Unfavorable Prognosis Factor Research Articles

Delay in diagnosis to treatment and impact on survival of gastric adenocarcinoma in a low income setting without screening facility

The treatment modality of gastric adenocarcinoma (GCA) depends on the stage of the disease at the clinical presentation. Long delays are probably an unfavorable factor for the patient's prognosis. A prospective longitudinal, study involving 145 consecutive GCA was conducted at the National Hospital of Sri Lanka (NHSL). The overall delay (in weeks) was recorded for each patient and divided into four periods-patient, endoscopy, pathology and treatment. The median and Interquartile Range (IQR) duration of delays were calculated and differences were explored with chi square test and Mann Whitney U test Survival analysis was done with Kaplan Meier technique and Cox regression. The median duration of delays for patient, endoscopy, histology reporting delay, other histology delay (specimen transfer delay and report receipt delay) and treatment were 18 (IQR 14–27), 2 (IQR 2–3), 3 (IQR 2–3), 2 (IQR 1–2) and 6 (IQR 4–8) weeks respectively. Delayed patient presentation to hospital was associated with significant adverse median survival 16 (IQR 11.5–22.5) weeks versus 20 (IQR 16–27.5) weeks, p = 0.004. Delay in initiating treatment was associated with significantly lower median survival 04 (IQR 4–6) weeks versus 06 (IQR 4–8) weeks, p = 0.003. Over 60% of both proximal and distal GCA presented at an advanced radiological stage (stage III/IV). The Kaplan Meier analysis showed that the higher hazard function was associated with a higher tumour stage and undergoing chemotherapy. Age of the patient and the treatment modality were significant predictors of the survival. Patient delay and delay in initiation of definitive treatment are the most important factors that adversely affect the outcomes of GCA. Public health interventions aiming to shorten the patient delay time with proper referral for specialist care would play an important role. Also, it is important to minimize these preventable delays and there should be time limits in producing the histopathology report and to establish online portals of hospital and laboratory information systems for easy access of histology reports in future.

High expression of CD8+ T-lymphocytes in the peritumoral zone of renal cancer as a factor of unfavorable prognosis

AIM: To evaluate the prognostic value of quantitative CD8+ T-lymphocyte counts in the peritumorotic zone of renal cell cancer.
 MATERIAL AND METHODS: The material of 74 patients after operative treatment for renal cell carcinoma with complete 5-year follow-up was retrospectively analyzed. Of the 74 patients, 56 were alive by the 5-year follow-up, and 18 had died of cancer. After immunohistochemical staining, CD8+ T-lymphocyte distribution density in the peritumorotic zone of carcinomas was determined in 3 representative fields of view at 400 magnification and correlated with the clinicopathological characteristics of neoplasms and overall 5-year patient survival rate.
 RESULTS: The high level of CD8+ T-lymphocyte infiltration in the peritumoral zone of carcinomas was seen in stages IIIIV of the disease (p=0.0000001), in tumors 7 cm (p=0.0000001), in Fuhrman grade IIIIV anaplasia (p=0.001), in metastases (p=0.0000001) and in the shorter total survival rate of patients (p=0.0003). High CD8+ T-lymphocyte count was also observed in men (p=0.001) and in cases of unclassified cancer.
 CONCLUSION: In the light of the need to search for new prognostic criteria in renal cancer, we conclude that a high level of peritumorous zone infiltration by CD8+ T-lymphocytes is an unfavorable prognostic factor. Assessment of peritumorous zone infiltration by CD8+ T-lymphocytes may serve as an additional prognostic factor in renal cell carcinoma.

Risk factors and dynamic nomogram for unfavorable prognosis of Marchiafava-Bignami disease.

Most patients with Marchiafava-Bignami disease (MBD) had unfavorable prognosis, with disability or death. We aimed to determine the risk factors of early unfavorable prognosis of MBD, and to develop a predictive nomogram for early unfavorable prognosis of MBD. MBD patients admitted to our hospital between 1 January 2013 and 31 December 2021 were included. Unfavorable prognosis was defined as mRS score ≥3, the independent risk factors for unfavorable prognosis of MBD with the odds ratio (OR) and 95% confidential interval (CI) acquired by multiple logistic regression were included in development of the predictive nomogram for early unfavorable prognosis of MBD, and the area under curve (AUC) of the receiver operating characteristic curve was calculated. The published case reports of MBD were used as the external validation group to verify the predictive ability of the nomogram. Independent risk factors for early unfavorable prognosis of MBD included Glasgow Coma Scale score (OR = 0.636, 95% CI = 0.506-0.800, p = 0.004) and pneumonia (OR = 2.317, 95% CI = 1.003-5.352, p = 0.049). The AUC of the nomogram was 0.852. Ninety-four case reports, a total of 100 cases of MBD were included as the external validation group, its AUC was 0.840. The online dynamic nomogram for early unfavorable prognosis of MBD was constructed. It is confirmed by external validation that the nomogram has a preferable predictive ability and clinical efficacy, and the dynamic online predictive nomogram is helpful for physicians to quickly assess the prognosis of MBD.

UCA1 executes an oncogenic role in pancreatic cancer by regulating miR-582-5p/BRCC3.

As a fatal disease, the mechanism of pancreatic cancer is unclear. Urothelial carcinoma antigen 1(UCA1), a long noncoding RNA (lncRNA) that was first reported in bladder cancer, acts as an oncogene. However, the regulatory role and mechanism of UCA1 in pancreatic cancer remain unknown. This study aims to investigate the expression level and prognostic value of UCA1 in pancreatic cancer tissues, the effects and mechanism of UCA1 in regulating cell proliferation, apoptosis and metastasis. UCA1 expression levels in tissues were detected by in situ hybridization (ISH) and the prognostic value was evaluated by univariate and multivariate survival analysis. For in vitro experiments, proliferation was evaluated by a cell count kit assay, Edu experiments, and a clone formation assay. Apoptosis was evaluated by fluorescence-activated cell sorting flow-cytometry. Cell migration and invasion capacities were detected by wound healing and transwell assays. Western blots were performed to detect apoptotic associated molecules and epithelial-mesenchymal transition (EMT) markers. For the in vivo experiment, subcutaneous transplantation models of pancreatic cancer in nude mice were established to observe the tumor growth. The regulatory mechanism of UCA1 was explored by proteomics, bioinformatic analysis, luciferase reporter assays, and rescue experiments. ISH staining revealed that UCA1 levels between cancer tissues (n=94) and tumor-adjacent tissues (n=73) did not show significant differences. Survival analysis indicated that high expression of UCA1 was an unfavorable prognosis factor for pancreatic cancer. Downregulation of UCA1 by siRNA significantly inhibited cell proliferation, decreased the capacities of cell migration and invasion, induced cell apoptosis, and inhibited EMT. Furthermore, we demonstrated that UCA1 positively regulated the expression of BRCC3 by inhibiting miR-582-5p. Rescue experiments indicated that either inhibiting the expression of miR-582-5p or enhancing expression of BRCC3 could partly attenuate the antitumor effects of downregulation of UCA1. UCA1 acted as an oncogene in pancreatic cancer by partly regulating miR-582-5p/BRCC3, which could be a new therapeutic target for pancreatic cancer.

An analysis of clinical characteristics and prognosis of endometrioid ovarian cancer based on the SEER database and two centers in China

PurposeTo assess the clinical characteristics and the risk factors related to the unfavorable prognosis of endometrioid ovarian carcinoma (EOVC) based on data from the Surveillance, Epidemiology, and End Results (SEER) database and two clinical centers in China.MethodsData were extracted from the SEER database and two clinical centers in China (2010 ~ 2021), 884 cases and 87 patients with EOVC were selected, respectively. Overall survival (OS) and progression-free survival (PFS) were compared among the different groups using Kaplan–Meier analysis. The Cox proportional-hazards model was used to identify independent prognostic factors related to EOVC. A nomogram was constructed based on the risk factors of the SEER database affecting prognosis and the discrimination and calibration of the nomogram were evaluated by C-index and calibration curves.ResultsThe average age at diagnosis of patients with EOVC in the SEER database and two centers in China was 55.77 ± 12.40 years and 47.14 ± 11.50 years, 84.7% and 66.6% of them were diagnosed at FIGO stage I ~ II, respectively. In the SEER database, age over 70 years, advanced FIGO stage, tumor grade 3, only unilateral salpingo-oophorectomy were independent risk factors of unfavorable prognosis. In two clinical centers in China, 27.6% of EOVC patients were diagnosed with synchronous endometriosis. Advanced FIGO stage, HE4 > 179 pmol/L and bilateral ovarian involvement significantly correlated with poor OS and PFS in Kaplan–Meier analysis. Body mass index (BMI) < 19.34 kg/m2 was an independent risk factor relating to OS and PFS. Additionally, C-index of internal and external verification for the nomogram were 0.812 and 0.754 respectively, revealing good accuracy and clinical applicability.ConclusionsMost patients were diagnosed at early stage, low grade and had better prognosis. Asian/Pacific Islander and Chinese diagnosed with EOVC were more likely to be younger than whites and blacks. Age, tumor grade and FIGO stage (SEER database) and BMI (two centers) are independent prognostic factors. HE4 appears to be more valuable in prognostic assessment compared with CA125. The nomogram had good discrimination and calibration for predicting prognosis, providing a convenient and reliable tool for clinical decision-making for patients with EOVC.

RISK FACTORS FOR UNFAVORABLE PROGNOSIS AND PROGRESSION OF CHRONIC HEART FAILURE IN COVID-19 PNEUMONIA

Introduction. Patients with chronic heart failure are vulnerable to coronavirus disease (COVID-19).&#x0D; Objectives. To investigate risk factors for unfavorable prognosis and progression of heart failure in hospitalized patients with chronic heart failure and COVID-19 pneumonia.&#x0D; Methods. A retrospective analysis of the medical records of 555 hospitalized patients diagnosed with COVID-19 was conducted. Subsequently, the data of 90 patients with chronic heart failure (CHF) and COVID-19 pneumonia from January – February 2021 were collected at Lviv Clinical Hospital of Emergency Medical Care. The following indices were evaluated: anthropometric and demographic data, complications, treatment results, results of clinical, laboratory, and instrumental examinations, and dynamic NT-proBNP.&#x0D; Results. CHF is recorded in 42.9% of hospitalized patients with COVID-19 and is accompanied by lower values of blood oxygen level (p=0.0474), hemoglobin (p=0.0090), prothrombin time (p=0.0196), prothrombin index (p=0.0196) and higher indicators of glucose (p=0.0032), creatinine (p=0.00001), interleukin-6 (p=0.0041). CHF decompensation is associated with lower values of body temperature (p=0.0047) and blood oxygen saturation (p=0.0076), while hemoglobin level (p=0.0026), higher creatinine values (p=0.0034), interleukin-6 (p=0.0300), aspartate aminotransferase (p=0.0035), troponin I (p=0.0061); are associated with the development of myocardial infarction (p=0.0014), acute arrhythmias (p=0.0011), hypertensive crisis (p=0.0096) and increased mortality (OR=5.72; 95). % CI: 1.84, 17.81; p=0.0026).&#x0D; Conclusions. CHF is common and often fatal in patients with COVID-19, especially in decompensated CHF. Low blood oxygen saturation, myocardial infarction, arrhythmia, hypertensive crisis, increased cardio cytolysis markers and pro-inflammatory cytokines preceding adverse cardiovascular risk factors contribute to CHF decompensation in patients with COVID-19.

#4879 PREDICTORS OF KIDNEY DISEASE PROGRESSION IN MALES WITH X-LINKED ALPORT SYNDROME

Abstract Background and Aims Alport's syndrome is the second most common monogenic cause of end-stage renal disease (ESRD). Males with X-linked Alport's syndrome (XLAS) have a high risk of early ESRD development. The aim of study was to determine the predictors of unfavorable renal prognosis in boys with XLAS. Method The children with genetically confirmed XLAS (n = 84, age 8.7±4.3 yrs, eGFR 102±16.2 ml/min/1.73 m2, 59 pts with missense COL4A5 mutations) were included in observation single center study (FU 6.9±2.4 yrs). Seventy three pts (q = 0.87) were treated with ACEi (age of start 7.6±3.3 yrs, dose for Ramipril 2.7±0.8 mg/m2/day). Arterial blood pressure (BP), proteinuria (Pr, mg/m2/day), eGFR (Schwartz equation, ml/min/1,73m2), gene mutation type and ACEi-treatment data (age of pts and disease stage at the therapy start, ACEi dosage, dynamics of Pr and eGFR) were obtained and updated for each patients. BP &amp;gt;90 perc for gender, age and height was defined as uncontrolled (uBP); Pr was categorised according to its level as a low (100-&amp;lt;250 mg/m2/day), moderate (≥250-500 mg/m2/day), high (≥500-1000 mg/m2/day) and nephrotic (≥1000 mg/m2/day). Gene mutations were divided into severe (nonsense, deletion, splicing) and less severe (missense) mutations. The eGFR&amp;lt;60 ml/min/1,73m2 was defined as primary outcome. Results Twenty pts (q = 0.24, age 13.5±2.96 yrs) reached the end point during observation period. Non-missense COL4A5 mutations (HR = 4.28, 95% CI 1.47-12.4, p = 0.007), uBP (HR = 20, 95% CI 4.68-29.6, p&amp;lt;0.001), persistent Pr &amp;gt;250 mg/m2/day (HR = 20, 95% CI 3.36-21, p&amp;lt;0.001), absence of ACEi treatment (HR = 10.7, 95% CI 2.45-14.7, p = 0.02) or start therapy at proteinuric stage of disease (HR = 20, 95% CI 2.2-13.8, p&amp;lt;0.001) were the risk factors of disease progression. Multiple regression analysis adjusted for age, initial eGFR revealed that late start of ACEi treatment (β = 0.23, p = 0.036), persistence of uBP (β = 0.26, p = 0.008) and Pr &amp;gt;250 mg/m2/day (β = 0.17, p = 0.04) had independent significance and predict unfavorable renal prognosis (R = 0.76, R2 = 0.57, p&amp;lt;0.000). Conclusion Persistent proteinuria and uncontrolled blood pressure, initiation of ACEi treatment at the proteinuric stage of glomerulopathy are the factors of unfavorable prognosis in male with XLAS.

Clinicopathological Analysis of Complicated Colorectal Cancer: A Five-Year Retrospective Study from a Single Surgery Unit.

Patients with primary colorectal cancer can present with obstructions, tumor bleeding, or perforations, which represent acute complications. This paper aimed to analyze and compare the clinical and pathological profiles of two patient groups: one with colorectal cancer and a related complication and another without any specific complication. We performed a five-year retrospective study on colorectal cancer patients admitted to a surgery unit and comparatively explored the main clinical and pathological features of the tumors belonging to the two groups. A total of 250 patients with colorectal cancer were included in the analysis. Of these, 117 (46.8%) had presented a type of complication. The comparative analysis that examined several clinical and pathological parameters showed a statistically significant difference for unfavorable prognosis factors in the group with complications. This was evident for features such as vascular and perineural invasion, lymph node involvement, pathological primary tumor stage, and TNM stage. Colorectal cancers with a related complication belonged to a group of tumors with a more aggressive histopathologic profile and more advanced stages. Furthermore, the comparable incidence of cases in the two groups of patients warrants further efforts to be made in terms of early detection and prognosis prediction of colorectal cancer.

Morphological and immunohistochemical analysis of tumor-infiltrating lymphocytes, M2 macrophages, BCL 6 and SOX10 in the tumor microenvironment of nodular cutaneous melanoma

Introduction. Cutaneous melanoma is one of the most aggressive malignant tumors, and its nodular form with vertical growth is characterized by unfavorable prognosis. However, in the recent years due to advances in basic oncology, a breakthrough in drug therapy of this pathology was made. To a great extent, it is linked to implementation of new therapy with checkpoint inhibitors. The best and longest response rates of cutaneous melanoma to this treatment were achieved compared to other oncological diseases. This fact can be explained by immunogenicity of cutaneous melanoma, high mutational load, as well as features of its tumor microenvironment, where in most cases high infiltration by immunocompetent cell is observed. However, immune cells vary by their composition and functions. Some of them can even promote tumor growth. Therefore, study of cell composition, degree and distribution of immune infiltration in the tumor can help identify potential factors of favorable and unfavorable prognosis for cutaneous melanoma which is important in clinical practice.Aim. To determine the frequency of CD3+-, CD4+-, CD8+-T-lymphocytes, CD163, BCL6 and SOX10 expression in patients with primary nodular cutaneous melanoma, as well as correlation of these markers with each other and standard morphological parameters for this non-epithelial malignant tumor.Materials and methods. In the study, the expression frequency of CD3+-, CD4+-, CD8+-T-lymphocytes, CD163, BCL6 and SOX10 in the postoperative material of 20 patients with true primary nodular cutaneous melanoma was measured using immunohistological analysis. The correlation of these markers with each other and standard morphological parameters was determined.Results. In most cases of nodular cutaneous melanoma, moderate and marked lymphocytic (immune) infiltration (grade II–III) was observed with no correlation with Breslow tumor thickness. Study of the ratio between CD4-positive T helpers and CD8-positive cytotoxic T lymphocytes in the tumor microenvironment showed that the number of the latter increased the higher was the degree of immune infiltrate. Markedness of macrophage infiltration directly correlated with markedness of lymphocytic infiltration. BCL6 expression in lymphocytes was observed in all cases of infiltration.Conclusion. Immune infiltrate in nodular cutaneous melanoma is a multicomponent, dynamic microenvironment containing both antitumor and tumor-promoting components with balance shifting to one or other side. Their qualitative, quantitative and, possibly, topographic ratios in the primary lesion of cutaneous melanoma affect the effectiveness of drugs and disease prognosis. Knowledge on the predominance of components negatively affecting tumor growth in the primary lesion can help an oncologist in selection of correct treatment tactics and disease observation.

Presence of schistosome eggs in lymph node predict unfavorable prognosis in schistosomal colorectal cancer.

The purpose of this study was to investigate the prognostic significance of schistosome eggs' location in schistosomal colorectal cancer (SCRC). 172 cases of SCRC were retrospectively analyzed. Patient clinicopathological parameters and survival rates were analyzed. There were 102 males and 70 females, the median age was 71 years (range, 44-91). All patients were followed, and the median time was 50.1 months (range, 1.0-79.7). There were 87 patients with PS1 (presence site 1, eggs deposited in the mucosa) and 85 patients with PS2 (presence site 2, eggs deposited in the muscularis propria or throughout the full thickness of the intestinal wall), 159 patients presented with eggs in cutting edge and 83 patients presented with eggs in lymph node (LN). Hepatic schistosomiasis was found in 27.3% of patients by imaging modalities and correlated to patients with PS2 ( P < 0.001) and LNs' eggs ( P < 0.001). Survival analyses showed that in stage III SCRC, eggs' presence in LN associated with worse DFS ( P = 0.004) or marginally worse OS ( P = 0.056), patients with PS2 had shorter OS ( P = 0.044). Multivariate analyses revealed hepatic schistosomiasis was an independent prognostic factor for DFS and OS in stage III SCRC ( P = 0.001, 0.002, respectively). In adjusted multivariate analysis, eggs' presence in LN was an independent prognostic factor for DFS in stage III SCRC ( P = 0.006). In stage III SCRC, eggs' presence in LN could predict poor prognosis and hepatic schistosomiasis was an independently unfavorable prognosis factor.

MiR-3133 is an unfavorable prognosis factor and tumor suppressor in colon cancer.

Dysregulated miRNAs have been demonstrated to be associated with the progression of colon cancer. The dysregulation of miR-3133 was observed in colon cancer, but its specific function was unclear. The functional role of miR-3133 in colon cancer was investigated in this study. A total of 113 colon cancer patients were included. miR-3133 expression was evaluated by PCR. The biological effects of miR-3133 in colon cancer cells were assessed with the help of the transwell and CCK8 assay. The prognostic value of miR-3133 was estimated by a series of statistical analyses. In mechanism, the interaction between miR-3133 and RUFY3 was evaluated by luciferase reporter. The significant downregulation of miR-3133 was observed in colon cancer, which showed a significant association with the advanced TNM stage and bad survival of patients. miR-3133 and TNM stage were identified as independent prognostic indicators of colon cancer. In vitro, the overexpression of miR-3133 exerted a dramatically inhibitory effect on cellular processes of colon cancer, which were enhanced by miR-3133 knockdown. Additionally, miR-3133 could negatively regulate the luciferase activity and expression of RUFY3, which was speculated as the underlying mechanism mediating the regulatory effect of miR-3133. miR-3133 functioned as a prognostic biomarker indicating the progression and prognosis of colon cancer, and it also served as a tumor suppressor via negatively regulating RUFY3, which provides a potential therapeutic target for colon cancer.

Preoperative frailty assessment could be a predictive factor for the prognosis of elderly patients undergoing coronary artery bypass grafting: a retrospective case-control study

BackgroundFrailty has been considered to be associated with major mortality and increased length of stay after cardiac surgery. This study aimed to explore the predictive potential of frailty assessment in the prognosis of elderly patients undergoing bypass surgery.MethodsThis study assessed the preoperative frailty according to the Fried’s frailty phenotype, and included 150 frail and 150 non-frail elderly patients (≥ 65 y) who underwent bypass surgery. The present study evaluated the prognosis of elderly patients based on sequential organ failure assessment (SOFA) score, and collected clinical indicators to construct logistic regression models with the prognosis as the dependent variable, to explore the potential predictive ability of preoperative frailty. Moreover, this study focused on the complications and analyzed the relationship between preoperative frailty and postoperative complications.ResultsIn the present study, 244 patients were divided into the favorable prognosis group and 56 patients were divided into the unfavorable prognosis group. Logistic regression analysis showed that increased myoglobin and high cardiac function classification were independent risk factors for unfavorable prognosis in elderly patients undergoing bypass surgery. The discrimination of the clinical prediction model was determined by the receiver operating characteristic (ROC) curve, and the area under curve (AUC) was 0.928. After adding preoperative frailty assessment, the AUC was improved to 0.939. This study found a significant correlation between preoperative frailty and postoperative complications, mainly in the circulatory system.ConclusionPreoperative frailty assessment could be a predictive factor for the prognosis of elderly patients undergoing coronary artery bypass grafting. According to our study, frailty assessment and appropriate intervention before bypass surgery may be beneficial to the enhanced recovery after cardiac surgery.Trial registrationThe clinical study was approved by the Medical Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (2021-SR-393). All patients signed an informed consent form.

Risk factors for unfavorable prognosis in patients with coronary artery disease and age-related disorders undergoing coronary artery bypass grafting

Highlights. Patients with coronary artery disease and age-related disorders (sarcopenia, osteopenic syndrome, osteosarcopenia) who underwent elective on-pump coronary artery bypass grafting are at higher risk of developing cardiovascular complications, non-infectious complications, and death.Musculoskeletal disorders (sarcopenia, osteopenic syndrome, osteosarcopenia) in combination with traditional predictors (age, diabetes mellitus, prior myocardial infarction and stroke, cancer) are risk factors for unfavorable prognosis of postoperative period of coronary artery bypass grafting. Aim. To assess risk factors for unfavorable prognosis in patients with coronary artery disease (CAD) undergoing elective on-pump coronary artery bypass grafting, taking into account age-related disorders (sarcopenia, osteopenic syndrome, osteosarcopenia).Methods. This single-center study included 387 CAD patients admitted for elective coronary artery bypass grafting. Taking into account the diagnosed age-related disorders, four groups of patients were formed. The first group consisted of 52 (13.4%) patients with sarcopenia, the second group was comprised of 28 (7.2%) patients with osteopenia (osteopenia/osteoporosis), the third group included 25 (6.5%) patients with osteosarcopenia, and the fourth group consisted of 282 (72.9%) participants with coronary artery disease and without musculoskeletal disorders (MSD). Risk factors for a composite endpoint (myocardial infarction, stroke, paroxysmal atrial fibrillation, cardiac rhythm disturbances) and death, and noninfectious complications (resternotomy for bleeding, pneumothorax aspiration and thoracentesis) were assessed.Results. The composite endpoint occurred more frequently in patients with osteopenia (group I – 9.6%, group II – 32.1%, group III – 12%, group IV – 12.8%; p = 0.029), and non-infectious complications occurred more frequently in patients with sarcopenia and osteosarcopenia (group I – 17.3%, group II – 7.1%, group III – 12%, group IV – 5.3%; p = 0.002). MSD were associated with the risk of composite endpoint (odds ratio (OR) 1.73, p = 0.035), and osteopenia increased it three-fold (OR 3.01, p = 0.046). Moreover, MSD were associated with higher risk of non-infectious complications (OR 1.71, p = 0.026), especially in patients with sarcopenia (OR 2.02, p = 0.034). The assessment of risk factors for unfavorable prognosis highlighted the presence of osteopenic syndrome (100 CU), prior stroke (88 CU) and myocardial infarction (85 CU). The risk of non-infectious complications was associated with prior ischemic events (ranking level for myocardial infarction – 100 CU, stroke – 75 CU), and MSD (89 CU) and its types (osteosarcopenia – 77 CU, osteopenia – 69 CU, sarcopenia – 52 CU).Conclusion. Age-related disorders in combination with MSD increase the risk of a composite endpoint and non-infectious complications by one to three times.

KRTCAP2 as an immunological and prognostic biomarker of hepatocellular carcinoma

Alterations in protein glycosylation affect tumor progression and immune responses in the tumor microenvironment. Keratinocyte-associated protein 2 (KRTCAP2) encodes the corresponding proteins involved in N-glycosylation. The clinical predictive significance and immune role of KRTCAP2 in hepatocellular carcinoma (HCC) largely remain elusive. Combining bioinformatics tools and multiplex immunohistochemistry analysis, we evaluated the KRTCAP2 expression in the HCC tumor microenvironment. The results showed that KRTCAP2 mRNA and protein expression were markedly increased in HCC tissues. Furthermore, high KRTCAP2 expression was an independent predictive factor of unfavorable prognosis in HCC. Moreover, high KRTCAP2 protein expression was associated with a lower proportion of CD8+ T cells and CD68+ macrophages in the stroma region. There was also a lower proportion of CD8+ T cells in the tumor region with high KRTCAP2 protein expression. Specifically, KRTCAP2 expression showed an inverse relationship with programmed cell death ligand-1 in HCC. Analysis of immunophenoscore showed that the low KRTCAP2 expression group had a stronger ability to predict response to immune checkpoint inhibitors. In conclusion, KRTCAP2 had a significant prognostic value for HCC and was correlated with the immune microenvironment. Our findings suggest that KRTCAP2 is a prognostic marker for HCC patients with potential clinical implications for predicting immunotherapeutic responsiveness.

Comparison of the treatment results in adult patients with acute Ph-negative lymphoblastic leukemia on protocols of the Russian multicenter studies ALL-2009 and ALL-2016

Introduction. Over the past 5 years, signifi cant progress has been achieved in the treatment of patients with Ph-negative acute lymphoblastic leukemia (ALL). Treatment results were compared between two protocols of the Russian multicenter studies «ALL-2009» and «ALL-2016», in which multicomponent high-dose consolidation was not used. The principle of continuity of treatment was observed with modifi cation of doses of cytostatic drugs depending on the depth of cytopenia.Aim – to compare the 5-year results of two studies and to determine the factors of unfavorable prognosis in the treatment of patients with ALL.Materials and methods. The studies were performed from April 2009 to April 2016 (ALL-2009) and from April 2016 to September 2021 (ALL-2016), and 596 patients were included: 330 in ALL-2009 and 266 in ALL-2016. The analysis was performed in March 2022. The median age of patients in ALL-2009 was 28 years (15–55), in ALL-2016 – 32.5 years (18–55). Cytogenetic studies were performed in 242 patients in ALL-2009 (73.3 %) and 236 patients in ALL-2016 (88.7 %). Patients in the ALL-2016 protocol underwent a centralized assessment of minimal residual disease (MRD) by fl ow cytometry on protocol +70 day (after completion of two induction phases), +133 and +190 days. Transplantation of allogeneic stem hematopoietic cells was performed in 7 % of patients in ALL-2009 and in 9 % in ALL-2016.Results. Overall, relapse-free survival (OS, RFS) and the probability of relapse for a period of 3 years from the moment of inclusion of patients in a particular study were 59 %, 63 % and 23 % for ALL-2009, and for ALL-2016 – 64 %, 59 % and 22 %, respectively. For patients with B-cell precursor ALL, two cytogenetic risk groups were formed, in which long-term survival rates differed signifi cantly: the standard group (hyperploid set of chromosomes and normal karyotype) – OS 63 %, RFS 70 %, and high cytogenetic risk (any abnormal karyotype, except for hyperploidy) – OS 49 %, RFS 52 % (р = 0.001, р = 0.0014). In T-ALL, cytogenetic markers had no prognostic value, but the immunophenotype of early T-cell precursor turned out to be an important predictor of poor prognosis (the probability of relapse was 52 % compared with 15 % for all other immunophenotypic variants). According to the results of centralized monitoring of MRD, it was determined that for B-cell precursor ALL, the signifi cant negative factors are the high cytogenetic risk group and positive MRD status at +70 day, and for T-cells, the early immunophenotype and positive MRD status at +133 day.

Opportunities for correction of immunosuppression in patients with COVID-19

Here, we review thematic publications in available literature sources of the databases PubMed, Scopus, Web of Science, eLibrary, 49 of which were dated of the years 19972022. Analysis of such reports is aimed at assessing features of cytokine storm-induced hyperinflammatory reaction with signs of immunosuppression accompanied by pronounced lymphopenia and lowered count of CD4+T helpers during severe COVID-19. The prognostic factor for unfavorable prognosis was based on the marker of systemic inflammatory reaction correlating with the disease severity the soluble IL-2 receptor as well as the neutrophil-to-lymphocyte ratio and the lymphocyte subset imbalance. An immunosuppressive therapy of severe forms of COVID-19, aimed at weakening the inflammatory response, exacerbates immune dysfunction by suppressing the T cell function, mainly due to Th1 lymphocytes involved in recognizing and eliminating intracellular pathogens particularly viruses. Upon that, cell-mediated immunity becomes compromised that relies on cytotoxic T-lymphocytes, natural killer cells and macrophages. Timely and targeted immunocorrection is required to prevent or reduce the immunosuppression that accompanies a severe disease course and leads to serious and prolonged complications, as well as to association of secondary infections. In fight against the cytokine storm, it is important not to miss a time point of developing immunosuppressive condition that transitions into immunoparalysis as follows from recent publications covering the tactics of treating immune-mediated complications of coronavirus infection. The review discusses opportunities for immunosuppressive therapy along with glucocorticosteroids and monoclonal antibodies blocking IL-6 or cognate receptors. Studies using mesenchymal stem cells (MSCs) to reduce systemic inflammatory response at COVID-19 are outlined in the review. The use of antigen-specific Treg and their combinations with antagonists of tumor necrosis factor- (TNF), interferon- (IFN) as well as low-dose IL-2 in patients with SARS-CoV-2 infection were analyzed. The prognostic perspectives for CAR-T cells and CAR-NK cells technology have been considered as novel therapeutic approaches aimed at training effector cells to recognize the surface SARS-CoV-2 virus spike-like (S) protein. The feasibility of a therapeutic approach is also emphasized by comparatively analyzed of efficacy of using IL-7 or IL-15 during lymphopenia in patients with COVID-19. Here, side effects complicating immunocorrection come to the fore. Critical evaluation of corrected immunosuppressive conditions in patients with COVID-19 in the post-COVID-19 period by using low-dose IL-2 therapy revealed its ability to repair cellular immune response. As a result, a low-dose IL-2 therapy is recommended as a cytokine replacement therapy in such patients with COVID-19 during hyper-to-hypo-inflammatory phase transition in immune response.

The Role of the NETosis Phenomena as a Function of Neutrophils in the Pathogenesis of Infection and Cancer

Neutrophils are one of the key barriers to anti-infective protection, an important mechanism of which is NETosis - the formation of neutrophil extracellular traps (NET). In recent years, this ambiguous biological phenomenon has been considered as a factor of unfavorable prognosis in some types of cancer. This review is devoted to the analysis of the role of NETosis in the pathogenesis of autoimmune diseases and other non-communicable diseases. The role of NET in malignant tumors, in particular in metastasis and progression of the tumor process, has been studied and data on the subpopulations of neutrophils – low-density neutrophils (LDN) and high-density neutrophils (HDN) in tumor processes have been analyzed. Further study of the phenomenon of netosis and the characteristics of peripheral blood neutrophils in cancer patients will be useful both for detailing the mechanisms of the metastatic cascade and for identifying their role as a biomarker and a possible therapeutic target.

Combination of ibrutinib and venetoclax followed by Chimeric Antigen Receptor T-cell therapy in the first line of treatment in an elderly patient with mantle cell lymphoma with hyperleukocytosis and mutation in the TP53 gene

Introduction. The tactics of therapy for elderly comorbid patients with mantle cell lymphoma with unfavorable prognosis factors (complex karyotype, 17p13 deletion, mutations in the TP53 gene) have not been developed. The use of intensive chemotherapy regimens and transplantation of allogeneic hematopoietic stem cells (allo-HSCT) is impossible due to severe comorbidity in elderly patients. A rational approach is the use of a combination of ibrutinib and venetoclax. As an alternative to allo-HSCT, a new option for elderly patients with poor prognostic factors is Chimeric Antigen Receptor T-cell therapy (CAR-T) cell therapy.Aim — to present the experience of using ibrutinib and venetoclax with CAR-T-cell therapy in the first line of treatment in an elderly patient with MCL with a mutation in the TP53 gene and hyperleukocytosis.Main findings. Patient M., 68 years old. The examination revealed hyperleukocytosis 978 × 109/L, anemia (55 g/L), thrombocytopenia (30 × 109/L), and splenomegaly 250 × 180 mm. According to the results of laboratory studies, the diagnosis of lymphoma from mantle cells with a complex karyotype, deletion 17p13, 13q14 and mutation p.R248W in exon 7 of the TP53 gene (VAF = 26 %) was verified. For cytoreductive purposes, two sessions of leukocytapheresis and prephase with cyclophosphamide (200 mg/m2) and dexamethasone (10 mg/m2) were performed. From day 3, therapy with ibrutinib 420 mg/day and venetoclax 100 mg/day was started. After 2 days, the leukocytes were 0.7 × 109/L, and the size of the spleen decreased, as a result of which the development of tumor lysis syndrome was noted. As a result of intensive therapy, the patient’s condition stabilized, which allowed him to resume treatment. After 7 days, the number of leukocytes was 2.5 × 109/L, neutrophils — 70 %, platelets — 90 × 109/L, hemoglobin — 95 g/L. According to immunophenotyping, the population of B-lymphocytes was 4 %. According to NGS data, the allelic load of the mutation in the TP53 gene is 0.8 %. The patient underwent anti-CD19 CAR-T-cell therapy and achieved complete remission. Three months after therapy, MRD remains-negative remission and the persistence of CAR-T cells is determined.

The oncogenic role of SNRPB in human tumors: A pan-cancer analysis.

Purpose: The purpose of this study was to explore the oncogenic role of small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) in human tumors. Materials and methods: Study cases were acquired from The Cancer Genome Atlas database, the Gene Expression Omnibus database, The Human Protein Atlas, and the Clinical Proteomic Tumor Analysis Consortium. We then used the R package and several online tools to analyze and visualize the role of SNRPB across tumors. Results: We found that the expression of SNRPB was significantly increased in 28 of 33 tumors, and higher expression was observed in late pathological and TNM stages. Significantly decreased levels of SNRPB promoter methylation were observed in 12 tumors. SNRPB was found to be a risk factor for decreased overall survival in 10 tumors (p < 0.05), a risk factor for decreased disease-specific survival in 8 tumors (p < 0.05), and a risk factor for decreased progression-free interval in 7 tumors (p < 0.05). The PPI network of SNRPB and the top 100 coexpressed genes revealed that CDK1, CDC6, AURKB, CCNB1, CCNA2, and CDC45 were the most closely interacting genes across tumors. The GO and KEGG enrichment analyses revealed that SNRPB and the above genes were mainly enriched with respect to functions in cell cycle-related genetic material replication, assembly, and distribution. SNRPB was significantly associated with immune cell infiltration and the expression of immunomodulation-related genes in several but not all tumors. Conclusion and limitations: The expression of SNRPB was significantly elevated in almost all tumors, and the decreased promoter methylation level may contribute to the elevated expression of SNRPB. SNRPB may facilitate the progression of pathological and TNM stages and is a risk factor for unfavorable prognosis across tumors. However, our research was based on data obtained from public databases, without further validation of our findings at the cellular and animal levels. Therefore, further studies are needed to clarify the oncogenic mechanism of SNRPB and its potential as a therapeutic target.

The Relationship Between Serum Netrin-1 Expression Levels and Prognosis in Revascularized Patients with Acute Ischemic Stroke.

This study aimed to explore the relationship between serum netrin-1 expression levels and acute prognosis in patients with acute ischemic stroke (AIS) within 24 hours after revascularization. A total of 121 revascularized patients admitted to the Jinshan Branch of the Shanghai Sixth People's Hospital, China, between July 2019 and July 2021 were selected as study subjects. The primary outcome was the modified Rankin Scale (mRS) score three months after revascularization: patients with an mRS score >2 were classified into the unfavorable prognosis group and others into the favorable prognosis group. Those with serum netrin-1 expression levels greater than the median of all patients were classified into the elevated protein group and others into the decreased protein group. Multivariate logistic regression analysis was used to analyze the independent risk factors for prognosis in patients with AIS after revascularization. The differences between the unfavorable prognosis group and the favorable prognosis group in gender, age, coronary heart disease, and netrin-1 levels were not statistically significant (p > 0.05). However, the National Institute of Health Stroke Scale (NIHSS) scores and number of patients with comorbid hypertension in the unfavorable prognosis group were significantly higher than in the favorable prognosis group (p < 0.05). Multivariate logistic regression analysis showed that NIHSS score before revascularization was an independent risk factor for unfavorable prognosis but that netrin-1 expression levels were not significantly associated with prognosis in patients after revascularization. Serum netrin-1 expression levels in the acute phase are not significantly associated with prognosis in patients with AIS after revascularization.