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Background: The interaction between mesenchymal stem cells (MSC) and Glioblastoma (GBM), although potentially of the highest importance, is ill-understood. This is due, in part, to the lack of relevant experimental models. The similarity between the in vitro situations and the in vivo situation can be improved by 3D co-culture as it reproduces key cell–cell interactions between the tumor microenvironment (TME) and cancer cells. Methods: MSC Can acquired characteristics of cancer associated fibroblasts (CAF) by being cultured with conditioned medium from GBM cultures and thus are called MSCCAF. We co Cultured MSCCAF with patient derived GBM in a scaffold 3D bioprinted model. We studied the response to current GBM therapy (e.g. Temozolomide + /Radiation) on the co cultures by bulk transcriptomic (RNA Seq) and epigenetic (ATAC Seq) analyses Results: The transcriptomic modifications induced by standard GBM treatment in bioprinted scaffolds of mono- or co-cultures of GBM ± MSC can be analyzed. We found that mitochondrial encoded OXPHOS genes are overexpressed under these conditions and are modified by both co-culture and treatment (chemotherapy ± radiation). We have identified two new markers of MSC/GBM interactions, one epigenetically regulated (i.e. TREM-1) associated with an increased overall survival in GBM patients and another implicated in post-transcriptional regulation (i.e. the long non-coding RNA, miR3681HG), which is associated with a reduced overall survival in GBM patients. [ABSTRACT FROM AUTHOR]

• This study highlights a high level of heterogeneity in treatment response to ETI for a series of clinical endpoint including FEV1, BMI, sweat chloride and patient symptoms. • A total of 10 % of patients had lower responses to ETI, i.e. reductions in sweat chloride concentration <27 mmol/L, increase in ppFEV1<2.5 points, reductions in BMI up to −0.13 SDS and no change in the CFQ-R respiratory score. • CFTR genotype and baseline clinical characteristics can explain a relevant part of the variability for changes in BMI (41 %) and self-reported respiratory symptoms (65 %). • CFTR genotype and baseline clinical characteristics can explain only a limited part of the variability for changes in sweat chloride concentration (24 %) and ppFEV1 (18 %). Highly effective modulators of the CFTR channel have been demonstrated to dramatically impact disease progression and outcome. However, real-world data indicates that the magnitude of the clinical benefit is not equal among all patients receiving the treatment. We aimed to assess the variability in treatment response (as defined by the 6-month change in sweat chloride concentration, forced expiratory volume in one second [ppFEV1], body mass index [BMI], and CF Questionnaire-Revised [CFQ-R] respiratory domain score) and identify potential predictors in a group of patients receiving Elexacaftor-Tezacaftor-Ivacaftor (ETI) triple combination therapy. This was a single-center, prospective cohort study enrolling adults with CF at a major center in Italy. We used linear regression models to identify a set of potential predictors (including CFTR genotype, sex, age, and baseline clinical characteristics) and estimate the variability in treatment response. The study included 211 patients (median age: 29 years, range: 12–58). Median changes (10–90th percentile) from baseline were: - 56 mEq/L (–76; –27) for sweat chloride concentration, +14.5 points (2.5; 32.0) for ppFEV1, +0.33 standard deviation scores (–0.13; 1.05) for BMI and +17 points (0; 39) for the CFQ-R respiratory domain score. The selected predictors explained 23 % of the variability in sweat chloride concentration changes, 18 % of the variability in ppFEV1 changes, 39 % of the variability in BMI changes, and 65 % of the variability in CFQ-R changes. This study highlights a high level of heterogeneity in treatment response to ETI, which can only be partially explained by the baseline characteristics of the disease. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate the prognostic value of the Mayo additive staging system (MASS) and minimal residual disease (MRD) in newly diagnosed multiple myeloma (NDMM) patients. Methods: A total of 238 NDMM patients were enrolled in Beijing Chaoyang Hospital. Fluorescence in‐situ hybridization and next‐generation flow cytometry were used to examine cytogenetic abnormalities and MRD, respectively. The patients were classified into three groups to compare the effects on progression‐free survival (PFS). Univariate and multivariate analyses were applied to identify the survival‐related factors. Results: For MASS group, the PFS was significant difference in MASS I, II, and III patients (p = 0.0006); the patients with sustained MRD‐negative, non‐sustained MRD‐negative, sustained MRD‐positive, and non‐sustained MRD‐positive were divided into Groups 1, 2, 3, and 4, respectively. The Group 1 patients had superior PFS than Groups 2 and 3 patients (p < 0.05), but no difference in PFS was observed for Group 2 versus Group 3, Group 2 versus Group 4, and Group 3 versus Group 4 patients. For the MASS and MRD groups, among Groups 2, 3, and 4, MASS I patients had a superior PFS, while III patients showed the opposite result. Strikingly, no difference in PFS for Group 1 patients regardless of the MASS stage was observed. Despite being in MASS II and III, the PFS of Group 1 patients was longer than those with the other three groups. Response to treatment was an independent prognostic factor for MM patients. Conclusion: Patients with an accumulation of high‐risk factors and MRD‐positive have poor outcomes. Sustained MRD‐negative may improve high‐risk patients' prognoses. [ABSTRACT FROM AUTHOR]

Background: Osteosarcomas are rare malignancies (<1% of all cancers) that produce an osteoid matrix. Osteosarcomas are the second most frequent type of primary bone tumor after multiple myeloma and the most prevalent primary bone tumor in children. The spectrum of imaging findings of these malignancies varies significantly, reflecting different histological subtypes. For instance, conventional osteosarcoma typically presents with a mixed radiological pattern (lytic and bone mineralization) or with a completely eburneous one; aggressive periosteal reactions such as sunburst, Codman triangle, and soft-tissue components are frequently displayed. On the other hand, telangiectatic osteosarcoma usually presents as a purely lytic lesion with multiple fluid–fluid levels on MRI fluid-sensitive sequences. Other typical and atypical radiological patterns of presentation in other subtypes of osteosarcomas are described in this review. In addition to the characteristics associated with osteosarcoma subtyping, this review article also focuses on imaging features that have been associated with patient outcomes, namely response to chemotherapy and event-free and overall survivals. This includes simple semantic radiological features (such as tumor dimensions, anatomical location with difficulty of radical surgery, occurrence of pathological fractures, and presence of distant metastases), but also quantitative imaging parameters from diffusion-weighted imaging, dynamic contrast-enhanced MRI, and 18F-FDG positron emission tomography and radiomics approaches. Other particular features are described in the text. Overall, this comprehensive literature review aims to be a practical tool for oncologists, pathologists, surgeons, and radiologists involved in these patients' care. [ABSTRACT FROM AUTHOR]

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Abstract Background The interaction between mesenchymal stem cells (MSC) and Glioblastoma (GBM), although potentially of the highest importance, is ill-understood. This is due, in part, to the lack of relevant experimental models. The similarity between the in vitro situations and the in vivo situation can be improved by 3D co-culture as it reproduces key cell–cell interactions between the tumor microenvironment (TME) and cancer cells. Methods MSC Can acquired characteristics of cancer associated fibroblasts (CAF) by being cultured with conditioned medium from GBM cultures and thus are called MSCCAF. We co Cultured MSCCAF with patient derived GBM in a scaffold 3D bioprinted model. We studied the response to current GBM therapy (e.g. Temozolomide + /Radiation) on the co cultures by bulk transcriptomic (RNA Seq) and epigenetic (ATAC Seq) analyses Results The transcriptomic modifications induced by standard GBM treatment in bioprinted scaffolds of mono- or co-cultures of GBM ± MSC can be analyzed. We found that mitochondrial encoded OXPHOS genes are overexpressed under these conditions and are modified by both co-culture and treatment (chemotherapy ± radiation). We have identified two new markers of MSC/GBM interactions, one epigenetically regulated (i.e. TREM-1) associated with an increased overall survival in GBM patients and another implicated in post-transcriptional regulation (i.e. the long non-coding RNA, miR3681HG), which is associated with a reduced overall survival in GBM patients.

Purpose: In people with cystic fibrosis (pwCF), elexacaftor/tezacaftor/ivacaftor (ETI) therapy is associated with an average improvement in FEV1 of 10–14%. However, a subset of individuals fails to achieve a clinically meaningful increase in spirometric indicators. In this study, we aimed to assess whether the lung clearance index (LCI2.5), a more sensitive indicator of lung involvement, improves following ETI initiation in this population. Methods: We conducted a prospective observational study in a specialized CF center in Italy. PwCF performed a spirometry and a multiple breath nitrogen washout test the day they initiated ETI therapy and after 6 and 12 months. They were grouped according to the 12-month change in FEV1 into two groups: Individuals who experienced a change in FEV1 ≥ a minimal clinically important difference (MCID) of 3% and those who did not. Mean changes in LCI2.5 were estimated using generalized estimating equations. Results: The study included 129 pwCF who initiated ETI at our center (Age Range: 12–36 years). In 20 subjects (15.5%), the FEV1 change was < MCID. These individuals had better baseline pulmonary function than those with FEV1 changes ≥ MCID (Median FEV1: 102.5 vs 87.0%), with the majority (90%) having FEV1 values ≥ 90%. Mean changes in LCI2.5 at 12-month follow-up visit were − 1.44 units (95% CI: − 2.12; − 0.75) in individuals with changes in FEV1 < MCID and − 2.64 units (95% CI: -3.05; -2.23) in those with values ≥ MCID. Conclusion: LCI2.5 is a useful measure to monitor the effectiveness of ETI in pwCF with normal spirometry and limited FEV1 change following treatment initiation. [ABSTRACT FROM AUTHOR]

Abstract In a prospective cohort study, we evaluated plasma PCT levels in 48 TB lymphadenitis (TBLN) and 41 TB pleuritis (TBPE) patients. Measurements of PCT were done in unstimulated plasma of microbiologically and clinically confirmed TBLN and TBPE patients registered for anti-TB treatment at a tertiary care hospital in Lahore, Pakistan. Plasma levels of PCT were found to be raised in 89% of the patients at baseline with a median of 1.5 ng/ml. Levels were higher (p = 0.001) in TBLN as compared to TBPE (2.69, 0.96 ng/ml). PCT levels were not related to the bacterial burden depicted by culture positivity in these patients. PCT showed a negative correlation with the severity of constitutional symptoms (rho = − 0.238, p = 0.034), and inflammatory biomarkers; ferritin (rho = − 0.43, p

In a prospective cohort study, we evaluated plasma PCT levels in 48 TB lymphadenitis (TBLN) and 41 TB pleuritis (TBPE) patients. Measurements of PCT were done in unstimulated plasma of microbiologically and clinically confirmed TBLN and TBPE patients registered for anti-TB treatment at a tertiary care hospital in Lahore, Pakistan. Plasma levels of PCT were found to be raised in 89% of the patients at baseline with a median of 1.5 ng/ml. Levels were higher (p = 0.001) in TBLN as compared to TBPE (2.69, 0.96 ng/ml). PCT levels were not related to the bacterial burden depicted by culture positivity in these patients. PCT showed a negative correlation with the severity of constitutional symptoms (rho = − 0.238, p = 0.034), and inflammatory biomarkers; ferritin (rho = − 0.43, p < 0.001), INF-γ (rho = − 0.314, p = 0.003), TNF-α (rho = − 0.220, p = 0.039), IL-6 (rho = − 0.224, p = 0.035), and several chemokines of CCL and CCXL group. Raised plasma levels of PCT did not decrease with anti-TB treatment, indicating it is not a good biomarker to monitor treatment response in TBLN and TBPE patients. More studies with a larger number of confirmed EPTB cases are needed to define the role of PCT and its interaction with other biomarkers in EPTB. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction This study aimed to evaluate the prognostic value of the Mayo additive staging system (MASS) and minimal residual disease (MRD) in newly diagnosed multiple myeloma (NDMM) patients. Methods A total of 238 NDMM patients were enrolled in Beijing Chaoyang Hospital. Fluorescence in‐situ hybridization and next‐generation flow cytometry were used to examine cytogenetic abnormalities and MRD, respectively. The patients were classified into three groups to compare the effects on progression‐free survival (PFS). Univariate and multivariate analyses were applied to identify the survival‐related factors. Results For MASS group, the PFS was significant difference in MASS I, II, and III patients (p = 0.0006); the patients with sustained MRD‐negative, non‐sustained MRD‐negative, sustained MRD‐positive, and non‐sustained MRD‐positive were divided into Groups 1, 2, 3, and 4, respectively. The Group 1 patients had superior PFS than Groups 2 and 3 patients (p

The radioiodine therapy is a one of the basic elements at combined treatment of differentiated thyroid cancer and is an alternative method for patients with distant metastases and a potentially high risk of tumor recurrence. It has been used in clinical practice for more than 80 years. The first report on the phenomenon of accumulation of 130I/131I in a metastatic focus of differentiated thyroid cancer was published by A. Keston et al. in 1942, and in 1946, the production of 131I was established, and the drug became available. In our country, radioiodine therapy has been widely used for the treatment of differentiated thyroid cancer since 1982.This article presents methodological recommendations for radioiodine therapy of patients with differentiated thyroid cancer, provides a modern examination algorithm, discusses the basic principles of laboratory, instrumental diagnostics and treatment approaches treatment of this disease.

This study aims to develop and validate a composite index, based on the integration of biomarkers, lung function parameters and clinical scores, for more accurate and informative risk stratification in patients with asthma. Through advanced multivariate analyses, the parameters most predictive of loss of control will be identified. An AI-based diagnostic algorithm will integrate these variables to construct the composite index, which will be prospectively validated in an independent cohort of patients. The objective is to evaluate the clinical applicability of the index, the impact on therapeutic management and outcomes of patients with asthma, to support clinicians in precision medicine for this complex disease. [ABSTRACT FROM AUTHOR]

IntroductionAnal squamous cell carcinoma (ASC) is a rare gastrointestinal malignancy showing an increased incidence over the past decades. YKL-40 is an immune modulator and pro-angiogenetic factor that showed a promising prognostic and predictive potential in several malignancies, but limited data are available for ASC. This study aims to provide an extensive evaluation of the prognostic and predictive role of YKL-40 in a multicenter cohort of ASC patients.MethodsWe retrospectively retrieved 72 consecutive cases of ASC diagnosed between February 2011 and March 2021. Both serum and tissue protein expression of YKL-40 were assessed, the latter in ASC tumor cells and peritumor immune cells.ResultsIncreased YKL-40 serum levels at the time of diagnosis were associated with older age (p = 0.035), presence of cardiovascular/metabolic comorbidities (p = 0.007), and death for any cause (p = 0.011). In addition, high serum levels of YKL-40 were associated with a poor prognosis (HR: 2.82, 95% CI: 1.01–7.84; p = 0.047). Protein expression of YKL-40 in ASC tumor cells was significantly associated with low tumor grade (p = 0.031), while the increased expression in peritumor immune cells was associated with a worse response of patients to chemoradiotherapy (p = 0.007). However, YKL-40 protein expression in ASC tumor cells or peritumor immune cells did not significantly impact patient overall survival.DiscussionIn conclusion, YKL-40 resulted a relevant prognostic (serum level) and predictive (tissue protein expression in peritumor immune cells) biomarker and can considerably improve ASC patient clinical management.

Background: Response to antipsychotics is subject to a wide interindividual variability, due to genetic and non-genetic factors. Several single nucleotide polymorphisms (SNPs) have been associated with response to antipsychotics in genome-wide association studies (GWAS). Polygenic risk scores (PRS) are a powerful tool to aggregate into a single measure the small effects of multiple risk alleles. Materials and methods: We studied the association between a PRS composed of SNPs associated with response to antipsychotics in GWAS studies (PRSresponse) in a real-world sample of patients (N = 460) with different diagnoses (schizophrenia spectrum, bipolar, depressive, neurocognitive, substance use disorders and miscellaneous). Two other PRSs composed of SNPs previously associated with risk of schizophrenia (PRSschizophrenia1 and PRSschizophrenia2) were also tested for their association with response to treatment. Results: PRSresponse was significantly associated with response to antipsychotics considering the whole cohort (OR = 1.14, CI = 1.03-1.26, p = 0.010), the subgroup of patients with schizophrenia, schizoaffective disorder or bipolar disorder (OR = 1.18, CI = 1.02-1.37, p = 0.022, N = 235), with schizophrenia or schizoaffective disorder (OR = 1.24, CI = 1.04-1.47, p = 0.01, N = 176) and with schizophrenia (OR = 1.27, CI = 1.04-1.55, p = 0.01, N = 149). Sensitivity and specificity were suboptimal (schizophrenia 62%, 61%; schizophrenia spectrum 56%, 55%; schizophrenia spectrum plus bipolar disorder 60%, 56%; all patients 63%, 58%, respectively). PRSschizophrenia1 and PRSschizophrenia2 were not significantly associated with response to treatment. Conclusion: PRSresponse defined from GWAS studies is significantly associated with response to antipsychotics in a real-world cohort; however, the results of the sensitivity-specificity analysis preclude its use as a predictive tool in clinical practice. [ABSTRACT FROM AUTHOR]

Response to antidepressants is related to hippocampal neurogenesis integrity, a process mediated by neurotrophins, such as Brain Derived Neurotrophic Factor (BDNF). In turn, pro-inflammatory state appears to reduce neurogenesis, and has been associated with refractory depressive states. We propose to analyze the human neural progenitor cells derived from the olfactory epithelium (HNPCs-OE) as an indicator of neurogenesis in humans. Therefore, we compared the number and content of HNPCs-OE in depressed patients taking antidepressants, according to response to treatment. Twenty depressed patients were followed during eight weeks after antidepressant treatment was prescribed. At the end evaluation they were divided in two groups according to Hamilton depression rating scale (HDRS) scores: responders and non-responders. We compared the number and components of HNPCs-OE between groups and observed an elevation of interleukine-8 in those patients who do not achieve response to treatment, BDNF levels were no related to antidepressant response. • Human neuronal progenitor cells derived from the olfactory epithelium were studied in depressed patients. • The cells number was higher in younger than older depressed patients. • The cells number was associated to depression scores after antidepressant treatment. • Increased interleukine-8 was observed in patients who did not achieve response to antidepressant. [ABSTRACT FROM AUTHOR]

Aplastic anemia (AA) is a rare, life-threatening hematological disease, with a poorly defined incidence. As the data available on AA varies substantially worldwide, a multicenter, ambispective, observational study was carried out between 2010 and 2019 to assess the incidence, clinical management and survival of AA at seven Spanish hospitals. The incidence of AA was 2.83 per million inhabitants per year, consistent with that reported previously in Europe, with a median age at diagnosis of 61 years-old (range 12–86), and a similar number of males and females. The initial diagnosis was severe or very severe AA in 55.8% of cases and 93.7% required transfusion. The most frequent first line therapy was anti-thymocyte globulin (ATG) plus cyclosporin A (CsA, 44.2%), followed by other CsA-based regimes (46.3%), with hematopoietic stem cell transplantation an infrequent 1st line therapy. The 6-month response rate was 68.2%, which then increased over a median follow-up of 3.9 years. The 5-year overall survival (5OS) was 73.6%, similar in severe (78.6%) and very severe AA patients (74.6%) but lower in moderate AA (MAA) patients (68.4%). The 5OS was 100% in 0–25 year-old patients but dropping to 58.3% in patients ≥ 60 years-old. At the last contact, 75.8% of the patients were alive. In conclusion, the incidence, characteristics and management of AA in our study are consistent with that reported previously. In terms of survival, although the global long-term OS rate was good, there is room for improvement, particularly in older patients. Finally, what appears to be a worse long-term survival of MAA patients, as reported previously, reinforces the importance of not underestimating this condition when diagnosed as MAA. [ABSTRACT FROM AUTHOR]

There is currently no consensus to determine which advanced melanoma patients will benefit from targeted therapy, immunotherapy, or a combination of both, highlighting the critical need to identify early-response biomarkers to advanced melanoma therapy. The goal of this review is to provide scientific rationale to highlight the potential role of metabolic imaging to assess response to targeted and/or immune therapy in melanoma cancer. For that purpose, a brief overview of current melanoma treatments is provided. Then, current knowledge with respect to melanoma metabolism is described with an emphasis on major crosstalks between melanoma cell metabolism and signaling pathways involved in BRAF-targeted therapy as well as in immune checkpoint inhibition therapies. Finally, preclinical and clinical studies using metabolic imaging and/or profiling to assess response to melanoma treatment are summarized with a particular focus on PET (Positron Emission Tomography) imaging and 13C-MRS (Magnetic Resonance Spectroscopy) methods. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Alzheimer's disease (AD) is a neurological disorder with variability in pathology and clinical progression. AD patients may differ in individual‐level benefit from amyloid beta removal therapy. METHODS: Random forest models were applied to the EMERGE trial to create an individual‐level treatment response (ITR) score which represents individual‐level benefit of high‐dose aducanumab relative to the placebo. This ITR score was used to test the existence of heterogeneity in treatment effect (HTE). RESULTS: We found statistical evidence of HTE in the Clinical Dementia Rating–Sum of Boxes (CDR‐SB;P = 0.034). The observed CDR‐SB benefit was 0.79 points greater in the group with the top 25% of ITR score compared to the remaining 75% (P = 0.020). Of note, the highest treatment responders had lower hippocampal volume, higher plasma phosphorylated tau 181 and a shorter duration of clinical AD at baseline. DISCUSSION: This ITR analysis provides a proof of concept for precision medicine in future AD research and drug development. Highlights: Emerging trials have shown a population‐level benefit from amyloid beta (Aβ) removal in slowing cognitive decline in early Alzheimer's disease (AD).This work demonstrates significant heterogeneity of individual‐level treatment effect of aducanumab in early AD.The greatest clinical responders to Aβ removal therapy have a pattern of more severe neurodegenerative process. [ABSTRACT FROM AUTHOR]

Introduction: In osteosarcoma, the most significant indicator of prognosis is the histologic changes related to tumor response to preoperative chemotherapy, such as necrosis. We have developed a method to measure the osteosarcoma treatment effect using whole slide image (WSI) with an open-source digital image analytical software Qupath. Materials and Methods: In Qupath, each osteosarcoma case was treated as a project. All H&E slides from the entire representative slice of osteosarcoma were scanned into WSIs and imported into a project in Qupath. The regions of tumor and tumor necrosis were annotated, and their areas were measured in Qupath. In order to measure the osteosarcoma treatment effect, we needed to calculate the percentage of total necrosis area over total tumor area. We developed a tool that can automatically extract all values of tumor and necrosis areas from a Qupath project into an Excel file, sum these values for necrosis and whole tumor respectively, and calculate necrosis/tumor percentage. Conclusion: Our method that combines WSI with Qupath can provide an objective measurement to facilitate pathologist's assessment of osteosarcoma response to treatment. The proposed approach can also be used for other types of tumors that have clinical need for post-treatment response assessment. [ABSTRACT FROM AUTHOR]

Recent studies have shown that MRI demonstrates promising results for evaluating the chemotherapy efficacy in bone sarcomas. This article reviews current methods for evaluating the efficacy of malignant bone tumors and the application of MRI in this area, and emphasizes the advantages and limitations of each modality. Level of Evidence: 5 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Abstract Background The development of drug resistance and high mortality rates are the major problems observed in non-small cell lung cancer (NSCLC). Biomarkers indicating and predicting disease development towards these unfavorable directions are therefore on high demand. Many studies have demonstrated that changes in miRNAs expression may be associated with a response to treatment and disease prognosis, thus suggesting its potential biomarker value for a broad spectrum of clinical applications. The aim of the present study was to investigate the expression level of miR-181a-5p, miR-630, and its targets in NSCLC tumor tissue and plasma samples; and to analyze its association with NSCLC patient’s response to treatment and disease prognosis. Methods The study was performed in 89 paired tissue specimens and plasma samples obtained from NSCLC patients who underwent surgical treatment at the Department of Thoracic Surgery and Oncology of the National Cancer Institute. Analysis of miR-181a-5p and miR-630 expression was performed by qRT-PCR using TaqMan miRNA specific primers. Whereas BCL2, LMO3, PTEN, SNAI2, WIF1 expression levels were identified with KAPA SYBR FAST qPCR Kit. Each sample was examined in triplicate and calculated following the 2-ΔΔCt method. When the p-value was less than 0.05, the differences were considered statistically significant. Results It was found that miR-181a-5p and miR-630 expression levels in NSCLC tissue and plasma samples were significantly decreased compared with control samples. Moreover, patients with low miR-181a-5p expression in tumor tissue and plasma had longer PFS rates than those with high miRNA expression. Decreased miR-630 expression in tumor was statistically significantly associated with better NSCLC patients’ OS. In addition, the expression of miR-181a-5p, as well as miR-630 in tumor tissue, are the statistically significant variables for NSCLC patients’ OS. Moreover, in NSCLC patient plasma samples circulating miR-181a-5p can be evaluated as significant independent prognostic factors for OS and PFS. Conclusions Our findings indicate the miR-181a-5p and miR-630 expression levels have the potential to prognose and predict and therefore improve the treatment individualization and the outcome of NSCLC patients. Circulating miR-181a-5p has the potential clinical value as a non-invasive biomarker for NSCLC.

Background: Response to antipsychotics is subject to a wide interindividual variability, due to genetic and non-genetic factors. Several single nucleotide polymorphisms (SNPs) have been associated with response to antipsychotics in genome-wide association studies (GWAS). Polygenic risk scores (PRS) are a powerful tool to aggregate into a single measure the small effects of multiple risk alleles.Materials and methods: We studied the association between a PRS composed of SNPs associated with response to antipsychotics in GWAS studies (PRSresponse) in a real-world sample of patients (N = 460) with different diagnoses (schizophrenia spectrum, bipolar, depressive, neurocognitive, substance use disorders and miscellaneous). Two other PRSs composed of SNPs previously associated with risk of schizophrenia (PRSschizophrenia1 and PRSschizophrenia2) were also tested for their association with response to treatment.Results: PRSresponse was significantly associated with response to antipsychotics considering the whole cohort (OR = 1.14, CI = 1.03–1.26, p = 0.010), the subgroup of patients with schizophrenia, schizoaffective disorder or bipolar disorder (OR = 1.18, CI = 1.02–1.37, p = 0.022, N = 235), with schizophrenia or schizoaffective disorder (OR = 1.24, CI = 1.04–1.47, p = 0.01, N = 176) and with schizophrenia (OR = 1.27, CI = 1.04–1.55, p = 0.01, N = 149). Sensitivity and specificity were sub-optimal (schizophrenia 62%, 61%; schizophrenia spectrum 56%, 55%; schizophrenia spectrum plus bipolar disorder 60%, 56%; all patients 63%, 58%, respectively). PRSschizophrenia1 and PRSschizophrenia2 were not significantly associated with response to treatment.Conclusion: PRSresponse defined from GWAS studies is significantly associated with response to antipsychotics in a real-world cohort; however, the results of the sensitivity-specificity analysis preclude its use as a predictive tool in clinical practice.

Background. Periodontitis is a chronic infectious disease affecting periodontium having multifactorial etiology, can cause significant systemic challengein addition to localized inflammation, tissue damage, and bone resorption. A serological marker of systemic inflammation known as C-reactive protein has been linked to an increased risk for a number of pathological conditions, including cardiovascular diseases. Aim. To estimate levels of serum C-reactive protein in healthy individuals and subjects with periodontal diseases and to compare serum C-reactive protein levels in subjects having periodontal disease pre-operatively & post-operatively. Materials and methods. The study was conducted on 60 subjects age ranging from 35 to 60 years. 30 individuals with healthy periodontium were in group 1 (control group) and the remaining 30 were diagnosed as adult periodontitis were in group 2 (experimental group). Periodontal examination done using gingival index, plaque index, periodontal pocket depth, and Russel's index. CRP levels were examined between group 1 and group 2 and in group 2 between baseline visit before treatment and 2 months after treatment. Results. The findings of this study show a significant connection between periodontal disease and the inflammatory marker CRP in the body, as well as a tendency for a significant decrease in serumCRP levels following periodontitis therapy. At baseline, there was a positive correlation among C-reactive protein, probing pocket depth, and Russell's index. Conclusion. As CRP is a key mediator for cardiovascular disease, an increase in C-reactive protein levels in periodontal diseases suggests a significant connection between periodontitis and cardiovascular diseases. Early periodontal treatment might decrease the severity of cardiovascular disease that already exists. This suggests that periodontal examination should be part of routine practicealong with cardiovascular examination. [ABSTRACT FROM AUTHOR]

Abstract Background The introduction of the novel therapy, Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been effective in improving weight gain in both clinical trials and real-world studies. However, the magnitude of this effect appears to be heterogeneous across patient subgroups. This study aims to identify potential determinants of heterogeneity in weight gain following 6-month ETI therapy. Methods We conducted a multicenter, prospective cohort study enrolling 92 adults with CF at two major CF centers in Italy with follow-up visit at one month and six months from ETI initiation. The treatment’s effect on weight changes was evaluated using mixed effect regression models that included subject-specific random intercepts and fixed effects for potential predictors of treatment response, time and a predictor-by-time interaction term. Results The mean weight gain at six months from the start of treatment was 4.6 kg (95% CI: 2.3–6.9) for the 10 patients with underweight, 3.2 kg (95% CI: 2.3-4.0) for the 72 patients with normal weight, and 0.7 kg (95% CI: -1.6-3.0) for the 10 patients with overweight. After six months of ETI treatment, 8 (80%) of the patients with underweight transitioned to the normal weight category, while 11 (15.3%) of the normal-weight patients became overweight. The major determinants of heterogeneity in weight gain were the baseline BMI and the presence of at least one CFTR residual function mutation, explaining 13% and 8% of the variability, respectively. Conclusions Our results indicate that ETI is highly effective in improving weight gain in underweight subjects with CF. However, our data also suggests the need for close monitoring of excess weight gain to prevent potential cardiometabolic complications.

Background Periodontitis is a chronic infectious disease affecting periodontium having multifactorial etiology, can cause significant systemic challengein addition to localized inflammation, tissue damage, and bone resorption. A serological marker of systemic inflammation known as C-reactive protein has been linked to an increased risk for a number of pathological conditions, including cardiovascular diseases. Aim To estimate levels of serum C-reactive protein in healthy individuals and subjects with periodontal diseases and to compare serum C-reactive protein levels in subjects having periodontal disease pre-operatively & post-operatively. Materials and methods The study was conducted on 60 subjects age ranging from 35 to 60 years. 30 individuals with healthy periodontium were in group 1 (control group) and the remaining 30 were diagnosed as adult periodontitis were in group 2 (experimental group). Periodontal examination done using gingival index, plaque index, periodontal pocket depth, and Russel’s index. CRP levels were examined between group 1 and group 2 and in group 2 between baseline visit before treatment and 2 months after treatment. Results The findings of this study show a significant connection between periodontal disease and the inflammatory marker CRP in the body, as well as a tendency for a significant decrease in serumCRP levels following periodontitis therapy. At baseline, there was a positive correlation among C-reactive protein, probing pocket depth, and Russell’s index. Conclusion As CRP is a key mediator for cardiovascular disease, an increase in C- reactive protein levels in periodontal diseases suggests a significant connection between periodontitis and cardiovascular diseases. Early periodontal treatment might decrease the severity of cardiovascular disease that already exists. This suggests that periodontal examination should be part of routine practicealong with cardiovascular examination.

Background: The development of drug resistance and high mortality rates are the major problems observed in non-small cell lung cancer (NSCLC). Biomarkers indicating and predicting disease development towards these unfavorable directions are therefore on high demand. Many studies have demonstrated that changes in miRNAs expression may be associated with a response to treatment and disease prognosis, thus suggesting its potential biomarker value for a broad spectrum of clinical applications. The aim of the present study was to investigate the expression level of miR-181a-5p, miR-630, and its targets in NSCLC tumor tissue and plasma samples; and to analyze its association with NSCLC patient’s response to treatment and disease prognosis. Methods: The study was performed in 89 paired tissue specimens and plasma samples obtained from NSCLC patients who underwent surgical treatment at the Department of Thoracic Surgery and Oncology of the National Cancer Institute. Analysis of miR-181a-5p and miR-630 expression was performed by qRT-PCR using TaqMan miRNA specific primers. Whereas BCL2, LMO3, PTEN, SNAI2, WIF1 expression levels were identified with KAPA SYBR FAST qPCR Kit. Each sample was examined in triplicate and calculated following the 2-ΔΔCt method. When the p-value was less than 0.05, the differences were considered statistically significant. Results: It was found that miR-181a-5p and miR-630 expression levels in NSCLC tissue and plasma samples were significantly decreased compared with control samples. Moreover, patients with low miR-181a-5p expression in tumor tissue and plasma had longer PFS rates than those with high miRNA expression. Decreased miR-630 expression in tumor was statistically significantly associated with better NSCLC patients’ OS. In addition, the expression of miR-181a-5p, as well as miR-630 in tumor tissue, are the statistically significant variables for NSCLC patients’ OS. Moreover, in NSCLC patient plasma samples circulating miR-181a-5p can be evaluated as significant independent prognostic factors for OS and PFS. Conclusions: Our findings indicate the miR-181a-5p and miR-630 expression levels have the potential to prognose and predict and therefore improve the treatment individualization and the outcome of NSCLC patients. Circulating miR-181a-5p has the potential clinical value as a non-invasive biomarker for NSCLC. [ABSTRACT FROM AUTHOR]

Simple Summary: Neoadjuvant immunochemotherapy (NICT) has demonstrated impressive short-term efficacy, with over half of patients experiencing significant tumor shrinkage and achieving major pathological responses (MPR). These findings highlight the pressing need for further investigation into strategies for organ preservation and radiotherapy adjustments in patients who achieve MPR. Our objective was to utilize non-invasive and accessible clinical assessments to predict pathological response before surgery. By employing enhanced CT scans, esophagograms, and esophagoscopy before and after neoadjuvant treatment, we collected objective and quantitative parameters that reflected the dynamic shrinkage of tumors. Subsequently, we constructed prediction models for pathological response using multivariate logistic regression based on those dynamic parameters. These models accurately predicted pathologic complete response (pCR) (AUC 0.879) and MPR (AUC 0.912) of the primary tumor after neoadjuvant immunochemotherapy. This advancement may significantly aid informed decision-making in patient management. To develop accurate and accessible prediction methods for assessing pathologic response following NICT prior to surgery, we conducted a retrospective study including 137 patients with esophageal squamous cell carcinoma (ESCC) who underwent surgery after two cycles of NICT between January 2019 and March 2022 at our center. We collected clinical parameters to evaluate the dynamic changes in the primary tumor. Univariate and multivariate analyses were performed to determine the correlations between these parameters and the pathologic response of the primary tumor. Subsequently, we constructed prediction models for pCR and MPR using multivariate logistic regression. The MPR prediction Model 2 was internally validated using bootstrapping and externally validated using an independent cohort from our center. The univariate logistic analysis revealed significant differences in clinical parameters reflecting tumor regression among patients with varying pathologic responses. The clinical models based on these assessments demonstrated excellent predictive performance, with the training cohort achieving a C-index of 0.879 for pCR and 0.912 for MPR, while the testing cohort also achieved a C-index of 0.912 for MPR. Notably, the MPR prediction Model 2, with a threshold cut-off of 0.74, exhibited 92.7% specificity and greater than 70% sensitivity, indicating a low rate of underestimating residual tumors. In conclusion, our study demonstrated the high accuracy of clinical assessment-based models in pathologic response prediction, aiding in decision-making regarding organ preservation and radiotherapy adjustments after induction immunochemotherapy. [ABSTRACT FROM AUTHOR]

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Background: The conventional treatment for patients with locally advanced colorectal tumors is preoperative chemo-radiotherapy (PCRT) preceding surgery. This treatment strategy has some long-term side effects, and some patients do not respond to it. Therefore, an evaluation of biomarkers that may help predict patients' response to PCRT is essential. Methods: We took advantage of genetic algorithm to search the space of possible combinations of features to choose subsets of genes that would yield convenient performance in differentiating PCRT responders from non-responders using a logistic regression model as our classifier. Results: We developed two gene signatures; first, to achieve the maximum prediction accuracy, the algorithm yielded 39 genes, and then, aiming to reduce the feature numbers as much as possible (while maintaining acceptable performance), a 5-gene signature was chosen. The performance of the two gene signatures was (accuracy = 0.97 and 0.81, sensitivity = 0.96 and 0.83, and specificity = 86 and 0.77) using a logistic regression classifier. Through analyzing bias and variance decomposition of the model error, we further investigated the involved genes by discovering and validating another 28-gene signature which possibly points towards two different sub-systems involved in the response of the patients to treatment. Conclusions: Using genetic algorithm as our gene selection method, we have identified two groups of genes that can differentiate PCRT responders from non-responders in patients of the studied dataset with considerable performance. Impact: After passing standard requirements, our gene signatures may be applicable as a robust and effective PCRT response prediction tool for colorectal cancer patients in clinical settings and may also help future studies aiming to further investigate involved pathways gain a clearer picture for the course of their research. [ABSTRACT FROM AUTHOR]

Pustular psoriasis is characterised by eruptions of neutrophilic sterile pustules. The European Rare and Severe Psoriasis Expert Network consensus defines pustular psoriasis into three subtypes; generalised pustular psoriasis (GPP), palmoplantar pustulosis and acrodermatitis continua of Hallopeau (ACH). Mixed forms are categorised according to their predominant features. However, the Japanese Dermatological Association includes ACH under the diagnosis of GPP. This article aims to review the similarities and differences between ACH and GPP. Based on our review, interleukin (IL)‐36RN mutations, the most frequent genetic findings in pustular psoriasis are found most commonly in GPP, followed by ACH. Genotypes of IL‐36RN mutations among GPP patients and ACH patients are different between European and Asian ethnicities. IL‐36 signalling pathway is the main mechanism. Metabolic diseases are common comorbidities and joint involvement can occur in 20.5%–36.4% of both conditions. Associated plaque psoriasis is more common in GPP than in ACH. Generally, ACH, even the generalised type, does not have systemic inflammation whereas GPP can occur with or without systemic inflammation. ACH can occur before, simultaneously, or after the development of GPP. However, response to treatment for GPP and ACH even in the same patients appear to be different. ACH seemed to be more recalcitrant to treatment than GPP but severe flare of GPP can lead to morbidity and mortality. Although GPP and ACH share genotypes and pathogenesis, we believe that ACH should be classified separately from GPP, and not under diagnosis of GPP. Future research is warranted to satisfactorily distinguish the two conditions. [ABSTRACT FROM AUTHOR]

Hypersensitivity pneumonitis (HP) is an exposure-related interstitial lung disease with two phenotypes—fibrotic and non-fibrotic. Genetic predisposition is an important factor in the disease pathogenesis and fibrosis development. Several genes are supposed to be associated with the fibrosing cascade in the lungs. One of the best-recognized and most prevalent is the common MUC5B gene promoter region polymorphism variant rs35705950. The aim of our study was to establish the frequency of the minor allele of the MUC5B gene in the population of patients with HP and to find the relationship between the MUC5B promoter region polymorphism and the development of lung fibrosis, the severity of the disease course, and the response to the treatment in patients with HP. Eighty-six consecutive patients with HP were tested for the genetic variant rs35705950 of the MUC-5B gene. Demographic, radiological, and functional parameters were collected. The relationship between the presence of the T allele and lung fibrosis, pulmonary function test parameters, and the treatment response were analyzed. The minor allele frequency in the study group was 17%, with the distribution of the genotypes GG in 69.8% of subjects and GT/TT in 30.2%. Patients with the GT/TT phenotype had significantly lower baseline forced vital capacity (FVC) and significantly more frequently had a decline in FVC with time. The prevalence of lung fibrosis in high-resolution computed tomography (HRCT) was not significantly increased in GT/TT variant carriers compared to GG ones. The patients with the T allele tended to respond worse to immunomodulatory treatment and more frequently received antifibrotic drugs. In conclusions: The frequency of MUC5B polymorphism in HP patients is high. The T allele may indicate a worse disease course, worse immunomodulatory treatment response, and earlier need for antifibrotic treatment. [ABSTRACT FROM AUTHOR]

Background & aimsWe created and validated a clinical decision support tool (CDST) to predict outcomes of vedolizumab therapy for ulcerative colitis (UC).MethodsWe performed logistic regression analyses of data from the GEMINI 1 trial, from 620 patients with UC who received vedolizumab induction and maintenance therapy (derivation cohort), to identify factors associated with corticosteroid-free remission (full Mayo score of 2 or less, no subscore above 1). We used these factors to develop a model to predict outcomes of treatment, which we called the vedolizumab CDST. We evaluated the correlation between exposure and efficacy. We validated the CDST in using data from 199 patients treated with vedolizumab in routine practice in the United States from May 2014 through December 2017.ResultsAbsence of exposure to a tumor necrosis factor (TNF) antagonist (+3 points), disease duration of 2 y or more (+3 points), baseline endoscopic activity (moderate vs severe) (+2 points), and baseline albumin concentration (+0.65 points per 1 g/L) were independently associated with corticosteroid-free remission during vedolizumab therapy. Patients in the derivation and validation cohorts were assigned to groups of low (CDST score, 26 points or less), intermediate (CDST score, 27-32 points), or high (CDST score, 33 points or more) probability of vedolizumab response. We observed a statistically significant linear relationship between probability group and efficacy (area under the receiver operating characteristic curve, 0.65), as well as drug exposure (P < .001) in the derivation cohort. In the validation cohort, a cutoff value of 26 points identified patients who did not respond to vedolizumab with high sensitivity (93%); only the low and intermediate probability groups benefited from reducing intervals of vedolizumab administration due to lack of response (P = .02). The vedolizumab CDST did not identify patients with corticosteroid-free remission during TNF antagonist therapy.ConclusionsWe used data from a trial of patients with UC to develop a scoring system, called the CDST, which identified patients most likely to enter corticosteroid-free remission during vedolizumab therapy, but not anti-TNF therapy. We validated the vedolizumab CDST in a separate cohort of patients in clinical practice. The CDST identified patients most likely to benefited from reducing intervals of vedolizumab administration due to lack of initial response. ClinicalTrials.gov no: NCT00783718.

Background: India ranks first in the global share of tuberculosis (TB). Active TB is also associated with elevated levels of B-Cell growth factors like B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). We aimed to study the circulating levels of ferritin, high-sensitivity C-reactive protein (hsCRP), BAFF, and APRIL in sputum-positive and sputum-negative active pulmonary TB (PTB) patients. Materials and Methods: We enrolled 90 sputum positive and 90 sputum-negative newly diagnosed PTB patients. All the patients underwent estimation of serum ferritin, hsCRP, BAFF, and APRIL before initiation of f Anti-Tubercular therapy (ATT), after 1 month of ATT, and after 2 months of ATT. We compared the change in the cytokines mentioned above in PTB subjects at baseline, after 01 and 02 months of the intensive phase of standard anti-tubercular therapy. Results: There was a significant difference between the serum BAFF levels at all times between the sputum-positive and sputum-negative groups (P < 0.001). There was a considerable increase in the APRIL level 2 months after initiation of ATT in both the groups (sputum positive group P = 0.004) (sputum negative group P < 0.001). There was a significant decrease in serum ferritin level and hsCRP after 2 months of ATT compared to baseline (P < 0.001) in both sputum positive and negative groups. Conclusion: Serum ferritin, hsCRP, and APRIL levels can be used to assess the treatment response in both sputum-positive and sputum-negative cases. Serum BAFF levels >587 pg/ml at baseline implies high probability of sputum smear positivity in a patient with PTB.

Introduction. Cancer mortality in diabetic patients has been reported to increase moderately compared to non-diabetic patients. The aim of the study aimed to assess the findings and identify radiotherapy's role in the comprehensive care of diabetic IBC patients with various hyperglycemia correction strategies. Methods. Patients with diabetes have shown a higher risk of radiation-induced cancer progression for tumor tissue, especially for inflammatory form. For 7 patients, to continue systematic chemotherapy with a scheme change (consecutive anthracyclines-taxanes, 2-week interval) and insulin with individual scheme for hyperglycemia correction on the basis of glycemic control – 1st group, the other (7 patients) – 2nd group, was given radiotherapy to the breast gland and lymphatic drainage ways. 45–50 Grey was prescribed for 25-28 fractions (per 1.8-2.0 Grey), 46–50 Grey in 23-25 fractions were used for zones of regional metastasis and for hyperglycemia correction metformin 2000 mg/day PO divided q8-12hr with meal on the basis of glycemic control. Results. Assessed were the number of patients who qualified for surgery and overall survival for 24 months. 2nd group showed a superior response following resistance to prior systemic treatment. Thus, 5 (71.41%) of the 7 patients exhibited a consistent response – complete or partial regression. There were only 2 individuals (28.61%) who responded to treatment among the patients who maintained chemotherapy. Conclusions. Breast cancer of the aggressive IBC variety requires multidisciplinary treatment from breast surgery, medical, and radiation oncology. Patients with diabetes appear to experience more side effects from radiation therapy than patients without the disease. Hyperglycemia, higher total RT doses, and radiosensitizers are a few techniques that can improve the impact of RT on local-regional management. Local-regional control rates for IBC are increasing with an individual patient strategy. Metformin also improves insulin resistance and has anticancer benefits.

Background: The introduction of the novel therapy, Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been effective in improving weight gain in both clinical trials and real-world studies. However, the magnitude of this effect appears to be heterogeneous across patient subgroups. This study aims to identify potential determinants of heterogeneity in weight gain following 6-month ETI therapy. Methods: We conducted a multicenter, prospective cohort study enrolling 92 adults with CF at two major CF centers in Italy with follow-up visit at one month and six months from ETI initiation. The treatment's effect on weight changes was evaluated using mixed effect regression models that included subject-specific random intercepts and fixed effects for potential predictors of treatment response, time and a predictor-by-time interaction term. Results: The mean weight gain at six months from the start of treatment was 4.6 kg (95% CI: 2.3–6.9) for the 10 patients with underweight, 3.2 kg (95% CI: 2.3-4.0) for the 72 patients with normal weight, and 0.7 kg (95% CI: -1.6-3.0) for the 10 patients with overweight. After six months of ETI treatment, 8 (80%) of the patients with underweight transitioned to the normal weight category, while 11 (15.3%) of the normal-weight patients became overweight. The major determinants of heterogeneity in weight gain were the baseline BMI and the presence of at least one CFTR residual function mutation, explaining 13% and 8% of the variability, respectively. Conclusions: Our results indicate that ETI is highly effective in improving weight gain in underweight subjects with CF. However, our data also suggests the need for close monitoring of excess weight gain to prevent potential cardiometabolic complications. Highlights: We reported heterogeneity in weight gain after 6 months of treatment with ETI. Baseline BMI and CFTR genotype predict heterogeneity in treatment response. People with underweight received the greatest benefit from ETI treatment. An amount of 15% of normal-weight subjects became overweight. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: In patients with low-risk differentiated thyroid cancer (DTC), remnant ablation with radioiodine (RA) after total thyroidectomy (TT) is controversial. No benefits have been demonstrated in terms of mortality or disease-free survival. Recent evidence found that RA did not improve mid-term outcomes. Purpose: To evaluate initial response to treatment and long-term follow-up status in low-risk DTC patients after TT vs. TT + RA with 131I 1.11 GBq (30 mCi). Methods: Prospective multicenter non-randomized study; 174 low-risk DTC that underwent TT were recruited an divided in two groups according to RA (87 ablated and 87 non-ablated). Response to treatment was evaluated at 6–18 months after thyroidectomy and at the end of follow-up with measurements of thyroglobulin, and anti-thyroglobulin antibodies levels, and neck ultrasonography. Results: Baseline characteristics of both groups were similar. Ablated patients: median age 45.5 years, 84% females, 95.4% papillary thyroid carcinoma (PTC), mean tumor size 16 mm; non-ablated: median age 45 years, 88.5% females, 96.6% PTC, mean tumor size 14 mm. Response to initial treatment was similar between both groups, with < 2% of structural incomplete response. Final status was evaluated in 139 cases (median follow-up of 60 months). Among ablated patients, 82.8% had no evidence of disease (NED), 12% had an indeterminate response (IR) and 5% a biochemical incomplete response (BIR). Non-ablated patients had NED in 90%, IR in 8.7% and BIR in 1.2%. No statistical difference was found between groups (p = 0.29). No patient had evidence of structural disease at the end of follow-up. Conclusions: Our findings support the recommendation against routine RA in low-risk DTC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors (ICIs) offer high efficacy of cancer treatment, but their use is limited to a subset of patients who respond well to the resetting of the immune system. To attempt to identify patients and predict response to ICI, tumour-based biomarkers such as PD-L1 expression or mutational tumour burden have been widely used but proved to be of insufficient accuracy. Here, we have deployed epigenetic profiling that detects specific chromosome conformations in the blood of the patients. It has been successfully used for predictive and prognostic applications. In this study, we developed and validated blood biomarkers for a checkpoint inhibitor response test that offers a significant increase in the accuracy of predicting positive response to ICI across multiple oncological indications. This new test is accurate, rapid, and minimally invasive. It could assist in treatment decisions, help to improve patient selection, and more efficiently manage costs. Background: Unprecedented advantages in cancer treatment with immune checkpoint inhibitors (ICIs) remain limited to only a subset of patients. Systemic analyses of the regulatory 3D genome architecture linked to individual epigenetic and immunogenetic controls associated with tumour immune evasion mechanisms and immune checkpoint pathways reveal a highly prevalent molecular profile predictive of response to PD-1/PD-L1 ICIs. A clinical blood test based on a set of eight (8) 3D genomic biomarkers has been developed and validated on the basis of an observational trial to predict response to ICI therapy. Methods: The predictive eight biomarker set is derived from prospective observational clinical trials, representing 280 treatments with Pembrolizumab, Atezolizumab, Durvalumab, Nivolumab, and Avelumab in a broad range of indications: melanoma, lung, hepatocellular, renal, breast, bladder, colon, head and neck, bone, brain, lymphoma, prostate, vulvar, and cervical cancers. Results: The 3D genomic eight biomarker panel for response to immune checkpoint therapy achieved a high accuracy of 85%, sensitivity of 93%, and specificity of 82%. Conclusions: This study demonstrates that a 3D genomic approach can be used to develop a predictive clinical assay for response to PD-1/PD-L1 checkpoint inhibition in cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer (EC) is one of the most common gynecological malignancies. Therefore, it is of great clinical importance to identify potential candidates for diagnostic and prognostic biomarkers in order to identify high-risk patients and obtain a more accurate prognosis in a timely manner. MicroRNAs (miRs) are small single-stranded RNAs that regulate gene expression and play a role in all steps of cancer development. The miRs expressed in endometrial tumor tissue are probably involved in cell proliferation and differentiation, apoptosis, and carcinogenesis. We reviewed the literature to identify potential miRs that may function as diagnostic, prognostic, or response to treatment markers in EC. In developed countries, endometrial cancer (EC) is one of the most common neoplasms of the female reproductive system. MicroRNAs (miRs) are a class of single-stranded noncoding RNA molecules with lengths of 19–25 nucleotides that bind to target messenger RNA (mRNA) to regulate post-transcriptional gene expression. Although there is a large amount of research focused on identifying miRs with a diagnostic, prognostic, or response to treatment capacity in EC, these studies differ in terms of experimental methodology, types of samples used, selection criteria, and results obtained. Hence, there is a large amount of heterogeneous information that makes it difficult to identify potential miR biomarkers. We aimed to summarize the current knowledge on miRs that have been shown to be the most suitable potential markers for EC. We searched PubMed and Google Scholar without date restrictions or filters. We described 138 miRs with potential diagnostic, prognostic, or treatment response potential in EC. Seven diagnostic panels showed higher sensitivity and specificity for the diagnosis of EC than individual miRs. We further identified miRs up- or downregulated depending on the FIGO stage, precursor lesions, and staging after surgery, which provides insight into which miRs are expressed chronologically depending on the disease stage and/or that are modulated depending on the tumor grade based on histopathological evaluation. [ABSTRACT FROM AUTHOR]

For people with psoriasis, biomarkers aiding in the personalization of treatment with biologics are needed. We examined the usefulness of several biomarkers of inflammation in this respect. The neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the systemic immune–inflammation index (SII) were measured in patients with psoriasis initiating TNF-α inhibitors (n = 131), IL-17/IL-17R inhibitors (n = 65), or IL-23/IL-12/23 inhibitors (n = 50). The blood levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)-γ, IL-17A, IL-6, soluble IL-6 receptor (sIL-6R), and soluble IL-6 signal transducer (sIL-6ST) were measured in patients initiating adalimumab (n = 62) or IL-17/IL-17R inhibitors (n = 24). Treatment response was defined by a psoriasis area and severity index (PASI) ≤ 2 three months after treatment initiation. Responders to TNF-α inhibitors had a lower NLR at baseline than non-responders (median and interquartile range (IQR) 2.15 (1.67–2.86) vs. 2.54 (1.88–3.55); p = 0.04). Responders to treatment with adalimumab had lower IL-6 levels at baseline than non-responders (0.99 (0.42–1.4) vs. 1.62 (0.96–2.41) pg/mL; p = 0.02). For the majority of patients, the IL-17A, IL-1β, and IFN-γ levels were below quantification limits. NLR and IL-6 may serve as predictive biomarkers of treatment response to TNF-α inhibitor therapy in patients with psoriasis. [ABSTRACT FROM AUTHOR]

A complex series of studies by Oelschlegel et al. in a murine model of cerebral malaria establishes a temporal sequence of events linking decreased venous efflux to impaired perfusion, edema, and neuroinflammation. The relevance to human cerebral malaria is discussed, including the heterogeneity recognized in recent investigations of cerebrovascular hemodynamics. [ABSTRACT FROM AUTHOR]

IntroductionTreatment of brain tumors in dogs can be associated with significant morbidity and reliable prognostic factors are lacking. Dynamic contrast-enhanced computed tomography (DCECT) can be used to assess tumor perfusion. The objectives of this study were to assess perfusion parameters and change in size of suspected brain tumors before and during radiotherapy (RT) depending on their location and find a potential correlation with survival.MethodsSeventeen client-owned dogs with suspected brain tumors were prospectively recruited. All dogs had a baseline DCECT to assess mass size, blood volume (BV), blood flow (BF), and transit time (TT). Twelve dogs had a repeat DCECT after 12 Gy of megavoltage RT. Survival times were calculated.ResultsIntra-axial masses had lower BF (p = 0.005) and BV (p