Risk Of Progression Research Articles

Integrative epidemiology and immuno-transcriptomics uncover a risk and potential mechanism for cutaneous lymphoma unmasking or progression with dupilumab therapy

There have been multiple reports of the anti-IL4Rα agent, dupilumab, as associated with the onset and/or progression of cutaneous T-cell lymphoma (CTCL). We sought to evaluate safety signals associated with dupilumab, with a focus on CTCL, and to evaluate possible underlying mechanism(s) for the potential association. First, we used the FDA pharmacovigilance database, FAERS, to evaluate if dupilumab was associated with CTCL including both positive controls (conjunctivitis, eosinophilia, and arthralgia) and exposure controls (other medications with similar indications including JAK-inhibitors and the anti-IL13, tralokinumab,) to reduce and evaluate confounding bias. Thereafter, we used publicly available bulk and single cell-RNA seq datasets to probe possible underlying mechanisms through which dupilumab might be associated with CTCL. Between January 2019 and Q2 of 2023, there were 181,575 unique reports of dupilumab related adverse events (AE) in FAERS with 606 of these being for a neoplasm. Dupilumab had 30.0 times the proportional reporting ratio (PRR) (95% CI: 25.0 - 35.9) for CTCL compared to all other medications in FAERS. The risk was highest in males aged 45-65. The PRR for conjunctivitis, eosinophilia, and arthralgia, known side effects of dupilumab, were 35.6 (34.4 - 36.8), 2.15 (2.00 - 2.31), and 2.14 (2.07 - 2.18) respectively. Using the log-count normalized PRR (AE score) to account for PRR inflation when reports were small, the top safety signals included conjunctivitis (AEscore 8.3) and CTCL (AEscore 4.9). Bulk RNA sequencing data showed changes in IL4RA and IL13RA1 expression in CTCL and in epidermal layers of atopic dermatitis (AD) biopsies. Single-cell transcriptomic studies revealed that this change was similar in AD and CTCL, and that keratinocytes seemed to be the most divergent cell type with regards to IL4R and IL13RA1. An effect on keratinocyte specific gene expression was also independently observed in available bulk RNA sequencing data. These data suggest that dupilumab might be causing an unmasking or progression of CTCL via the same mechanism through which it improves atopic dermatitis: IL13 receptor blockade, which leads to increased IL13 in the local milieu, driving CTCL stimulation and progression. However, these associations need further evaluation given the inherent limitations of the FAERS database and our non-experimental approach.

The Relationship Between Rim-like Enhancement on Pre-ablation Contrast-enhanced Ultrasound of Colorectal Liver Metastasis and Early Intrahepatic Progression After Thermal Ablation: A Preliminary Study

ObjectiveTo investigate the relationship between the rim-like enhancement pattern on pre-ablation contrast-enhanced ultrasound (CEUS) of colorectal liver metastasis (CRLM) and the therapeutic efficacy of percutaneous microwave ablation (MWA). MethodsPatients with CRLM underwent MWA and were evaluated using CEUS before ablation in our hospital between February 2020 and February 2023 were enrolled in this retrospective study. The enhancement patterns of CRLM were assessed by two radiologists and classified as rim-like enhancement and non-rim-like enhancement patterns. The therapeutic outcomes, including cumulative intrahepatic progression rate and early intrahepatic progression rate, were followed up and analyzed. ResultsOverall, 50 patients with 121 nodules were enrolled. Rim-like enhancement pattern was observed in 18 patients (18/50, 36.0%). The cumulative intrahepatic progression rate was significantly higher in the rim-like enhancement group than the rate in the non-rim-like enhancement group (p = 0.022). The early intrahepatic progression rate in the rim-like enhancement group was also significantly higher than the rate in the non-rim-like enhancement group (12/17, 70.6% vs. 6/24, 25.0%, p = 0.005). The multivariable analysis demonstrated that the rim-like enhancement pattern of CRLM was a significant risk factor associated with early intrahepatic progression after MWA (p = 0.013). ConclusionRim-like enhancement pattern on pre-ablation CEUS of CRLM was associated with a higher risk of intrahepatic progression after MWA.

Risk of cancer progression of non-atypical endometrial hyperplasia in a diverse patient population: A long-term, follow-up study

Risk of cancer progression of non-atypical endometrial hyperplasia in a diverse patient population: A long-term, follow-up study

Modern aspects of therapy of metabolic associated liver disease in patients with type 2 diabetes mellitus

Metabolic associated fatty liver disease (MAFLD) is currently the most common liver disease. The main risk factors for its development are poor nutrition, sedentary lifestyle and obesity. MAFLD is associated with various cardiometabolic conditions – lipid metabolism disorders, cardiovascular pathology and carbohydrate metabolism disorders. The association of MAFLD and type 2 diabetes mellitus (DM) is common among patients, since these diseases have a common pathogenesis link – insulin resistance. The combination of these diseases has a mutual negative effect on each other and increases the risks of cardiovascular diseases, hospitalizations, as well as the risks of liver fibrosis progression. Therefore, the detection of MAFLD and its treatment in type 2 DM are extremely important to improve the patient’s prognosis. Diagnostics of MAFLD includes laboratory and instrumental research methods. The “gold standard” of diagnostics is considered to be liver biopsy, but due to the fact that this method is invasive, it is rarely used and only for differential diagnostics of MAFLD with other liver pathologies. The most accessible instrumental method for detecting liver steatosis is ultrasound. Treatment of MAFLD primarily involves lifestyle changes (rational nutrition with limitation of simple carbohydrates and animal fats, adequate physical activity) and weight loss. Also, hypoglycemic drugs used to treat type 2 diabetes (metformin, pioglitazone, glucagon-like peptide-1 agonists) can have a certain positive effect on MAFLD. Essential phospholipids, which have membrane-stabilizing, antioxidant and antifibrotic effects, are also an important component of MAFLD treatment. A number of domestic and foreign studies have shown the high efficiency of Essential Phospholipids both in relation to biochemical parameters in patients with a combination of type 2 diabetes and MAFLD, and in relation to ultrasound signs, improving the function and structure of the liver in MAFLD, as well as slowing the progression of liver fibrosis.

Evaluation of an Active Rehabilitation Program With Early Weightbearing and No Immobilization After Tibial Tubercle Distalization.

Abnormal patellar height (patella alta) has been reported to be one of the main predisposing factors for recurrent patellar dislocation, and it can be surgically corrected by distalizing tibial tubercle osteotomy (DTTO). Rehabilitation after DTTO often includes limitations on weightbearing and restrictions on knee range of motion by means of bracing, increasing the risk of slow progression of the rehabilitation. An active rehabilitation program with no restrictions on weightbearing and range of movement would yield a low risk of postoperative complications and a fast recovery period. Case series; Level of evidence, 4. Included were 102 consecutive knees in 80 patients who underwent DTTO between January 2010 and December 2017. In the majority of knees (89.2%), the patient underwent simultaneous medial patellofemoral ligament reconstruction. The mean age of the patients at the time of surgery was 19.39 ± 8.02 years, and 80.4% of the knees (82/102) were of female patients. The patients underwent an active rehabilitation program with immediate weightbearing as tolerated and active quadriceps and hip muscle exercises with no immobilization or bracing. The protocol was active (patient unsupervised), including daily exercises, as instructed by a physical therapist. Crutches were recommended for the first 3 to 4 weeks. There were 3 acute failures of fixation (2.9% of knees) requiring revision surgery. In these cases, the patients had a fall, slip, or knee-twisting accident during the first 6 weeks after surgery. Two late failures characterized by tibial stress fracture at the distal part of the osteotomy level occurred at 2 and 3 months postoperatively and were considered unrelated to the early rehabilitation process. The stress fracture rate was 2%, and the overall DTTO failure rate was 6.9%. With the active rehabilitation program, adverse effects such as knee stiffness, arthrofibrosis, or delayed ability to perform daily activities were rare. An active rehabilitation program after DTTO was found to be safe and effective. Furthermore, the risk of failure related to surgical fixation strength and of later stress fracture was low.

Primary hyperparathyroidism with intrathyroidal location of parathyroid adenoma

Primary hyperparathyroidism is a common endocrine disease with high morbidity and mortality from all causes. The disease can be asymptomatic and for a long time remain undiagnosed, which leads to untimely surgical treatment, increases the risks of development and progression of severe disabling complications and worsens patients prognosis. In clinical practice there are certain difficulties in diagnosing this pathology. One of the urgent problems is the search for the source of parathyroid hormone hyperproduction, especially in case of atypical location of paraаdenoma. The most common atypical locations of altered parathyroid glands are thymus, retroor paraesophageal space, retropharyngeal space, mediastinum and thyroid gland. The frequency of intrathyroidal masses of parathyroid glands, in the thyroid parenchyma or under its capsule, ranges on average from 2 to 3%, but according to some authors can reach 18–22%. With such localization of paraadenomas there is a need for their differential diagnosis, first of all, with nodular formations of the thyroid gland. In addition, the absence of additional laboratory studies parathormone and calcium blood levels does not allow timely suspicion of the disease, and cytologic examination of the material obtained by fine-needle aspiration puncture biopsy does not allow reliable differentiation of the altered parathyroid gland. This article presents a clinical case of a patient with primary hyperparathyroidism with intrathyroidally located parathyroid adenoma, for a long time long identified as a “nodular goiter,” and provides a brief review of the methods that identify an intrathyroidally located parathyroma. Despite the abundance of diagnostic methods in visualization of intrathyroidal parathyroid glands, today the most appropriate seems to be expert ultrasound examination with assessment of the parathyroid hormone level in a washout after fine-needle aspiration, supplemented, if necessary, by scintigraphy and single-photon emission computed tomography combined with computed tomography or multispiral computed tomography.

Population Health Management and Guideline-Concordant Care in CKD: A Secondary Analysis of K-CHAMP.

Gaps in guideline-concordant care for chronic kidney disease (CKD) lead to poor outcomes. The Kidney Coordinated HeAlth Management Partnership (K-CHAMP) cluster randomized trial tested the effect of a population health management intervention versus usual care on CKD progression and evidence-based care delivery in the primary care setting. K-CHAMP included adults aged 18-85 years with eGFR <60 mL/min/1.73m2 and moderate-high risk of CKD progression who were not seeing a nephrologist. The multi-faceted intervention included nephrology e-consult, pharmacist-led medication management, and patient education. In this post-hoc analysis, we evaluate the effectiveness of K-CHAMP on guideline-concordant care processes (blood pressure and glycemic control, annual albuminuria testing), and medication exposure days (ACEi/ARB, moderate-high intensity statin, SGLT-2i, GLP-1RA). Given multiplicity of outcomes, Benjamini-Hochberg method was used to control false discovery rate (FDR). All 1,596 (754 intervention, 842 usual care) enrolled patients (mean age 74±9 years, eGFR 37±8 mL/min/1.73m2, 928 (58%) female, 127 (8%) Black) were analyzed. After a median 17-month follow-up, intervention arm patients had significantly higher exposure days per year to SGLT-2i (56 vs 32 days, relative benefit 1.72, 95% CI 1.14-2.30) and GLP-1RA (78 vs 29 days, relative benefit 2.65, 95% CI 1.59-3.71) compared to usual care in adjusted analysis. At study initiation in 2019, similar proportion of patients were prescribed SGLT-2i and/or GLP-1RA in intervention and control arm (8% vs 6% respectively, rate ratio 1.23, 95% CI 0-2.99), but by 2022, prescription of these medications was significantly higher in intervention arm (44% vs 27% respectively, rate ratio 1.63, 95% CI 1.32-1.94). There was no significant difference in any process measures or exposure days to ACEi/ARB in patients with albuminuria or moderate-high intensity statin. K-CHAMP was effective in accelerating implementation of SGLT-2i and GLP-1RA but did not increase ACEi/ARB in patients with albuminuria or moderate-high intensity statin use, or improve blood pressure control, glycemic control, or albuminuria testing in individuals with CKD in the primary care setting.

Hypnotics and Mortality in Idiopathic Pulmonary Fibrosis: Hospital and National Data-based Analysis

Patients with idiopathic pulmonary fibrosis (IPF) may suffer from insomnia and use hypnotics. However, the effect of the use of hypnotics on their clinical course remains unclear. Is the use of hypnotics associated with an increased risk of mortality in patients with IPF? This study included 99 and 123 patients with IPF from the Hamamatsu and Seirei hospital-based cohorts, respectively, and 30,218 patients with IPF from the national claims database of Japan (NDB cohort). To analyze the association of hypnotic use with outcomes avoiding immortal time bias, multivariable Cox models with time-dependent covariates and target trial emulation with a new user design were employed for the hospital- and NDB-based cohorts, respectively. In the cohorts studied, the 3-year cumulative incidence of new use of hypnotics after IPF diagnosis was 13.4%-24.1%. In both the hospital-based cohorts, the continuous use of hypnotics was associated with an increased risk of all-cause mortality and disease progression. In the NDB cohort, the continuous use of hypnotics was also associated with an increased risk of all-cause mortality. Subgroup analysis found associations between the continuous use of hypnotics and increased mortality regardless of sex and comorbidities, excluding certain subpopulations. This study found that continuous use of hypnotics was associated with an increased risk of mortality in patients with IPF. Given the relatively high cumulative incidence of hypnotic use in this population, there is an urgent need to reassess the appropriate use of hypnotics for patients with IPF.

Gut microbiome metabolites, molecular mimicry, and species-level variation drive long-term efficacy and adverse event outcomes in lung cancer survivors

The influence of the gut microbiota on long-term immune checkpoint inhibitor (ICI) efficacy and immune-related adverse events (irAEs) is poorly understood, as are the underlying mechanisms. We performed gut metagenome and metabolome sequencing of gut microbiotas from patients with lung cancer initially treated with anti-PD-1/PD-L1 therapy and explored the underlying mechanisms mediating long-term (median follow-up 1167 days) ICI responses and immune-related adverse events (irAEs). Results were validated in external, publicly-available datasets (Routy, Lee, and McCulloch cohorts). The ICI benefit group was enriched for propionate (P=0.01) and butyrate/isobutyrate (P=0.12) compared with the resistance group, which was validated in the McCulloch cohort (propionate P<0.001, butyrate/isobutyrate P=0.002). The acetyl-CoA pathway (P=0.02) in beneficial species mainly mediated butyrate production. Microbiota sequences from irAE patients aligned with antigenic epitopes found in autoimmune diseases. Microbiotas of responsive patients contained more lung cancer-related antigens (P=0.07), which was validated in the Routy cohort (P=0.02). Escherichia coli and SGB15342 of Faecalibacterium prausnitzii showed strain-level variations corresponding to clinical phenotypes. Metabolome validation reviewed more abundant acetic acid (P=0.03), propionic acid (P=0.09), and butyric acid (P=0.02) in the benefit group than the resistance group, and patients with higher acetic, propionic, and butyric acid levels had a longer progression-free survival and lower risk of tumor progression after adjusting for histopathological subtype and stage (P<0.05). Long-term ICI survivors have coevolved a compact microbial community with high butyrate production, and molecular mimicry of autoimmune and tumor antigens by microbiota contribute to outcomes. These results not only characterize the gut microbiotas of patients who benefit long term from ICIs but pave the way for "smart" fecal microbiota transplantation. Registered in the Chinese Clinical Trial Registry (ChiCTR2000032088). This work was supported by Beijing Natural Science Foundation (7232110), National High Level Hospital Clinical Research Funding (2022-PUMCH-A-072, 2023-PUMCH-C-054), CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-C&T-B-010).

Population-based in silico modeling of anatomical shape variation of the knee and its impact on joint loading in knee osteoarthritis.

Anatomical knee joint features and osteoarthritis (OA) severity are associated, however confirming causals link to altered knee loading is challenging. This study leverages statistical shape models (SSM) to investigate the relationship between joint shape/alignment and knee loading during gait in knee OA(KOA) patients to understand their contribution to elevated medial knee loading in OA. Musculoskeletal (MSK) models were created for the mean as well as the first eightSSM principal modes of variation (-3,-2,-1, +1, +2, +3 standard deviations for each mode) and used as input to a MSK modeling framework. Using an identical KOA gait pattern (i.e., joint kinematics and ground reaction forces), we ran simulations for each MSK model and evaluated medial compartment loading magnitude and contact distribution at the instant of first and second peak of knee joint loading. An increase in external rotation, posterior tibia translation and a decrease in medial joint space and medial femoral condylar size predisposed the medial compartment knee joint to overloading during gait. This was coupled with an anterior and medial shift in contact location with increasing external rotated tibial position and increasing posterior tibial translation with respect to the femur. Next, results also highlighted a posterior shift of the medial compartment loading location with decreasing medial joint space. This study provides important population-based insights on how knee shape and alignment predispose individuals with KOA to elevated medial compartmental knee loading. This information can be crucial in assessing the risk for medial KOA development and progression.

Long non-coding RNAs as prognostic biomarkers in non-muscle invasive bladder cancer: A systematic review

Traditional prognostic tools for non-muscle invasive bladder cancer (NMIBC) often overestimate progression and recurrence risks, underscoring the need for more precise biomarkers. While long non-coding ribonucleic acids (lncRNAs) have been reviewed in bladder cancer, no review has focused on NMIBC. The aim of this study was to address this gap by investigating the role of lncRNAs in predicting NMIBC survival and progression. A systematic review was conducted using PubMed, Scopus, and Cochrane databases as of July 31, 2024. Prognostic studies investigating the association between lncRNA expression and survival outcomes, such as cancer-specific survival, disease-free survival, recurrence-free survival, or overall survival, using Kaplan-Meier curves or hazard ratios, were included. A total of three studies were analyzed, involving 279 NMIBC patients and focusing on three lncRNAs: urothelial cancer associated 1 (UCA1), growth arrest-specific 5 (GAS5), and up-regulated in non-muscle invasive bladder cancer (UNMIBC). Increased UCA1 expression was strongly associated with poor disease-free survival (hazard ratio (HR): 1.974; 95%CI: 1.061–3.673; p=0.032) and progression-free survival (HR: 3.476; 95%CI: 1.187–10.18; p=0.023). Reduced GAS5 expression was significantly associated with poor disease-free survival (HR: 2.659; 95%CI: 1.348–5.576; p=0.005) and progression-free survival (HR: 6.628; 95%CI: 1.494–29.40; p=0.013). Higher level of UNMIBC was strongly associated with poor recurrence-free survival (HR: 2.362; 95%CI: 1.504–4.837; p=0.007). In conclusion, lncRNAs have potential as prognostic biomarkers in NMIBC, with UCA1 and UNMIBC overexpression and GAS5 underexpression being significant in predicting disease recurrence and progression, highlighting the clinical relevance of monitoring these lncRNAs to improve prognosis and guide treatment decisions.

Network-based hub biomarker discovery for glaucoma

ObjectiveGlaucoma is an optic neuropathy and the leading cause of irreversible blindness worldwide. However, the early detection of glaucoma remains challenging, as chronic forms of glaucoma remain largely asymptomatic until...

Seasonal influences on the efficacy of anti-programmed cell death (ligand) 1 inhibitors in lung cancer.

Seasonal variations in systemic immunity have been reported. This study aimed to evaluate whether seasonality affects the efficacy of anticancer immunotherapy. A total of 604 patients with lung cancer receiving single anti-programmed cell death (ligand) 1 (anti-PD-[L]1) inhibitors from two prospective observational cohorts were screened. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Patients were classified into two groups according to the season when the treatment started: winter (November-February) and other seasons (March-October). Kaplan-Meier analysis and Cox proportional hazards models were fitted to evaluate the impact of seasonality on survival. For validation, propensity score matching was performed. A total of 484 patients with advanced non-small cell lung cancer were included. In an unmatched population, multivariable analysis demonstrated that the winter group (n=173) had a significantly lower risk of progression or death from immunotherapy than the other group (n=311) (PFS: hazard ratio [HR],0.77 [95% confidence interval (CI), 0.62-0.96]; p=.018; OS: HR,0.77 [95% CI, 0.1-0.98]; p=.032). In a propensity score-matched population, the winter group (n=162) showed significantly longer median PFS (2.8 months [95% CI, 1.9-4.1 months] vs. 2.0 months [95% CI, 1.4-2.7 months]; p=.009) than the other group (n=162). The winter group's median OS was also significantly longer than that of the other group (13.4 months [95% CI, 10.2-18.0 months] vs. 8.0 months [95% CI, 3.6-8.7 months]; p=.012). The trend toward longer survival in the winter group continued in subgroup analyses. Starting an anti-PD-(L)1 inhibitor in winter was associated with better treatment outcomes in patients with lung cancer compared to other seasons.

Oxidative stress in the alveolar lavage fluid of children with Mycoplasma pneumoniae pneumonia.

To investigate the correlation between oxidative stress in the bronchoalveolar lavage fluid (BALF) of children with Mycoplasma pneumoniae pneumonia (MPP) and the clinical characteristics of severe MPP (SMPP) and refractory MPP (RMPP). Clinical and BALF-related data were collected from 83 patients with MPP, of which 29 had SMPP and 54 had general MPP (GMPP); 37 patients were in the RMPP group and 46 in the non-RMPP group. The levels of malondialdehyde (MDA) and advanced oxidation protein products (AOPP) as well as the activity levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in BALF were detected. Logistic regression analyses were performed on MDA, AOPP, SOD, GSH-PX, gender, heat peak, neutrophil percentage, C-reactive protein, lactate dehydrogenase, d-dimer, lung consolidation, sputum embolus, and pleural effusion. The levels of MDA and AOPP in the BALF of the MPP group were significantly higher than those in the control group (p < .05), whereas SOD and GSH-PX levels were lower than those in the control group (p < .05). The BALF AOPP levels in the RMPP group were higher than those in the non-RMPP group, and the SOD and GSH-PX levels in the BALF were lower than those in the non-RMPP group; the difference was statistically significant (p < .05). The levels of MDA and AOPP in the BALF of children in the SMPP group were higher than those in the GMPP group, and the levels of SOD and GSH-PX were lower than those in the GMPP group, with statistically significant differences (p < .05). The C-index of the logistic regression model was 0.960 (95% confidence interval 0.958-0.963), which indicates that the model has good predictive ability. Advanced oxidation protein products may be a marker for predicting the conditions of SMPP and RMPP, and the prediction model can assess the risk of progression in children to RMPP, which is conducive to clinical diagnosis and treatment.

Gestational Diabetes Mellitus and Subsequent Risks of Diabetes and Cardiovascular Diseases: the Life Course Perspective and Implications of Racial Disparities.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications worldwide and the prevalence is continuously rising globally. Importantly, GDM is not an isolated complication of pregnancy. Growing evidence suggests that individuals with GDM, compared to those without GDM, have an increased risk of subsequent type 2 diabetes (T2D) and cardiovascular diseases (CVD). Substantial racial and ethnic disparities exist in the risk of GDM. However, the role of race and ethnicity in the progression from GDM to T2D and CVD remains unclear. The purpose of the current review is to summarize recent research about GDM and its life-course impacts on cardiometabolic health, including 1) the peak time of developing T2D and CVD risks after GDM, 2) the racial and ethnic disparities in the risk cardiometabolic diseases after GDM, 3) the biological plausibility and underlying mechanisms, and 4) recommendations for screening and prevention of cardiometabolic diseases among individuals with GDM, collectively to provide an updated review to guide future research. Growing evidence has indicated that individuals with GDM had greater risks of T2D (7.4 to 9.6 times), hypertension (78% higher), and CDV events (74% higher) after GDM than their non-GDM counterparts. More recently, a few studies also suggested that GDM could slightly increase the risk of mortality. Available evidence suggests that key CVD risk factors such as blood pressure, plasma glucose, and lipids levels are all elevated as early as < 1year postpartum in individuals with GDM. The risk of T2D and hypertension is likely to reach a peak between 3-6years after the index pregnancy with GDM compared to normal glycemia pregnancy. Cumulative evidence also suggests that the risk of cardiometabolic diseases including T2D, hypertension, and CVD events after GDM varies by race and ethnicity. However, whether the risk is higher in certain racial and ethnic groups and whether the pattern may vary by the postpartum cardiometabolic outcome of interest remain unclear. The underlying mechanisms linking GDM and subsequent T2D and CVD are complex, often involving multiple pathways and their interactions, with the specific mechanisms varying by individuals of different racial and ethnic backgrounds. Diabetes and CVD risk screening among individuals with GDM should be initiated early during postpartum and continue, if possible, frequently. Unfortunately, adherence to postpartum glucose testing with either obstetrician or primary care providers remained poor among individuals with GDM. A life-course perspective may provide critical information to address clinical and public health gaps in postpartum screening and interventions for preventing T2D and CVD risks in individuals with GDM. Future research investigating the racial- and ethnic-specific risk of progression from GDM to cardiometabolic diseases and the role of multi-domain factors including lifestyle, biological, and socio-contextual factors are warranted to inform tailored and culture-appropriate interventions for high-risk subpopulations. Further, examining the barriers to postpartum glucose testing among individuals with GDM is crucial for the effective prevention of cardiometabolic diseases and for enhancing life-long health.

Levels of IL-6 and IL-8 in complicated versus uncomplicated urinary tract infection

Background: Urinary tract infections (UTIs) are one of the world's most frequent infectious diseases, affecting 150 million people each year and resulting in severe morbidity and high medical expenditures. UTIs can be clinically defined as uncomplicated UTIs (uUTIs) or complicated UTIs (cUTIs) to differentiate infections of benign origin from those with a higher risk of recurrence or progression to severe pathology. The aim of this study was to evaluate interleukin-6 (IL-6) and IL-8 as potential biomarkers in differentiating complicated and uncomplicated Methods: Ninety samples of urine were collected. There were 43 samples from healthy controls and 47 samples from UTI patients, those who have been clinically diagnosed with UTIs by the urologist. The serum IL-6 and IL-8 were measured using an enzyme-linked immunosorbent assay and commercially available kits. Results: The levels of both IL-6 and IL-8 were significantly higher in UTI patient then in control subjects (p=0.001, p=0.001). A significant difference was observed in the mean of level IL-6 between culture positive UTI patients and culture negative UTI patients (p=0.014). In addition, the type of bacterial growth, a significant difference was observed in the mean of serum IL-6 and IL-8 level in UTI caused by gram negative bacteria in comparison with UTI caused by gram positive bacteria. Conclusion: High levels of IL-6 are associated with the growth of gram-negative bacteria, and this indicates that gram-negative bacteria could induce stronger inflammatory responses than gram-positive bacteria. IL-8 levels are higher in UTIs caused by gram-negative bacteria. This result further supported the evidence that gram-negative bacteria are potent inducers of inflammatory responses.

Subjective Cognitive Decline Patterns in Patients with Migraine, with or without Depression, versus Non-depressed Older Adults

Purpose: Cognitive decline is a common complaint in young patients with migraine, especially those with depression. Independent of psychiatric factors such as depression, subjective cognitive decline (SCD) is associated with an elevated risk of progression to dementia. This study aimed to investigate patterns of subjective cognitive complaints between migraineurs with or without depression and non-depressed older adults.Methods: This retrospective study included 331 outpatients with SCD (293 from a headache clinic and 38 from a memory clinic). SCD was diagnosed as “yes” based on two questions about SCD. The Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess cognitive function. The SCD Questionnaire (SCD-Q) with three subdomains was analyzed to compare SCD between groups.Results: Among patients with SCD, significant differences in duration of education were found among the groups—specifically, migraineurs with depression (12.39 years) had longer education than non-depressed older adults (10.50 years) and shorter education than migraineurs without depression (14.28 years). The total MMSE and MoCA scores did not differ between migraineurs with and without depression. Regarding SCD-Q scores, migraineurs with depression showed higher scores overall and in all cognitive domains than migraineurs without depression, with no significant difference compared to non-depressed older adults. Conclusion: Although the depressed migraineurs with SCD were younger and more educated than the non-depressed older adults with SCD, both groups reported similarly high levels of SCD. Higher levels of surveillance for cognitive decline are warranted for migraineurs with depression who have SCD.

Development and internal and external validation of a nomogram model for predicting the risk of chronic kidney disease progression in IgA nephropathy patients.

IgA nephropathy (IgAN) is the most common primary glomerular disease in chronic kidney disease (CKD), exhibiting significant heterogeneity in both clinical and pathological presentations. We aimed to explore the risk factors influencing short-term prognosis (≥90 days) and to construct a nomogram model for evaluating the risk of CKD progression in IgAN patients. Clinical and pathological data of patients diagnosed with IgAN through biopsy at two centers were retrospectively collected. Logistic regression was employed to analyze the training cohort dataset and identify the independent predictors to construct a nomogram model based on the final variables. The predictive model was validated both internally and externally, with its performance assessed using the area under the curve (AUC), calibration curves, and decision curve analysis. Out of the patients in the modeling group, 129 individuals (41.6%) did not achieve remission following 3 months of treatment, indicating a high risk of CKD progression. A multivariate logistic regression analysis demonstrated that body mass index, urinary protein excretion, and tubular atrophy/interstitial fibrosis were identified as independent predictors for risk stratification. A nomogram model was formulated utilizing the final variables. The AUCs for the training set, internal validation set, and external validation set were 0.746 (95% confidence intervals (CI) [0.691-0.8]), 0.764 (95% CI [0.68-0.85]), and 0.749 (95% CI [0.65-0.85]), respectively. The validation of the subgroup analysis also demonstrated a satisfactory AUC. This study developed and validated a practical nomogram that can individually predict short-term treatment outcomes (≥90 days) and the risk of CKD progression in IgAN patients. It provides reliable guidance for timely and personalized intervention and treatment strategies.

Impact of microvascular invasion risk on tumor progression of hepatocellular carcinoma after conventional transarterial chemoembolization.

To assess tumor progression in patients with hepatocellular carcinoma (HCC) without macrovascular invasion who underwent treatment with conventional transarterial chemoembolization (cTACE) based on microvascular invasion (MVI) risk within 2 years. This retrospective investigation comprised adult patients with HCC who had either liver resection or cTACE as their first treatment from January 2016 to December 2021. A predictive model for MVI was developed and validated using preoperative clinical and MRI data from patients with HCC treated with liver resection. The MVI predictive model was applied to patients with HCC receiving cTACE, and differences in tumor progression between the MVI high- and low-risk groups were examined throughout 2 years. The MVI prediction model incorporated nonsmooth margin, intratumoral artery, incomplete or absent tumor capsule, and tumor DWI/T2WI mismatch. The area under the receiver operating characteristic curve (AUC) for the prediction model, in the training cohort, was determined to be 0.904 (95% CI, 0.862-0.946), while in the validation cohort, it was 0.888 (0.782-0.994). Among patients with HCC undergoing cTACE, those classified as high risk for MVI possessed a lower rate of achieving a complete response after the first tumor therapy and a higher risk of tumor progression within 2 years. The MVI prediction model developed in this study demonstrates a considerable degree of accuracy. Patients at high risk for MVI who underwent cTACE treatment exhibited a higher risk of tumor progression within 2 years.

Serum Osmolality as a Predictor of Renal Function Decline: A Retrospective Cohort Study.

Background and Aims: Dehydration is a prevalent and costly healthcare concern, linked to heightened risks of acute kidney injury and in-hospital mortality. Despite its significance, limited evidence exists regarding its prevalence and correlation with renal function decline in apparently healthy individuals. This retrospective cohort study aimed to investigate the prevalence and association of dehydration with renal function decline and the development or progression of chronic kidney disease (CKD) in the general population. Methods: The medical records of subjects undergoing annual health check-ups from 2016 to 2019 at a single center in Taiwan were analyzed, and those with CKD stage V, insufficient data, or an increased estimated glomerular filtration rate (eGFR) were excluded. Serum osmolality, eGFR, and relevant parameters were measured. Logistic regression and Kaplan-Meier analyses were used to assess associations between osmolality and CKD-related outcomes. Results: Among the 4449 eligible subjects, those in the higher osmolality quartiles had an elevated risk of CKD or CKD progression. Multivariate analyses identified age, systolic blood pressure, serum osmolality, uric acid, proteinuria, and a history of diabetes as independent risk factors, with high-density lipoprotein being protective. Cumulative incidence curves demonstrated a significant increase in the risk of CKD with increasing osmolality levels. Restricted cubic spline analyses confirmed a nonlinear relationship between osmolality and CKD risk. Conclusions: Elevated serum osmolality independently predicted renal function decline and CKD development in apparently healthy individuals, and this effect persisted after adjusting for established risk factors. Our findings underscore the importance of addressing dehydration as a modifiable risk factor for CKD.