Independent Predictor Of Survival Research Articles

Association between defibrillation-to-adrenaline interval and short-term outcomes in patients with out-of-hospital cardiac arrest and an initial shockable rhythm

AimThe optimal timing of adrenaline administration after defibrillation in patients with out-of-hospital cardiac arrest (OHCA) and an initial shockable rhythm is unknown. We investigated the association between the defibrillation-to-adrenaline interval and clinical outcomes. MethodsBetween 2011 and 2020, we enrolled 1,259,960 patients with OHCA into a nationwide prospective population-based registry in Japan. After applying exclusion criteria, 20,905 patients with an initial shockable rhythm documented at emergency medical services (EMS) arrival who received adrenaline after defibrillation were eligible for this study. Multivariable logistic regression analysis was used to predict favourable short-term outcomes: prehospital return of spontaneous circulation (ROSC), 30-day survival, or a favourable neurological outcome (Cerebral Performance Category 1 or 2) at 30 days. Patients were categorised into 2-minute defibrillation-to-adrenaline intervals up to 18 min, or more than 18 min. ResultsAt 30 days, 1,618 patients (8%) had a favourable neurological outcome. The defibrillation-to-adrenaline interval in these patients was significantly shorter than in patients with an unfavourable neurological outcome [8 (5–12) vs 11 (7–16) minutes; P < 0.001]. The proportion of patients with prehospital ROSC, 30-day survival, or a favourable neurological outcome at 30 days decreased as the defibrillation-to-adrenaline interval increased (P < 0.001 for trend). Multivariable analysis revealed that a defibrillation-to-adrenaline interval of > 6 min was an independent predictor of worse prehospital ROSC, 30-day survival, or neurological outcome at 30 days when compared with an interval of 4–6 min. ConclusionA longer defibrillation-to-adrenaline interval was significantly associated with worse short-term outcomes in patients with OHCA and an initial shockable rhythm.

Early histological transformation of follicular lymphoma to diffuse large B-cell lymphoma indicating adverse survival: A population-based analysis and validation.

The histological transformation (HT) of follicular lymphoma (FL) is a crucial biological event. The study aimed to evaluate the incidence, clinicial characteristics, prognosis and impact of HT time on survival of FL transforming to diffuse large B-cell lymphoma in population-based large-scale cohorts. A retrospective cohort study of FL with HT was performed in the Surveillance, Epidemiology, and End Results database. The Hematological Malignancy Research Network FL cohort and Aristotle study FL cohort were used to assess the external validity. Among 44,127 FL cases from the Surveillance, Epidemiology, and End Results database, 1311 cases were pathology-proven recorded to transform to diffuse large B-cell lymphoma. The cumulative rates of HT at 5, 10, and 15 years after FL diagnosis were estimated to be 1.19%, 2.93%, and 5.01%, respectively. Significantly worse overall survival and cancer-specific survival were exhibited in patients with HT than those without HT. Early HT (transformation of FL within 48 months after FL diagnosis [TOD48]) was an independent predictor for adverse overall survival of HT patients, regardless of treatment modalities before transformation. The adverse prognostic effect of TOD48 was validated in the Hematological Malignancy Research Network cohort and Aristotle study cohort. Older age (>75 years) and B symptoms within FL at diagnosis were the independent risk factors of TOD48. Furthermore, a novel prognostic model combining TOD48 with Follicular Lymphoma International Prognostic Index (TOD48-FLIPI) was constructed and validated for risk stratification. TOD48 was a risk indicator of HT, and the novel prognostic model "TOD48-FLIPI" for HT patients was proposed.

THE EFFECT OF THORACIC TRAUMA SCORING SYSTEM IN THORACIC TRAUMA PATIENTS WITH RIB FRACTURE

ABSTRACT Objective Rib fractures are common in thoracic trauma patients. There are various factors, including flail chest, pulmonary contusion, and accompanying conditions, affecting morbidity and mortality. The study aimed to identify high-risk patients for morbidity and mortality with a scoring system that the authors created. Methods Cases over the age of 18 admitted due to trauma and diagnosed with rib fractures between January 01, 2019, and March 01, 2023, were included. Trauma scores were determined by applying the new trauma scoring system. Trauma scores and other variables regarding morbidity and mortality were evaluated. Results A total of 1023 cases were included in the study. The total trauma scores were higher in bilateral and multiple fractures. In those without respiratory failure, the total score was statistically significantly lower than in the groups with respiratory failure. The total score was significantly higher in those who needed surgery, those who were hospitalized, and those who needed intensive care compared to the non-surgical groups. However, there was no correlation between intensive care unit stay and total score. Trauma mechanism, presence of additional extrathoracic pathology, and thoracic trauma-age score were independent predictors of survival. Conclusion The present study demonstrated that the number of rib fractures and the presence of pulmonary contusion did not have an effect on mortality and morbidity. The presence of extrathoracic pathology and age significantly affect survival.

Genetic profiles of oligometastatic non-small cell lung cancer and corresponding brain metastases.

In patients with oligometastatic non-small cell lung cancer, systemic therapy in combination with local ablative treatment of the primary tumor and all metastatic sites is associated with improved prognosis. For patient selection and treatment allocation, further knowledge about the molecular characteristics of the oligometastatic state is necessary. Here, we performed a genetic characterization of primary non-small cell lung cancer and corresponding brain metastases. We retrospectively identified patients with oligometastatic non-small cell lung cancer and synchronous (<3 months) or metachronous (>3 months) brain metastases who underwent surgical resection of both primary tumor and brain metastases. Mutation profiling of formalin-fixed paraffin-embedded tumor cell blocks was performed by targeted next generation sequencing using the oncomine focus assay panel. Sequencing was successful in 46 paired samples. An oncogenic alteration was present in 31 primary tumors (67.4%) and 40 brain metastases (86.9%). The alteration of the primary tumors was preserved in the corresponding brain metastases in 29 out of 31 cases (93.5%). The most prevalent oncogenic driver in both primary tumors and brain metastases was a KRAS mutation (n = 21). In 16 patients (34.8%), the brain metastasis harbored additional oncogenic alterations. The presence of a private genetic alteration in the brain metastasis was an independent predictor of shorter overall survival. In oligometastatic non-small cell lung cancer, brain metastases retain the main genetic alterations of the primary tumors. Patients may profit from targeted inhibition of mutated KRAS. Additional private genetic alterations in the brain metastases are dismal.

Remote monitoring is an independent predictor of better survival in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillators

Abstract Introduction Despite improvements in pharmacotherapy and advancements in invasive techniques, patients with ischemic cardiomyopathy are at high risk of adverse events and death. Strategies aimed at improving prognosis, including patient-centered individualization of care are needed. Remote monitoring (RM) of patients with heart failure, which allows for a continuous assessment of device- and some patient-related parameters, has been shown to reduce the risk of hospitalization and death, although no analyses were focused specifically on patients with ischemic cardiomyopathy after percutaneous coronary intervention (PCI). Purpose To determine whether RM is associated with outcomes in patients with ischemic cardiomyopathy after percutaneous coronary intervention. Methods The clinical, echocardiographic and angiographic data of consecutive patients with ICM and ICD or CRT-D, who had undergone PCI were obtained from the single-centre COMMIT-HF registry. Each consecutive patient with ICM was offered RM at the discretion of the treating physician. The RM center in our facility monitors patients with cardiac implantable devices in all working days. In case of any clinical, or device-related events potentially requiring reaction, patients are telephonically invited to contact healthcare system, either in the local emergency departments, or in our hospital, or outpatient clinic. Patients supervised with RM undergo routine in-person visits in the outpatient device clinic every 12 months. In the conventional arm, routine visits in the outpatient clinic occur every 6 months. The long-term data were acquired from the National Health Fund – the sole Polish healthcare provider. The primary outcome of the study was 36-month all-cause mortality. Results In the years 2009-2017, there were a total of 1019 patients with ICM and ICD, who underwent PCI, and those constituted the study group. Of those, 227 (22.3%) were monitored remotely, while the remaining were treated conventionally. The studied groups did not differ significantly, apart from that the patients with RM had a history of CABG, and had a lower mean left ventricular ejection fraction (LVEF, 26% vs 32%, p&amp;lt;0.001) than subjects without RM, while the percentage of CRT-D devices was significantly higher in patients with RM (36.2% vs 6.2%, p&amp;lt;0.001). The 36-month all-cause mortality rate was 18.9% in patients monitored remotely and 25.3% in subjects without RM (p log rank = 0.028). In the multivariable analysis, RM was identified as an independent predictor of lower mortality. The other variables independently associated with higher survival were lower age, absence of anemia, optimal glomerular filtration rate, and higher LVEF. Conclusions Remote monitoring of patients with ischemic cardiomyopathy is independently associated with lower all-cause mortality in a real-world cohort of patients with ICDs.Baseline characteristicsMultivariable analysis

#1487 Preoperative ultrasound vascular mapping as a predictor of arteriovenous fistula survival: a prospective cohort study

Abstract Background and Aims The morbidity and mortality of hemodialysis (HD) patients is directly related to the vascular access (VA) type. The arteriovenous fistula (AVF) is considered the VA of choice. When compared to the use of catheter, the use of AVF encompasses a lower infectious complications rate and a higher survival rate. The use of catheter has been independently associated with an increased risk of morbidity and mortality, especially during the first year of treatment. It is essential that HD programs maintain a high incidence and prevalence of AVF as a VA. For that reason, a multidisciplinary management is mandatory, with the collaboration of nephrologists, vascular surgeons, radiologists, and nurses. All patients who have an indication of AVF should have a prior ultrasound vascular mapping performed by the nephrologist to determine the most appropriate type of AVF. According to guidelines, there are several factors that increase the risk of AVF failure including advanced age, history of smoking, diabetes mellitus and peripheral vascular disease, among others. Therefore, the aim of this study is to determine the benefits of performing a preoperative ultrasound vascular mapping in terms of AVF survival. The secondary objective is to associate some risk factors to a higher rate of AVF failure. Method We conducted a prospective cohort study between January 2020 and December 2023. The viability of AVF was compared between AVF resulting from a preoperative ultrasound vascular mapping and those AVF without previous mapping. A multivariate analysis was performed with the entire population to determine the factors related to AVF survival. Results This study analyzed a total of 136 AVF, both native and prosthetic. Our population included 106 patients, mostly men (69.79%), with a median age of 68 years old (IR: 56-76), and history of smoking in a 39.10%, of diabetes in a 42.43%, and of peripheral vascular disease in a 17.54%. A preoperative ultrasound vascular mapping was previously performed in 107 AVF (78.7%). A total of 93 AVF were functional (68.4%). Regarding the analyzed risk factors of AVF failure (including advanced age and history of smoking, diabetes mellitus and peripheral vascular disease, and elbow/wrist AVF), we observed that advanced age and elbow AVF were related to higher survival of the AVF (p = 0.048 and p = 0.01 respectively). In the multivariate analysis we observed that advanced age and elbow AVF were independent predictors of AVF survival (p = 0.038 and p = 0.001, respectively). When comparing the cohorts, in the AVFs were the preoperative vascular ultrasound was performed, 78 AVF were functional (72.9%). In the AVFs were no mapping was performed, 15 AVF were functional (51.7%). This difference was statistically significant (p = 0.03). This implies a 21.2% increase in the probability of AVF survival when performing our AVF mapping. Conclusions The performance of a preoperative ultrasound vascular mapping by the nephrologist in our population has been associated to a significant increase in AVF survival. For that reason, we consider that it is an indispensable tool for the creation and monitoring of VA. When analyzing risk factors classically associated to AVF failure, we found that advanced age and elbow AVF were independent predictors of higher AVF survival. Other risk factors, such as history of diabetes mellitus, smoking, and peripheral arterial disease, were not significantly related to AVF failure in our population.

#1439 Risk factors and significance of a reduction of serum albumin after start of PD

Abstract Background and Aims A reduction in the serum level of albumin following the initiation of peritoneal dialysis (PD) has been reported to associate with impaired survival. Our aim was to identify pre-PD risk factors of drop of serum albumin, and to estimate how a decrease in albumin level affects PD patients’ survival prognosis. Method We included all adult patients who had been on PD for at least half a year in the Helsinki area in Finland during the years 2004 to 2019. Patients who had a dialysis history longer than 1 year before transferal to PD were excluded. We analysed the serum albumin level at start of PD and the last available albumin level before 6 months after start of PD. A 20% reduction of serum albumin was considered significant. Logistic regression was used to assess the association between risk factors (age, sex, primary kidney disease, comorbidities, laboratory variables) and a 20% drop of serum albumin. Cox regression was employed to study the effect of albumin drop on survival with adjustment for confounders. Results Of 379 patients, 80 (21%) showed a reduction of serum albumin of at least 20% after start of PD. High age, high albumin level at start of PD, high level of HDL cholesterol and low level of ionized calcium all associated independently with the risk of an albumin drop in the logistic regression analysis. The albumin level at start (hazard ratio 0.94 per one g/l increment, 95% CI 0.89-0.98) and a 20% or larger drop of albumin level (HR 2.3, 95% CI 1.4-3.9) were connected to impaired survival irrespective of each other. Other independent predictors of worse survival were high age, peripheral vascular disease, a history of stroke, and diabetes. Conclusion A drop of serum albumin after start of PD is frequent and associates with impaired survival. Drop of albumin is more common among elderly patients and those with high values HDL cholesterol or low levels of ionized calcium.

#2555 C4d—a novel predictor of the disease progression and treatment failure in primary focal segmental glomerulosclerosis?

Abstract Background and Aims Complement system seems to play a role in the pathogenesis of primary focal segmental glomerulosclerosis (pFSGS) where, due to unpredictable clinical course and outcome, novel prognostic factors are sought. The split product of C4 and tissue marker of complement activation, C4d, is a potential candidate whose prognostic significance was determined in this study. Method Patients &amp;gt;18 years with features consistent with pFSGS (full blown nephrotic syndrome, diffuse podocyte foot processes effacement and exclusion of known causes of FSGS), were recruited from our Hospital registry of kidney biopsies, from 2003 to 2021. Patients with end-stage renal disease (ESRD) defined as eGFR &amp;lt;15 ml/min/1.73 m2 were not included. Every renal biopsy specimen was analyzed by light, immunofluorescence and electron microscopy with additional immunochemistry for C4d performed on paraffin-embedded tissue using monoclonal rabbit antibody (detection system Ventana BenchMark Ultra). Samples with at least one non-globally sclerosed glomerulus (GSG) were examined by two renal pathologists who classified every non-GSG into C4d positive and negative. Based on ratio of C4d+ non-GGS/total N of non-GSG and C4d+ nonsclerotic glomeruli (NSG)/total N of NSG, patients were stratified into two groups: &amp;lt;50% and ≥50%. Primary outcome was defined as composite of ESRD and initial eGFR declining &amp;gt;50%. Failure to meet criteria for at least partial remission at the last follow-up visit according to KDIGO 2021 Guidelines was defined as treatment failure. Numeric variables are shown as median with interquartile range (IQR) and P value &amp;lt;0.05 was considered as significant. Results Relevant data of 58 included patients with renal outcomes are shown in Table. Median follow up was 90.7 (IQR 48-167) months. Patients with ≥50% of C4d+ non-GSG had higher proportion of treatment failure (Table) and worse renal survival (log-rank test, p = 0.006). In multivariate Cox regression analysis, after inclusion of age, sex, initial eGFR and 24-h proteinuria, IFTA, serum albumin and C4d category, only C4d ≥50% (HR = 4.077, 95% CI 1.101-15.09, p = 0.035) and IFTA (HR = 1.052, 95% CI 1.019-1.085, p = 0.002) remained independent predictors of progression to defined endpoint. Likewise, patients with ≥50% of C4d+ NSG/total N of NSG had higher proportion of treatment failure (chi-square, p = 0.03) and worse renal survival (log-rank, p = 0.037). Conclusion C4d deposition is an independent predictor of disease progression, treatment failure and renal survival in pFSGS. Significant influence of NSG-C4d deposition on disease progression may indicate pathophysiological role of the complement system activation in pFSGS independently of the presence of glomerular sclerosis.

When is neoadjuvant chemotherapy indicated in rectal neuroendocrine tumors? An analysis of the National Cancer Database

BackgroundRectal neuroendocrine tumors (rNET) are rare and challenging to manage. While most patients with small rNET can be definitively treated with local excision, the role of chemotherapy in general and neoadjuvant therapy particularly in managing advanced rNET has not been well established. Therefore, this study aimed to determine which patients with rNET may gain a survival benefit from neoadjuvant chemotherapy.MethodsA retrospective cohort analysis of all patients who underwent surgical resection of rNET in the US National Cancer Database (NCDB) (2004–2019) was performed. First, univariate and multivariate Cox regression analyses were performed to determine the independent predictors of poor overall survival (OS) and define the high-risk groups. Afterward, stratified OS analyses were performed for each high-risk group to assess whether neoadjuvant chemotherapy had a survival benefit in each group.ResultsA total of 1837 patients (49.8% female; mean age 56.6 ± 12.3 years) underwent radical resection of a rNET. Tumors > 20 mm in size, clinical T4 tumors, poorly differentiated tumors, and metastatic disease were independent predictors of worse OS and were defined as high-risk groups. Neoadjuvant chemotherapy did not have a significant survival benefit in any of the high-risk groups, except for patients with high-grade rNETs where neoadjuvant therapy significantly improved OS to a mean of 30.9 months compared with 15.9 months when neoadjuvant therapy was not given (p = 0.006).ConclusionsNeoadjuvant chemotherapy improved the OS of patients with high-grade rNET by 15 months and may be indicated for this group.

Prognostic significance of pan-immune-inflammation value in hepatocellular carcinoma treated by curative radiofrequency ablation: potential role for individualized adjuvant systemic treatment

Background This study aimed to explore the prognostic role of pan-immune-inflammation value (PIV) and develop a new risk model to guide individualized adjuvant systemic treatment following radiofrequency ablation (RFA) for early-stage hepatocellular carcinoma (HCC). Materials and methods Patients with early-stage HCC treated by RFA were randomly divided into training cohort A (n = 65) and testing cohort B (n = 68). Another 265 counterparts were enrolled into external validating cohort C. Various immune-inflammatory biomarkers (IIBs) were screened in cohort A. Prognostic role of PIV was evaluated and validated in cohort B and C, respectively. A nomogram risk model was built in cohort C and validated in pooled cohort D. Clinical benefits of adjuvant anti-angiogenesis therapy plus immune checkpoint inhibitor (AA-ICI) following RFA was assessed in low- and high-risk groups. Results The cutoff point of PIV was 120. High PIV was an independent predictor of unfavorable recurrence-free survival (RFS) and overall survival (OS). RFS and OS rates of patients with high PIV were significantly lower than those with low PIV both in cohort B (P RFS=0.016, P OS=0.011) and C (P RFS<0.001, P OS<0.001). The nomogram model based on PIV, tumor number and BCLC staging performed well in risk stratification in external validating cohort C. Adjuvant AA-ICI treatment showed an added benefit in OS (p = 0.011) for high-risk patients. Conclusions PIV is a feasible independent prognostic factor for RFS and OS in early-stage HCC patients who received curative RFA. The proposed PIV-based nomogram risk model could help clinicians identify high-risk patients and tailor adjuvant systemic treatment and disease follow-up scheme.

High MAL2 expression predicts shorter survival in women with triple-negative breast cancer.

Due to its lack of conventional surface receptors, triple-negative breast cancer (TNBC) is inherently resistant to most targeted therapies. MAL2 overexpression prompts endocytosis, conferring resistance to novel therapeutics. This study explores the role of MAL2 and PD-L1 in TNBC patients' prognosis. We performed immunohistochemical analysis on 111 TNBC samples collected from 76 patients and evaluated the expression of MAL2 and PD-1. We expanded the study by including The Cancer Genome Atlas (TCGA) cohort. MAL2 expression did not correlate with stage, grade, tumor size, lymph node invasion, metastasis, and PD-1 expression. Patients with high MAL2 had significantly lower 5-year survival rates (71.33% vs. 89.59%, p = 0.0224). In the tissue microarray cohort (TMA), node invasions, size, recurrence, and low MAL2 (HR 0.29 [CI 95% 0.087-0.95]; p < 0.05) predicted longer patients' survival. In the TCGA cohort, patients with low MAL2 had significantly longer overall survival and disease-specific survival than patients with high MAL2. Older age and high MAL2 expression were the only independent predictors of shorter patient survival in the BRCA TCGA cohort. High MAL2 predicts unfavorable prognosis in triple-negative breast cancer, and its expression is independent of PD-1 levels and clinicopathological features of TNBC.

Nucleobindin 2 inhibits senescence in gastric carcinoma

Here, we focused on the role of Nucleobindin 2 (NUCB2), a multifunctional protein, in gastric carcinoma (GC) progression. NUCB2 expression was investigated in 150 GC cases (20 non-invasive (pT1) and 130 invasive (pT2/pT3/pT4) tumors) by immunohistochemistry (IHC), and in situ hybridization for detection of the mRNA in 21 cases. Using GC cell lines, we determined whether NUCB2 expression was associated with specific cellular phenotypes. In GC clinical samples, NUCB2 was transcriptionally upregulated when compared to normal tissues. High NUCB2 expression was associated with clinicopathological factors including deep tumor invasion, lymphovascular invasion, lymph node metastasis, and advanced clinical stages, and was a significant independent predictor of unfavorable progression-free survival in 150 non-invasive and invasive GC patients. Similar findings were also evident in 72 invasive GC cases in which patients received post-operative chemotherapy, but not in 58 invasive tumors from patients who did not receive the chemotherapy. In cell lines, NUCB2 knockout inhibited proliferation, susceptibility to apoptosis, and migration capability by inducting cellular senescence; this was consistent with higher proliferation and apoptotic indices in the NUCB2 IHC-high compared to NUCB2 IHC-low GC cases. NUCB2-dependent inhibition of senescence in GC engenders aggressive tumor behavior by modulating proliferation, apoptosis, and migration.

Extracellular volume-based scoring system for tracking tumor progression in pancreatic cancer patients receiving intraoperative radiotherapy

ObjectivesTo investigate the value of extracellular volume (ECV) derived from portal-venous phase (PVP) in predicting prognosis in locally advanced pancreatic cancer (LAPC) patients receiving intraoperative radiotherapy (IORT) with initial stable disease (SD) and to construct a risk-scoring system based on ECV and clinical-radiological features.Materials and methodsOne hundred and three patients with LAPC who received IORT demonstrating SD were enrolled and underwent multiphasic contrast-enhanced CT (CECT) before and after IORT. ECV maps were generated from unenhanced and PVP CT images. Clinical and CT imaging features were analyzed. The independent predictors of progression-free survival (PFS) determined by multivariate Cox regression model were used to construct the risk-scoring system. Time-dependent receiver operating characteristic (ROC) curve analysis and the Kaplan–Meier method were used to evaluate the predictive performance of the scoring system.ResultsMultivariable analysis revealed that ECV, rim-enhancement, peripancreatic fat infiltration, and carbohydrate antigen 19-9 (CA19-9) response were significant predictors of PFS (all p < 0.05). Time-dependent ROC of the risk-scoring system showed a satisfactory predictive performance for disease progression with area under the curve (AUC) all above 0.70. High-risk patients (risk score ≥ 2) progress significantly faster than low-risk patients (risk score < 2) (p < 0.001).ConclusionECV derived from PVP of conventional CECT was an independent predictor for progression in LAPC patients assessed as SD after IORT. The scoring system integrating ECV, radiological features, and CA19-9 response can be used as a practical tool for stratifying prognosis in these patients, assisting clinicians in developing an appropriate treatment approach.Critical relevance statementThe scoring system integrating ECV fraction, radiological features, and CA19-9 response can track tumor progression in patients with LAPC receiving IORT, aiding clinicians in choosing individual treatment strategies and improving their prognosis.Key PointsPredicting the progression of LAPC in patients receiving IORT is important.Our ECV-based scoring system can risk stratifying patients with initial SD.Appropriate prognostication can assist clinicians in developing appropriate treatment approaches.Graphical

Outcomes of patients with acute severe autoimmune hepatitis: Predictors of non-response to corticosteroids and need for liver transplantation.

Acute severe autoimmune hepatitis (AS-AIH) is an evolving concept and the outcomes and optimal treatment have been less studied. In this study, we aimed to investigate the outcomes of patients with AS-AIH and predictors of non-response to corticosteroid therapy and need for liver transplantation. In a retrospective cohort, we included patients with AS-AIH admitted to our liver center. We defined AS-AIH based on the international autoimmune hepatitis group score as acute presentation of AIH with an international normalized ratio (INR)≥1.5 and without liver cirrhosis and hepatic encephalopathy. All patients received high dose corticosteroid therapy. Treatment response was defined as liver transplant free survival at 4months after presentation. Factors associated with response to corticosteroids and survival of patients were studied. In total, 61 patients with AS-AIH were included. Forty-seven patients responded to corticosteroid therapy. In the multivariate regression model, baseline INR (odds ratio [OR]: 0.184; 95% confidence interval [CI]: 0.048-0.699; p=0.013) and delayed versus early initiation of corticosteroid (after vs. before 5days of presentation) (OR: 0.189; 95% CI: 0.039-0.919; p=0.039) were independent predictors of clinical non-response to corticosteroid therapy. In the multivariable Cox regression model, baseline INR level (OR: 2.542; 95% CI: 1.188-5.440; p=0.016) and delayed initiation of corticosteroids (OR: 3.578; 95% CI: 1.084-11.812; p=0.036) were independent predictors of liver transplant free survival at 6months after diagnosis. Delayed initiation of corticosteroid therapy might be predictive of clinical non-response to medical therapy and need for liver transplantation in patients with AS-AIH.

Impact of perioperative high-protein nutritional support on postoperative outcomes in the treatment of primary lung cancer: Russian prospective multicenter comparative study (NUTRILUNC-study)

BACKGROUND: Up to 60% of lung cancer pts experience weight loss. Prevalence of sarcopenia in patients (pts) with non-small cell lung cancer (NSCLC) is about 43% and is an independent predictor of worse overall survival. It was shown that nutritional support improves outcomes in pts with cancer. AIM: To evaluate impact of perioperative nutritional support on surgical treatment outcomes of patients with NSCLC. MATERIALS AND METHODS: Patients with primary NSCLC (n=112, 69 males), aged 57,2±8,2, awaiting lung surgery and being at risk of malnutrition (Nutritional Risk Screening Assessment 2002 score ≥3) were randomized into 2 groups. Study group (n=55) received oral nutritional support (Nutridrink Compact Protein, Nutricia LLC), 250 ml/d (36 g of protein, 612 kcal) for 14 d before and 14 d after surgery in addition to standard diet. Control group (n=57) had a standard diet. The number of respiratory complications after surgery, length of hospitalization, anthropometric, functional, laboratory parameters, quality of life (according to Quality of Life Questionnaire Core-30) were assessed. Results were presented as mean ± standard deviation. Differences were considered significant at p ≤0.05. RESULTS: In the study group there were fewer respiratory complications (p 0.01), and a shorter length of hospitalization (p=0.03). Body weight in the study group did not change significantly, while in the control group it decreased (0.15±3.7 kg versus loss of 3.47±3.6 kg). Results of six-minute walk test and hand grip dynamometry were higher in the study group then in the control group (411.8±56.0 m versus 383.2±52.1 m; 33.5±8.4 kg versus 27.1±6.8 kg). Quality of life was better in the study group, p 0.05. The total protein and albumin levels were higher in the study group (70.9±5.6 g/l versus 63.1±4.0 g/l; 38.5±5.8 g/l versus 33.2±3.0 g/l). One patient in study group experienced 1st grade diarrhea. CONCLUSION: In patients with NSCLC at risk of malnutrition perioperative nutritional support with high protein oral nutritional support has a positive effect on surgical treatment outcomes.

IL-38 promotes the development of prostate cancer.

Prostate Cancer (PCa) remains a significant concern in male cancer-related mortality. Tumour development is intricately regulated by the complex interactions between tumour cells and their microenvironment, making it essential to determine which is/are key factor(s) that influence the progression of PCa within the tumour microenvironment. The current study utilised histopathology and immunohistochemistry to determine the expression of IL-38 in PCa and analysed the correlation between the expression level of IL-38 within PCa and clinical pathological characteristics. There was a significant increase in IL-38 expression in PCa tissues compared to adjacent non-PCa tissues (P < 0.0001). In addition, IL-38 expression was significantly higher in tumour cells with a high proliferation index compared to those with a low value-added index. ROC curve analysis demonstrated that IL-38 has high specificity and sensitivity for the diagnosis of PCa (AUC=0.76). Moreover, we Probed the cellular source of IL-38 in prostate cancer tissue by immunofluorescence double staining. Additionally, within PCa, the expression of IL-38 was inversely correlated with the expression levels of CD8 and PD-1. Survival analysis revealed a significantly lower overall survival rate for PCa patients with high IL-38 expression (P=0.0069), and when IL-38 was co-expressed with CD8, the survival rate of the IL-38high/CD8low group was decreased significantly. Multivariate analysis indicated that the expression level of IL-38 and TNM staging were independent predictors of survival in PCa patients. These findings suggest that IL-38 plays a crucial role in the development of PCa, and the exploration of the correlation between IL-38 and various immune factors in the tumour microenvironment further reveals its mechanism of action, making it a potential target for immunotherapy in PCa.

Endocrine toxicity is an independent predictor of survival in lung cancer patients treated with immune checkpoint inhibitors

Endocrine toxicity is an independent predictor of survival in lung cancer patients treated with immune checkpoint inhibitors

The value of the current histological scores and classifications of ANCA glomerulonephritis in predicting long-term outcome

Abstract Background and Aims Three different histological scores- histopathologic classification (Berden), Renal Risk Score (RRS) and the Mayo Clinic Chronicity Score (MCCS) for ANCA associated glomerulonephritis (ANCA-GN) were compared to evaluate their association with patient and kidney prognosis of ANCA-GN. Methods Patients aged &amp;gt; 18 years with at least one year of follow-up and biopsy-proven ANCA-GN entered this retrospective study. Renal biopsies were classified according to Berden's classification, RRS and MCCS. The first endpoint was end-stage kidney disease (ESKD), defined as chronic dialysis or glomerular filtration rate (GFR) &amp;lt;15 ml/min/1.73m2. The second endpoint was ESKD or death. Results Of 152 patients 84 were males, with median age of 63.8 years and followed for 46.9 (IQR 12.8–119) months, 59 (38.8%) reached the first endpoint and 20 died. The Kaplan-Meier curves showed that Berden and RRS were associated with first (Berden: p = 0.004, RRS: p &amp;lt; 0.001) and second endpoint (Berden: p = 0.001, RRS: p &amp;lt; 0.001), MCCS with the first endpoint only when minimal + mild vs moderate + severe groups were compared (p = 0.017) and with the second endpoint (p &amp;lt; 0.001). Among the clinical/histological presentation features, arterial hypertension (OR = 2.75, CI = 1.50–5.06, p = 0.0011), serum creatinine (OR = 1.17, CI = 1.09–1.25, p &amp;lt; 0.0001), and the percentage of normal glomeruli (OR = 0.97, CI = 0.96–0.99, p = 0.009) were the independent predictors of ESKD at multivariate analysis (MA). When the three scores were included in MA, RRS (OR = 2.21, CI = 1.15–4.24, p = 0.017) and MCCS (OR = 2.03, CI = 1.04–3.95, p = 0.037), remained predictive of ESKD but Berden (OR = 1.17, CI = 0.62–2.22, p = 0.691) did not. Conclusion RRS and MCCS scores were independent predictors of kidney survival together with high serum creatinine and arterial hypertension at diagnosis, while Berden classification did not.

Lipocalin-2 as a prognostic marker in patients with acute exacerbation of idiopathic pulmonary fibrosis

BackgroundLipocalin-2 (LCN2) is a secretory glycoprotein upregulated by oxidative stress; moreover, patients with idiopathic pulmonary fibrosis (IPF) have shown increased LCN2 levels in bronchoalveolar lavage fluid (BALF). This study aimed to determine whether circulatory LCN2 could be a systemic biomarker in patients with IPF and to investigate the role of LCN2 in a bleomycin-induced lung injury mouse model.MethodsWe measured serum LCN2 levels in 99 patients with stable IPF, 27 patients with acute exacerbation (AE) of IPF, 51 patients with chronic hypersensitivity pneumonitis, and 67 healthy controls. Further, LCN2 expression in lung tissue was evaluated in a bleomycin-induced lung injury mouse model, and the role of LCN2 was investigated using LCN2-knockout (LCN2 -/-) mice.ResultsSerum levels of LCN2 were significantly higher in patients with AE-IPF than in the other groups. The multivariate Cox proportional hazards model showed that elevated serum LCN2 level was an independent predictor of poor survival in patients with AE-IPF. In the bleomycin-induced lung injury mouse model, a higher dose of bleomycin resulted in higher LCN2 levels and shorter survival. Bleomycin-treated LCN2 -/- mice exhibited increased BALF cell and protein levels as well as hydroxyproline content. Moreover, compared with wild-type mice, LCN2-/- mice showed higher levels of circulatory 8-isoprostane as well as lower Nrf-2, GCLC, and NQO1 expression levels in lung tissue following bleomycin administration.ConclusionsOur findings demonstrate that serum LCN2 might be a potential prognostic marker of AE-IPF. Moreover, LCN2 expression levels may reflect the severity of lung injury, and LCN2 may be a protective factor against bleomycin-induced acute lung injury and oxidative stress.

Abstract PO1-11-11: A Novel Body Composition Risk Score (B-Score) and Overall Survival among Patients with Early-Stage Breast Cancer

Abstract Background: Measurements (amount, distribution, and radiodensity) of muscle and adipose tissue were reported to be individually associated with overall survival in breast cancer survivors, but they were not typically combined to develop an overall risk score. Such a score can identify patients at high risk of death and prioritize patients in need of lifestyle interventions. Objectives: We developed a novel body composition risk score (B-Score) by combining multiple tissue measurements. Methods: We included 3105 patients with stage II or III breast cancer (diagnosed from 2000 to 2013) at Kaiser Permanente Northern California and Dana Farber Cancer Institute. From CT scans at diagnosis, we used the third lumber vertebrae as the landmark to assess areas (cm2) and radiodensity (HU) of muscle and adipose tissue. We divided the area by height2 (m2) to derive the index and measured the average HU of the tissue area as the radiodensity, which acts as a marker of tissue 'quality' to be indicative of lipid content, inflammation, and angiogenesis. Out of all tissue measurements, we considered skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI) and SAT radiodensity as they were independent predictors for overall survival. Each measurement was dichotomized using optimal stratification, with low SMI (&amp;lt; 40.1cm2/m2), high SATI (≥75.7cm2/m2), and high SAT radiodensity (≥ -97.2HU) considered risk factors. We calculated B-Score as the sum of these factors and estimated its association with overall survival using Cox proportional hazards regression with adjustment for clinicopathologic factors. Results: Mean (standard deviation) age at diagnosis was 53.9 (11.8) years, 2161 (70.1%) were Non-Hispanic White, 1880 (60.5%) were stage II, and 919 (29.6%) died over a median follow-up of 10.7 years. Most patients (60.6%) had only one body composition risk factor (B-Score = 1). Compared to those with no body composition risk factors (B-Score = 0), the risk of death increased with more body composition risk factors: the adjusted hazard ratios were 1.10 (95% CI: 0.85, 1.42), 1.47 (95% CI: 1.12, 1.92), and 2.11 (95% CI: 1.26, 3.53) for B-Scores of 1, 2, and 3, respectively (Ptrend &amp;lt; 0.001). Conclusions: More unfavorable body composition characteristics were associated with increased risks of overall mortality in a dose-response manner. Considering body composition measurements together as a composite score (B-Score) may prove a useful tool to identify patients at high risk of death following breast cancer diagnosis. Table. Adjusted Associations of the Body Composition Risk Score (B-Score) with Overall Mortality Among Patients with Early-Stage Breast Cancer Abbreviations: HR, hazard ratio. a Areas (cm2) and radiodensity (HU) of skeletal muscle and subcutaneous adipose tissue (SAT) were extracted from the single axial CT slice at the third lumbar vertebra. The body composition risk score was defined as the sum of three risk factors: low skeletal muscle index (SMI; &amp;lt;40.1cm2/m2), high SAT index (SATI; ≥75.7cm2/m2), and high SAT radiodensity (≥ -97.2HU). b Adjusted for age (years), race and ethnicity (Asian, Black, Hispanic, Non-Hispanic White, and Others), stage (II, III), ER (ER+, ER-), PR (PR+, PR-), HER2 (HER2+, HER2-, unknown), smoking (current, former, never), Charlson comorbidity index (0, 1-2, ≥3), and BMI (&amp;lt;18.5, 28.5-24.9, 25-29.9, and ≥30 kg/m2). For the trend test, B-Score was considered as a continuous variable with adjustment for the above covariates. Citation Format: En Cheng, Bette Caan, Wendy Chen, Carla Prado, Elizabeth Cespedes Feliciano. A Novel Body Composition Risk Score (B-Score) and Overall Survival among Patients with Early-Stage Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-11-11.