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Cureus Jul 2024Aim The study aimed to evaluate the predictive factors that determined stone-free rate (SFR) after retrograde intrarenal surgery (RIRS). Materials and methods This...
Aim The study aimed to evaluate the predictive factors that determined stone-free rate (SFR) after retrograde intrarenal surgery (RIRS). Materials and methods This prospective study was conducted on 183 patients undergoing RIRS for renal stones. Patients were categorized into two groups, depending on stone-free status one month following the procedure. SFR was defined as the complete absence of stones or stones <4 mm. The parameters studied included patient demographics, presence of hydronephrosis, presence of preoperative double J-stent, abnormal renal anatomy, and stone characteristics (stone burden, stone number, stone density, stone location, lower pole infundibulopelvic angle, and lower pole renal infundibular length (RIL)). Univariate and multivariate analyses were performed to identify risk factors for residual stones. We assessed the predictive ability of the RIRS score and Resorlu-Unsal stone score (RUSS) for evaluating SFR utilizing receiver operating characteristic (ROC) analysis. Results 183 patients were included in the study with a median age of 51 years. 131 (71.6%) patients were declared stone-free after the procedure. The mean stone size and density were 16.9 SD±7.5 mm and 1038 SD±342 Hounsfield units (HU) respectively. Stone-free patients had lower stone size (14.3 mm vs. 23.6 mm, p<0.01) and stone density (970 HU vs. 1211 HU, p<0.01) compared to non-stone-free patients. Patients with residual stones had steeper lower pole renal infundibulopelvic angle (RIPA) (31.3° vs. 40.7°, p<0.01) and longer RIL (26.6 mm vs. 21.1 mm, p<0.01). Stone multiplicity (p<0.01), lower pole stone location (p<0.01), and renal malformations (p<0.01) were significant influencing factors for residual renal stones after RIRS. Multivariate analysis revealed stone size, stone density (HU), and stone location as independent predictors for SFR after RIRS. Among the scoring systems, the RIRS score had the highest diagnostic accuracy for SFR (area under the curve (AUC): -0.882, 95% CI-0.828-0.936). Conclusion Stone size, stone density (HU), and stone number are important predictors of SFR after RIRS. Lower pole stone location and abnormal renal anatomy play a substantial role in determining SFR after RIRS. In lower pole stones, a long RIL and acute RIPA negatively influence SFR. Additionally, the RIRS score was found to be a better predictor for SFR than the RUSS score.
PubMed: 38957512
DOI: 10.7759/cureus.63627 -
Oncoimmunology 2024Gut microbiota impacts responses to immune checkpoint inhibitors (ICI). A high level of have been associated with a positive response to ICI in multiple cancer types....
Gut microbiota impacts responses to immune checkpoint inhibitors (ICI). A high level of have been associated with a positive response to ICI in multiple cancer types. Here, based on fecal shotgun metagenomics data, we show in two independent cohorts of patients with non-small cell lung cancer and advanced melanoma that a high level of at baseline is positively associated with a better clinical response to ICI. In MCA205 tumor-bearing mice, administration of strain EXL01, already in clinical development for Inflammatory Bowel Disease, restores the anti-tumor response to ICI in the context of antibiotic-induced microbiota perturbation at clinical and tumor transcriptomics level. In vitro, EXL01 strain enhances T cell activation in the presence of ICI. Interestingly, oral administration of EXL01 strain did not induce any change in fecal microbiota diversity or composition, suggesting a direct effect on immune cells in the small intestine. strain EXL01 will be evaluated as an adjuvant to ICI in multiple cancers in the near future.
Topics: Immune Checkpoint Inhibitors; Animals; Humans; Mice; Gastrointestinal Microbiome; Faecalibacterium prausnitzii; Female; Carcinoma, Non-Small-Cell Lung; Melanoma; Feces; Male; Lung Neoplasms; Cell Line, Tumor; Mice, Inbred C57BL
PubMed: 38957477
DOI: 10.1080/2162402X.2024.2374954 -
Frontiers in Immunology 2024Enteric glial cells (EGCs) are an essential component of the enteric nervous system (ENS) and play key roles in gastrointestinal development, homeostasis, and disease.... (Review)
Review
Enteric glial cells (EGCs) are an essential component of the enteric nervous system (ENS) and play key roles in gastrointestinal development, homeostasis, and disease. Derived from neural crest cells, EGCs undergo complex differentiation processes regulated by various signalling pathways. Being among the most dynamic cells of the digestive system, EGCs react to cues in their surrounding microenvironment and communicate with various cell types and systems within the gut. Morphological studies and recent single cell RNA sequencing studies have unveiled heterogeneity among EGC populations with implications for regional functions and roles in diseases. In gastrointestinal disorders, including inflammatory bowel disease (IBD), infections and cancer, EGCs modulate neuroplasticity, immune responses and tumorigenesis. Recent evidence suggests that EGCs respond plastically to the microenvironmental cues, adapting their phenotype and functions in disease states and taking on a crucial role. They exhibit molecular abnormalities and alter communication with other intestinal cell types, underscoring their therapeutic potential as targets. This review delves into the multifaceted roles of EGCs, particularly emphasizing their interactions with various cell types in the gut and their significant contributions to gastrointestinal disorders. Understanding the complex roles of EGCs in gastrointestinal physiology and pathology will be crucial for the development of novel therapeutic strategies for gastrointestinal disorders.
Topics: Humans; Neuroglia; Enteric Nervous System; Animals; Gastrointestinal Diseases
PubMed: 38957473
DOI: 10.3389/fimmu.2024.1408744 -
Frontiers in Immunology 2024There is a reciprocal relationship between extracellular matrix (ECM) remodelling and inflammation that could be operating in the progression of severe COVID-19. To...
There is a reciprocal relationship between extracellular matrix (ECM) remodelling and inflammation that could be operating in the progression of severe COVID-19. To explore the immune-driven ECM remodelling in COVID-19, we in this explorative study analysed these interactions in hospitalised COVID-19 patients. RNA sequencing and flow analysis were performed on peripheral blood mononuclear cells. Inflammatory mediators in plasma were measured by ELISA and MSD, and clinical information from hospitalised COVID-19 patients (N=15) at admission was included in the analysis. Further, we reanalysed two publicly available datasets: (1) lung tissue RNA-sequencing dataset (N=5) and (2) proteomics dataset from PBCM. ECM remodelling pathways were enriched in PBMC from COVID-19 patients compared to healthy controls. Patients treated at the intensive care unit (ICU) expressed distinct ECM remodelling gene profiles compared to patients in the hospital ward. Several markers were strongly correlated to immune cell subsets, and the dysregulation in the ICU patients was positively associated with plasma levels of inflammatory cytokines and negatively associated with B-cell activating factors. Finally, our analysis of publicly accessible datasets revealed (i) an augmented ECM remodelling signature in inflamed lung tissue compared to non-inflamed tissue and (ii) proteomics analysis of PBMC from severe COVID-19 patients demonstrated an up-regulation in an ECM remodelling pathway. Our results may suggest the presence of an interaction between ECM remodelling, inflammation, and immune cells, potentially initiating or perpetuating pulmonary pathology in severe COVID-19.
Topics: Humans; COVID-19; Leukocytes, Mononuclear; Extracellular Matrix; Male; Female; Middle Aged; SARS-CoV-2; Aged; Cytokines; Proteomics; Lung; Adult
PubMed: 38957465
DOI: 10.3389/fimmu.2024.1379570 -
Frontiers in Immunology 2024Previous studies have revealed that Galectin-9 (Gal-9) acts as an apoptosis modulator in autoimmunity and rheumatic inflammation. In the present study, we investigated...
BACKGROUND
Previous studies have revealed that Galectin-9 (Gal-9) acts as an apoptosis modulator in autoimmunity and rheumatic inflammation. In the present study, we investigated the potential role of Gal-9 as a biomarker in patients with rheumatoid arthritis (RA), especially as an indicator of functional limitations and radiographic joint damage.
METHODS
A total of 146 patients with RA and 52 age- and sex-matched healthy controls were included in this study. Clinical data including disease activity, physical function, and radiographic joint damage were assessed. Functional limitation was defined as the Stanford Health Assessment Questionnaire (HAQ) disability index >1. Subjects with joint erosion >0 or joint space narrowing >0 were considered to have radiographic joint damage. Serum Gal-9 levels were detected by an enzyme-linked immunosorbent assay. Univariate and multivariate logistic regression analysis were used to evaluate the association between Gal-9 and high disease activity and functional limitations, and a prediction model was established to construct predictive nomograms.
RESULTS
Serum levels of Gal-9 were significantly increased in patients with RA compared to those in healthy controls (median 13.1 ng/mL vs. 7.6 ng/mL). Patients with RA who were older (>65 years), had a longer disease duration (>5 years), longer morning stiffness (>60mins), elevated serum erythrocyte sedimentation rate and C-reactive protein, and difficult-to-treat RA had significantly higher Gal-9 levels than those in the corresponding control subgroups (all p <0.05). Patients with RA were divided into two subgroups according to the cut-off value of Gal-9 of 11.6 ng/mL. Patients with RA with Gal-9 >11.6 ng/mL had a significantly higher core clinical disease activity index, HAQ scores, Sharp/van der Heijde modified Sharp scores, as well as a higher percentage of advanced joint damage (all p<0.05) than patients with Gal-9 ≤11.6 ng/mL. Accordingly, patients with RA presenting either functional limitations or radiographic joint damage had significantly higher serum Gal-9 levels than those without (both p <0.05). Furthermore, multivariate logistic regression analysis showed that a serum level of Gal-9 >11.6 ng/mL was an independent risk factor for high disease activity (OR=3.138, 95% CI 1.150-8.567, p=0.026) and presence of functional limitations (OR=2.455, 95% CI 1.017-5.926, p=0.046), respectively.
CONCLUSION
Gal-9 could be considered as a potential indicator in patients with RA, especially with respect to functional limitations and joint damage.
Topics: Humans; Arthritis, Rheumatoid; Galectins; Female; Male; Middle Aged; Biomarkers; Aged; Adult; Severity of Illness Index; Case-Control Studies; Joints
PubMed: 38957462
DOI: 10.3389/fimmu.2024.1419676 -
Frontiers in Endocrinology 2024This study aimed to construct a machine learning model using clinical variables and ultrasound radiomics features for the prediction of the benign or malignant nature of...
OBJECTIVE
This study aimed to construct a machine learning model using clinical variables and ultrasound radiomics features for the prediction of the benign or malignant nature of pancreatic tumors.
METHODS
242 pancreatic tumor patients who were hospitalized at the First Affiliated Hospital of Guangxi Medical University between January 2020 and June 2023 were included in this retrospective study. The patients were randomly divided into a training cohort (n=169) and a test cohort (n=73). We collected 28 clinical features from the patients. Concurrently, 306 radiomics features were extracted from the ultrasound images of the patients' tumors. Initially, a clinical model was constructed using the logistic regression algorithm. Subsequently, radiomics models were built using SVM, random forest, XGBoost, and KNN algorithms. Finally, we combined clinical features with a new feature RAD prob calculated by applying radiomics model to construct a fusion model, and developed a nomogram based on the fusion model.
RESULTS
The performance of the fusion model surpassed that of both the clinical and radiomics models. In the training cohort, the fusion model achieved an AUC of 0.978 (95% CI: 0.96-0.99) during 5-fold cross-validation and an AUC of 0.925 (95% CI: 0.86-0.98) in the test cohort. Calibration curve and decision curve analyses demonstrated that the nomogram constructed from the fusion model has high accuracy and clinical utility.
CONCLUSION
The fusion model containing clinical and ultrasound radiomics features showed excellent performance in predicting the benign or malignant nature of pancreatic tumors.
Topics: Humans; Pancreatic Neoplasms; Machine Learning; Female; Male; Retrospective Studies; Ultrasonography; Middle Aged; Aged; Adult; Nomograms; Radiomics
PubMed: 38957447
DOI: 10.3389/fendo.2024.1381822 -
Frontiers in Endocrinology 2024Amphiregulin (AR) is a growth factor that resembles the epidermal growth factor (EGF) and serves various functions in different cells. However, no systematic studies or...
BACKGROUND
Amphiregulin (AR) is a growth factor that resembles the epidermal growth factor (EGF) and serves various functions in different cells. However, no systematic studies or reports on the role of AR in human oocytes have currently been performed or reported. This study aimed to explore the role of AR in human immature oocytes during maturation (IVM) and fertilization (IVF) in achieving better embryonic development and to provide a basis for the development of a pre-insemination culture medium specific for cumulus oocyte complexes (COCs).
METHODS
First, we examined the concentration of AR in the follicular fluid (FF) of patients who underwent routine IVF and explored the correlation between AR levels and oocyte maturation and subsequent embryonic development. Second, AR was added to the IVM medium to culture immature oocytes and investigate whether AR could improve the effects of IVM. Finally, we pioneered the use of a fertilization medium supplemented with AR for the pre-insemination culture of COCs to explore whether the involvement of AR can promote the maturation and fertilization of IVF oocytes, as well as subsequent embryonic development.
RESULTS
A total of 609 FF samples were examined, and a positive correlation between AR levels and blastocyst formation was observed. In our IVM study, the development potential and IVM rate of immature oocytes, as well as the fertilization rate of IVM oocytes in the AR-added groups, were ameliorated significantly compared to the control group (All P < 0.05). Only the IVM-50 group had a significantly higher blastocyst formation rate than the control group (P < 0.05). In the final IVF study, the maturation, fertilization, high-quality embryo, blastocyst formation, and high-quality blastocyst rates of the AR-added group were significantly higher than those of the control group (All P < 0.05).
CONCLUSION
AR levels in the FF positively correlated with blastocyst formation, and AR involvement in pre-insemination cultures of COCs can effectively improve laboratory outcomes in IVF. Furthermore, AR can directly promote the maturation and developmental potential of human immature oocytes at an optimal concentration of 50 ng/ml.
Topics: Humans; Amphiregulin; Fertilization in Vitro; Female; Oocytes; In Vitro Oocyte Maturation Techniques; Adult; Cumulus Cells; Follicular Fluid; Embryonic Development; Pregnancy; Culture Media; Embryo Culture Techniques; Blastocyst
PubMed: 38957445
DOI: 10.3389/fendo.2024.1428147 -
Frontiers in Neuroanatomy 2024Extraocular muscles are innervated by two anatomically and histochemically distinct motoneuron populations: motoneurons of multiply-innervated fibers (MIF), and of...
INTRODUCTION
Extraocular muscles are innervated by two anatomically and histochemically distinct motoneuron populations: motoneurons of multiply-innervated fibers (MIF), and of singly-innervated fibers (SIF). Recently, it has been established by our research group that these motoneuron types of monkey abducens and trochlear nuclei express distinct ion channel profiles: SIF motoneurons, as well as abducens internuclear neurons (INT), express strong Kv1.1 and Kv3.1b immunoreactivity, indicating their fast-firing capacity, whereas MIF motoneurons do not. Moreover, low voltage activated cation channels, such as Cav3.1 and HCN1 showed differences between MIF and SIF motoneurons, indicating distinct post-inhibitory rebound characteristics. However, the ion channel profiles of MIF and SIF motoneurons have not been established in human brainstem tissue.
METHODS
Therefore, we used immunohistochemical methods with antibodies against Kv, Cav3 and HCN channels to (1) examine the human trochlear nucleus in terms of anatomical organization of MIF and SIF motoneurons, (2) examine immunolabeling patterns of ion channel proteins in the distinct motoneurons populations in the trochlear and abducens nuclei.
RESULTS
In the examination of the trochlear nucleus, a third motoneuron subgroup was consistently encountered with weak perineuronal nets (PN). The neurons of this subgroup had -on average- larger diameters than MIF motoneurons, and smaller diameters than SIF motoneurons, and PN expression strength correlated with neuronal size. Immunolabeling of various ion channels revealed that, in general, human MIF and SIF motoneurons did not differ consistently, as opposed to the findings in monkey trochlear and abducens nuclei. Kv1.1, Kv3.1b and HCN channels were found on both MIF and SIF motoneurons and the immunolabeling density varied for multiple ion channels. On the other hand, significant differences between SIF motoneurons and INTs were found in terms of HCN1 immunoreactivity.
DISCUSSION
These results indicated that motoneurons may be more variable in human in terms of histochemical and biophysiological characteristics, than previously thought. This study therefore establishes grounds for any histochemical examination of motor nuclei controlling extraocular muscles in eye movement related pathologies in the human brainstem.
PubMed: 38957435
DOI: 10.3389/fnana.2024.1411154 -
Neurosurgical Focus: Video Jul 2024Hemispheric epilepsy is quite frequent in children, compared with adults, and encompasses pathological substrates as diverse as hemimegalencephaly, Rasmussen...
Hemispheric epilepsy is quite frequent in children, compared with adults, and encompasses pathological substrates as diverse as hemimegalencephaly, Rasmussen encephalitis, Sturge-Weber syndrome, and porencephaly, among others. These patients most often become pharmacoresistant and thus require surgical management. Although anatomical hemispherectomy is a possibility, the technique that is favored by most epilepsy surgery centers worldwide is functional hemispherotomy, which results in equivalent outcomes with fewer postoperative complications. Therefore, it is essential that pediatric epilepsy neurosurgeons become familiar with these techniques. The present video describes in detail all surgical aspects of the perisylvian hemispherotomy.
PubMed: 38957430
DOI: 10.3171/2024.4.FOCVID2451 -
Pathology Oncology Research : POR 2024The delivery of neoadjuvant and perioperative therapies for non-small cell lung cancer has been radically altered by significant advances and by the incorporation of... (Review)
Review
The delivery of neoadjuvant and perioperative therapies for non-small cell lung cancer has been radically altered by significant advances and by the incorporation of targeted therapies as well as immune checkpoint inhibitors alone or alongside conventional chemotherapy. This evolution has been particularly notable in the incorporation of immunotherapy and targeted therapy into the treatment of resectable NSCLC, where recent FDA approvals of drugs such as nivolumab and pembrolizumab, in combination with platinum doublet chemotherapy, have led to considerable improvements in pathological complete response rates and the potential for enhanced long-term survival outcomes. This review emphasizes the growing importance of biomarkers in optimizing treatment selection and explores the impact of emerging studies that challenge existing treatment paradigms and investigate novel therapeutic combinations poised to redefine standard of care practices. Furthermore, the discussion extends to the unmet needs within perioperative treatment assessment and prognostication, highlighting the prospective value of biomarkers in evaluating treatment responses and prognosis.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Neoadjuvant Therapy; Biomarkers, Tumor; Prognosis
PubMed: 38957347
DOI: 10.3389/pore.2024.1611817