; United Kingdom; Retrospective Studies; Uric Acid; Gout Suppressants; Risk Factors; Middle Aged; Biomarkers; Treatment Outcome; Gout; Time Factors; Databases, Factual; Follow-Up Studies
PubMed: 38873862
DOI: 10.1002/clc.24297 -
Frontiers in Immunology 2024The intricate immune mechanisms governing mucosal healing following intestinal damage induced by cytotoxic drugs remain poorly understood. The goal of this study was to...
The intricate immune mechanisms governing mucosal healing following intestinal damage induced by cytotoxic drugs remain poorly understood. The goal of this study was to investigate the role of lymphotoxin beta receptor (LTβR) signaling in chemotherapy-induced intestinal damage. LTβR deficient mice exhibited heightened body weight loss, exacerbated intestinal pathology, increased proinflammatory cytokine expression, reduced IL-22 expression, and proliferation of intestinal epithelial cells following methotrexate (MTX) treatment. Furthermore, LTβRIL-22 mice succumbed to MTX treatment, suggesting that LTβR- and IL-22- dependent pathways jointly promote mucosal repair. Although both LTβR ligands LIGHT and LTβ were upregulated in the intestine early after MTX treatment, LIGHT mice, but not LTβ mice, displayed exacerbated disease. Further, we revealed the critical role of T cells in mucosal repair as T cell-deficient mice failed to upregulate intestinal LIGHT expression and exhibited increased body weight loss and intestinal pathology. Analysis of mice with conditional inactivation of LTβR revealed that LTβR signaling in intestinal epithelial cells, but not in Lgr5 intestinal stem cells, macrophages or dendritic cells was critical for mucosal repair. Furthermore, inactivation of the non-canonical NF-kB pathway member RelB in intestinal epithelial cells promoted MTX-induced disease. Based on these results, we propose a model wherein LIGHT produced by T cells activates LTβR-RelB signaling in intestinal epithelial cells to facilitate mucosal repair following chemotherapy treatment.
Topics: Animals; Intestinal Mucosa; Lymphotoxin beta Receptor; Signal Transduction; Mice; Mice, Knockout; Transcription Factor RelB; Methotrexate; Epithelial Cells; Mice, Inbred C57BL; Interleukin-22; Interleukins
PubMed: 38873613
DOI: 10.3389/fimmu.2024.1388496 -
BMC Nephrology Jun 2024TAFRO syndrome is a rare disorder that causes thrombocytopenia, generalized oedema, fever, organ enlargement, and renal impairment. Few reports have suggested an...
BACKGROUND
TAFRO syndrome is a rare disorder that causes thrombocytopenia, generalized oedema, fever, organ enlargement, and renal impairment. Few reports have suggested an association with vaccines, and few cases have undergone renal biopsy. TAFRO syndrome is often severe and fatal, and its cause is unknown. We report a case of TAFRO syndrome that occurred after vaccination with the coronavirus disease 2019 (COVID-19) vaccine.
CASE PRESENTATION
An 82-year-old woman received two doses of the BNT162b2 mRNA vaccine 3 weeks apart. Two weeks later, she was admitted to the hospital with oedema, accompanied with renal failure and thrombocytopenia. After close examination, she was diagnosed with TAFRO syndrome. She was treated with steroids, cyclosporine, and thrombopoietin receptor agonists. The patient was discharged after several months in remission.
CONCLUSIONS
Although an incident of TAFRO syndrome after COVID-19 vaccination has been previously reported, this is a rare case in which the patient went into remission and was discharged. A renal biopsy was also performed in this case, which was consistent with previous reports. The favorable treatment course for TAFRO syndrome provides valuable insights.
Topics: Humans; Female; Cyclosporine; Aged, 80 and over; Thrombocytopenia; BNT162 Vaccine; Immunosuppressive Agents; COVID-19 Vaccines; Edema; COVID-19
PubMed: 38872134
DOI: 10.1186/s12882-024-03630-x -
Neurology(R) Neuroimmunology &... Jul 2024To report CD19 B-cell counts and possible adverse effects on infants of mothers exposed to anti-CD20 mAbs ≤6 months before/during pregnancy or lactation.
OBJECTIVES
To report CD19 B-cell counts and possible adverse effects on infants of mothers exposed to anti-CD20 mAbs ≤6 months before/during pregnancy or lactation.
METHODS
We conducted a retrospective study using data from the German nationwide neuroimmunologic pregnancy registry. Inclusion criteria involved infants whose mothers received anti-CD20 mAbs ≤6 months before/during pregnancy or lactation, with ≥1 postnatal CD19 B-cell count. Main outcomes were absolute and relative CD19 B-cell counts. Comparison with reference values was performed conservatively in a subgroup with maternal exposure ≤3 months before/during pregnancy. Additional outcomes included pregnancy results, severe infections, and lymphocyte counts.
RESULTS
The cohort comprised 49 infants (F:M 25:24) exposed to anti-CD20 mAbs ≤6 months before/during pregnancy or lactation. CD19 B-cell and lymphocyte counts in 40 infants with maternal exposure ≤3 months before/during pregnancy were comparable with normative values. Only 2 cases of complete CD19 B-cell depletion occurred after second-trimester and third-trimester ocrelizumab exposure, with repopulation observed within 2 months. Exclusive lactation exposure had no significant effect on infants' absolute CD19 B-cell counts.
DISCUSSION
Administering anti-CD20 mAbs before or at the pregnancy onset, or during lactation, seems safe without significant impact on infant B-cell development. However, second-trimester or third-trimester exposure can cause CD19 B-cell depletion due to placental transfer, necessitating monitoring and postponing live vaccines.
Topics: Humans; Female; Pregnancy; Infant, Newborn; B-Lymphocytes; Retrospective Studies; Lactation; Male; Adult; Antigens, CD20; Infant Health; Prenatal Exposure Delayed Effects; Antigens, CD19; Lymphocyte Count; Rituximab; Immunologic Factors; Infant
PubMed: 38870458
DOI: 10.1212/NXI.0000000000200264 -
Clinical and Applied... 2024Aspirin is a widely used antiplatelet medication to prevent blood clots, reducing the risk of cardiovascular event. Healthcare providers need to be mindful of the risk...
BACKGROUND
Aspirin is a widely used antiplatelet medication to prevent blood clots, reducing the risk of cardiovascular event. Healthcare providers need to be mindful of the risk of aspirin-induced bleeding and carefully balancing its benefits against potential risks. The objective of this study was to create a practical nomogram for predicting bleeding risk in patients with a history of myocardial infarction treating with aspirin.
METHODS
A total of 2099 myocardial infarction patients with aspirin were enrolled. The patients were randomly divided into two groups, with a 7:3 ratio, for model development and internal validation. Boruta analysis was utilized to identify clinically significant features associated with bleeding. Logistic regression model based on independent bleeding risk factors was constructed and presented as a nomogram. Model performance was assessed from three aspects: identification, calibration, and clinical utility.
RESULTS
Boruta analysis identified eight clinical features from 25, and further multivariate logistic regression analysis selected four independent risk factors: hemoglobin, platelet count, previous bleeding, and sex. A visual nomogram was created based on these variables. The model achieved an area under the curve of 0.888 (95% CI: 0.845-0.931) in the training dataset and 0.888 (95% CI: 0.808-0.968) in the test dataset. Calibration curve analysis showed close approximation to the ideal curve. Decision curve analysis demonstrated favorable clinical net benefit for the model.
CONCLUSIONS
Our study focused on creating and validating a model to evaluate bleeding risk in patients with a history of myocardial infarction treated with aspirin, which demonstrated outstanding performance in discrimination, calibration, and net clinical benefit.
Topics: Humans; Nomograms; Myocardial Infarction; Aspirin; Hemorrhage; Female; Male; Middle Aged; Aged; Risk Factors; Platelet Aggregation Inhibitors; Risk Assessment
PubMed: 38870349
DOI: 10.1177/10760296241262789