Baseline Depressive Symptoms as a Predictor of Incident Dementia in a Prospectively Followed Cohort of Elders with Essential Tremor.

INTRODUCTION: Essential tremor (ET) patients may exhibit a variety of non-motor features, including cognitive decline and depressive symptoms. Studies of several neurodegenerative diseases link depression to cognitive decline, suggesting depression is an early marker of dementia. We examined whether baseline depressive symptoms predict incident dementia in elders with ET. METHODS: Hundred and forty-one ET cases aged 70 years or older at baseline, enrolled in a prospective study of cognitive performance, took part in evaluations at baseline and at 18, 36, 54, and 72 months. Participants completed the Geriatric Depression Scale (GDS), a 30-item self-report measure of depressive symptoms, and a battery of neuropsychological tests and functional assessments, from which we derived cognitive diagnoses at each evaluation. Cox proportional hazards regression equations determined incident dementia risk based on participants' baseline depression scores. RESULTS: Mean baseline age was 81.5 ± 6.7 years. Higher baseline GDS scores were associated with increased risk of dementia in an unadjusted model (hazards ratio [HR] = 1.11, 95% confidence interval [CI] = 1.02-1.20, p = 0.01) and after controlling for baseline age, education, number of medications, and tremor onset age (HR = 1.13, 95% CI = 1.02-1.25, p = 0.02). CONCLUSION: Baseline depression scores predicted incident dementia in elders with ET. With each one-point increase in baseline depression score, there was a 13% increase in incident dementia risk. Given the published data that reported depression may be twice as high in elders with ET compared to controls, this association is particularly worrisome in the ET population.

Using clinician and patient input to assess utility, accuracy, efficiency, and therapeutic implementation of a new data-driven digital therapeutic for personalized clinical eating disorder treatment: Awaken digital guide.

OBJECTIVE: Eating disorders (EDs) take a life every 52 minutes and treatments are ineffective for ∼50% of individuals. Though EDs are heterogeneous illnesses, current evidence-based treatments take a "one-size-fits-all" approach. Network-Informed Personalized Treatment is a new promising treatment for EDs, but clinician-patient-friendly software tools are needed to integrate this guidance system into routine treatment. Adoption is key for impact, necessitating the inclusion of clinicians in the software development. The current pilot assessed a new data-driven clinician-guidance therapeutic. METHOD: A two-part pilot was analyzed for quantitative (0-not at all to 10-extremely) and qualitative input on user perception through quantitative and open-ended prompted questions evaluating using personalizing ED treatment with the Awaken Digital Guide therapeutic. RESULTS: Results demonstrated that clinicians in a focus group (N = 9) and clinician/patient dyads within implementation (N = 10) endorsed improved efficiency, effectiveness, self-awareness, and accuracy using Awaken Digital Guide compared to current treatment as suggested by quantitative and qualitative results. Both clinicians and patients rated the tool positively (6.8-9.6/5.8-8.6, respectively) with an average rating of good and excellent. CONCLUSION: Findings suggest that ED-specialized clinicians desire data-driven guidance on personalizing ED treatment. Users perceive Awaken Digital Guide therapeutic with potential to increase collaboration, motivation, efficiency, and effectiveness of ED personalized treatment.

LncRNA MRPL39 inhibits cell proliferation and migration by regulating miR-130/TSC1 axis in non-small cell lung cancer.

Currently, the effect of miR-130 on non-small cell lung cancer (NSCLC) remains controversial. In this study, the expression of miR-130 and lncRNA MRPL39 in tumor and non-tumor tissues of NSCLC patients was examined using real-time PCR (RT-PCR) and correlated with the prognosis of NSCLC. The phenotypic effects of miR-130 and MRPL39 on proliferation and migration of NSCLC cell line A549 cells were assessed through CCK-8 and Transwell assays with miR-130 mimic and MRPL39 (mitochondrial ribosomal protein L39) overexpressed plasmid transfection. StarBase/TargetScan analysis and dual-luciferase reporter gene assays were conducted to investigate the relationship between MRPL39, miR-130, and Tuberculosis sclerosis 1 (TSC1). MiR-130 was overexpressed, and MRPL39 was downregulated in NSCLC tissues and cells. Inhibition of miR-130 expression and overexpression of MRPL39 resulted in the inhibition of the viability and migration of A549 cells. MRPL39 is a potential upstream regulatory long non-coding RNA of miR-130, and its expression is negatively regulated by miR-130. TSC1 was identified as a target of miR-130, suppressing the antitumor effects of FGD5-AS1 silencing on GBM cells. After overexpression of MRPL39, the mRNA and protein levels of TSC1 in A549 cells significantly increased. However, after transfection with miR-130 mimic, the up-regulation of mRNA and protein was inhibited, leading to the suppression of cell proliferation and migration.

Fasting plasma lactate as a possible early clinical marker for metabolic disease risk.

BACKGROUND AND AIM: Elevated fasting plasma lactate concentrations are evident in individuals with metabolic diseases. However, it has yet to be determined if these associations exist in a young, healthy population as a possible early marker for metabolic disease risk. The purpose of this study was to determine if indices of the metabolic syndrome are related to plasma lactate concentrations in this population. METHODS: Fifty (29 ± 7 yr) men (n = 19) and women (n = 31) classified as overweight (26.4 ± 1.8 kg/m2) participated in this observational study. Blood pressure and blood metabolites were measured after an overnight fast. Lactate was also measured before and after a three-day eucaloric high-fat (70 %) diet. The homeostatic model assessment for insulin resistance (HOMA-IR) was calculated as a measure of insulin resistance. Visceral adipose tissue mass was determined via dual X-ray absorptiometry. RESULTS: Triglycerides (r = 0.55, p=<0.0001), HOMA-IR (r = 0.53, p=<0.0001), and systolic and diastolic (both, r = 0.36, p = 0.01) blood pressures associated with fasting plasma lactate. No differences in visceral adipose tissue existed between the sexes (p = 0.41); however, the relationship between visceral adipose tissue and lactate existed only in females (r = 0.59, p = 0.02) but not in males (p = 0.53). Fasting lactate and HOMA-IR increased in males (p = 0.01 and p = 0.02, respectively), but not females, following a three-day high-fat diet. CONCLUSION: Indices of the metabolic syndrome associated with fasting plasma lactates in young relatively healthy individuals. Fasting lactate also increased in a sex-specific manner after a three-day high fat diet. Thus, lactate could become a clinical marker for metabolic disease risk.

High-sensitivity immunoassay on interdigitated electrode to detect osteoporosis biological marker.

Osteoporosis is with porous bones, which refers to a decrease in the bone mineral density and weakens the bones to become brittle. Osteoporosis often progresses without any pain or symptoms until the bone fractures. Monitoring the condition of bone regularly helps to identify the bone that weakens at its earlier stages. In general, radiological techniques have been used to measure bone mineral density, are expensive, and the procedures are complicated. Therefore, researchers are focusing on the alternative method of biomarker quantification to identify bone mineral density. This research work was focused on quantifying the osteoporosis biomarker of C-terminal telopeptide of type I collagen (CTX-I) on an interdigitated electrode (IDE) sensor. Gold nanomaterial-modified anti-CTX-I antibody was attached to silica nanomaterial-decorated IDE and then identified by CTX-I interaction. Higher immobilization of antibodies was recorded on diamond-modified IDE through gold nanoparticles, and detected CTX-I as low as 0.5 pg/mL [y = 1.5507x - 0.9043 R2 = 0.9715], determined on a linear curve at the range 0.5-3.5 ng/mL. Further, specific identification of CTX-I was confirmed by control performances with osteopontin, IL-6, and anti-IgG antibody.

Glutathionyl Hemoglobin and Its Emerging Role as a Clinical Biomarker of Chronic Oxidative Stress.

Hemoglobin is one of the proteins that are more susceptible to S-glutathionylation and the levels of its modified form, glutathionyl hemoglobin (HbSSG), increase in several human pathological conditions. The scope of the present review is to provide knowledge about how hemoglobin is subjected to S-glutathionylation and how this modification affects its functionality. The different diseases that showed increased levels of HbSSG and the methods used for its quantification in clinical investigations will be also outlined. Since there is a growing need for precise and reliable methods for markers of oxidative stress in human blood, this review highlights how HbSSG is emerging more and more as a good indicator of severe oxidative stress but also as a key pathogenic factor in several diseases.

Apelin/APJ system protects placental trophoblasts from hypoxia-induced oxidative stress through activating PI3K/Akt signaling pathway in preeclampsia.

BACKGROUND: Preeclampsia is a placentally induced syndrome with diverse clinical presentation that currently has no cure. Oxidative stress is a potent inducer of placental dysfunction. The apelin receptor (APJ) system is a pleiotropic pathway with a potential for therapeutic targeting in preeclampsia. This study examines the alteration of circulating apelin levels and placental APJ expression in preeclampsia and investigates whether apelin/APJ system can protect placental trophoblast from hypoxia-induced oxidative stress injury through PI3K/AKT signaling pathway. RESULTS: Our results confirmed that maternal apelin concentration was increased in women with preeclampsia, but APJ expression was reduced in the preeclamptic placentas. Apelin-13 treatment not only specifically attenuated CoCl2-induced superoxide production, but also prevented CoCl2-induced reduction of SOD activity and SOD1 expression. In addition, apelin-13 suppressed CoCl2-induced apoptosis by increasing the expression of bcl-2/bax ratio and by decreasing the expression of active caspase-3 in placental trophoblasts. Furthermore, we found that apelin-13 binding APJ activated the PI3K and AKT kinases and inhibition of PI3K kinase significantly blocked the anti-oxidative effects of apelin-13 in placental trophoblasts. CONCLUSIONS: Decrease of placental APJ expression is associated with oxidative stress-induced placental dysfunction in preeclampsia, and increased circulating apelin could be a moderately successful marker to differentiate subjects with preeclampsia from healthy pregnant women. Inhibition of superoxide production and caspase-3 cleavage, together with upregulation of SOD activity/expression and bcl-2/bax ratio, could be the potential molecular mechanisms by which apelin-13/APJ protects placental trophoblasts from oxidative stress injury.

Thrombophilic gene polymorphisms and recurrent pregnancy loss: a systematic review and meta-analysis.

PURPOSE: Recurrent pregnancy loss (RPL) is affecting 1-4% of women who conceive approximately, and no cause could be found in more than 50% of women suffering from RPL. Inherited thrombophilias have got increasing attention in women with unexplained RPL, so we aim to explore the relationship among these most common thrombophilic polymorphisms and RPL through a literature review and meta-analysis. METHODS: Observational studies from PubMed, Embase, Cochrane, and Web of Science from 1997 to 7 April 2022 were searched. For each genetic variant, a fixed or random-effect model was used according to the heterogeneity test to calculate pooled ORs and 95% CIs for both dominant and recessive genetic models. Egger's line regression test was used to assess publication bias. The quality of the included articles was assessed by the Newcastle Ottawa scale. RESULTS: A total of 124 articles comprising 17,278 RPL patients and 16,021 controls were included. Results showed that hyperhomocysteinemia (MTHFR) C677T (dominant model: OR, 1.43; 95% CI, 1.25-1.64; recessive model: OR, 1.60; 95% CI, 1.36-1.87), MTHFR A1298C (dominant model: OR, 1.66; 95% CI, 1.26-2.18; recessive model: OR, 1.79; 95% CI, 1.42-2.26), PAI-1 4G/5G (dominant model: OR, 1.67; 95% CI, 1.36-2.06; recessive model: OR, 1.80; 95% CI, 1.39-2.32), angiotensin-converting enzyme I/D (OR, 1.23; 95% CI, 1.00-1.53), Factor XIII V34L (OR, 1.38; 95% CI, 1.02-1.87), and ß-fibrinogen-455G/A (OR, 1.60; 95% CI, 1.02-2.51) were significantly associated with RPL. CONCLUSION: This study provides potentially useful clinical markers to evaluate the risk of RPL or to help unexplained RPL patients identify possible causes, which may allow for targeted treatment.

Developmental language disorder in Chinese children: A systematic review of research from 1997 to 2022.

Developmental language disorder (DLD) is one of the most common neurodevelopmental disorders. The influences of DLD on language development have been delineated in detail in English. The same is not true for Chinese, a group of Sinitic languages with distinct typological features that may modify the profile of DLD crosslinguistically. We conducted a systematic search of English and Chinese journal databases and reviewed 59 studies on the manifestations of DLD in Chinese. Methodological quality appraisal of the literature revealed several areas of improvement to enhance transparency and replicability. A bibliometric analysis indicated a steep growth trajectory of this literature. Examination of the participant selection and diagnostic criteria revealed limitations and calls for the development of assessment tools and increased knowledge of evidenced-based diagnostic practice. Areas of deficits demonstrated by Chinese children with DLD were synthesized qualitatively and discussed in light of the literature on clinical markers of DLD in English.

Immune-related adverse events correlate with the efficacy of PD-1 inhibitors combination therapy in advanced cholangiocarcinoma patients: A retrospective cohort study.

Background: Whether irAEs can predict the efficacy of PD-1 inhibitors in cholangiocarcinoma (CCA) has not been assessed. Therefore, this study aims to investigate the correlation between irAEs and the therapeutic effect of PD-1 inhibitors combination therapy in patients with advanced CCA. Methods: All patients with CCA who were consecutively admitted to the inpatient unit of our hospital and received PD-1 inhibitors combination therapy between September 2020 and April 2022 were screened. In total, 106 patients with CCA were screened out. We then followed up these patients until October 2022. Due to perioperative use (n=28), less than 2 cycles of PD-1 inhibitor therapy (n=9), incomplete data (n=8) and no pathological report (n=2), 59 patients were included in the final analysis. The patients were divided into the irAEs cohort and the non-irAEs cohort according to whether they experienced irAEs or not. The Log-Rank test was performed to compare the difference in survival time between these two cohorts. We then applied multivariate COX regression analysis to investigate whether irAEs were independent prognostic factors for survival in patients with advanced CCA. Results: Finally, 32 patients were included in the irAEs cohort and 27 patients in the non-irAEs cohort. A total of 32 patients (54.2%) had any-grade irAEs, of which 4 patients (6.8%) had grade 3-4 irAEs. The most common irAEs were thyroid toxicity (30.5%) and dermatologic toxicity (30.5%). There were no notable differences in demographics and clinical characteristics between the irAEs and non-irAEs cohorts, except for total bilirubin level (P=0.026) and relapse (P=0.016). The disease control rate (DCR) in the irAEs cohort was higher than in the non-irAEs cohort (90.6% vs 70.4%, P=0.047). Median overall survival (OS) and median progression-free survival (PFS) were better in the irAEs cohort than in the non-irAEs cohort (OS: 21.2 vs 10.0 months, P<0.001; PFS: 9.0 vs 4.4 months, P=0.003). Multivariate COX regression analysis showed that irAEs were independent prognostic factors for OS and PFS (OS: HR=0.133, 95% CI: 0.039-0.452, P=0.001; PFS: HR=0.435, 95% CI: 0.202-0.934, P=0.033). Conclusion: IrAEs correlated with improved DCR, OS, and PFS in advanced CCA patients receiving PD-1 inhibitors combination therapy.

Tackling hypo and hyper sensory processing heterogeneity in autism: From clinical stratification to genetic pathways.

As an integral part of autism spectrum symptoms, sensory processing issues including both hypo and hyper sensory sensitivities. These sensory specificities may result from an excitation/inhibition imbalance with a poorly understood of their level of convergence with genetic alterations in GABA-ergic and glutamatergic pathways. In our study, we aimed to characterize the hypo/hyper-sensory profile among autistic individuals. We then explored its link with the burden of deleterious mutations in a subset of individuals with available whole-genome sequencing data. To characterize the hypo/hyper-sensory profile, the differential Short Sensory Profile (dSSP) was defined as a normalized and centralized hypo/hypersensitivity ratio from the Short Sensory Profile (SSP). Including 1136 participants (533 autistic individuals, 210 first-degree relatives, and 267 controls) from two independent study samples (PARIS and LEAP), we observed a statistically significant dSSP mean difference between autistic individuals and controls, driven mostly by a high dSSP variability, with an intermediated profile represented by relatives. Our genetic analysis tended to associate the dSSP and the hyposensitivity with mutations of the GABAergic pathway. The major limitation was the dSSP difficulty to discriminate subjects with a similar quantum of hypo- and hyper-sensory symptoms to those with no such symptoms, resulting both in a similar ratio score of 0. However, the dSSP could be a relevant clinical score, and combined with additional sensory descriptions, genetics and endophenotypic substrates, will improve the exploration of the underlying neurobiological mechanisms of sensory processing differences in autism spectrum.

Optimized Metabotype Definition Based on a Limited Number of Standard Clinical Parameters in the Population-Based KORA Study.

The aim of metabotyping is to categorize individuals into metabolically similar groups. Earlier studies that explored metabotyping used numerous parameters, which made it less transferable to apply. Therefore, this study aimed to identify metabotypes based on a set of standard laboratory parameters that are regularly determined in clinical practice. K-means cluster analysis was used to group 3001 adults from the KORA F4 cohort into three clusters. We identified the clustering parameters through variable importance methods, without including any specific disease endpoint. Several unique combinations of selected parameters were used to create different metabotype models. Metabotype models were then described and evaluated, based on various metabolic parameters and on the incidence of cardiometabolic diseases. As a result, two optimal models were identified: a model composed of five parameters, which were fasting glucose, HDLc, non-HDLc, uric acid, and BMI (the metabolic disease model) for clustering; and a model that included four parameters, which were fasting glucose, HDLc, non-HDLc, and triglycerides (the cardiovascular disease model). These identified metabotypes are based on a few common parameters that are measured in everyday clinical practice. These metabotypes are cost-effective, and can be easily applied on a large scale in order to identify specific risk groups that can benefit most from measures to prevent cardiometabolic diseases, such as dietary recommendations and lifestyle interventions.

Can Immune-related adverse events serve as clinical biomarkers of PD-1/PD-L1 inhibitor efficacy in Pan-Cancer Patients?

Although PD-1/PD-L1 inhibitors are widely used as first-line treatment for patients with advanced tumors or as adjuvant therapy for patients with early-stage tumors, their efficacy is only 15-60%. Increasing evidence has demonstrated that biomarkers such as PD-L1 expression levels, microsatellite instability, and tumor mutation burden may assist in predicting the anti-tumor efficacy of PD-1/PD-L1 inhibitors. However, their clinical application value is limited, and there is currently a dearth of specific clinical markers to monitor or predict the efficacy of PD-1/PD-L1 inhibitors. Recently, studies have exposed that the efficacy of PD-1/PD-L1 inhibitors is positively correlated with immune-related adverse events (irAEs), suggesting that the latter may effectively predict anti-tumor efficacy. While there are controversies, a systematic understanding of the reasons and influencing factors of its correlation is still lacking. Therefore, this review aimed to introduce and discuss the latest research on the correlation between the efficacy of PD-1/PD-L1 inhibitors and irAEs. We identified that this positive correlation might be related to adipose tissue, T cells, pharmacokinetic characteristics, and antigen spread. In addition, the severity of irAEs, the duration of the use of PD-1/PD-L1 inhibitors, the comprehensive evaluation method of the severity of irAEs, and the genetic determinants are potentially the most significant bias factors when evaluating this correlation.

Past-tense inflection of non-verbs: a potential clinical marker of developmental language disorder in Swedish children.

AIM: In this paper, we explore the performance of past-tense inflection of non-verbs (NVI) in children with developmental language disorder (DLD) and in typically developing controls, to investigate its accuracy as a clinical marker for Swedish-speaking children with DLD. Further, we investigate the relationship between NVI, nonword-repetition, and family history. METHODS: The sample consists of 36 children with DLD (mean age 9;5 years) and 60 controls (mean age 9;2 years). RESULTS: The DLD group performed significantly lower than the controls on the NVI task, with a large effect size of the difference (d = 1.52). Analysis of the clinical accuracy of NVI resulted in 80.6% sensitivity and 76.6% specificity. NVI was significantly and moderately associated with nonword-repetition in the controls, but not in the DLD group. A positive family history, 80.6% in the DLD group and 6.9% in the controls, was associated with lower performance on NVI. When controlling for group (DLD and controls), a non-significant association between family history and performance on the NVI task was found. CONCLUSIONS: NVI is a potential clinical marker of DLD in Swedish school-aged children, but the current NVI task does not reach the level of being acceptable. Further development of the NVI task is warranted to improve its accuracy.

Circulating miRNAs as Potential Biomarkers for Celiac Disease Development.

Background & Aims: Celiac disease (CeD), an immune-mediated disease with enteropathy triggered by gluten, affects ~1% of the general European population. Currently, there are no biomarkers to predict CeD development. MicroRNAs (miRNAs) are short RNAs involved in post-transcriptional gene regulation, and certain disease- and stage-specific miRNA profiles have been found previously. We aimed to investigate whether circulating miRNAs can predict the development of CeD. Methods: Using next-generation miRNA-sequencing, we determined miRNAs in >200 serum samples from 53 participants of the PreventCD study, of whom 33 developed CeD during follow-up. Following study inclusion at 3 months of age, samples were drawn at predefined ages, diagnosis (first anti-transglutaminase antibody (TGA) positivity or diagnostic biopsy) and after the start of a gluten-free diet (GFD). This allowed identification of circulating miRNAs that are deregulated before TGA positivity. For validation of the biomarkers for CeD and GFD response, two additional cohorts were included in subsequent meta-analyses. Additionally, miRNAs were measured in duodenal biopsies in a case-control cohort. Results: 53 circulating miRNAs were increased (27) or decreased (26) in CeD versus controls. We assessed specific trends in these individual miRNAs in the PreventCD cohort by grouping the pre-diagnostic samples of the CeD patients (all had negative TGA) by how close to seroconversion (first sample positive TGA) the samples were taken. 8/53 miRNAs differed significantly between controls and samples taken <1 year before TGA positivity: miR-21-3p, miR-374a-5p, 144-3p, miR-500a-3p, miR-486-3p let-7d-3p, let-7e-5p and miR-3605-3p. 6/26 downregulated miRNAs reconstituted upon GFD, including miR-150-5p/-3p, whereas no upregulated miRNAs were downregulated upon GFD. 15/53 biomarker candidates also differed between CeD biopsies and controls, with a concordant direction, indicating that these circulating miRNAs might originate from the intestine. Conclusions: We identified 53 circulating miRNAs that are potential early biomarkers for CeD, of which several can be detected more than a year before TGA positivity and some start to normalize upon GFD.

The Role of Ki67 in Evaluating Neoadjuvant Endocrine Therapy of Hormone Receptor-Positive Breast Cancer.

Ki67 is a proliferation marker. It has been proposed as a useful clinical marker for breast cancer subtype classification, prognosis, and prediction of therapeutic response. But the questionable analytical validity of Ki67 prevents its widespread adoption of these measures for treatment decisions in breast cancer. Currently, Ki67 has been tested as a predictive marker for chemotherapy using clinical and pathological response as endpoints in neoadjuvant endocrine therapy. Ki67 can be used as a predictor to evaluate the recurrence-free survival rate of patients, or its change can be used to predict the preoperative "window of opportunity" in neoadjuvant endocrine therapy. In this review, we will elaborate on the role of Ki67 in neoadjuvant endocrine therapy in breast cancer.

Single-Cell RNA Sequencing Revealed CD14+ Monocytes Increased in Patients With Takayasu's Arteritis Requiring Surgical Management.

Objectives: Takayasu Arteritis (TA) is a highly specific vascular inflammation and poses threat to patients' health. Although some patients have accepted medical treatment, their culprit lesions require surgical management (TARSM). This study aimed at dissecting the transcriptomes of peripheral blood mononuclear cells (PBMCs) in these patients and to explore potential clinical markers for TA development and progression. Methods: Peripheral blood were collected from four TA patients requiring surgical management and four age-sex matched healthy donors. Single cell RNA sequencing (scRNA-seq) was adopted to explore the transcriptomic diversity and function of their PBMCs. ELISA, qPCR, and FACS were conducted to validate the results of the analysis. Results: A total of 29918 qualified cells were included for downstream analysis. Nine major cell types were confirmed, including CD14+ monocytes, CD8+ T cells, NK cells, CD4+ T cells, B cells, CD16+ monocytes, megakaryocytes, dendritic cells and plasmacytoid dendritic cells. CD14+ monocytes (50.0 vs. 39.3%, p < 0.05) increased in TA patients, as validated by FACS results. TXNIP, AREG, THBS1, and CD163 increased in TA patients. ILs like IL-6, IL-6STP1, IL-6ST, IL-15, and IL-15RA increased in TA group. Conclusion: Transcriptome heterogeneities of PBMCs in TA patients requiring surgical management were revealed in the present study. In the patients with TA, CD14+ monocytes and gene expressions involved in oxidative stress were increased, indicating a new treatment and research direction in this field.

Adverse Events as a Potential Clinical Marker of Antitumor Efficacy in Ovarian Cancer Patients Treated With Poly ADP-Ribose Polymerase Inhibitor.

BACKGROUND: PARP inhibitor (PARPi) is an important progress in ovarian cancer treatment. The available evidence suggests that BRCA mutation and homologous recombination deficiency (HRD) are effective biological markers for PARPi. Here we investigated the relationship between adverse events (AEs) and efficacy of PARPi in ovarian cancer patients. METHODS: Seventy-eight patients with ovarian cancer patients underwent Olaparib and Niraparib from July 2018 to July 2020 were analyzed. AEs were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. Chi-square test or fisher exact tests was performed to observe the association between categorical variables. Logistic regression analysis was conducted to investigate the independent variables for disease control response (DCR). Progression-free survival (PFS) was compared between AEs variables by log-rank test. RESULTS: Patients with AEs in the first one week had a higher DCR compared with those after one week (86.11% versus 60.98%, p=0.013). Patients with serious AEs (SAEs) had a significantly higher DCR (81.40% versus 60.60%, p=0.045). There were associations between anemia and DCR in both occurrence (79.63% versus 56.52%, p=0.037) and grade (100% versus 73.17%, p=0.048). The median PFS of patients with hematological toxicity was longer than that of patients with no-hematological toxicity (30 versus 20 weeks, p=0.047). Patients with hematological toxicity within four weeks had prolonged median PFS than those with hematological toxicity after four weeks (40 versus 22 weeks, p=0.003). CONCLUSIONS: The early presence of AEs and SAEs in hematological toxicity of PARPi were related to the antitumor efficacy, which might be a valid and easily measurable clinical marker in ovarian cancer patients.

Systematic review-Time to malignant transformation in low-grade gliomas: Predicting a catastrophic event with clinical, neuroimaging, and molecular markers.

BACKGROUND: Despite an initially indolent course, all WHO grade II, LGGs inevitably transform to malignant, WHO grades III and IV, without current curative options. Malignant transformation (MT) remains unpredictable with limited prognostic markers to steer timing of interventions. The aim of this study was to review and assign predictive value to specific clinical, molecular, and radiological markers impacting MT, thereby justifying timely therapeutic interventions. METHODS: Searches of MEDLINE, Embase, and Cochrane databases were conducted from inception to April 28, 2021 and outputs were analysed in accordance with PRISMA protocol. RESULTS: From an initial 5,032 articles, 33 articles were included, totalling 5672 patients. Forty-three prognostic factors were registered to significantly impact MT. These were categorised as 7 clinical; 14 neuroimaging; 8 biological/molecular; 3 volumetric; 5 topological; 3 histological; and 3 treatment-related. Following analysis, 10 factors were highlighted: the pre-operative prognosticators were 1. presentation with epileptic seizures; 2. VDE > 8 mm/y; 3. VDE > 4 mm/y; 4. rCBV > 1.75; 5. PTV ≥ 5 cm (65 ml); 6. PTV ≥ 100 ml; and 7. cortical involvement. The post-operative prognosticators were: (1) IDH-wt, (2) TP53 mutation, and (3) temozolomide monotherapy. CONCLUSIONS: The management of LGGs remains controversial, as conservative and invasive treatment may be associated with MT and impaired quality of life, respectively. Our review indicates that MT can be predicted by specific metrics in VDE, PTV, and rCBV, alongside cortical involvement. Additionally, patients with IDH-wt tumours TP53 mutations, or receiving TMZ monotherapy are more likely to undergo MT. Our data may form the basis of a predictive scoring system.

A 10-year cross-sectional retrospective study on Kawasaki disease in Iranian children: incidence, clinical manifestations, complications, and treatment patterns.

BACKGROUND: Kawasaki disease (KD) as an acute, systemic vasculitis is the leading cause of acquired heart disease in children under the age of 5 years. METHODS: A 10-year cross-sectional retrospective study was designed to assess 190 Iranian children with KD during 2008-2018. Demographic data, clinical and laboratory manifestations from the onset of symptoms to diagnosis, clinical signs and symptoms, and subsequent treatments were evaluated to predict hospitalization stay, complications, and response to treatment. RESULTS: Children with KD had a male-to-female ratio of 1.18:1 and an average age of 36 months. There was an insignificantly more incidence of KD in cold seasons. The most frequent symptoms were fever (92.6%), oral mucus membrane changes (75.8%), bilateral bulbar conjunctival injection (73.7%), polymorphous skin rash (73.2%), peripheral extremity changes (63.7%), and cervical lymphadenopathy (60.0%). The rate of gastrointestinal, cardiac, joint, and hepatic complications was determined to be 38.4, 27.9, 6.8, and 4.2%, respectively. 89.5% of patients received intravenous immunoglobulin (IVIG) plus aspirin as the first line of treatment, while, 16.3% of them needed an extra second line of treatment. Significantly low serum sodium levels and high platelet counts were detected in KD patients with cardiac complications. Cardiac complications often were more encountered in patients who did not respond to the first line of treatment. Higher platelet count, lower serum sodium amount, and C-reactive protein (CRP) level were significantly associated with a need for an additive second line of treatment. A significant relationship between hospitalization stay and hemoglobin level was found. CONCLUSION: As most of the clinical manifestations and complications were following other reports released over the past few years, such data can be confidently used to diagnose KD in Iran. Seasonal incidence and a positive history of recent infection in a notable number of patients may provide clues to understand possible etiologies of KD. Laboratory markers can successfully contribute to health practitioners with the clinical judgment of the need for additional treatments, possible complications, and hospitalization duration.