Unfavorable Prognosis Factor Research Articles

Боковой амиотрофический склероз и его маски, коморбидная патология с быстрым летальным исходом: клинический случай

INTRODUCTION. Despite the fact that more than 150 years have passed since the first mention of amyotrophic lateral sclerosis (ALS), the issues of etiology, pathogenesis, diagnosis and treatment of this disease are still not fully resolved. However, the results of recent research in the field of genetics with the identification of genes associated with ALS, understanding the mechanisms of disease development and, as a result, the creation of effective drugs give hope that in the near future the disease will cease to be fatal. AIM. To analyze domestic and foreign publications on the etiology, pathogenesis, diagnosis and treatment of amyotrophic lateral sclerosis. To present a clinical case of a patient with amyotrophic lateral sclerosis. MATERIAL AND METHODS. The analysis of domestic and foreign publications for the period 1997-2024 is carried out. The sources of the Russian scientific electronic library eLibrary, RSCI databases, PubMed were used. CASE PRESENTATION. A patient is presented who, at the age of 56, developed mixed paresis of the right hand, followed by the development of mixed tetraparesis and simultaneously bulbar syndrome within 3 months. Differential diagnosis was performed between spondylogenic cervical myelopathy, endocrinopathy and ALS. Based on anamnestic data, clinical picture, rate of progression of symptoms, results of electroneuromyography, lack of improvement against the background of therapy, the main diagnosis was made: amyotrophic lateral sclerosis, a primary generalized form with mixed tetraparesis, bulbar syndrome. 2 weeks after discharge from the hospital in a stable condition, the patient was diagnosed with COVID-19 coronavirus infection, with a rapid fatal outcome from respiratory failure (7 months after the debut of ALS). CONCLUSION. A feature of the described ALS case is a rather rare primary generalized form of the disease (having such unfavorable prognosis factors as the development of bulbar syndrome at the beginning of the disease, a short time period from the appearance of the first symptoms to diagnosis), the presence of masking pathology in the form of spondylogenic myelopathy and the addition of COVID-19 with a rapid fatal outcome. With all the severity of ALS and an unfavorable prognosis, the presence of comorbid pathology can make the course of the disease even more dramatic. KEYWORDS: amyotrophic lateral sclerosis, comorbid pathology, coronavirus infection (COVID-19)

[Translated article] Survival Analysis and Prognostic Factors in a Case Series of 148 Cutaneous T-Cell Lymphomas

Background and ObjectiveCutaneous T-cell lymphomas (CTCL) such as mycosis fungoides (MF) and Sézary syndrome (SS) are rare lymphomas with varying prognoses. The aim of the study was to describe the survival of a cohort of patients with MF/SS and evaluate the prognostic factors impacting disease survival. Materials and MethodsAll cases of MF/SS diagnosed from 2008 through 2022 were retrospectively analyzed. The demographic variables, histological parameters, and analytical data were analyzed too. Progression-free survival (PFS) and disease-specific survival (DSS) were calculated. ResultsA total of 148 cases were included. A total of 121 (82%) and 27 cases were diagnosed with MF, and SS, respectively. A total of 37 patients (25%) experienced progression at some point disease progression. The median PFS and median DSS were 127 and 135 months, respectively. Age >60 years, diagnosis of SS, the presence of large cell transformation (LCT) at diagnosis, folliculotropism in early stages, high Ki-67 expression, the presence of the clonal T-cell receptor (TCR) in blood, elevated LDH and B2M levels, and advanced stages (IIB, IVA, T3, T4, N3/Nx) were associated with worse prognosis across the entire cohort. ConclusionsStage IVA and the presence of LCT at diagnosis stood out as independent factors of unfavorable prognosis. LCT was the variable that most significantly impacted the patients’ survival and was closely associated with tumor skin involvement and stage IIB.

Excessive accumulation of epicardial adipose tissue promotes microvascular obstruction formation after myocardial ischemia/reperfusion through modulating macrophages polarization

BackgroundOwing to its unique location and multifaceted metabolic functions, epicardial adipose tissue (EAT) is gradually emerging as a new metabolic target for coronary artery disease risk stratification. Microvascular obstruction (MVO) has been recognized as an independent risk factor for unfavorable prognosis in acute myocardial infarction patients. However, the concrete role of EAT in the pathogenesis of MVO formation in individuals with ST-segment elevation myocardial infarction (STEMI) remains unclear. The objective of the study is to evaluate the correlation between EAT accumulation and MVO formation measured by cardiac magnetic resonance (CMR) in STEMI patients and clarify the underlying mechanisms involved in this relationship.MethodsFirstly, we utilized CMR technique to explore the association of EAT distribution and quantity with MVO formation in patients with STEMI. Then we utilized a mouse model with EAT depletion to explore how EAT affected MVO formation under the circumstances of myocardial ischemia/reperfusion (I/R) injury. We further investigated the immunomodulatory effect of EAT on macrophages through co-culture experiments. Finally, we searched for new therapeutic strategies targeting EAT to prevent MVO formation.ResultsThe increase of left atrioventricular EAT mass index was independently associated with MVO formation. We also found that increased circulating levels of DPP4 and high DPP4 activity seemed to be associated with EAT increase. EAT accumulation acted as a pro-inflammatory mediator boosting the transition of macrophages towards inflammatory phenotype in myocardial I/R injury through secreting inflammatory EVs. Furthermore, our study declared the potential therapeutic effects of GLP-1 receptor agonist and GLP-1/GLP-2 receptor dual agonist for MVO prevention were at least partially ascribed to its impact on EAT modulation.ConclusionsOur work for the first time demonstrated that excessive accumulation of EAT promoted MVO formation by promoting the polarization state of cardiac macrophages towards an inflammatory phenotype. Furthermore, this study identified a very promising therapeutic strategy, GLP-1/GLP-2 receptor dual agonist, targeting EAT for MVO prevention following myocardial I/R injury.

Downregulation of DIP2B as a prognostic marker inhibited cancer proliferation and migration and was associated with immune infiltration in lung adenocarcinoma via CCND1 and MMP2

BackgroundDIP2B is related to cancer progression. This study investigated the roles and pathways of DIP2B in lung adenocarcinoma (LUAD). MethodsDIP2B expression and the relationship between survival time of cancer patients and DIP2B expression were analyzed. The relationship between DIP2B expression and survival time in LUAD patients was evaluated by a meta-analysis. Cox and survival analyses were used to evaluate the prognostic factors and construct a prognostic nomogram. The mechanisms and effects of DIP2B and the relationship between DIP2B expression and the immune microenvironment were investigated using bioinformatics, CCK-8, western blotting, and transwell experiments. ResultsDIP2B was overexpressed in LUAD tissues. DIP2B overexpression was associated with shorter prognosis and was an unfavorable risk factor for prognosis in LUAD patients. DIP2B co-expressed genes were involved in cell division, DNA repair, cell cycle, and others. Inhibition of DIP2B expression could downregulate the proliferation, migration, and invasion of LUAD A549 and H1299 cells, which was related to the decrease in CCND1 and MMP2 protein expression. BRCA1 overexpression was associated with short prognosis, and the nomogram formed by DIP2B and BRCA1 was associated with a poor prognosis in LUAD patients. DIP2B expression correlated with immune cells (such as CD8 T cells, Tcm, and iDCs) and cell markers. ConclusionDIP2B is a potential biomarker of poor prognosis and the immune microenvironment in LUAD. Inhibition of DIP2B expression downregulated cancer cell proliferation, migration, and invasion, which might be related to the decrease in CCND1 and MMP2 protein expression. DIP2B-related nomograms might be useful tools for predicting the prognosis of LUAD patients.

Factors of unfavorable prognosis in patients with non-high risk pulmonary embolism

Abstract Introduction Pulmonary embolism (PE) nowadays is the third leading cause of death in the structure of cardiovascular mortality after myocardial infarction and stroke. Most of patients (pts) with PE are with non-high risk. According to the latest guidelines PESI and sPESI scores are used to predict 30-day outcome of non-high-risk pts. Nevertheless, the question of additional factors which are not included in PESI and sPESI scores and which may be associated with prognosis in such pts remains poorly understood. Purpose To identify factors associated with in-hospital mortality in non-high-risk PE pts. Methods A retrospective analysis of 635 medical cards of pts with diagnosis "PE" hospitalized in our clinical hospital during 2017 – 2023 period. The diagnosis was verified by multispiral computed tomography angiography (CTPA) of pulmonary arteries and/or by autopsy. There were 530 non-high-risk pts (83,4%). Pts were divided into groups: І group - pts who were discharged from hospital with improved status (479 – 90,4%), II group - pts who died in hospital (51 – 9,6%). Clinical, anamnestic, laboratory and instrumental parameters were measured. Statistical analysis was performed. Results According to multivariate analysis of variance, independent factors, which were associated with in-hospital mortality in pts with non-high-risk PE, were: the presence of atrial fibrillation, obesity, age, history of venous thromboembolism, lower levels of O2 saturation, systolic blood pressure (SBP) and higher pulmonary artery pressure (PAP). ROC analysis was performed to determine the thresholds of factors that were associated with in-hospital mortality: SBP ≤124 mmHg, HR≥110 bpm, PAP ≥54 mmHg, age>54 yo. Conclusions The factors which were associated with in-hospital mortality in pts with non-high-risk PE were: age, SBP, history of VTE, obesity, AF; blood saturation level, pulmonary artery pressure level.

Immune cell infiltration and prognostic index in cervical cancer: insights from metabolism-related differential genes.

Cervical cancer remains a significant gynecologic malignancy in both China and the United States, posing a substantial threat to women's lives and health due to its high morbidity and mortality rates. Altered energy metabolism and dysregulated mitochondrial function play crucial roles in the development, growth, metastasis, and recurrence of malignant tumors. In this study, we aimed to predict prognosis and assess efficacy of anti-tumor therapy in cervical cancer patients based on differential genes associated with mitochondrial metabolism. Transcriptomic data and clinical profiles of cervical cancer patients were retrieved from the TCGA and GEO databases. Differential gene-related cellular pathways were identified through GO, KEGG, and GSEA analyses. Prognostic indices were constructed using LASSO regression analysis. Immune cell infiltration was assessed using CIBERSORT and ssGSEA, and the correlation between immune checkpoint inhibitor genes and differential genes was examined. Tumor mutation load (TMB) and its association with prognostic indices were analyzed using nucleotide variant data from the TCGA database. Patient response to immunotherapy and sensitivity to antitumor drugs were determined using the TIDE algorithm and the oncoPredic algorithm, respectively. A prognostic index based on metabolism-related differential genes was developed to predict the clinical outcome of cervical cancer patients, enabling their classification into two distinct subtypes. The prognostic index emerged as an independent risk factor for unfavorable prognosis. The high-index group exhibited a significantly worse overall prognosis, along with elevated tumor mutation burden (TMB), increased immune cell infiltration, and lower TIDE scores, indicating a potential benefit from immunotherapy. Conversely, the low-index group demonstrated increased sensitivity to metabolism-related antitumor agents, specifically multikinase inhibitors. The aim of this study was to develop a prognostic index based on differential genes associated with mitochondrial metabolism, which could be used to predict cervical cancer patients' prognoses. When combined with TIDE and TMB analyses, this prognostic index offers insights into the immune cell infiltration landscape, as well as the potential efficacy of immunotherapy and targeted therapy. Our analysis suggests that the Iron-Sulfur Cluster Assembly Enzyme (ISCU) gene holds promise as a biomarker for cervical cancer immunotherapy.

Dynamics of the State of Arterial Stiffness as a Possible Pathophysiological Factor of Unfavorable Long-Term Prognosis in Patients after Coronary Artery Bypass Grafting.

Patients with coronary artery disease (n = 251) in whom CAVI was assessed using the VaSera VS-1000 device before and one year after CABG. Groups with improved CAVI or worsened CAVI were identified. We assessed the following events at follow-up: all-causes death, myocardial infarction, and stroke/transient ischemic attack. All-causes death was significantly more common in the group with worsened CAVI (27.6%) than in the group with CAVI improvement (14.8%; p = 0.029). Patients with worsened CAVI were more likely to have MACE, accounting for 42.2% cases, compared with patients with CAVI improvement, who accounted for 24.5%; p = 0.008. Worsened CAVI (p = 0.024), number of shunts (p = 0.006), and the presence of carotid stenosis (p = 0.051) were independent predictors of death from all causes at 10-year follow-up after CABG. The presence of carotid stenosis (p = 0.002) and the group with worsened CAVI after a year (p = 0.008) were independent predictors of the development of the combined endpoint during long-term follow-up. Patients with worsening CAVI one year after CABG have a poorer prognosis at long-term follow-up than patients with improved CAVI. Future research would be useful to identify the most effective interventions to improve CAVI and correspondingly improve prognosis.

Comparison of sex differences on outcomes after aneurysmal subarachnoid hemorrhage: a propensity score-matched analysis

ObjectiveSex differences in outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) remain controversial. Therefore, the aim of this study was to investigate the sex differences in the prognosis of patients with aSAH.MethodsThis study retrospectively analyzed the clinical data of aSAH patients admitted to the Department of Neurosurgery of General Hospital of Northern Theater Command, from April 2020 to January 2022. The modified Rankin Scale (mRS) was used to evaluate outcomes at 3-month post-discharge. Baseline characteristics, in-hospital complications and outcomes were compared after 1:1 propensity score matching (PSM).ResultsA total of 665 patients were included and the majority (63.8%) were female. Female patients were significantly older than male patients (59.3 ± 10.9 years vs. 55.1 ± 10.9 years, P < 0.001). After PSM, 141 male and 141 female patients were compared. Comparing postoperative complications and mRS scores, the incidence of delayed cerebral ischemia (DCI) and hydrocephalus and mRS ≥ 2 at 3-month were significantly higher in female patients than in male patients. After adjustment, the analysis of risk factors for unfavorable prognosis at 3-month showed that age, sex, smoking, high Hunt Hess grade, high mFisher score, DCI, and hydrocephalus were independent risk factors.ConclusionFemale patients with aSAH have a worse prognosis than male patients, and this difference may be because females are more vulnerable to DCI and hydrocephalus.

Predictors of Unfavorable Prognosis in Patients with Heart Failure After Cardioverter-Defibrillator Implantation According to the Prospective Part of the Kuzbass Registry.

Identification of clinical and instrumental predictors for non-arrhythmic death in patients with heart failure (HF) and implantable cardioverter-defibrillator (ICD). Through a telephone survey and examination of medical records from hospital and polyclinic databases, data were obtained on the alive/dead status and causes of death for 260 patients with heart failure (HF) and ICD included in the Kuzbass Registry of Patients with ICD. The follow-up period was 1.5 years. Clinical and instrumental parameters entered into the registry before the ICD implantation were included in a univariate and multivariate step-by-step analysis using the logistic (for qualitative variables) and linear (for quantitative variables) regression with calculation of regression coefficients and construction of a prognostic regression model. The quality of the created model was assessed using a ROC analysis. During the observation period, 54 (20.8%) patients died. In 21 (38.8%) patients, death occurred in the hospital and was caused by acute decompensated heart failure in 15 (71.4%) patients, myocardial infarction in 3 (14.3%) patients, stroke in 1 (4.7%) patient, and pneumonia in 2 (9.5%) patients. 33 (61.2%) patients died outside the hospital; the cause of death was stated as the underlying disease associated with acute decompensated heart failure: in 9 (27.2%) patients, dilated cardiomyopathy; in 1 (3.0%) patient, rheumatic mitral disease; and in 23 (69.7%) patients, ischemic cardiomyopathy. According to the univariate regression model, the risk of death in the long-term period was increased by the QT interval prolongation (U 2.41, p = 0.0161); elevated pulmonary artery systolic pressure (U 4.30, p=0.0000) and increased left atrial size according to echocardiography (U 2.98, p=0.0029); stage IIB HF (OR 2.41; 95% CI: 1.26-4.6), NYHA III-IV (OR 3.03; 95% CI: 1.58-5.81); chronic obstructive pulmonary disease (OR 5.24; 95% CI: 2.04-13.45); and lack of optimal drug therapy (ODT) for HF before ICD implantation (OR 2.41; 95% CI: 1.29-4.49). The multivariate analysis identified the most significant factors included in the prognostic regression model: pulmonary artery systolic pressure above 45 mm Hg, social status, chronic obstructive pulmonary disease, and lack of ODT for HF. To ensure a maximum benefit from ICD, the factors that increase the likelihood of non-arrhythmic death should be considered before making a decision on ICD implantation. Particular attention should be paid to mandatory ODT for HF as the main modifiable risk factor for unfavorable prognosis.

Levels of cardiac biomarkers and three-year survival rate in hospitalized patients with heart failure and community-acquired pneumonia

Aim. To evaluate the impact of community-acquired pneumonia (CAP) on the levels of cardiac biomarkers and long-term survival rate in patients with heart failure (HF).Material and methods. The prospective observational single-center study included 132 patients (73 men, 59 women); mean age — 72,3±12,1 years, consecutively hospitalized at Clinical Hospital № 4 of the I. M. Sechenov First Moscow State Medical University with decompensated heart failure in the period from March 2018 to December 2019. The main (n=40) and comparison group (n=92) included patients with and without clinical and CT signs of CAP, respectively.Results. Patients with HF and CAP and HF without CAP were comparable in sex, age, and severity of HF. CAP in most patients met the criteria for non-severe pneumonia (average CURB-65 score — 1,55±0,73). The levels of N-terminal probrain natriuretic peptide (NT-proBNP) in patients with HF with CAP (1188,9 [439; 2493] pg/ml) were insignificantly higher than in patients with HF without CAP (839,6 [413; 1900]) pg/ml (p&gt;0,05). A similar pattern was noted for the soluble growth stimulation expressed gene 2 (sST2) (30,85 [12,8; 59,6] ng/ml vs 22,8 [15,2; 44,7] ng/ml, p&gt;0,05). The haptoglobin level in patients with CAP was significantly lower (732 [315; 1312] ng/l), compared to the group without CAP (1270 [902; 2022] ng/l, p=0,0022). No differences in the concentrations of galectin-3, copeptin and hepcidin were detected. The one-year mortality rate of patients who underwent CAP was 27,3%, and without CAP — 7,2% (p&lt;0,001), while the three-year mortality rate was 44,9% and 21,4%, respectively (p=0,0004). Elevated levels of NT-proBNP and sST2, along with age over 75 years and left ventricular ejection fraction &lt;40%, are additional factors of poor prognosis in patients with HF and CAP.Conclusion. CAP in patients with HF does not have a significant effect on most cardiac biomarkers, but significantly worsens the prognosis. Independent factors of unfavorable prognosis in patients with HF and CAP are age over 75 years, left ventricular ejection fraction &lt;40%, increased NT-proBNP and sST2 levels.

Identification of molecular characteristics of hepatocellular carcinoma with microvascular invasion based on deep targeted sequencing.

As an indicator of tumor invasiveness, microvascular invasion (MVI) is a crucial risk factor for postoperative relapse, metastasis, and unfavorable prognosis in hepatocellular carcinoma (HCC). Nevertheless, the genetic mechanisms underlying MVI, particularly for Chinese patients, remain mostly uncharted. We applied deep targeted sequencing on 66 Chinese HCC samples. Focusing on the telomerase reverse transcriptase (TERT) promoter (TERTp) and TP53 co-mutation (TERTp+/TP53+) group, gene set enrichment analysis (GSEA) was used to explore the potential molecular mechanisms of the TERTp+/TP53+ group on tumor progression and metastasis. Additionally, we evaluated the tumor immune microenvironment of the TERTp+/TP53+ group in HCC using multiplex immunofluorescence (mIF) staining. Among the 66 HCC samples, the mutated genes that mostly appeared were TERT, TP53, and CTNNB1. Of note, we found 10 cases with TERTp+/TP53+, of which nine were MVI-positive and one was MVI-negative, and there was a co-occurrence of TERTp and TP53 (p < 0.05). Survival analysis demonstrated that patients with the TERTp+/TP53+ group had lower the disease-free survival (DFS) (p = 0.028). GSEA results indicated that telomere organization, telomere maintenance, DNA replication, positive regulation of cell cycle, and negative regulation of immune response were significantly enriched in the TERTp+/TP53+ group (all adjusted p-values (p.adj) < 0.05). mIF revealed that the TERTp+/TP53+ group decreased CD8+ T cells infiltration (p = 0.25) and enhanced PDL1 expression (p = 0.55). TERTp+/TP53+ was significantly enriched in MVI-positive patients, leading to poor prognosis for HCC patients by promoting proliferation of HCC cell and inhibiting infiltration of immune cell surrounding HCC. TERTp+/TP53+ can be utilized as a potential indicator for predicting MVI-positive patients and poor prognosis, laying a preliminary foundation for further exploration of co-mutation in HCC with MVI and clinical treatment.

Опыт применения устекинумаба у бионаивных пациентов с болезнью Крона, имеющих факторы неблагоприятного прогноза: реальная клиническая практика

The purpose of this study was to study the effectiveness of ustekinumab (UST) depending on the dosage regimen (90 mg subcutaneously once every 8 or 12 weeks) in patients with Crohn's disease (CD) who have unfavorable prognosis factors. Material and methods. To assess the effectiveness of the drug, we included in the study 38 patients with CD who had unfavorable prognosis factors, who were randomized into two groups of patients who received the drug in a 90 mg subcutaneous regimen once every 12 weeks (1-st group, n = 20) and 90 mg subcutaneously once every 8 weeks (2-nd group, n = 18). The gender and age of the patient were analyzed, including at the time of diagnosis, the severity and prevalence of CD; the presence of intestinal complications; the presence and localization of extra-intestinal manifestations; previous treatment was analyzed. Results. Clinical response and clinical remission were achieved in 19 (95.0%) patients of the first group and 18 (100.0%) patients of the second group (p &gt; 0.05). Clinical remission was maintained (without the need for optimization of therapy) by the 52 week of follow-up in 18 (90.0%) patients, in the second group – 18 (100.0%) patients (p = 0.516). In the 1-st group 10 (50.0%) patients achieved and maintained endoscopic remission by the 52 week of follow-up, in the 2-nd group – 16 (88.9%) patients (p = 0.01492). During one year of follow-up, 10 (50.0%) patients of the 1-st group maintained clinical and endoscopic remission of CD, 8 (40.0%) patients maintained clinical response and clinical remission (a decrease of ≥ 100 points from the initial CDAI), 16 (88.9%) patients in the 2-nd group maintained clinical and endoscopic remission of CD. Clinical response and clinical remission were maintained in 2 (11.1%) patients. Clinical and endoscopic remission in patients with CD receiving the drug was achieved in the 2-nd group (p = 0.01492). Without steroidal remission in patients in 1-st group was 65.0%, and in in 2-nd group about 95% (p = 0.04502). Conclusion. This clinical observation demonstrated statistically significantly higher therapeutic efficacy (clinico-endoscopic, without steroidal remission) in CD patients with adverse prognosis factors receiving UST 90 mg subcutaneously every 8 weeks.

Evaluating Clinical Presentations and Diagnostic Procedures in Pediatric Autoimmune Hepatitis

Background: The aim of the current research was to assess the clinical manifestations and diagnostic methods used in juvenile cases of Autoimmune Hepatitis (AIH). Methods: This study employed a retrospective cross-sectional design to investigate pediatric patients diagnosed with AIH at Children’s Medical Center Hospital, which is affiliated to Tehran University of Medical Sciences (TUMS), Tehran, Iran. The study included patients who received routine examinations, treatments, and follow-ups during the period from 2018 to 2021. Results: The present investigation encompassed the evaluation of 52 pediatric patients, mostly female, with a mean age of 7.76 years. The vast majority of patients have encountered the occurrence of acute AIH. Positive findings for the Anti-Smooth Muscle Antibodies (ASMA) test were seen in 50% of the patients. The mean score for fibrosis in the observed individuals was 2.56, whereas the mean value for the Hepatitis Activity Index (HAI) in a subset of 29 patients was found to be 7.34. One patient succumbed to the condition, one case underwent transplantation, and another individual was identified as a candidate for liver transplantation. Conclusion: Patients with AIH saw a decrease in long-term survival. There was no observed disparity in prognosis based on gender; nevertheless, it was noted that males had a shorter lifespan, perhaps attributable to an earlier beginning of the illness. The presence of cirrhosis at the time of diagnosis constituted a significant risk factor for unfavorable prognosis, as it was associated with an elevated overall risk of mortality owing to liver dysfunction.

Looking through the imaging perspective: the importance of imaging necrosis in glioma diagnosis and prognostic prediction - single centre experience.

The aim of the study was to investigate the diagnostic value of imaging necrosis (Imnecrosis) in grading, predict the genotype and prognosis of gliomas, and further assess tumor necrosis by dynamic contrast-enhanced MR perfusion imaging (DCE-MRI). We retrospectively included 150 patients (104 males, mean age: 46 years old) pathologically proved as adult diffuse gliomas and all diagnosis was based on the 2021 WHO central nervous system (CNS) classification. The pathological necrosis (Panecrosis) and gene mutation information were collected. All patients underwent conventional and DCE-MRI examinations and had been followed until May 31, 2021. The Imnecrosis was determined by two experienced neuroradiologists. DCE-MRI derived metric maps have been post-processed, and the mean value of each metric in the tumor parenchyma, peritumoral and contralateral area were recorded. There was a strong degree of inter-observer agreement in defining Imnecrosis (Kappa = 0.668, p < 0.001) and a strong degree of agreement between Imnecrosis and Panecrosis (Kappa = 0.767, p < 0.001). Compared to low-grade gliomas, high-grade gliomas had more Imnecrosis (85.37%, p < 0.001), and Imnecrosis significantly increased with the grade of gliomas increasing. And Imnecrosis was significantly more identified in IDH-wildtype, 1p19q-non-codeletion, and CDKN2A/B-homozygous-deletion gliomas. Using multivariate Cox regression analysis, Imnecrosis was an independent and unfavorable prognosis factor (Hazard Ratio = 2.113, p = 0.046) in gliomas. Additionally, extravascular extracellular volume fraction (ve) in tumor parenchyma derived from DCE-MRI demonstrated the highest diagnostic efficiency in identifying Panecrosis and Imnecrosis with high specificity (83.3% and 91.9%, respectively). Imnecrosis can provide supplementary evidence beyond Panecrosis in grading, predicting the genotype and prognosis of gliomas, and ve in tumor parenchyma can help to predict tumor necrosis with high specificity.

Predictors for unfavorable prognosis after stroke with perforator artery disease.

Perforator artery disease (PAD) is an important subtype of ischemic stroke. The risk factors affecting the prognosis of patients with PAD are unclear. This study aimed to investigate the risk factors affecting the unfavorable prognosis of PAD. Patients with PAD were enrolled from Dushu Lake Hospital Affiliated to Soochow University and diagnosed as stroke with PAD during the period from September 2021 to July 2023 and followed up with a modified Rankin Scale (mRS) after 90 days, defining the mRS of 0-2 as a group with favorable prognosis, and 3-6 as a group with unfavorable functional outcome. Logistic regression was used to identify predictors for PAD. Multiple logistic regression analysis and receiver operating characteristics (ROC) were used to identify predictors of unfavorable prognosis. Of the 181 enrolled patients, 48 (26.5%) were identified with unfavorable prognosis. On multivariate analysis, increased age (OR = 1.076, 95% CI: 1.012 ~ 1.144, p = 0.019), higher National Institutes of Health Stroke Scale (NIHSS) score at admission (OR = 2.930, 95% CI: 1. 905 ~ 4.508, p < 0.001), and increased neutrophil-to-lymphocyte ratio (NLR) (OR = 3.028, 95% CI: 1.615 ~ 5.675, p = 0.001) were independent risk factors for unfavorable prognosis in patients with PAD, and the area under the receiver operating characteristic curve was 0.590, 0.905, and 0.798, and the multi-factor diagnostic model (Model 2) showed reliable diagnostic specificity and sensitivity (area under the curve = 0.956, p < 0.001, specificity 0.805, sensitivity 0.958, accuracy 0.845). Increased baseline NLR and NIHSS score and aging may be independent risk factors for unfavorable prognosis of patients with PAD. NLR can be used as a potential biological indicator to predict the prognosis of stroke with PAD.

Chronic lymphocytic leukemia in combination with COVID-19: clinical features and unfavorable prognosis factors

Background. At the end of 2019, a new coronavirus infection caused by the SARS-CoV-2 virus was registered. In March 2020, the first cases of COVID-19 were detected in Moscow. Patients with chronic lymphocytic leukemia, characterized by profound immune dysfunction, have risk factors for severe viral disease.Aim. To identify risk factors for hospital mortality and severe course of COVID-19, as well as to optimize therapeutic and preventive measures.Materials and methods. The analysis included 238 patients (142 (59 %) men and 96 (41 %) women) with chronic lymphocytic leukemia and COVID-19 with a median age of 66 (37-90) years, who were hospitalized at City Clinical Hospital No. 52 (Moscow) between April 2020 and April 2023. To compare hospital mortality and severity of COVID-19, patients were divided into 2 groups depending on the hospitalization period: 2020-2021 and 2022-2023, which correlates with the prevalence of some SARS-CoV-2 variants from December 2021 and changes in Moscow epidemiological situation.Results. Overall hospital mortality rate in 2020-2021 was 25 % (n = 45). Age over 73 years was a significant unfavorable factor in men. Cardiovascular diseases increase the risk of death by 2.3 times. Patients with a Charlson Comorbidity Index of 6 or more have a 2.2 times greater risk of death. A history of 1 or more lines of immunochemotherapy increased the risk of hospital mortality by 1.5 times. Relapse/progression of the disease were factors of unfavorable prognosis for patient survival. Binet stage C also showed a significant unfavorable prognosis. When studying all cases of death (n = 51), complications such as myelotoxic agranulocytosis, secondary bacterial complications and severe interstitial pulmonary damage &gt;75 % were identified.Conclusion. Coronavirus infection caused by SARS-CoV-2 represents an infectious threat among patients with chronic lymphocytic leukemia and may affect the regimen and tactics of antitumor therapy. The use of a full range of preventive measures, vaccination and pre-exposure prophylaxis in this cohort of patients is of great importance.

Assessment of renal and cardiovascular risks in patients with type 2 diabetes when using non-steroidal mineralocorticoid receptor antagonists

Background. Given the proven excessive activation of the renin-angiotensin-aldosterone system and the clinical manifestations of hypertension, mostly of renal origin, there is a need to optimize antihypertensive therapy aimed at an active nephroprotection. The purpose of the study is to carry out a comprehensive assessment of kidney and heart risk factors in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) and to justify the administration of non-steroidal mineralocorticoid receptor antagonists to these patients. Materials and methods. In a prospective cohort study, 88 patients with type 2 diabetes were examined: group 1 — estimated glomerular filtration rate (eGFR) &lt; 60 ml/min/m2, group 2 — eGFR ≥ 60 ml/min/m2. eGFR was evaluated according to the CKD-EPI (Chronic Kidney Disease Epidemiology Colla­boration) formula based on serum creatinine. GFR category was defined according to the KDIGO (Kidney Disease: Improving Global Outcomes) criteria. The albumin-creatinine ratio was calcula­ted. The level of glycated hemoglobin (HbA1c) was assessed by the method of high-performance liquid chromatography. Aldosterone was evaluated by immunoenzymatic method. Results. In patients with eGFR &lt; 60 ml/min/m2, the albumin-creatinine ratio in daily urine is statistically significantly higher compared to group 2. Patients with eGFR &lt; 60 ml/min/m2 had an average uric acid level of 410.3 ± 98.8 μmol/l, which is statistically significantly higher than in those with eGFR ≥ 60 ml/min/m2 — 321.10 ± 74.54 μmol/l. A statistically significant correlation between the level of uric acid and markers of renal dysfunction was found only in patients with eGFR &lt; 60 ml/min/m2. Aldosterone levels were higher in the first group. No statistical difference was found between the average value of HbA1c in the studied groups. Conclusions. Numerous factors of unfavorable prognosis regarding kidney and heart risks have been identified: hypertension, increased albumin-creatinine ratio and cholesterol, unsatisfactory compensation of diabetes, obesity. There is an increase in the frequency of resistant hypertension, hyperuricemia, and hyperaldosteronism in patients with decreased eGFR. In patients with diabetic kidney damage on the background of type 2 diabetes, the administration of finerenone, a non-steroidal mine­ralocorticoid receptor antagonist, at a dose of 10–20 mg/day is pathogenetically justified.

Análisis de supervivencia y factores pronósticos en una serie de 148 casos de linfomas cutáneos de células T

Background and ObjectiveCutaneous T-cell lymphomas (CTCL) such as mycosis fungoides (MF) and Sézary syndrome (SS) are rare lymphomas with varying prognoses. The aim of the study was to describe the survival of a cohort of patients with MF/SS and evaluate the prognostic factors impacting disease survival. Materials and MethodsAll cases of MF/SS diagnosed from 2008 through 2022 were retrospectively analyzed. The demographic variables, histological parameters, and analytical data were analyzed too. Progression-free survival (PFS) and disease-specific survival (DSS) were calculated. ResultsA total of 148 cases were included. A total of 121 (82%) and 27 cases were diagnosed with MF, and SS, respectively. A total of 37 patients (25%) experienced progression at some point disease progression. The median PFS and median DSS were 127 and 135 months, respectively. Age >60 years, diagnosis of SS, the presence of large cell transformation (LCT) at diagnosis, folliculotropism in early stages, high Ki-67 expression, the presence of the clonal T-cell receptor (TCR) in blood, elevated LDH and B2M levels, and advanced stages (IIB, IVA, T3, T4, N3/Nx) were associated with worse prognosis across the entire cohort. ConclusionsStage IVA and the presence of LCT at diagnosis stood out as independent factors of unfavorable prognosis. LCT was the variable that most significantly impacted the patients’ survival and was closely associated with tumor skin involvement and stage IIB.

ALKHB5-demethylated lncRNA SNHG15 promotes myeloma tumorigenicity by increasing chromatin accessibility and recruiting H3K36me3 modifier SETD2.

Chromatin instability plays a crucial role in multiple myeloma (MM) relapse and progression, but its mechanism remains obscure. Here, we uncovered that m6A-demethylase ALKBH5 upregulated and stabilized long noncoding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15), which was elevated in MM and positively correlated with unfavorable clinical prognosis factors. ALKBH5-SNHG15 axis participated in viability and migration/invasion of myeloma cell lines and MM-xenografted SCID/NOD mice. Mechanically, ALKBH5 promoted the expression of trimethylated histone H3 at lysine 36 (H3K36me3) methyltransferase SETD2 through lncRNA SNHG15-mediated protein stability. ALKBH5-SNHG15 axis increased chromatin accessibility and altered the H3K36me3 enrichment at the gene body, which is responsible for transcription elongation. Our study suggested a novel epigenetically interaction of N6-methyladenosine (m6A) methylation, lncRNA SNHG15, and histone SETD2/H3K36me3 modifications in myeloma progression, indicating that ALKBH5 and lncRNA SNHG15 could serve as potential novel therapeutic targets for MM treatment.NEW & NOTEWORTHY To our knowledge, this study first demonstrated the prognostic significance and biological function of long noncoding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) in multiple myeloma (MM), and indicated a novel revelation on the effect of N6-methyladenosine (m6A)-regulated lncRNA on MM tumorigenicity. Moreover, the novel chromatin-regulatory mechanism of lncRNA by interacting with epigenetic modifiers including m6A demethylase ALKBH5 and H3K36me3 methyltransferase SETD2 in myeloma progression elucidated intricate mechanism of tumor pathogenesis.

Prognostic Factors and Treatment Strategy in Patients with Hodgkin Lymphoma and HIV Infection Treated with ABVD and CART: A Retrospective Study from Spanish Group Geltamo

Background Hodgkin lymphoma (HL) is one of the most frequent non-AIDS defining neoplasm in people living with HIV (PLWH). Since the widespread use of combined antiretroviral therapy (cART), the incidence of most types of non-Hodgkin lymphoma affecting PLWH have decreased, but the incidence of HL has increased. The International Prognostic Score (IPS) is the most widely used score for HL. However, its implementation in PLWH is still controversial. Current HL treatment guidelines consider early and advanced stage. In function of the presence of unfavorable risk factors in early stages, an interim PET-CT can be used to guide therapeutic strategy. Unfavorable risk factors have been described by international groups (EORT, GHSG, NCI-C, and NCCN), which are: ≥3-4 involved lymph node areas, elevated RDW, age ≥50 years, ≥1 extranodal involvement and presence of B symptoms. There is a lack of evidence of the impact of this strategy in patients with HIV. Methods Retrospective multicentric study of patients with HIV infection diagnosed with HL in 9 hospitals from the GELTAMO group in Spain, from 1995 to 2022. All patients were treated with ABVD and cART +/- radiotherapy. The main clinical and biological variables were collected. Peripheral absolute neutrophil, lymphocyte and monocyte counts were studied, including L/M ratio and CD4 + lymphocyte count. Moreover, serum lactate dehydrogenase (LDH), albumin and RDW were evaluated. Univariable and multivariable analysis were performed using the binary logistic regression model for complete response (CR) rate and Cox proportional-hazards regression model for overall survival (OS) and progression-free survival (PFS). Survival curves were plotted by the Kaplan-Meier method and compared by the log-rank test. Results Ninety patients were retrospectively analyzed with a median follow up of 5.89 [0,4;24,78] years. The characteristics of the patients are summarized in Table 1. Extranodal involvement, hemoglobin &amp;lt;105 g/L, leucocytosis, high RDW, hypoalbuminemia and high LDH were associated with worse probabilities of complete response (CR) achievement. In the univariate analysis, bone marrow involvement and monocytes count ≥0.6 x10^9/L were associated with shorter overall survival (OS) and progression free survival (PFR) probabilities. A lymphocyte/monocyte (L/M) ratio &amp;lt;1.09 was associated with shorter PFR probabilities. By multivariable analysis, only monocyte count ≥0.6 x10^9/L emerged as an unfavorable prognostic factor for OS and PFS ( Figure 1). Data about treatment strategy and CR achievement is described in Table 1. Most patients (74%) presented advanced stage and the presence of unfavorable prognostic factors (described by international groups) was detected in most of the patients with localized stages ( Table 1). Conclusions High monocyte count is a strong prognostic factor which can be used in PLWH with HL. Most patients with HL and HIV infection present an advanced stage at diagnosis or a localized stage with unfavorable prognosis factors. In patients with localized stage, interim PET-CT guided strategy seems to be feasible.