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Immuno-oncology Technology Jun 2024Immune-related adverse events (IRAEs) during therapy with immune checkpoint inhibitors (ICIs) are common, and their management sometimes requires glucocorticoids (GCs)....
Effect of glucocorticoids for the management of immune-related adverse events on outcome in melanoma patients treated with immunotherapy-a retrospective and biomarker study.
BACKGROUND
Immune-related adverse events (IRAEs) during therapy with immune checkpoint inhibitors (ICIs) are common, and their management sometimes requires glucocorticoids (GCs). Predictors for development of IRAEs and data about the impact of GCs on clinical outcome are missing. We evaluated the impact of GCs to treat IRAEs on clinical outcome, and plasmatic inflammatory proteins as predictors for IRAEs.
PATIENTS AND METHODS
Patients with melanoma ( = 98) treated with ICIs at Karolinska University Hospital were included. Clinical information and data regarding prescription of systemic GCs were collected. Baseline plasma samples ( = 57) were analyzed for expression of 92 inflammatory proteins.
RESULTS
Forty-four patients developed at least one IRAE requiring systemic GCs and the most common was hypocortisolemia ( = 11). A median overall survival of 72.8 months for patients developing IRAEs requiring GCs, 17.7 months for those who did not, and 1.4 months for individuals receiving GCs at baseline was observed in Kaplan-Meier curves ( = 0.001). In immortal time bias adjusted analysis, patients receiving steroids to treat IRAE survived slightly longer, even though this time trend was not statistically significant. The median overall survival was 29 months for those treated with GCs within 60 days after ICIs start and was not reached for patients receiving GCs later. The number of ICI cycles was higher in subjects receiving GCs after 60 days ( = 0.0053). Hypocortisolemia occurred mainly in males (10/11) and correlated with favorable outcome. Male patients with hypocortisolemia had lower expression of interleukin 8, transforming growth factor-α, and fibroblast growth factor 5 and higher expression of Delta/Notch-like epidermal growth factor-related receptor.
CONCLUSIONS
GCs may be used to treat IRAEs without major concern. GCs early during ICIs may, however, impact clinical outcome negatively. The prognostic value of hypocortisolemia and inflammation proteins as biomarkers should be further investigated.
PubMed: 38952418
DOI: 10.1016/j.iotech.2024.100713 -
Health Science Reports Jul 2024Postoperative delirium (POD) is a common postoperative complication, especially in patients over 60 years, with an incidence ranging from 15% to 50%. In most cases, POD...
BACKGROUND
Postoperative delirium (POD) is a common postoperative complication, especially in patients over 60 years, with an incidence ranging from 15% to 50%. In most cases, POD manifests in the first 5 days after surgery. Multiple contributing risk factors for POD have been detected. Besides the predisposing factors such as higher age, cognitive impairment, high blood pressure, atrial fibrillation, and past stroke, pathophysiological mechanisms like neuroinflammation are also considered as contributing factors.
METHODS
In a subanalysis of the "PRe- Operative Prediction of postoperative DElirium by appropriate SCreening" (PROPDESC) study, the preoperative laboratory values of sodium, potassium, total protein, hemoglobin concentration (Hgb), and white blood cells as well as the biomarkers creatinine, HbA1c, NT-pro-BNP, high sensitive Troponin T (hsTnT), and C-reactive protein (CRP) were assessed to investigate a possible relationship to the occurrence of POD.
RESULTS
After correction for age, physical status classification, surgery risk after Johns Hopkins, and operative discipline (cardiac surgery vs. noncardiac surgery), male patients with a Hgb <13 g/dL had significantly higher odds for POD ( = 0.025). Furthermore, patients with CRP ≥ 10 mg/L, HbA1c value ≥ 8.5% as well as patients with hypernatraemia (>145 mmol/L) presented significantly higher odds to develop POD ( = 0.011, < 0.001, and = 0.021, respectively). A raised (>14-52 ng/L) or high (>52 ng/L) hsTnT value was also associated with a significantly higher chance for POD compared to the patient group with hsTnT <14 ng/L ( < 0.001 and = 0.016, respectively).
CONCLUSIONS
Preoperative Hgb, CRP, HbA1c, sodium, and hsTnT could be used to complement and refine the preoperative screening for patients at risk for POD. Further studies should track these correlations to investigate the potential of targeted POD protection and enabling hospital staff to initiate POD-preventing measures in time.
PubMed: 38952405
DOI: 10.1002/hsr2.2219 -
Frontiers in Endocrinology 2024Blood counts and biochemical markers are among the most common tests performed in hospitals and most readily accepted by patients, and are widely regarded as reliable... (Observational Study)
Observational Study
Assessing causal associations of blood counts and biochemical indicators with pulmonary arterial hypertension: a Mendelian randomization study and results from national health and nutrition examination survey 2003-2018.
BACKGROUND
Blood counts and biochemical markers are among the most common tests performed in hospitals and most readily accepted by patients, and are widely regarded as reliable biomarkers in the literature. The aim of this study was to assess the causal relationship between blood counts, biochemical indicators and pulmonary arterial hypertension (PAH).
METHODS
A two-sample Mendelian randomization (MR) analysis was performed to assess the causal relationship between blood counts and biochemical indicators with PAH. The genome-wide association study (GWAS) for blood counts and biochemical indicators were obtained from the UK Biobank (UKBB), while the GWAS for PAH were sourced from the FinnGen Biobank. Inverse variance weighting (IVW) was used as the primary analysis method, supplemented by three sensitivity analyses to assess the robustness of the results. And we conducted an observational study using data from National Health and Nutrition Examination Survey (NHANES) 2003-2018 to verify the relationship.
RESULTS
The MR analysis primarily using the IVW method revealed genetic variants of platelet count (OR=2.51, 95% CI 1.56-4.22, P<0.001), platelet crit(OR=1.87, 95% CI1.17-7.65, P=0.022), direct bilirubin (DBIL)(OR=1.71, 95%CI 1.18-2.47,P=0.004), insulin-like growth factor (IGF-1)(OR=0.51, 95% CI 0.27-0.96, P=0.038), Lipoprotein A (Lp(a))(OR=0.66, 95% CI 0.45-0.98, P=0.037) and total bilirubin (TBIL)(OR=0.51, 95% CI 0.27-0.96, P=0.038) were significantly associated with PAH. In NHANES, multivariate logistic regression analyses revealed a significant positive correlation between platelet count and volume and the risk of PAH, and a significant negative correlation between total bilirubin and PAH.
CONCLUSION
Our study reveals a causal relationship between blood counts, biochemical indicators and pulmonary arterial hypertension. These findings offer novel insights into the etiology and pathological mechanisms of PAH, and emphasizes the important value of these markers as potential targets for the prevention and treatment of PAH.
Topics: Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Female; Male; Middle Aged; Biomarkers; Nutrition Surveys; Pulmonary Arterial Hypertension; Adult; Blood Cell Count; Polymorphism, Single Nucleotide; Aged; Bilirubin; Platelet Count
PubMed: 38952391
DOI: 10.3389/fendo.2024.1418835 -
Heliyon Jun 2024To investigate the physical properties of commercially available multipurpose soft contact lens solutions in Ghana.
PURPOSE
To investigate the physical properties of commercially available multipurpose soft contact lens solutions in Ghana.
METHODS
pH (Kelilong ICL-099 pH meter, China), osmolality (OSMOMAT 3000, GONOTEC, Germany), surface tension (Sigma 700 Tensiometer, Sweden), and viscosity (CFOC-200 Viscometer, Cannon Company, USA) of various soft contact lens multipurpose solutions (MPS) were measured in triplicates at room temperature. Viscosity measurements were also taken at 34 °C ocular surface temperature. The solutions examined were Opti-Free Replenish (OFR), Trufresh (TF), Avizor (AV), Freshlook (FL), and Refresh (RF).
RESULTS
Several solutions were largely hypo-osmotic in the range of 108-231 mOsm/kg, the exception being Avizor, which had osmolality values that were closer to human tears (301 ± 0.58 mOsm/kg). The range of pH values of the solutions (6.33-8.24, mean (SD) = 7.53 ± 0.18) fell within the reported tolerable range for the ocular surface (6.20-9.00). Surface tension values ranged from 35.86 to 42.27 mNm with a mean of 38.49 ± 2.32 mNm. The average viscosity of most solutions at room temperature (25 °C) was 1.44 ± 0.49 cP with a range of 1.04-2.15 cP. Significantly lower values ranging from 0.79 to 1.58 cP were obtained at ocular surface temperature (34 °C), = 0.0001).
CONCLUSIONS
The physical properties of many of the solutions used as MPS in Ghana are markedly variable. Nevertheless, pH, surface tension, and viscosity fall within the acceptable limits of ocular physiological tolerance; except for osmolality, which majority were outside the reported tolerable range for the ocular surface. This information may partly explain the reason some patients exhibit strong preferences for certain care systems and should aid clinical decision-making when prescribing eye care systems to patients.
PubMed: 38952357
DOI: 10.1016/j.heliyon.2024.e32491 -
Heliyon Jun 2024Ovarian cancer (OC) ranks as the fifth most prevalent neoplasm in women and exhibits an unfavorable prognosis. To improve the OC patient's prognosis, a pioneering risk...
BACKGROUND
Ovarian cancer (OC) ranks as the fifth most prevalent neoplasm in women and exhibits an unfavorable prognosis. To improve the OC patient's prognosis, a pioneering risk signature was formulated by amalgamating disulfidptosis-related genes.
METHODS
A comparative analysis of OC tissues and normal tissues was carried out, and differentially expressed disulfidptosis-related genes (DRGs) were found using the criteria of |log2 (fold change) | > 0.585 and adjusted P-value <0.05. Subsequently, the TCGA training set was utilized to create a prognostic risk signature, which was validated by employing both the TCGA testing set and the GEO dataset. Moreover, the immune cell infiltration, mutational load, response to chemotherapy, and response to immunotherapy were analyzed. To further validate these findings, QRT-PCR analysis was conducted on ovarian tumor cell lines.
RESULTS
A risk signature was created using fourteen differentially expressed genes (DEGs) associated with disulfidptosis, enabling the classification of ovarian cancer (OC) patients into high-risk group (HRG) and low-risk group (LRG). The HRG exhibited a lower overall survival (OS) compared to the LRG. In addition, the risk score remained an independent predictor even after incorporating clinical factors. Furthermore, the LRG displayed lower stromal, immune, and estimated scores compared to the HRG, suggesting a possible connection between the risk signature, immune cell infiltration, and mutational load. Finally, the QRT-PCR experiments revealed that eight genes were upregulated in the human OC cell line SKOV3 compared with the human normal OC line IOSE80, while six genes were down-regulated.
CONCLUSIONS
A fourteen-biomarker signature composed of disulfidptosis-related genes could serve as a valuable risk stratification tool in OC, facilitating the identification of patients who may benefit from individualized treatment and follow-up management.
PubMed: 38952356
DOI: 10.1016/j.heliyon.2024.e32273 -
Archives of Pathology & Laboratory... Jul 2024Unlike parotid fine-needle aspiration biopsy, standardized reporting for core needle biopsy (CNB) and incisional biopsy (IB) is not established.
Performance Characteristics of Incisional and Core Needle Biopsies for Diagnosis in Parotid Gland: Single-Institutional Experience and Assessment of the Value of a Milan System for Reporting Salivary Gland Cytopathology-Like Risk Stratification Model.
CONTEXT.—
Unlike parotid fine-needle aspiration biopsy, standardized reporting for core needle biopsy (CNB) and incisional biopsy (IB) is not established.
OBJECTIVE.—
To examine the value of risk stratification by a Milan System for Reporting Salivary Gland Cytopathology (MSRSGC)-like classifier for parotid CNB/IB.
DESIGN.—
Five hundred ninety-two parotid biopsy records (CNB = 356, IB = 236) were retrieved (1994-2022) along with clinicopathologic data. Diagnoses were transformed to an MSRSGC-like classifier and compared with end points including risk of malignancy.
RESULTS.—
Over time, CNB was progressively more used compared with IB. Overall malignancy call rate was 223 of 592 (37.7%). Common specific diagnoses included Warthin tumor, lymphoma subtypes, and metastatic squamous cell carcinoma for CNB and IB, in addition to pleomorphic adenoma for CNB. Descriptive diagnoses were still frequent. Nondiagnostic rates were higher in CNB (26 of 356; 7.30%) than IB (5 of 236; 2.12%; P <.001). Tissue volumes significantly influenced CNB adequacy, with minimum and optimal volumes of 4.76 mm³ (J index, receiver operating characteristic curve) and 12.92 mm³ (95th percentile of distribution), respectively. One hundred forty-four patients (112 CNBs) had follow-up resections; diagnoses were concordant for 66 of 73 adequate CNBs (90.41%). Our restructured risk grouping of MSRSGC categories performed robustly in terms of risk of malignancy (sensitivity = 85.5%, specificity = 100%, accuracy = 92.3%, area under the curve = 0.9677).
CONCLUSIONS.—
Although CNB and IB are amenable to a risk stratification system, there are some differences as compared with fine-needle aspiration biopsy, particularly given the high baseline prevalence of malignancy. Specific diagnoses are often feasible and concordant with resection. CNB tissue volume can inform optimal and minimal sampling recommendations for adequacy.
PubMed: 38952287
DOI: 10.5858/arpa.2024-0051-OA -
Turkish Journal of Orthodontics Jun 2024To compare the reliability of two scoring systems for detecting white spot lesions (WSLs) from clinical photographs captured during debonding of fixed orthodontic...
OBJECTIVE
To compare the reliability of two scoring systems for detecting white spot lesions (WSLs) from clinical photographs captured during debonding of fixed orthodontic appliances.
METHODS
Digital images of 58 healthy adolescents (34 females and 24 males) were examined, depicting 384 buccal surfaces of maxillary incisors, canines, and first premolars. Three trained examiners (E1, E2 and E3) independently evaluated the fully anonymized photos in a randomized order using the Gorelick index (GI) and the modified International Caries Detection and Assessment System (ICDAS II). A 1-2-week interval separated the scorings. Spearman's rank correlation coefficient, Fisher's z-test, and the interclass correlation coefficient (ICC) were applied to compare the scoring methods and express examiner agreement.
RESULTS
The two scoring systems showed a moderate to strong positive relationship, but inter-examiner variations were significant (p<0.05). We found moderate to good reliability (ICC 0.60 to 0.84) with the ICDAS II system and good to excellent values with the GI (ICC 0.72 to 0.94), depending on the examiner. The agreement concerning the sound surfaces and the most severe WSLs was perfect, whereas the scoring of the milder lesion stages appeared more uncertain.
CONCLUSION
A moderate to strong positive relationship was demonstrated between the two methods when scoring the presence and severity of WSLs from digital images. Significant inter-examiner variations affected reliability.
PubMed: 38952228
DOI: 10.4274/TurkJOrthod.2023.2022.58 -
ESC Heart Failure Jul 2024Anaemia has been reported as poor predictor in heart failure with preserved ejection fraction (HFpEF). The aim of this study was to evaluate the impact of changes in...
AIMS
Anaemia has been reported as poor predictor in heart failure with preserved ejection fraction (HFpEF). The aim of this study was to evaluate the impact of changes in haemoglobin (Hb) from discharge to 1 year after discharge on the prognosis using a lower cut-off value of Hb than the World Health Organization (WHO) criteria.
METHODS AND RESULTS
First, 547 HFpEF cases were divided into two groups, Hb < 11.0 g/dL (n = 218) and Hb ≥ 11.0 g/dL (n = 329), according to Hb at discharge, and further were divided according to Hb 1 year after discharge into Hb < 11.0 g/dL (G1, n = 113), Hb ≥ 11.0 g/dL (G2, n = 105), Hb < 11.0 g/dL (G3, n = 66), and Hb ≥ 11.0 g/dL (G4, n = 263), respectively. Major adverse cardiovascular events (MACE) was defined as composite of all-cause death and heart failure readmission after a visit 1 year after discharge. The cut-off value of Hb was analysed by the receiver operating characteristics curve that predicts MACE. We examined the incidence rate of MACE between G4 and other subgroups and verified predictors of improving or worsening anaemia and covarying factors with change in Hb. In multivariate Cox proportional hazard model, MACE was significantly higher in G3 with worsening anaemia from Hb ≥ 11.0 g/dL to <11.0 g/dL than G4 with persistently Hb ≥ 11 g/dL (adjusted hazard ratio (HR): 3.14 [95% confidence interval (CI), 1.76-5.60], P < 0.001). MACE was not significantly different between G2 with improving anaemia from Hb < 11.0 g/dL to ≥ 11.0 g/dL and G4 (adjusted HR: 1.37 [95% CI, 0.68-2.75], P = 0.38). In multivariate logistic regression analysis, independent predictors of improving anaemia were male [odds ratio (OR): 0.45], chronic obstructive pulmonary disease (OR: 10.3), prior heart failure hospitalization (OR: 0.38), and estimated glomerular filtration rate (OR: 1.04). Independent predictors of worsening anaemia were age (OR: 1.07), body mass index (BMI) (OR: 0.86), clinical frailty scale score (OR: 1.29), Hb at discharge (OR: 0.63), and use of angiotensin-converting-enzyme inhibitor or angiotensin II receptor blocker (OR: 2.76). In multivariate linear regression analysis, covarying factors with change in Hb were BMI (β = -0.098), serum albumin (β = 0.411), and total cholesterol (β = 0.179).
CONCLUSIONS
Change in haemoglobin after discharge using a lower cut-off value than WHO criteria has prognostic impact in patients with HFpEF.
PubMed: 38952180
DOI: 10.1002/ehf2.14927 -
Ophthalmic Research Jul 2024To evaluate the long-term effectiveness and safety of XEN45 implant, either alone or in combination with cataract surgery, in patients with glaucoma.
INTRODUCTION
To evaluate the long-term effectiveness and safety of XEN45 implant, either alone or in combination with cataract surgery, in patients with glaucoma.
METHODS
Retrospective and single center study conducted on consecutive patients who underwent a XEN45 implant, either alone or in combination with cataract surgery, between November 2016 and October 2021. The primary endpoint was the mean IOP lowering from preoperative values.
RESULTS
Among the 230 screened patients, 206 eyes (176 patients) were included. Fifty-three (25.7%) eyes had undergone XEN-alone and 153 (74.3%) eyes had undergone a combined procedure (XEN+Phacoemulsification). The mean preoperative intraocular pressure (IOP) was significantly higher in the XEN-alone (22.2±5.9 mmHg) than in the XEN+Phaco (19.8±4.5 mmHg) group (p=0.0035). In the overall study population, the mean preoperative IOP was significantly lowered from 20.5±5.0 mmHg to 15.8±4.4 at year-4, p<0.0001. The mean preoperative (95% CI) IOP was significantly lowered from 22.2 (20.6 to 23.8) mmHg and 19.8 (19.1 to 20.6) mmHg to 15.6 (12.2 to 16.9) mmHg and 15.9 (15.2 to 16.5) mmHg at year-4 in the XEN-alone and XEN+Phaco groups, respectively (p<0.0001 each, respectively). The number of ocular hypotensive medications was significant reduced from 2.6±1.0 drugs to 1.3±1.3 drugs, with no significant differences between XEN-alone and XEN+Phaco groups (p=0.1671). On the first postoperative day, 62 (30.1%) eyes presented some type of complication. Fifteen (7.3%) eyes underwent a needling procedure.
CONCLUSION
XEN45, either alone or in combination with phacoemulsification, significantly lowered the IOP and reduce the need of ocular hypotensive medication in the long-term.
PubMed: 38952136
DOI: 10.1159/000539504 -
Kidney & Blood Pressure Research Jul 2024To explore the factors affecting mild cognitive impairment in patients with chronic kidney disease who are not undergoing dialysis, and to construct and validate a...
INTRODUCTION
To explore the factors affecting mild cognitive impairment in patients with chronic kidney disease who are not undergoing dialysis, and to construct and validate a nomogram risk prediction model.
METHODS
Using a convenience sampling method, 383 non-dialysis chronic kidney disease (CKD) patients from two tertiary hospitals in Chengdu were selected between February 2023 and August 2023 to form the modeling group. The patients were divided into a mild cognitive impairment group (n=192) and a non-mild cognitive impairment group (n=191), and factors such as demographics, disease data, and sleep disorders were compared between the two groups. Univariate and multivariate binary logistic regression analyses were used to identify independent influencing factors, followed by collinearity testing, and construction of the regression model. The final risk prediction model was presented through a nomogram and an online calculator, with internal validation using Bootstrap sampling. For external validation, 137 non-dialysis CKD patients from another tertiary hospital in Chengdu were selected between October 2023 and December 2023.
RESULTS
In the modeling group, 192 (50.1%) of the non-dialysis CKD patients developed mild cognitive impairment, and in the validation group, 56 (40.9%) patients developed mild cognitive impairment, totaling 248 (47.7%) of all sampled non-dialysis CKD patients. Age, educational level, Occupation status, Use of smartphone, sleep disorders, hemoglobin, and platelet count were independent factors influencing the occurrence of mild cognitive impairment in non-dialysis CKD patients (all P<0.05). The model evaluation showed an area under the ROC curve of 0.928, 95%CI (0.902, 0.953) in the modeling group, and 0.897, 95%CI (0.844, 0.950) in the validation group. The model's Youden index was 0.707, with an optimal cutoff value of 0.494, sensitivity of 0.853, and specificity of 0.854, indicating good predictive performance; calibration curves, Hosmer-Lemeshow test, and clinical decision curves indicated good calibration and clinical benefit. Internal validation results showed a consistency index (C-index) of 0.928, 95%CI (0.902, 0.953).
CONCLUSION
The risk prediction model developed in this study shows excellent performance, demonstrating significant predictive potential for early screening of mild cognitive impairment in non-dialysis chronic kidney disease patients. The application of this model will provide a reference for healthcare professionals, helping them formulate more targeted intervention strategies to optimize patient treatment and management outcomes.
PubMed: 38952104
DOI: 10.1159/000540025