-
Journal For Immunotherapy of Cancer Jun 2024Immune checkpoint inhibitors (ICIs) can elicit anticancer immune responses, but predictive biomarkers are needed. We measured programmed death ligand 1 (PD-L1)...
Exploring the predictive potential of programmed death ligand 1 expression in healthy organs and lymph nodes as measured by F-BMS986-192 PET: pooled analysis of data from four solid tumor types.
INTRODUCTION
Immune checkpoint inhibitors (ICIs) can elicit anticancer immune responses, but predictive biomarkers are needed. We measured programmed death ligand 1 (PD-L1) expression in organs and lymph nodes using F-BMS-986192 positron emission tomography (PET)-imaging and looked for correlations with response and immune-related adverse events.
METHODS
Four F-BMS-986192 PET studies in patients with melanoma, lung, pancreatic and oral cancer, receiving ICI treatment, were combined. Imaging data (organ standardized uptake value (SUV), lymph node SUV) and clinical data (response to treatment and incidence of immune-related adverse events) were extracted.
RESULTS
Baseline PD-L1 uptake in the spleen was on average higher in non-responding patients than in responders (spleen SUV 16.1±4.4 vs 12.5±3.4, p=0.02). This effect was strongest in lung cancer, and not observed in oral cancer. In the oral cancer cohort, benign tumor-draining lymph nodes (TDLNs) had higher PD-L1 uptake (SUV 3.3 IQR 2.5-3.9) compared with non-TDLNs (SUV 1.8, IQR 1.4-2.8 p=0.04). Furthermore, in the same cohort non-responders showed an increase in PD-L1 uptake in benign TDLNs on-treatment with ICIs (+15%), while for responders the PD-L1 uptake decreased (-11%). PD-L1 uptake did not predict immune-related adverse events, though elevated thyroid uptake on-treatment correlated with pre-existing thyroid disease or toxicity.
CONCLUSION
PD-L1 PET uptake in the spleen is a potential negative predictor of response to ICIs. On-treatment with ICIs, PD-L1 uptake in benign TDLNs increases in non-responders, while it decreases in responders, potentially indicating a mechanism for resistance to ICIs in patients with oral cancer.
Topics: Humans; B7-H1 Antigen; Lymph Nodes; Positron-Emission Tomography; Male; Female; Neoplasms; Immune Checkpoint Inhibitors; Middle Aged; Aged
PubMed: 38886117
DOI: 10.1136/jitc-2024-008899 -
Physiological Reports Jun 2024Although the liver is the largest metabolic organ in the body, it is not alone in functionality and is assisted by "an organ inside an organ," the gut microbiota. This... (Review)
Review
Although the liver is the largest metabolic organ in the body, it is not alone in functionality and is assisted by "an organ inside an organ," the gut microbiota. This review attempts to shed light on the partnership between the liver and the gut microbiota in the metabolism of macronutrients (i.e., proteins, carbohydrates, and lipids). All nutrients absorbed by the small intestines are delivered to the liver for further metabolism. Undigested food that enters the colon is metabolized further by the gut microbiota that produces secondary metabolites, which are absorbed into portal circulation and reach the liver. These microbiota-derived metabolites and co-metabolites include ammonia, hydrogen sulfide, short-chain fatty acids, secondary bile acids, and trimethylamine N-oxide. Further, the liver produces several compounds, such as bile acids that can alter the gut microbial composition, which can in turn influence liver health. This review focuses on the metabolism of these microbiota metabolites and their influence on host physiology. Furthermore, the review briefly delineates the effect of the portosystemic shunt on the gut microbiota-liver axis, and current understanding of the treatments to target the gut microbiota-liver axis.
Topics: Gastrointestinal Microbiome; Humans; Liver; Animals; Nutrients; Bile Acids and Salts
PubMed: 38886098
DOI: 10.14814/phy2.16114 -
RMD Open Jun 2024To compare the risk of cardiovascular events among Janus kinase inhibitors (JAKIs), biological disease-modifying antirheumatic drugs (bDMARDs) (tumour necrosis factor...
Increased risk of cardiovascular events under the treatments with Janus kinase inhibitors versus biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a retrospective longitudinal population-based study using the Japanese health insurance database.
OBJECTIVES
To compare the risk of cardiovascular events among Janus kinase inhibitors (JAKIs), biological disease-modifying antirheumatic drugs (bDMARDs) (tumour necrosis factor inhibitors (TNFIs) and non-TNFIs) and methotrexate (MTX) in Japanese patients with rheumatoid arthritis (RA).
METHODS
Using Japanese claims data, patients with RA were enrolled in this study if they had at least one ICD-10 code (M05 or M06), were new users of JAKIs, bDMARDs or MTX between July 2013 and July 2020 and being 18 years old or older. The incidence rate (IR), IR ratio and adjusted hazard ratio (aHR (95% CI)) of cardiovascular events including venous thromboembolism, arterial thrombosis, acute myocardial infarction and stroke were calculated. A time-dependent Cox regression model adjusted for patient characteristics at baseline was used to calculate aHR.
RESULTS
In 53 448 cases, IRs/1000 patient-years of the overall cardiovascular events were 10.1, 6.8, 5.4, 9.1 and 11.3 under the treatments with JAKIs, bDMARDs, TNFIs, non-TNFIs and MTX, respectively. The adjusted HRs of JAKIs for overall cardiovascular events were 1.7 (1.1 to 2.5) versus TNFIs without MTX and 1.7 (1.1 to 2.7) versus TNFIs with MTX.
CONCLUSIONS
Among patients with RA, individuals using JAKIs had a significantly higher risk of overall cardiovascular events than TNFIs users, which was attributed to the difference in the risk between JAKIs and TNFIs versus MTX. These data should be interpreted with caution because of the limitations associated with the claims database.
Topics: Humans; Arthritis, Rheumatoid; Female; Male; Antirheumatic Agents; Middle Aged; Cardiovascular Diseases; Janus Kinase Inhibitors; Japan; Aged; Retrospective Studies; Longitudinal Studies; Methotrexate; Adult; Incidence; Databases, Factual; Risk Factors; Insurance, Health; East Asian People
PubMed: 38886005
DOI: 10.1136/rmdopen-2023-003885 -
RMD Open Jun 2024To compare longitudinal changes in spirometric measures between patients with rheumatoid arthritis (RA) and non-RA comparators.
OBJECTIVE
To compare longitudinal changes in spirometric measures between patients with rheumatoid arthritis (RA) and non-RA comparators.
METHODS
We analysed longitudinal data from two prospective cohorts: the UK Biobank and COPDGene. Spirometry was conducted at baseline and a second visit after 5-7 years. RA was identified based on self-report and disease-modifying antirheumatic drug use; non-RA comparators reported neither. The primary outcomes were annual changes in the per cent-predicted forced expiratory volume in 1 s (FEV%) and per cent predicted forced vital capacity (FVC%). Statistical comparisons were performed using multivariable linear regression. The analysis was stratified based on baseline smoking status and the presence of obstructive pattern (FEV/FVC <0.7).
RESULTS
Among participants who underwent baseline and follow-up spirometry, we identified 233 patients with RA and 37 735 non-RA comparators. Among never-smoking participants without an obstructive pattern, RA was significantly associated with more FEV% decline (β=-0.49, p=0.04). However, in ever smokers with ≥10 pack-years, those with RA exhibited significantly less FEV% decline than non-RA comparators (β=0.50, p=0.02). This difference was more pronounced among those with an obstructive pattern at baseline (β=1.12, p=0.01). Results were similar for FEV/FVC decline. No difference was observed in the annual FVC% change in RA versus non-RA.
CONCLUSIONS
Smokers with RA, especially those with baseline obstructive spirometric patterns, experienced lower FEV% and FEV/FVC decline than non-RA comparators. Conversely, never smokers with RA had more FEV% decline than non-RA comparators. Future studies should investigate potential treatments and the pathogenesis of obstructive lung diseases in smokers with RA.
Topics: Humans; Arthritis, Rheumatoid; Male; Spirometry; Female; Middle Aged; Longitudinal Studies; Prospective Studies; Smoking; Aged; Forced Expiratory Volume; Vital Capacity; Pulmonary Disease, Chronic Obstructive; Adult; United Kingdom
PubMed: 38886003
DOI: 10.1136/rmdopen-2024-004281 -
CMAJ : Canadian Medical Association... Jun 2024
Review
Topics: Humans; Food Hypersensitivity; Infant; Child, Preschool; Administration, Oral; Desensitization, Immunologic; Allergens
PubMed: 38885980
DOI: 10.1503/cmaj.231478 -
CMAJ : Canadian Medical Association... Jun 2024
Topics: Humans; Wildfires; Smoke; Canada
PubMed: 38885979
DOI: 10.1503/cmaj.240135 -
Swiss Medical Weekly Jun 2024Benign tracheal stenosis is relatively rare but remains a significant chronic disease due to its drastic symptoms including dyspnoea and inspiratory stridor, and...
BACKGROUND
Benign tracheal stenosis is relatively rare but remains a significant chronic disease due to its drastic symptoms including dyspnoea and inspiratory stridor, and consequent negative effect on quality of life. Traditionally, the surgical approach by resection of the stenotic tracheal segment has been the therapy of choice. However, endoscopic techniques have arisen and may offer a safe and less invasive alternative.
OBJECTIVES
The aim of the retrospective study was to evaluate procedure-related safety and outcome of endoscopic treatment of benign tracheal stenosis at a single centre.
METHODS
The study included all patients at our institution who between 2013 and 2022 had received endoscopic treatment of benign tracheal stenosis by rigid tracheoscopy, radial incision by electric papillotomy needle and dilation (endoscopic tracheoplasty) followed by triamcinolone acetonide as a local submucosal injection and additionally, from 2020, budesonide inhalation.
RESULTS
A total of 22 patients were treated in a total of 38 interventions, each resulting in immediate improvement of symptoms. There were no peri-interventional complications or mortality. Of the 38 interventions, 11 received no triamcinolone acetonide administration, resulting in a 54.5% recurrence rate after an average of 21.1 (±18.0) months, while 27 had local triamcinolone acetonide, with a 37% recurrence rate. Since 2020, we additionally initiated post-interventional budesonide inhalation as recurrence prophylaxis for newly admitted patients and patients with recurrences(n = 8), of whom only one (12.5%) has to date experienced a recurrence.
CONCLUSION
Our results indicate that endoscopic tracheoplasty offers a safe and successful, minimally invasive alternative to open surgery for patients with benign tracheal stenosis. We recommend local administration of triamcinolone into the mucosa as an additional treatment to decrease the risk of recurrence. However, given the uncontrolled study design and low sample size, safety and effectiveness cannot be conclusively demonstrated. Nonetheless, our findings suggest promising avenues for further investigation. Further studies on the additional benefit of inhaled corticosteroids are warranted.
Topics: Humans; Tracheal Stenosis; Female; Male; Retrospective Studies; Middle Aged; Endoscopy; Adult; Triamcinolone Acetonide; Treatment Outcome; Dilatation; Recurrence; Aged; Budesonide; Quality of Life; Glucocorticoids
PubMed: 38885613
DOI: 10.57187/s.3363 -
PloS One 2024A retrospective study was conducted to explore the urinary expression of α 1-microglobulin (α1MG) and β2-microglobulin (β2MG) in patients with human immunodeficiency...
BACKGROUND
A retrospective study was conducted to explore the urinary expression of α 1-microglobulin (α1MG) and β2-microglobulin (β2MG) in patients with human immunodeficiency virus (HIV) infection, aiming to evaluate their predictive capability for renal injury.
METHOD
One hundred and five male HIV-infected patients treated with Tenofovir (TDF) regimen (TDF+3TC or the third drug TDF/FTC+) were selected between March 1, 2021, and March 1, 2022, in Wuhan Jinyintan Hospital. Three months after TDF treatment, the renal function injury was evaluated with the standard creatinine clearance rate. The urinary levels of α1MG and β2MG were compared between the initiation of TDF treatment and three months thereafter. Spearman correlation was utilized to analyze the correlation between the urinary expression of α1MG and β2MG and renal injury in HIV patients. The logistic regression was used to analyze the predictive value of urinary α1MG and β 2-microglobulin expression in renal injury.
RESULTS
Up to the first follow-up, 29 (27.6%) cases of the 105 male HIV patients had varying degrees of renal function injury, including 14 (13.3%) mild injury, 9 (8.6%) moderate injury, and 6 (5.7%) severe injury cases. Patients with severe renal injury had the highest levels of urinary α1MG and β2MG expression while those with mild injury demonstrated higher levels compared to the non-injury group (P < 0.05). Spearman correlation analysis indicated that urinary α1MG and β2MG were positively correlated with renal impairment in HIV patients (Rho = -0.568, and -0.732; P < 0.001). The ROC curve analysis demonstrated that the area under the curve (AUC) for urine α1MG and β2MG in predicting kidney damage among HIV patients were 0.928, 0.916, and 0.889, respectively. The sensitivity values were 96.55%, 82.76%, and 89.66% while the specificity values were 84.07%, 94.51%, and 89.29% for urine α1MG and β2MG, respectively.
CONCLUSION
The expression level of urinary α1MG and β2MG in HIV patients was significantly higher compared to normal people. Detection of these two indexes can enable early determination of renal injury and its severity in HIV patients.
Topics: Humans; Male; beta 2-Microglobulin; Alpha-Globulins; Tenofovir; HIV Infections; Biomarkers; Middle Aged; Adult; Retrospective Studies; Anti-HIV Agents; Acute Kidney Injury
PubMed: 38885284
DOI: 10.1371/journal.pone.0303442 -
PloS One 2024Most US children with acute otitis media [AOM] receive prompt antibiotic treatment, though guidelines encourage watchful waiting. Previous systematic reviews of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Most US children with acute otitis media [AOM] receive prompt antibiotic treatment, though guidelines encourage watchful waiting. Previous systematic reviews of antibiotics versus watchful waiting have focused on symptom resolution and RCTs, limiting the assessment of serious, rare complications. We sought to evaluate these complications by including observational studies.
METHODS
RCTs and observational studies that compared antibiotics to placebo or watchful waiting for pediatric clinician diagnosed AOM were identified [PubMed/MEDLINE, Embase, Cochrane Database of Systematic Reviews, Central Register of Controlled Trials, and Web of Science] and reviewed for meta-analysis. Two reviewers independently extracted study characteristics, patient characteristics, and outcomes. We assessed publication bias, study bias with ROBINS-1 and RoB-2 and used random-effects models to assess treatment effects.
RESULTS
24 studies were included. Antibiotics decreased the risk of acute mastoiditis [incidence 0.02%, RR 0.48, 95% CI 0.40-0.59; NNT 5,368]. This protective effect may be underestimated because of misclassification of non-suppurative conditions as AOM. Intracranial complications remained too rare to assess. Antibiotics markedly increased the risk of adverse effects [incidence 10.5%, RR 1.49, 1.27-1.73; NNH 23]. Studies used non-specific criteria for acute mastoiditis, potentially underestimating treatment effects.
CONCLUSIONS
Prompt antibiotic therapy reduces the risk for some AOM complications. The NNT to prevent serious, rare complications is high, while the NNH is relatively low. Large-scale population-based observational studies using real-world datasets with validated measures of severe complications are needed to improve understanding of risk factors for serious AOM complications, facilitate more selective antibiotic therapy, and optimize individual outcomes and public health.
Topics: Humans; Anti-Bacterial Agents; Otitis Media; Child; Acute Disease; Child, Preschool; Mastoiditis; Randomized Controlled Trials as Topic
PubMed: 38885271
DOI: 10.1371/journal.pone.0304742 -
PloS One 2024Tear matrix metalloproteinase (MMP)-9 is an inflammatory signal in patients with dry eye (DE). In the present study, to understand the action mechanism of probiotic...
Tear matrix metalloproteinase (MMP)-9 is an inflammatory signal in patients with dry eye (DE). In the present study, to understand the action mechanism of probiotic LB101 (Lactobacillus plantarum NK151 and Bifidobacterium bifidum NK175 [4:1] mix) against DE, we investigated its effect on tear amount and inflammatory marker expression levels in mice with unilateral exorbital lacrimal gland excision/atropine-benzalkonium chloride application (EB) or fecal microbiota transplantation from mice with EB (eFMT). Oral gavage of LB101 increased EB-suppressed tear amount and decreased EB-induced blinking number. Furthermore, LB101 decreased EB-induced TNF-α, IL-1β, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva, while EB-suppressed IL-10 and occludin expression increased. LB101 also decreased EB-induced TNF-α and IL-1β expression and NF-κB+CD11c+ cell population in the colon. eFMT also decreased tear amount and increased blinking number in the transplanted mice. eFMT increased TNF-α, IL-1β, and MMP-9 expression and TNF-α+ and NF-κB+CD11c+ cell populations in the conjunctiva and TNF-α and IL-1β expression and NF-κB+CD11c+ cell populations in the colon. Oral gavage of LB101 increased eFMT-suppressed tear amount and decreased eFMT-induced blinking number. Furthermore, LB101 decreased TNF-α, IL-1β, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva and TNF-α and IL-1β expression and NF-κB+CD11c+ cell population in the colon, while eFMT-suppressed IL-10 and occludin expression decreased. Furthermore, LB101 increased eFMT-suppressed Muribaculaceae, Prevotellaceae, and Lactobacillaceae populations in the gut microbiota, while eFMT-induced Bacteroidaceae population decreased. These findings suggest that DE may cause gut dysbiosis, which may be a risk factor for DE, and LB101 may alleviate DE with gut inflammation by suppressing the expression of MMP-9 and proinflammatory cytokines TNF-α and IL-1β with the regulation of gut microbiota-involved NF-κB signaling.
Topics: Animals; Matrix Metalloproteinase 9; Dry Eye Syndromes; Gastrointestinal Microbiome; Mice; NF-kappa B; Probiotics; Signal Transduction; Mice, Inbred C57BL; Tears; Fecal Microbiota Transplantation; Tumor Necrosis Factor-alpha; Conjunctiva
PubMed: 38885258
DOI: 10.1371/journal.pone.0303423