Remission Group Research Articles

The importance of ultrasound examination in care of juvenile idiopathic arthritis patients: 9 months follow-up study.

Juvenile idiopathic arthritis (JIA) is a group of rare musculoskeletal disorders with chronic inflammation of joints, typically manifesting before the age of 16 years. The assessment of disease activity remains pivotal in JIA treatment decisions, particularly during clinical remission. While musculoskeletal ultrasound (MSUS) has shown promise in detecting subclinical synovitis, longitudinal data on MSUS features in JIA remains limited. The aim of this study was to evaluate the prevalence of subclinical synovitis observed in MSUS over a follow-up period in JIA patients. Additionally, it sought to assess the consistency and correlation between clinical findings, standardized composite clinical score (JADAS10), and MSUS-detected synovitis during 9 months follow-up. a prospective single-center study was conducted, enrolling all consecutive JIA patients (excluding systemic JIA) seen at the study center in one year period. At three-months intervals over a 9 months period (M0, M3, M6 and M9), patients underwent clinical examination, laboratory tests, and MSUS assessment. Data on demographic characteristics, disease profile, and treatment were collected. Patients were categorized into active disease (ACT) or remission (REM) groups based on Wallace criteria and JADAS10 scores using previously validated thresholds. The ultrasound assessments adhered to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) pediatric group, covering 40 joints, were performed by two ultrasonographers at every visit. Subclinical synovitis was defined as synovitis detected exclusively by MSUS. Spearman's correlation coefficients (rs) were used to evaluate the association between MSUS, clinical data, and outcome measures, such as active joint count (ACJ), patient's/parent's global assessment of disease activity (PaGA), physician's global assessment of disease activity (PhGA) and JADAS10. subclinical synovitis was evident in 5.2% of all joints and in 80.6% of the patients at baseline. During the follow-up period, signs of subclinical synovitis decreased to 3.8% of joints, however, the proportion of affected patients remained high (67.7%), with the majority in REM group. Despite the consistent strong correlation between PaGA and PhGA throughout the study (rs > 0.895; p < 0.001), both measures displayed moderate (rs = 0.647; p < 0.001) to weak (rs = 0.377; p = 0.04) correlations with MSUS findings. Notably, PaGA remained significantly correlated with MSUS at the M9 visit (rs = 0.377, p = 0.04), while PhGA showed no correlation (p = 0.094). The study results indicate the persistence of subclinical inflammation detected by MSUS in a significant proportion of JIA patients, even during clinical remission. Moreover, the findings suggest that conventional measurements of JIA activity may be insufficient for assessing patients in clinical remission.

Atmospheric environment and persistence of pediatric asthma: A population-based cohort study.

Asthma is a heterogeneous disease with different outcomes. For children with asthma at the age of 7 years, 67-75% are symptom-free as adults. Data on the important link between childhood and adult asthma are sparse. We aimed to investigate factors associated with persistence of childhood asthma over three years of follow-up by linking data between Korea childhood Asthma Study (KAS) and their matched claims data from Health Insurance Review and Assessment Service (HIRA). We analyzed data from 450 preadolescent children aged 7 to 10 years and classified them into remission or persistence groups. Baseline clinical characteristics and exposure to air pollution materials including PM2.5 and PM10 during three years of follow-up were compared. The main outcome was asthma persistence which was defined as the presence of asthma episodes with healthcare utilization and prescription of asthma medications within three years after KAS enrollment. At the third year of follow-up, after stepwise regression analysis, lower age at enrollment (adjusted odds ratio (aOR): 0.79; 95% confidence interval (CI): 0.64-0.96), male sex (aOR: 1.66; 95%CI: 1.05-2.63), proximity from an air-polluting facility (aOR: 2.4; 95%CI: 1.34-4.29), higher level outdoor PM2.5 (aOR: 1.1; 95%CI: 1.02-1.20), and higher rate of doctor-diagnosed food allergy (FA) (aOR: 2.33; 95%CI: 1.06-5.12) were significantly associated with persistence. We discovered various independent risk factors for the persistence of childhood asthma. By linking HIRA claims data, we could clarify risk factors for persistence in a well-defined study population.

Correlations of Cancer-Related Fatigue with Clinicopathological Features and Quality of Life in Gastric Cancer.

To explore the correlations of cancer-related fatigue (CRF) with clinicopathological features and quality of life in gastric cancer. Using a convenient sampling method, 230 patients with gastric cancer admitted to our hospital from March 2020 to July 2022 were collected. They were divided into the fatigue group (n = 152) and the nonfatigue group (n = 78) according to the presence/absence of CRF. Relevant data were collected and compared. Statistically significant differences were found between the two groups in age ratio (χ 2 = 41.671, P < 0.001), T stage ratio (χ 2 = 9.973, P = 0.019), N stage ratio (P < 0.001), PS score (P < 0.001), and the degree of gastric cancer thickening (14.21 ± 3.32 vs. 12.12 ± 3.81 mm, t = 4.572, P < 0.001). Patients with gastric cancer had the lowest CRF Brief Fatigue Inventory (BFI) score for general activities (2.26 ± 0.37) and high scores for work activities (6.23 ± 0.24) and enjoyment of life (7.11 ± 1.34). Pearson's correlation analysis revealed a positive correlation between patient emotions and the CRF BFI score (r = 0.443, P = 0.001). Patients with mild, moderate, and severe CRF showed statistically significant differences in physical functioning (83.34 ± 21.12 vs. 65.23 ± 21.14 vs. 32.25 ± 17.29, F = 15.382, P < 0.001), role emotional (72.53 ± 21.21 vs. 67.33 ± 27.56 vs. 54.37 ± 26.45, F = 14.483, P < 0.001), fatigue (49.12 ± 18.44 vs. 54.61 ± 26.64 vs. 67.51 ± 14.27, F = 13.581, P < 0.001), bodily pain (56.56 ± 25.12 vs. 76.43 ± 21.71 vs. 80.32 ± 12.39, F = 14.582, P < 0.001), appetite reduction (57.45 ± 25.47 vs. 69.51 ± 16.21 vs. 76.23 ± 27.58, F = 14.592, P < 0.001), and overall health status and quality of life (67.21 ± 19.45 vs. 53.43 ± 22.32 vs. 43.43 ± 12.52, F = 16.494, P < 0.001). After chemotherapy, the average CRF BFI scores of the partial remission (PR), disease stability (SD), and disease progression (PD) groups all reduced than those before chemotherapy (all P < 0.05). At 3 months of follow-up, a comparison of the average CRF BFI scores with those before chemotherapy revealed a decrease in the SD and PR groups and an increase in the PD group. In conclusion, CRF is correlated with age, T stage, and N stage in gastric cancer. The later the T and N stages, the more significant the effect on fatigue. Moreover, CRF can also affect the quality of life in gastric cancer, and the severer the CRF, the poorer the quality of life.

The specificity of the auditory P300 responses and its association with clinical outcomes in youth with psychosis risk syndrome

BackgroundSchizophrenia often occurs in youth, and psychosis risk syndrome (PRS) occurs before the onset of psychosis. Assessing the neuropsychological abnormalities of PRS individuals can help in early identification and active intervention of mental illness. Auditory P300 amplitude defect is an important manifestation of attention processing abnormality in PRS, but it is still unclear whether there are abnormalities in the attention processing of rhythmic compound tone stimuli in PRS individuals, and whether the P300 amplitude induced by these stimuli is specific to PRS individuals and related to their clinical outcomes. MethodsIn total, 226 participants, including 122 patients with PRS, 51 patients with emotional disorders (ED), and 53 healthy controls (HC) were assessed. Baseline electroencephalography was recorded during the compound tone oddball task. The event-related potentials (ERPs) induced by rhythmic compound tone stimuli of two frequencies (20-Hz, 40-Hz) were measured. Almost all patients with PRS were followed up for 12 months and reclassified into four groups: PRS-conversion, PRS-symptomatic, PRS-emotional disorder, and PRS-complete remission. The differences in baseline ERPs were compared among the clinical outcome groups. ResultsRegardless of the stimulation frequency, the average P300 amplitude were significantly higher in patients with PRS than in those with ED (p = 0.003, d = 0.48) and in HC (p = 0.002, d = 0.44) group. The average P300 amplitude of PRS-conversion group was significantly higher than that of the PRS-complete remission (p = 0.016, d = 0.72) and HC group (p = 0.001, d = 0.76), and the average P300 amplitude of PRS-symptomatic group was significantly higher than that of the HC group (p = 0.006, d = 0.48). Regardless of the groups (PRS, ED, HC) or the PRS clinical outcome groups, the average P300 amplitude induced by 20-Hz tone stimulation was significantly higher than that induced by 40-Hz stimulation (ps < 0.001, Ƞ2 = 0.074–0.082). The average reaction times of PRS was significantly faster than that of ED (p = 0.01, d = 0.38), and the average reaction times of the participants to 20-Hz target stimulation was significantly faster than that to 40-Hz target stimulation (p < 0.001, d = 0.21). ConclusionThe auditory P300 amplitude induced by rhythmic compound tone stimuli is a specific electrophysiological manifestation of PRS, and the auditory P300 amplitude induced by compound tone stimuli shows promise as a putative prognostic biomarker for PRS clinical outcomes, including conversion to psychosis and clinical complete remission.

Efficacy and Safety of Conversion Surgery for Advanced Hepatocellular Carcinoma After Hepatic Arterial Infusion Chemotherapy.

The aim of this study was to investigate the efficacy and safety of conversion surgery for advanced hepatocellular carcinoma (HCC) after hepatic arterial infusion chemotherapy (HAIC). Data from 172 HCC patients treated at Sun Yat-sen University Cancer Center between January 2016 and June 2021 with effective assessment of HAIC treatment response were retrospectively analyzed. Clinical pathological data, treatment process, survival, and occurrence of adverse events were recorded. Patients were grouped according to whether they achieved imaging remission after HAIC, underwent conversion surgery, and met the surgical resection criteria. Efficacy and safety were analyzed. The median progression-free survival (PFS) and overall survival (OS) in the imaging remission group were 8.6 months and 26.3 months, respectively, which were longer than the 4.6 months (P<0.05) and 15.6 months (P<0.05) in the nonremission group. Compared with 6.7 months and 18.9 months in the HAIC maintenance group, the median PFS and median OS in the conversion surgery group were 16.5 months (P<0.05) and 45.0 months (P<0.05), but there was a higher risk of treatment-related hemoglobin decrease, alanine aminotransferase increase, aspartate aminotransferase increase, and total bilirubin increase (P<0.05). The risk of biliary fistula, abdominal hemorrhage and ascites in the HAIC conversion surgery group was higher than that of the single surgery group (P<0.05). Compared with the conversion surgery group, the median PFS and median OS of patients in the HAIC maintenance group who met the resection criteria were shorter: 7.1 months (P<0.05) and 21.7 months (P<0.05), respectively. All adverse events during the study were less than moderate, and no toxicity-related deaths occurred during follow-up. HAIC-based conversion therapy had acceptable toxic effects and could effectively stabilize intrahepatic lesions in advanced HCC, improve the survival benefit of patients, and provide some patients with the opportunity for conversion surgery to further improve prognosis.

Changes in cytokine complexes in children with autoimmune diseases with different effectiveness of their biological therapy

Introduction. Cytokines (CC) play an important pathogenetic role in the development of autoimmune diseases. Over the past decade, there has appeared a huge number of biological drugs that target certain cytokines. The main problem remains the choice of a suitable biological drug, as up to 40% of patients do not respond to treatment or become resistant to it. Aim: to identify informative cytokine complexes in children with psoriasis, MS, and IBD with different efficacy of biological therapy. &#x0D; Materials and methods. Two hundred eighty eight children with autoimmune diseases were examined against the background of supportive biological therapy. Patients were divided into groups of exacerbation and remission depending on the lesion area index PASI for psoriasis (PS), clinical activity indices PUCAI for ulcerative colitis (UC), PCDIA for Crohn’s disease (CD), by the pre­sence of foci of demyelination on MRI for patients with multiple sclerosis (MS). All patients underwent a study of 25 cytokines in serum samples using multiplex analysis (X-MAP technology).&#x0D; Results. In PS, MS, UC, and CD patients, an increase in pathogenetically significant cytokine profiles associated with cells (c) and functions (f) of M1 cells, Th1, Th2, Th17 was revealed in the exacerbation of diseases relative to the groups in remission. There was a significant decrease in the levels of cytokines and cytokine complexes in patients with MS relative to patients with PS, UC and CD, with the exception of cTh1. Threshold values of the level of cytokine complexes above which the development of an exacerbation of the disease can be expected were obtained: for PS — 1431.1 pg/ml (fTh22 — IL13 + Il22), for PC — 33.1 pg/ml (cTh1 — IFN-γ + IL12p70 + TNF-β + IL2), UC — 20.9 pg/ml (M1 — IL-1 + IL-6 + TNF-α), CD — 1986 pg/ml (fIL12 — IL12 + IL23 + IL27).&#x0D; Conclusion. To assess the effectiveness of biological therapy and to predict the condition of patients, it is possible to evaluate specific cytokine complexes for a specific pathology.

Comparison of fecal calprotectin levels and endoscopic scores for predicting relapse in patients with ulcerative colitis in remission.

Although the usefulness of endoscopic scores, such as the Mayo Endoscopic Subscore (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and Ulcerative Colitis Colonoscopic Index of Severity (UCCIS), and biomarkers such as fecal calprotectin (FC) for predicting relapse in ulcerative colitis (UC) has been reported, few studies have included endoscopic scores for evaluating the entire colon. To compare the usefulness of FC value and MES, UCEIS, and UCCIS for predicting relapse in patients with UC in clinical remission. In total, 75 patients with UC in clinical and endoscopic remission who visited our institution between February 2019 and March 2022 were enrolled. The diagnosis of UC was confirmed based on the clinical presentation, endoscopic findings, and histology, according to the current established criteria for UC. Fecal samples were collected the day before or after the colonoscopy for measurement of FC. Endoscopic evaluations were performed using MES, UCEIS, and UCCIS. The primary outcome measure of this study was the assessment of the association between relapse within 12 mo and MES, UCEIS, UCCIS, and FC. The secondary outcome was the comparison between endoscopic scores and biomarkers in enrolled patients with UC with mucosal healing. FC and UCCIS showed a significant correlation with UCEIS (r = 0.537, P < 0.001 and r = 0.957, P < 0.001, respectively). Receiver-operating characteristic analysis for predicting MES 0 showed that the area under the curve of UCCIS was significantly higher than that of FC (P < 0.01). During the 1-year observation period, 18 (24%) patients experienced a relapse, and both the FC and UCCIS of the relapse group were significantly higher than that of the remission group. The cut-off values for predicting relapse were set at FC = 323 mg/kg and UCCIS = 10.2. The area under the curve of the receiver-operating characteristic analysis for predicting relapse did not show a significant difference between FC and UCCIS. The accuracy of the endoscopic scores and biomarkers in predicting relapse was 86.7% for UCCIS, 85.3% for UCEIS, 76.0% for FC, and 73.3% for MES. The three endoscopic scores and FC may predict UC relapse during clinical remission. Among these scores, UCEIS may be the most useful in terms of ease of evaluation and accuracy.

Radiological predictive remission factors of pulmonary involvement in systemic sarcoidosis: a computed tomography scan study.

As little is known about the prognostic value of CT scan findings at onset in patients presenting with sarcoidosis, we aimed to identify factors independently associated with radiological remission of pulmonary involvement in systemic sarcoidosis on CT scan findings. We conducted a retrospective descriptive and analytic study of patients with a biopsy proven systemic sarcoidosis. We compared patients on radiological remission (group 1) to those on stabilization or progression (group 2). Multivariate analysis of variables significantly associated with radiological remission in univariate analysis was performed using binary logistic regression. Out of 65 records of systemic sarcoidosis, 43 were analyzed. 18.6% where male and 81.6% female with a sex-ratio of 0.22 and a mean age at diagnosis of 47.2 ±13.6 years. We found atypical lesions in CT scan findings in 16 patients (37.2%). Comparative pulmonary CT scan findings at admission and at 12 months follow-up revealed 13 patients (30.2%) in remission (group1) and 30 patients in radiological stabilization or progression (group 2). On multivariate analysis, lymphopenia, calcifications, and typical CT scan findings at presentation were predictive factors of remission of pulmonary involvement in systemic sarcoidosis (aOR=27.57; 95%IC=2.67-284.63; p=0.005) (aOR= 37.2; 95%IC= 2.08-663.89; p= 0.014) (aOR=47.1; 95%IC= 1.79-1238.7; p=0.021) respectively. In patients with systemic sarcoidosis with no lymphopenia at onset or calcifications or typical CT scan findings at presentation, we suggest a close follow-up as well as an intensive treatment.

MECHANISMS OF THROMBOTIC READINESS STATE FORMATION IN CARDIOLOGICAL PATIENTS WITH ACTIVE ONCOLOGICAL PROCESS

Today cardiovascular diseases and oncopathology are leading causes in the structure of mortality worldwide. The complexity of diagnostics of haemocoagulation complications in this comorbid pathology remains an urgent problem at present. The aim of our study was to investigate the mechanisms of thrombotic readiness state formation using the thrombodynamics test on the example of patients with cardiovascular diseases (CHD, arterial hypertension) and aggravated oncoanamnesis depending on the activity of oncoprocess. The study was conducted in 100 patients aged 37 – 86 years: 60 patients with active oncoprocess (group 1) and 40 patients with oncoprocess in remission (group 2). Clinical, anamnestic and laboratory data were studied using a statistical analysis. The main attention was paid to the thrombodynamics test indicators (both velocity and structural). It was found that the most informative indicators of the haemostasis system state estimation in patients with cardiovascular pathology and aggravated oncoanamnesis depending on the oncoprocess activity are thrombodynamic indices both velocity and structural. Almost half of cardiological patients with an aggravated oncoanamnesis had a state of thrombotic readiness irrespective of the activity of the oncological process. These indices were higher in active oncopathology than in oncopathology in remission. At the same time no differences in the data of standard coagulogram in both groups could be revealed. Application of thrombodynamics test in cardiological patients with oncoanamnesis allows to reveal the states of thrombotic readiness and to establish the degree of influence of oncoprocess activity on the formation of this state, which demonstrates fundamentally new aspects of diagnostics of procoagulant states in patients of this profile.

Switching Vedolizumab from IV to SC Injection in Inflammatory Bowel Disease Patients with Active Disease: Real-World Experience from a German IBD Cohort.

Vedolizumab (VDZ) for subcutaneous (SC) injection was approved for use in Europe in 2020 and the US in 2023. Promising efficacy and tolerability have been proven in pivotal trials. However, real-world data on the SC use of VDZ, especially in patients with active disease, are still lacking. We aimed to determine treatment persistence and the drug's efficacy in inflammatory bowel disease (IBD) patients with active disease in comparison to patients in clinical remission. Patients treated for IBD in a tertiary care center from July 2020 to December 2021 were included in this study. Clinical and biochemical parameters and data on treatment adherence were collected. VDZ trough levels and disease activity before and after the switch from intravenous (IV) to SC injections were monitored during routine checkups and were retrospectively analyzed. The patients were followed up until week 20. Eighty-two patients were included in the study. Of them, 35 patients had active disease (35/82 = 43%) at the time of the switch and 47 patients (47/82 = 57%) were in remission. In total, 10 patients experienced switch failure, 5 were switched back to IV VDZ, and 5 were swapped to a different biologic agent. We observed an increase in VDZ trough levels from the switch to week 8 and from the switch to week 20 in the remission group. Vedolizumab trough levels of 7.4, 51.4, and 33.45 ug/mL at the switch, week 8, and week 20 were identified to discriminate between remission and disease activity in our cohort. There was no new safety signal detected during the study period. The switch from IV to SC VDZ proved to be efficient, safe, and even capable of reducing residual disease activity.

Th9/IL-9 may participate in the pathogenesis of multiple myeloma.

This research is aimed to evaluate the correlation between Th9-associated cytokine levels in MM patients, clinical features, and therapy. Peripheral blood samples were taken in 52 MM patients and 20 healthy volunteers matched by sex and age. The patients with MM were separated into two groups: the untreated group (27) and the remission group (25). An enzyme-linked immunosorbent assay (ELISA) was used to measure the IL-9 plasma levels. The levels of Th9-associated cytokines' mRNA expression (IL-9, PU.1, and IRF4) were measured in RT-qPCR. We also analyzed the correlations between the IL-9 plasma levels and the clinical parameters of newly diagnosed MM patients. The IL-9 plasma levels and the Th9-associated cytokines (IL-9, PU.1, and IRF4) mRNA levels in newly diagnosed MM patients were significantly elevated than those in healthy volunteers and significantly decreased after achieving remission. Moreover, PU.1 and IRF4 had a positive correlation with the IL-9 mRNA expression. Then, we found that the upregulation of IL-9 plasma levels correlates with the severity of anemia and decreased albumin Levels. The results demonstrate that Th9/IL-9 may be involved in the pathogenesis of MM and is correlated with worse patient conditions such as lower hemoglobin and serum albumin. More work is necessary to confirm whether they might serve as a useful therapeutic target and prognostic marker for MM.

Infantile epileptic spasms syndrome: a cohort study of 88 children

BackgroundThis study aimed to investigate and analyze the risk factors for non-etiology-specific infantile spasms (IS) and unrelieved clinical symptoms after treatment.MethodsEighty-eight children with IS who were treated at our hospital from March 2018 to December 2021 were included in the study. The children were divided into etiology-specific (n = 46) and nonetiology-specific (n = 42) groups, based on the diagnostic results, and remission (n = 45) and nonremission (n = 43) groups, based on clinical outcomes after treatment. The clinical data from patients in the etiology-specific and nonetiology-specific groups and the remission and nonremission groups were compared. Risk factors for non-etiology-specific IS were identified using logistic regression analysis.ResultsGender, family history, birth status, and metabolic abnormalities were significantly different between the etiology-specific and non-etiology-specific groups. Gender and metabolic abnormalities were risk factors for nonetiology-specific IS. Family history, birth status, metabolic abnormalities, and brain magnetic resonance imaging were significantly different between the remission and nonremission groups, and different etiologies were risk factors for unrelieved symptoms after treatment.ConclusionThe occurrence of nonetiology-specific IS is associated with gender and metabolic abnormalities in children. After medication, unrelieved IS symptoms are associated with etiologies.

Clinical profiles in multiple myeloma patients with extreme survivals: a study from a National Medical Center in China

ABSTRACT Objectives The clinical outcomes of multiple myeloma (MM) patients are highly variable in the real-world setting. Some MM patients may have clinical endings that do not abide by the book. We aim to describe features of MM patients with extreme survivals in real-world practice. Methods This retrospective study enrolled 941 patients consecutively visited a national medical center, China, between July 1995 and December 2021. Among patients, we identified two groups of MM patients with extreme survivals, 56 were in the long-term remission (LR) group with progression-free survival (PFS) ≥ 60 months, and 82 were in the rapid progression (RP) group with PFS ≤ 6 months. Results CRAB features, of which hypercalcemia, renal insufficiency, and anemia were more common in the RP group, except for bone disease, with a comparable incidence at diagnosis in both groups (88.8 vs 85.7%, P = 0.52). High-risk cytogenetics was detected in 45.7% of patients in the RP group. Of note, 14.3% of MM patients in the LR group harbored del (17p). According to the Revised International Staging System (R-ISS), 9% of patients belonged to stage I in the RP group, and 19% of patients in the LR group were found in stage III. There were 8 (15.7%) patients in the LR group only achieved partial response (PR) as the best response. Median time to best response (TBR) for LR and RP group patients was 4.6 and 1.4 months, respectively. Conclusions The disparities in the survivals of MM patients indicated that some unexpected factors have influenced the outcomes in the real-world setting.

The Potential Utility of Cerebral Fluid sLR11 and sIL-2R As a Marker for CNS Involvement of Malignant Lymphoma

Introduction: LR11 is a type I membrane protein that releases serum-soluble LR11 (sLR11) by proteolytic shedding. In the past, we reported that patients with acute leukemia and malignant lymphoma showed significantly increased serum sLR11 levels compared to those in normal controls. The diagnosis of central nervous system involvement of malignant lymphoma (CNS ML) is often difficult to diagnose by cytology. This study analyzed the potential utility of cerebral fluids (CFs) sLR11 and sIL-2R as diagnostic markers for CNS ML. Materials and Methods: We enrolled patients suspected of CNS ML and administrated intrathecal anticancer drugs from 2017 to 2023. We analyzed CFs levels of sLR11 and sIL-2R, and cytological malignant grades. Then, we analyzed the relationship between changes in these CFs markers and clinical outcomes. Results: We studied 26 patients (16 men and 10 women; mean age: 72 years old). The 20 patients were diagnosed as CNS ML in clinical conditions, and the other 6 patients were treated with prevention because of ML of the testis and adrenal glands. The sLR11 of CFs levels significantly and positively correlated with the sIL-2R of CFs levels (r = 0.6618, p = 0.0002) (Figure 1A). As shown in Figure 1B, in CNS invasion groups, only four patients showed class V in the cytology of CFs, the other patients showed negative results. There were no relations between the number of cell numbers and sLR11 and sIL-2R of CFs. As shown in Figure 2, the levels of sLR11 of CFs in diagnosis tended to be higher (p = 0.1831) in the CNS invasion group (36.5±30.0 ng/ml) than in the no-invasive group (23.9±5.8 ng/ml). The levels of sIL-2R of CFs in diagnosis were significantly higher (p = 0.0035) in the CNS invasion group (986.0±1274.3 U/ml) than in the no-invasive group (74.2±78.2 U/ml). The LR11 and sIL-2R of CFs post-treatment were lower in the remission group (n=9; 13.46±6.37 ng/ml, &amp;lt;50.0 U/ml) than non-remission group (n=5; 22.40±14.32 ng/ml, 78.4±41.1 U/ml), p = 0.2861, 0.0629 respectively. Conclusions: Patients diagnosed with CNS ML showed high levels of sLR11 and sIL-2R of CFs. These two may be good markers for evaluating diagnosis and treatment effects. Further examination of a large number of cases is required to elucidate these mechanisms.

The Novel Biomarkers for Predicting Prognosis and Recurrence in Primary Central Nervous System Lymphoma: Exosomal Protein and Exosomal microRNA

Abstract Purpose Primary central nervous system lymphoma (PCNSL) is a highly heterogeneous tumor. Therefore, it is crucial to identify biomarkers that can dynamically monitor disease progression for individualized treatment and to improve prognosis. Exosomes carry a large amount of genetic and proteomic information and are stable and easy to obtain. They play important roles in disease diagnosis, treatment, and prognosis. This study aimed to evaluate the use of cerebrospinal fluid (CSF) exosomes in patients with PCNSL as biomarkers of tumor evolution. Methods From October 2021 to October 2022, patients diagnosed with PCNSL via pathology were selected from Beijing Tiantan Hospital affiliated to Capital Medical University. None of the patients had received any cancer-related treatment before diagnosis. Primary intraocular lymphoma and HIV-positive patients were excluded. Clinical information and laboratory findings of patients were recorded in detail. The responses were evaluated according to the response criteria formulated by the International Primary Nervous System Lymphoma Cooperation Group in 2005. According to the time of collecting CSF samples, the patients were divided into diagnosis group (before treatment, n=12), treatment group (after 2-4 treatment cycles, n=11) and complete remission (CR) group (achieved CR after 6 treatment cycles, n=11). We analyzed and compared the exosomal protein concentrations and microRNA expression in the CSF of patients in different groups using western blotting and quantitative reverse transcription PCR. Results There are CD20-positive exosomes in the CSF of patients with PCNSL (Figure 1). In the diagnosis group, the exosomal protein concentration of patients who achieved CR after 2 cycles induction treatment (early remission) was significantly lower than that of patients who did not achieve early remission (p=0.03). Higher exosomal protein concentrations (p=0.022) and exosomal miR-3681-3p expression (p=0.036) at diagnosis were significantly associated with shorter progression-free survival (Figure 2). The expression levels of miR-21-5p (p=0.001), miR-29b-3p (p=0.043), and miR-101-3p (p=0.007) in exosomes were significantly higher in the diagnosis group than in the CR group. Higher exosomal protein concentrations (p=0.012) and exosomal miR-101-3p expression (p=0.013) after CR were significantly associated with recurrence and shorter disease-free survival (Figure 2). The predictive efficacy of exosomal protein concentration and exosomal has-miR-101-3p in PCNSL was analyzed. The area under the receiver operator characteristic curve (AUC) was 0.833 (95% confidence interval 0.524-1.000; p&amp;lt;0.05) and 0.917 (95% confidence interval 0.731-1.000; p=0.033), respectively. Conclusions Exosomes in CSF may have the potential to evaluate prognosis and predict recurrence in PCNSL. It provides clinicians with selectable biomarkers for dynamic evaluation of disease progression.

Influencing factors of cancer-related fatigue in acute leukemia patients: A cross-sectional study

PurposeTo investigate influencing factors of cancer-related fatigue (CRF) in adult patients with acute leukemia (AL). MethodsA total of 288 adult patients diagnosed with acute leukemia in West China Hospital were included in this study. A cross-sectional survey, including the Clinical Information Questionnaire, the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Pittsburgh Sleep Quality Index (PSQI), and Hospital Anxiety and Depression Scale (HAD), was provided to the patients. Hierarchical multiple linear regression analyses were conducted to evaluate the associations of the variable factors and the AL patients’ CRF. ResultsThe CRF score of AL patients was 33.25 ± 10.35. Gender, age, albumin level, depression, anxiety status of the patients and treatment cycles were identified as influencing factors of CRF in AL patients (P < 0.05). The CRF level of acute leukemia patients in the complete remission group was lower than that of patients who were not achieving complete remission. Depression, anxiety, age, employment, albumin, and sleep disturbance were independent influencing factors for CRF in patients who were not achieving complete remission. ConclusionsAcute leukemia patients who are female, older, hypoalbuminemia，or in the induction therapy have a higher risk of developing a high degree of CRF. Clinical staff should pay more attention to the CRF of patients who were not achieving complete remission. Early screening and aggressive intervention could be adopted in caring for these patients.

Characteristics of Patients with Subjective Sleep Problems after Cognitive Behavioral Therapy for Insomnia: Secondary Analyses of a Randomized Controlled Trial.

Objective Cognitive behavioral therapy for insomnia (CBT-I) is the first-line treatment for insomnia, but half of the patients do not reach remission. This study aimed to explore subjective remission by investigating the characteristics of patients who reported lingering sleep problems after CBT-I. Methods Secondary analyses of a randomized controlled trial of group CBT-I in 72 primary care patients with insomnia disorder. Sociodemographic characteristics and outcomes (insomnia severity, sleep variables, hypnotics use, fatigue, depressive symptoms, and dysfunctional beliefs/attitudes), including baseline data and symptom change, were investigated in relation to patients' posttreatment response to the yes-or-no question "Would you say that you have sleep problems?" Results A total of 56.9% of patients reported sleep problems after CBT-I. At baseline, they had worse depressive symptoms (14.9 (SD 7.5) vs. 10.2 (SD 5.9), p = 0.006) and more awakenings (2.6 (SD 1.5) vs. 1.8 (SD 1.3), p = 0.034) than those in subjective remission from sleep problems. Patients in the non-remission and remission groups showed similar improvements in sleep, fatigue, and depressive symptoms, but patients in the non-remission group had improved less in insomnia severity, dysfunctional beliefs/attitudes about sleep, and hypnotic use. In patients with more pronounced depressive symptoms before CBT-I, change in depressive symptoms during treatment partially explained subjective remission from sleep problems. Discussion More severe depressive symptoms prior to CBT-I and less improvements in depressive symptoms during treatment predicted remaining subjective sleep problems after treatment. These findings highlight the importance of assessing depressive symptoms in primary care patients with insomnia, as patients with pronounced depressive symptoms may need tailored treatment.

Neutrophil gelatinase-associated lipocalin (NGAL) and inflammatory markers in schizophrenia: A comparative analysis of drug-naive schizophrenia patients, remitted patients, and healthy controls

This study aims to examine the plasma concentrations of NGAL and other inflammatory parameters, including TNF-α, IL-1β, and IFN-γ, in schizophrenia patients and healthy volunteers. It also investigates potential associations between these biomarkers and symptom severity in schizophrenia and the utility of NGAL as a potential diagnostic and monitoring biomarker for schizophrenia. The study included 49 drug-naive schizophrenia patients (DNS), 59 patients with schizophrenia in remission (REM) on antipsychotic treatment, and 58 healthy volunteers (HC). The Positive and Negative Symptoms Evaluation Scale (PANSS) was utilized to assess the severity of symptoms in schizophrenia patients. Plasma levels of TNF-α, IL-1β, IFN-γ, and NGAL were measured for all participants. NGAL levels were significantly lower in the DNS group than in HC. Significantly lower TNF-α levels were observed in both the DNS and REM groups compared to the HC group. Notably, a statistically significant positive correlation was detected between TNF-α and NGAL levels. The findings of this study are noteworthy, as they demonstrate that drug-naive individuals with schizophrenia exhibit significantly diminished levels of NGAL and TNF-α compared to healthy controls. These identified biomarkers hold promise for providing valuable insights into the complex and evolving pathophysiology of schizophrenia.

Intricate role of intestinal microbe and metabolite in schizophrenia

BackgroundThe brain-gut axis has gained increasing attention due to its contribution to the etiology of various central nervous system disorders. This study aims to elucidate the hypothesis that schizophrenia is associated with disturbances in intestinal microflora and imbalance in intestinal metabolites. By exploring the intricate relationship between the gut and the brain, with the goal of offering fresh perspectives and valuable insights into the potential contribution of intestinal microbial and metabolites dysbiosis to the etiology of schizophrenia.MethodsIn this study, we used a 16S ribosomal RNA (16S rRNA) gene sequence–based approach and an untargeted liquid chromatography-mass spectrometry-based metabolic profiling approach to measure the gut microbiome and microbial metabolites from 44 healthy controls, 41 acute patients, and 39 remission patients, to evaluate whether microbial dysbiosis and microbial metabolite biomarkers were linked with the severity of schizophrenic symptoms.ResultsHere, we identified 20 dominant disturbances in the gut microbial composition of patients compared with healthy controls, with 3 orders, 4 families, 9 genera, and 4 species. Several unique bacterial taxa associated with schizophrenia severity. Compared with healthy controls, 145 unusual microflora metabolites were detected in the acute and remission groups, which were mainly involved in environmental information processing, metabolism, organismal systems, and human diseases in the Kyoto encyclopedia of genes and genomes pathway. The Sankey diagram showed that 4 abnormal intestinal and 4 anomalous intestinal microbial metabolites were associated with psychiatric clinical symptoms.ConclusionsThese findings suggest a possible interactive influence of the gut microbiota and their metabolites on the pathophysiology of schizophrenia.

DNMTs-mediated SOCS3 methylation promotes the occurrence and development of AML.

As a tumor suppressor gene, SOCS3 inhibits the growth of tumor cells by regulating JAK/STAT signaling pathway through negative feedback. This study aimed to investigate the biological function and mechanism of SOCS3 methylation mediated by DNMTs in the development of AML. Bone marrow samples were collected from 70 AML patients and 20 healthy volunteers. The expression and methylation status of each gene were detected by RT-qPCR, western blot and MS-PCR, and the growth and apoptosis rate of leukemia cell lines were detected by CCK-8 and flow cytometry. The effects of changes in SOCS3 gene expression and methylation status of AML cell lines were observed by gene transfection and gene knockdown. The methylation rate of SOCS3 in AML initial treatment group was significantly higher than that in the remission group and the normal control group (60% vs. 0%, 0%). The expression of SOCS3 in the SOCS3 methylation group was significantly lower than that in the non-methylated group and control group, while the expression of DNMT1, DNMT3a, p-JAK2, p-STAT3 and p-STAT5 were significantly higher than those in the non-methylated group and control group. Demethylation treatment, SOCS3 transfection and DNMT3a knockdown could up-regulate the expression of SOCS3, which decreased the proliferation and increased the apoptosis of leukemia cell lines. SOCS3 methylation mediated by DNMTs promotes the occurrence and development of AML and can be used as a potential biomarker for the diagnosis and efficacy evaluation of AML.