Prognostic Factors Research Articles

Increased coexpression of PD-L1 and IDO1 is associated with poor overall survival in patients with NK/T-cell lymphoma.

Immunotherapy with programmed cell death 1 ligand 1 (PD-L1) blockade was effective in patients with NK/T-cell lymphoma. In addition to PD-L1, indoleamine 2,3-dioxygenase-1 (IDO1) is one of the most promising immunotherapeutic targets. High proportions of PD-L1 and IDO1 proteins were observed by immunohistochemistry (IHC) from 230 newly diagnosed patients with NK/T lymphoma with tissue samples from three cancer centers and were associated with poor overall survival (OS) in patients with NK/T lymphoma. Importantly, the coexpression of PD-L1 and IDO1 was related to poor OS and short restricted mean survival time in patients with NK/T lymphoma and was an independent prognostic factor in the training cohorts, and which was also validated in 58 NK/T lymphoma patients (GSE90597). Moreover, a nomogram model constructed with PD-L1 and IDO1 expression together with age could provide concise and precise predictions of OS rates and median survival time. The high-risk group in the nomogram model had a positive correlation with CD4 + T-cell infiltration in the validation cohort, as did the immunosuppressive factor level. Therefore, high PD-L1 and IDO1 expression was associated with poor OS in patients with NK/T lymphoma. PD-L1 and IDO1 might be potential targets for future immune checkpoint blockade (ICB) therapy for NK/T lymphoma.

#1650 Synergistic effects of mineral bone disorder (MBD) markers and iron metabolism markers on QT prolongation in maintenance haemodialysis patients

Abstract Background and Aims Prolonged QT interval is known to be common in maintenance haemodialysis (HD) patients, and QT prolongation is a risk for the development of fatal arrhythmias and cardiovascular complications. Previously, we showed that low Ca and low or high P before dialysis were associated with QT prolongation in HD patients. In this study, we aimed to investigate the effect of abnormalities in MBD markers such as Ca and P on QT time when added to abnormalities in markers of iron metabolism, a known cardiac prognostic factor due to abnormal energy metabolism in the myocardium. Method A cross-sectional study was conducted on adult maintenance HD patients enrolled in the 2020 Japanese Society for Dialysis Therapy Annual Survey. Patients with dialysis frequency less than 3 times per week and patients with absent serum Ca, serum P, transferrin saturation (TSAT), serum ferritin, and QTc were excluded. After describing patient characteristics, an analytical-epidemiological study was conducted with serum Ca, P, TSAT, and serum ferritin as exposure and QTc >500 msec as outcome. Exposure was defined as cut off values for Ca, P, TSAT, and serum ferritin of 8.4/10, 3.5/6, 20/40, and 100/300, respectively according to JSDT guideline. Adjusted variables in the multivariate analysis were age, gender, history of dialysis, BMI, and presence or absence of diabetes, previous cardiovascular disease, P adsorption medication, vitamin D analogue use, calcimimetics use. Missing values were addressed using Multiple Imputation by Chained Equations. All analyses were performed using STATA 18.0. The significance level was set at 5%. Results 169 705 patients were analysed. Among all subjects, 65.6% were male, mean age was 69.7 years (standard deviation (SD) 12.4), 50.6% had comorbid diabetes, 24.1% had previous cardiovascular disease, and mean serum Ca and P levels were 8.6 mg/dL (SD 0.7) and 5.2 mg/dL (SD 35.8), respectively. The mean QTc was 452 msec (SD 37.9). In multivariate analysis, the increased risk of QT prolongation in the low Ca, low P, and high P categories was further increased with low TSAT and cancelled with high TSAT (Table). In contrast, no such effect was appeared for ferritin. Conclusion The present study suggests that the association between lower serum Ca and lower and higher serum P levels and QTc prolongation in maintenance haemodialysis patients may be enhanced at low TSAT levels and weakened at normal and high TSAT levels.

In situ analysis of CCR8+ regulatory T cells in lung cancer: suppression of GzmB+ CD8+ T cells and prognostic marker implications

BackgroundCCR8-expressing regulatory T cells (Tregs) are selectively localized within tumors and have gained attention as potent suppressors of anti-tumor immunity. This study focused on CCR8+ Tregs and their interaction with CD8+ T cells in the tumor microenvironment of human lung cancer. We evaluated their spatial distribution impact on CD8+ T cell effector function, specifically granzyme B (GzmB) expression, and clinical outcomes.MethodsA total of 81 patients with lung squamous cell carcinoma (LSCC) who underwent radical surgical resection without preoperative treatment were enrolled. Histological analyses were performed, utilizing an automated image analysis system for double-stained immunohistochemistry assays of CCR8/Foxp3 and GzmB/CD8. We investigated the association of CCR8+ Tregs and GzmB+ CD8+ T cells in tumor tissues and further evaluated the prognostic impact of their distribution profiles.ResultsHistological evaluation using the region of interest (ROI) protocol showed that GzmB expression levels in CD8+ T cells were decreased in areas with high infiltration of CCR8+ Tregs, suggesting a suppressive effect of CCR8+ Tregs on T cell cytotoxicity in the local tumor microenvironment. Analysis of the association with clinical outcomes showed that patients with more CCR8+ Tregs and lower GzmB expression, represented by a low GzmB/CCR8 ratio, had worse progression-free survival.ConclusionsOur data suggest that local CCR8+ Treg accumulation is associated with reduced CD8+ T cell cytotoxic activity and poor prognosis in LSCC patients, highlighting the biological role and clinical significance of CCR8+ Tregs in the tumor microenvironment. The GzmB/CCR8 ratio may be a useful prognostic factor for future clinical applications in LSCC.

Outcomes for potentially Resectable patients undergoing primary chemoradiation treatment for T1-T2 HPV Negative oropharyngeal squamous cell carcinoma.

Transoral surgical resectability (TOS) is a prognostic factor for patients with HPV+ T1-2 oropharyngeal squamous cell carcinoma (OPSCC) disease undergoing radiotherapy (RT), but it is unclear whether this holds for HPV-negative (HPV-) patients. We aimed to compare outcomes of potential TOS-candidates vs. non-TOS candidates, among patients who underwent RT/CRT for early T-stage HPV- OPSCC. For patients treated with RT/CRT for early T-stage HPV-negative OPSCC between 2014 and 2021, pretreatment imaging was reviewed by four head-and-neck surgeons, masked to clinical outcomes, to assess primary-site suitability for TOS. Extracapsular extension (ECE) was assessed by a head-and-neck neuroradiologist. We compared outcomes based on surgical resectability relating to: (1) the primary site tumor alone, and (2) the primary site plus the absence/presence of ECE (overall assessment). Kaplan-Meier curves for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were compared using the log-rank test. Seventy patients were included in the analysis. The primary site was TOS-favorable in 46/70 (66%). Based on the overall assessment, 41/70 (58.6%) were TOS-favorable. The 3-year OS, DSS and PFS for primary site TOS-favorable versus unfavorable were OS: 76.9% versus 37.4%; DSS: 78.1% versus 46.2%, PFS: 69.9% versus 41.3%, (log-rank test = 0.01, 0.03, 0.04; respectively). Additionally, patients with an overall assessment of TOS favorability demonstrated better survival outcomes compared with TOS-unfavorable patients (OS: 77.3% vs. 46.2%; DSS: 78.2% vs. 56.5%, PFS: 72.3% vs. 42.1%, log-rank test = 0.01, 0.04, 0.01; respectively). Patients with TOS-favorable HPV-negative early T-stage OPSCC have superior survival outcomes than TOS-unfavorable patients.

#2478 Multiparametric magnetic resonance imaging predicts decline of kidney function but does not perform better than diffusion-weighted MRI alone

Abstract Background and Aims Renal cortical interstitial fibrosis, typically measured by biopsy, is a critical factor for kidney function prognosis. Diffusion-weighted magnetic resonance imaging (DW-MRI) has emerged as a novel promising non-invasive method to assess the degree of fibrosis. We have previously shown that there is a strong correlation between the cortico-medullary apparent diffusion coefficient difference (ΔADC) and histologically assessed fibrosis. We also developed a model based on ΔADC, eGFR and proteinuria that calculates a risk score for future renal function decline. Multiparametric MRI combines DW-MRI with other sequences and can provide synchronized insights into perfusion, diffusion, oxygenation, and tissue characterization (T1 and T2 mappings). Our current research evaluates whether additional multiparametric MRI sequences increase the power of the DW-MRI based model to predict renal function decline. Method We used data from 197 patients with either chronic kidney disease (42) or allograft kidneys (155). Each participant underwent a biopsy followed by a multiparametric MRI within the following week. The median follow-up period was 2.2 years, during which laboratory parameters were recorded. The primary endpoint was defined as a rapid decline in kidney function, characterized by a reduction in eGFR of over 30%, or the initiation of dialysis. Prognostic factors for the primary outcome were analyzed using both univariable and multivariable Cox regression models, incorporating MRI parameters (ΔADC, cortical and ΔT1, cortical and ΔT2), eGFR, and proteinuria. Results At baseline, mean eGFR was 54.5 ml/min/1.73 m2 (SD 23.8) and mean proteinuria was 0.90 g/24 h (SD 2.4). Rapid decline of renal function occurred in 54 patients after a median time of 1.1 years (interquartile range, 0.9–2.1 years). In univariable survival analysis, cortical T1 measure and cortico-medullar difference ΔT2 have showed the best association to rapid kidney function decline. Compared to our previously established model incorporating ΔADC, eGFR, and proteinuria, adding cortical T1 did not significantly improve the hazard ratio (from 4.62 (95% CI: 1.56–13.67) to 4.36 (95% CI: 1.46–13.02) with cortical T1 inclusion). Harrell's C-index marginally increased with cortical T1, suggesting no significative improvement in prognostic capacity (0.77 versus 0.79 with cortical T1). Additionally, adjusting the regression model for ΔT2 yielded no enhancement in predictive power. Conclusion Our results did not demonstrate an enhancement of the prognostic power of the composite score with the inclusion of additional MRI sequences. Consequently, no clear benefit of multiparametric MRI on top of DW-MRI was observed. Additional research is required to investigate this issue more thoroughly.

#968 Impact of the presence of acute kidney injury at the time of renal biopsy on long-term prognosis of IgA nephropathy

Abstract Background and Aims IgA nephropathy is the most common primary glomerular disease and an important cause of end-stage renal disease. Factors such as decreased renal function, persistent proteinuria, hypertension, and older age predict a poor prognosis in IgA nephropathy. Current international prediction tools for IgA nephropathy determine prognosis based on renal function using estimated glomerular filtration rate (eGFR) at the time of kidney biopsy. However, we observed differences in prognosis between patients with and without concurrent acute kidney injury (AKI) at the time of kidney biopsy. Therefore, we aimed to investigate whether renal function at the time of renal biopsy is a suitable indicator for assessing the long-term prognosis of patients with IgA nephropathy with AKI. Method We retrospectively analyzed a total of 185 patients who were diagnosed with IgA nephropathy between 2009 and 2016 at the Gyeongsang National University Hospital. Clinical data, including pathological, demographic, and laboratory findings of patients, were used. We divided the patients into two groups based on the progression rate of kidney function per year, ‘Progression’ or ‘Non-progression group’. AKI was defined according to the KDIGO Clinical Practice Guidelines. Results Among a total of 185 patients, 113 showed a sustained decline in eGFR of more than 1 ml/min/1.73 m2 per year. The mean eGFR level of the non-progression group was significantly lower than that of the progression group (p = 0.027). The percentage of patients with AKI in the non-progression group was 25%, which was higher than that in the progression group (p < 0.001). The two groups had no significant differences in comorbid disease, medications at kidney biopsy, and treatment. In sub-analysis, the mean eGFR at kidney biopsy was significantly lower than that in the non-AKI group (p < 0.001). The mean estimated risk, calculated by the international prediction tool, was significantly lower in the AKI group. On the other hand, the mean rate of actual GFR decline per year was higher in the non-AKI group (p < 0.001). Conclusion We confirmed a discrepancy between the predicted prognosis and the actual decline in GFR, particularly in the AKI group. We found that AKI at the time of renal biopsy was a good long-term prognostic factor. There is a need to conduct further research to confirm whether this is due to early detection of AKI and early active treatment.

#1397 Predictive factors for bioprosthetic valve stenosis and prognostic factors for survival following TAVR in hemodialysis patients with severe AS

Abstract Background and Aims Transcatheter aortic valve replacement (TAVR) is a promising option for the treatment of severe aortic valve stenosis (AS) in patients undergoing hemodialysis. Although the incidence of bioprosthetic valve deterioration (SVD) after TAVR has been reported to be lower than after surgical aortic valve replacement (SAVR), hemodialysis itself is still associated with a high risk of SVD. Until now, the factors that determine the prognosis of TAVR in hemodialysis patients were unknown. We previously reported that preoperative hypomagnesemia was correlated with an increase in postoperative mean aortic valve pressure gradient (MPG), an index of bioprosthetic valve stenosis as one of the indicators of SVD, in hemodialysis patients (Ren Fail. 2022 Dec;44(1):1083-1089). However, the study had a limited sample size of 24 cases, which raised concerns about statistical power. Therefore, we re-evaluate predictors of SVD and life expectancy in a larger number of post-TAVR hemodialysis patients. Methods From April 2012 to November 2021, all 100 hemodialysis patients treated with TAVR at Osaka University Hospital were included in the analysis. Pre- and post-operative demographic and laboratory data were analyzed by linear mixed-effects model and cox proportional hazards model. Results During the follow-up period (maximum 7 years), 4 out of 100 patients required re-TAVR (valve-in-valve) due to valve stenosis. The MPG increased over time with the lower preoperative serum Mg concentration (linear mixed-effects mode; +1.40 mmHg/year per 1mg/dl lower in Mg, p=0.006). However, serum calcium, phosphate, and intact PTH levels had no significant effect on the increase in MPG. In addition, a higher preoperative left ventricular ejection fraction (LVEF) was associated with a lower risk of death in a multivariate Cox proportional hazards model (hazard ratio [HR] 0.97 per 1% increase in LVEF; P=0.02). Conclusions Consistent with our previous report, preoperative hypomagnesemia was associated with increased MPG after TAVR. In addition, preoperative low cardiac function (LVEF<40%) may be a risk factor for postoperative mortality in dialysis patients. This was a single-center observational study, and the number of patients was still small, so our data may not be necessarily applicable to every patient. Further research is needed to identify a prognostic predictor of SVD and mortality, that will lead to the prevention of adverse outcomes in hemodialysis patients.

#2622 Very late renal recovery in patient with light chain cast nephropathy: the prognostic value of renal biopsy

Abstract Background and Aims Renal biopsy is not necessary to assess LCCN (Light Chain Cast Nephropathy) in patients with laboratory features suggestive of the disease. However, it has been shown that the histological picture often correlates with renal outcome. We present the case of a 55-year-old man with no significant previous medical history that was evaluated in the emergency department for a stage 3 AKI (sCr 17.3 mg/dl, eGFR 3 ml/min/1.73 m2). Laboratory tests showed a Lambda Micromolecular Myeloma (K chains 44.6 mg/l, λ 4160 mg/l and K/ λ 0.01); Bence Jones not evaluable due to anuria. Bone marrow plasmacytosis was 70%. Method The patient started chemotherapy with Bortezomib and Dexamethasone and hemodialysis thrice a week with a PMMA hemofilter in order to improve the FLC (Free Light Chain) removal rate. After three months of treatment the patient achieved a complete hematologic response but he didn't reach any renal response. In order to assess a more precise renal prognosis a kidney biopsy was performed. The histopathological exam showed a Cast Nephropathy (< 5 casts/mm2) associated with low grade interstitial fibrosis and tubular atrophy (IFTA +1). After 5 cycles with Bortezomib and Dexamethasone, one year after onset, the patient underwent ASCT (Autologous Stem Cell Transplantation). Results In the following months, a progressive increase in renal function allowed us to perform a gradual reduction of dialysis rate, until discontinuation occurred 16 months after disease onset. To date, three years after onset, complete hematologic and renal remission persists with an eGFR of 20 ml/min/1.73 m2. Conclusion Renal biopsy, performed even several months after disease onset, could play a pivotal role in cases of LCCN with a discordance between hematologic and renal response. A low cast number and low IFTA grade are known to be positive prognostic factors for renal outcome and they can predict a renal recovery that sometimes could be exceptionally late.

Safe Stop IPI-NIVO trial: early discontinuation of nivolumab upon achieving a complete or partial response in patients with irresectable stage III or metastatic melanoma treated with first-line ipilimumab-nivolumab – study protocol

BackgroundPatients with irresectable stage III or metastatic melanoma presenting with poor prognostic factors are usually treated with a combination of immune checkpoint inhibitors (ICIs), consisting of ipilimumab and nivolumab. This combination therapy is associated with severe immune related adverse events (irAEs) in about 60% of patients. In current clinical practice, patients are usually treated with ICIs for up to two years or until disease progression or the occurrence of unacceptable AEs. The incidence of irAEs gradually increases with duration of treatment. While durable tumour responses have been observed after early discontinuation of treatment, no consensus has been reached on optimal treatment duration. The objective of the Safe Stop IPI-NIVO trial is to evaluate whether early discontinuation of ICIs is safe in patients with irresectable stage III or metastatic melanoma who are treated with combination therapy.MethodsThe Safe Stop IPI-NIVO trial is a nationwide, multicentre, prospective, single-arm, interventional study in the Netherlands. A total of 80 patients with irresectable stage III or metastatic melanoma who are treated with combination therapy of ipilimumab-nivolumab and have a complete or partial response (CR/PR) according to RECIST v1.1 will be included to early discontinue maintenance therapy with anti-PD-1. The primary endpoint is the rate of ongoing response at 12 months after start of ICI. Secondary endpoints include ongoing response at 24 months, disease control at different time points, melanoma specific and overall survival, the incidence of irAEs and health-related quality of life.DiscussionFrom a medical, healthcare and economic perspective, overtreatment should be prevented and shorter treatment duration of ICIs is preferred. If early discontinuation of ICIs is safe for patients who are treated with the combination of ipilimumab-nivolumab, the treatment duration of nivolumab could be shortened in patients with a favourable tumour response.Trial registrationClinicalTrials.gov ID NCT05652673, registration date: 08–12-2022.

#2710 The importance of monitoring creatinine, hematuria, and proteinuria in relation to kidney outcomes in patients with ANCA-associated vasculitis

Abstract Background and Aims Patients with ANCA-associated vasculitis (AAV) often a have kidney involvement and it has been shown that a decreased glomerular filtration rate at entry is associated with a worse outcome both for patient and kidney survival. However, some patients present with a low kidney function at entry, but recover during treatment. Thus, it may be interesting to see if the kidney function after starting treatment is more accurate predicting outcome than the one at entry. The aim of our study was to determine the prognostic significance of proteinuria, hematuria and serum creatinine monitoring in patients with AAV Method The dataset included 848 patients with newly diagnosed AAV who participated in 7 RCTs (1995-2012), and median follow-up time of the entire cohort was 8 years (IQR: 2.9-13.6). Creatinine, hematuria, and proteinuria was recorded at baseline, 3, 6, 9, 12, and 18 months after randomization. Kidney outcome was defined as permanent dialysis dependency during follow-up or kidney transplantation. Receiver operating characteristic curves (ROC) were calculated and screening performance of cut-off scores was evaluated using the Youden Index. A multivariate Cox regression model was performed to examine the factors associated with the kidney outcome. Results Median baseline Creatinine was 176 µmol/L (IQR: 97-388.5), 114 µmol/L (IQR: 88-171) at 3 months, 110 µmol/L (IQR: 89-160) at 6 months, 110 µmol/L (IQR: 89-155) at 12 months, and 102 µmol/L (IQR: 84-132.6) at 18 months. Within 12 months, the AUC of Creatinine was the highest at 0.87 (95% CI: 0.79-0.95; SE: 0.05; p-value: 0.04) to predict kidney outcome. For the cut-off point of 135 µmol/L, 12-month-Creatinine achieved a sensitivity of 83% and specificity of 76% (LR+: 3.35, LR-: 0.23). The ROC curves for hematuria, showed that the highest AUC was found at 9 months (AUC: 0.71; SE: 0.04; 95% CI: 0.64-0.78; p = 0.032) (Fig. 1). Examination of the ROC curve of proteinuria > 0.5/24 h, revealed that the highest AUC corresponded to the baseline determination (AUC: 0.64; SE: 0.08; 95% CI: 0.48-0.80), but there was no statistically significant difference observed among the AUC values of proteinuria across the monitored periods. In the multivariable Cox regression model, MPA diagnosis, creatinine at 12 months, and age > 65 years old were independent prognostic factors for the kidney outcome. The model including Creatinine at 12 months was more robust than the model including baseline Creatinine (Harrell's C: 0.84 and 0.76, respectively) Conclusion The best diagnostic accuracy for ESKD in ROC curves was shown by serum creatinine at 12 months (AUC: 0.87; SE: 0.05; 95% CI 0.79-0.95; p-value: 0.04). Hematuria was a predictor of the kidney outcome of moderate quality (AUC 0.71; SE 0.04; 95% CI: 0.64-0.78), while proteinuria > 0. 5 g/24 h had a modest and non-significant AUC (AUC 0.64; SE 0.08; 95% CI 0.48-0.80). Serum creatinine at 12 months was found to be an independent prognostic factor for kidney outcome, while haematuria and albuminuria during follow up within the first 18 months did not seem to add any impact on outcome. Reevaluation of renal prognosis at 12 months might be useful to reassess treatment in patients with AAV. Taken together, these findings suggest than incorporating biomarker monitoring into clinical-analytical predictive models can provide a more nuanced and accurate method for predicting renal outcomes as the disease progresses.

CLEC7A regulates M2 macrophages to suppress the immune microenvironment and implies poorer prognosis of glioma

BackgroundGliomas constitute a category of malignant tumors originating from brain tissue, representing the majority of intracranial malignancies. Previous research has demonstrated the pivotal role of CLEC7A in the progression of various cancers, yet its specific implications within gliomas remain elusive. The primary objective of this study was to investigate the prognostic significance and immune therapeutic potential of CLEC7A in gliomas through the integration of bioinformatics and clinical pathological analyses.MethodsThis investigation involved examining and validating the relationship between CLEC7A and glioma using samples from Hospital, along with data from TCGA, GEO, GTEx, and CGGA datasets. Subsequently, we explored its prognostic value, biological functions, expression location, and impact on immune cells within gliomas. Finally, we investigated its potential impact on the chemotaxis and polarization of macrophages.ResultsThe expression of CLEC7A is upregulated in gliomas, and its levels escalate with the malignancy of tumors, establishing it as an independent prognostic factor. Functional enrichment analysis revealed a significant correlation between CLEC7A and immune function. Subsequent examination of immune cell differential expression demonstrated a robust association between CLEC7A and M2 macrophages. This conclusion was further substantiated through single-cell analysis, immunofluorescence, and correlation studies. Finally, the knockout of CLEC7A in M2 macrophages resulted in a noteworthy reduction in macrophage chemotaxis and polarization factors.ConclusionCLEC7A expression is intricately linked to the pathology and molecular characteristics of gliomas, establishing its role as an independent prognostic factor for gliomas and influencing macrophage function. It could be a promising target for immunotherapy in gliomas.

#2727 Acute kidney in patients with ANCA associated vasculitis

Abstract Background and Aims Renal involvement in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is considered an emergency situation. Early diagnosis and treatment significantly improve prognosis. The aim of this study was to investigate the characteristics of acute kidney injury (AKI) in ANCA-associated vasculitis and assess its developmental aspects. Method Our study, conducted in the Internal Medicine Department A of Charles Nicole Hospital over a four-year period (January 2018-August 2022), was retrospective and descriptive. The diagnosis of ANCA vasculitis was made based on the ACR 1990 and/or EULAR 2012 criteria. The severity of AKI was categorized according to the KDIGO AKI classification. Results Seventeen patients were included, with a mean age of 51 ± 17.42 years and a sex ratio of 0.42. The primary clinical presentation of AKI was rapidly progressive glomerulonephritis (n=11), followed by acute nephritic syndrome (n=4). Pneumo-renal syndrome was observed in 4 patients. Proteinuria and hematuria were present in all 17 patients, with 4 being oligoanuric on dipstick. The mean creatinine level was 584 μmol/L, ranging from 125 to 1151 μmol/L. Thirteen patients had KDIGO stage 3 AKI on admission. The predominant histological lesion was extracapillary crescentic glomerulonephritis, based on the Berden classification (n=6). Hemodialysis was initiated immediately in 12 cases, and plasma exchange was performed in 10 cases. The average follow-up time was 24 months, ranging from 3 months to 4 years. Evolution was marked by partial remission in 7 cases, with a mean creatinine of 173 μmol/L. Progression to end-stage renal disease (ESRD) occurred in 10 cases. Relapses, presenting as pneumo-renal syndrome, were observed in 4 patients. Seven patients succumbed, with vasculitis being the cause of death in 3 cases. In univariate analysis, age >70 years was associated with progression to ESRD (p=0.03). No factor studied emerged as a prognostic factor for overall survival. Conclusion The presence and severity of AKI in ANCA-associated vasculitis are linked to a poorer prognosis, affecting both patient and renal survival.

#746 Lactic acidosis in patients with acute kidney injury treated with renal replacement therapy in intensive care unit

Abstract Background and Aims Lactic acidosis (LA) is the most common cause of metabolic acidosis in hospitalised patients. LA is frequent in intensive care unit (ICU) patients with acute kidney injury (AKI) treated with renal replacement therapy (RRT). The aim of our study was to analyse the impact of LA on mortality. Method We conducted a retrospective observational study in a tertiary care hospital with a 12-bed ICU. During the study period of 4 years before the COVID pandemic, 2939 patients were admitted to the ICU, 503 patients were diagnosed with AKI and 210 of them required RRT. Due to missing data, we retrospectively analysed only 176 patients. LA was defined as a serum lactate concentration above 4 mmol/L on admission to the ICU. Demographic data, comorbidities, laboratory data at ICU admission and 30-day survival after ICU admission were obtained from the medical record. Survival was estimated using the Kaplan-Meier method, and factors associated with 30-day mortality were assessed in a Cox regression. Results The mean age of patients was 63.4±12.9 years, and 68.2% were men. Sixty-five (36.9%) of patients had LA. The prevalence of comorbidities prior to admission and baseline laboratory values are shown in Table 1. All patients were treated with RRT, 137 (77.8%) with continuous RRT and 39 (22.2%) with intermittent hemodialysis. The mean ICU stay was 14.6 ± 12 days, and 114 (64.8%) patients died during the observational period of 30 days. A Kaplan-Meier survival analysis showed that the survival was statistically significantly lower (log-rank; p = 0.027) in the group of patients with LA (Fig. 1). Univariate Cox regression analysis showed that LA was a significant predictor of 30-day survival (HR 1.51; 95% CI 1.038-2.197; p = 0.031). In the multivariate Cox regression analysis, which included age, gender, diabetes, hypertension, LA and C-reactive protein, only age (HR 1.029; 95% CI 1.011-1.046; p = 0.001) and LA (HR 1.515; 95% CI 1.030-2.228; p = 0.035) were independent predictors of mortality. Conclusion LA on ICU admission is an independent, highly prognostic factor for death within 30 days of admission in patients with AKI treated with RRT.

Abdominal Parietal Metastasis from Cervical Cancer: A Review of One of the Most Uncommon Sites of Recurrence Including a Report of a New Case

Introduction: Cervical cancer is the fourth most common cancer in women, the highest mortality being found in low- and middle-income countries. Abdominal parietal metastases in cervical cancer are a very rare entity, with an incidence of 0.1–1.3%, and represent an unfavorable prognostic factor with the survival rate falling to 17%. Here, we present a review of cases of abdominal parietal metastasis in recent decades, including a new case of a 4.5 cm abdominal parietal metastasis at the site of the scar of the former drain tube 28 months after diagnosis of stage IIB cervical cancer (adenosquamous carcinoma), treated by external radiotherapy with concurrent chemotherapy and intracavitary brachytherapy and subsequent surgery (type B radical hysterectomy). The tumor was resected within oncological limits with the histopathological result of adenosquamous carcinoma. The case study highlights the importance of early detection and appropriate treatment of metastases in patients with cervical cancer. The discussion explores the potential pathways for parietal metastasis and the impact of incomplete surgical procedures on the development of metastases. The conclusion emphasizes the poor prognosis associated with this type of metastasis in cervical cancer patients and the potential benefits of surgical resection associated with systemic therapy in improving survival rates.

#2992 Risk and prognostic factors for post-transplantation lymphoproliferative disease in solid organ transplant recipients—a multicenter analysis

Abstract Background and Aims Post-transplantation lymphoproliferative disorder (PTLD), a potentially fatal complication of transplantation, affects solid organ transplant recipients at different rates, depending on organ graft type: the risk greater in lung transplant recipients (LngTRs), lower for liver transplant recipients (LTRs) and lowest for kidney transplant recipients (KTR). In this study we aimed to investigate the factors affecting the development and treatment outcomes of PTLD and compare their effect on KTRs, LTRs and LngTRs. Method In this retrospective cohort study we have included all KTRs, LTRs and LngTRs diagnosed with PTLD at six transplantation centers in Poland. The data collected from medical records included: immunosuppression (IS), viral infections, PTLD type, treatment and outcomes. Chi-squared test was used to assess the differences in group composition. To determine the impact of variables upon PTLD time of onset and patient survival, univariate Cox regression was used. p-values below 0.05 were considered statistically significant. Results We enrolled 50 KTRs, 36 LTRs and 5 LngTRs from 6 transplantation centers in Poland. Based on the data from the most contributing centers in each group, the prevalence of PTLD was 0.82% of KTRs, 2.03% LTRs and 1.51% of LngTRs. Two thirds of the enrolled patients were male, the median age at first transplantation was 40 years for KTRs, 45 for LTRs and 25 for LngTRs (Table 1). The groups significantly differed in IS treatment: steroid (GCS) and cyclosporin (CsA) use was more frequent in KTRs (p<0.001 and p<0.001 and respectively), tacrolimus (TAC) and anti-CD25 induction in LTRs (p ≤ 0.001 and p<0.001 respectively), sirolimus (RAPA) in LngTRs (p<0.001). KTRs were the latest to develop PTLD (126 months after transplantation, p<0.001). In all groups Monomorphic B-cell PTLD was the most frequent. Initial IS treatment reduction was used in 80-86% of patients, R-CHOP chemotherapy was most common in LTRs (p=0.021), other chemotherapy regimens in KTRs (p=0.031). TAC had the opposite effect on PTLD time of onset in KTRs (HR=2.18, p=0.013) and LTRs (HR=0.18, p=0.036). The overall survival at the end of observation period was 26% for KTRs, 58% for LTRs and 80% for LngTRs. Loss to follow up was most frequent in KTRs at 26%. Patient survival was not affected by PTLD treatment. Conclusion KTRs develop PTLD later than LTRs and LngTRs, and time of disease onset is associated with TAC use. Lower survival in KTRs may result from the longer follow-up period compared to other solid organ transplant recipients.

Prognostic and predictive value of interstitial lung abnormalities and EGFR mutation status in patients with non-small cell lung cancer

BackgroundTo determine the predictive value of interstitial lung abnormalities (ILA) for epidermal growth factor receptor (EGFR) mutation status and assess the prognostic significance of EGFR and ILA in patients with non-small cell lung cancer (NSCLC).MethodsWe reviewed 797 consecutive patients with a histologically proven diagnosis of primary NSCLC from January 2013 to October 2018. Of these, 109 patients with NSCLC were found to have concomitant ILA. Multivariate logistic regression analysis was used to identify the significant clinical and computed tomography (CT) findings in predicting EGFR mutations. Cox proportional hazard models were used to identify significant prognostic factors.ResultsEGFR mutations were identified in 22 of 109 tumors (20.2%). Multivariate analysis showed that the models incorporating clinical, tumor CT and ILA CT features yielded areas under the receiver operating characteristic curve (AUC) values of 0.749, 0.838, and 0.849, respectively. When combining the three models, the independent predictive factors for EGFR mutations were non-fibrotic ILA, female sex, and small tumor size, with an AUC value of 0.920 (95% confidence interval[CI]: 0.861–0.978, p < 0.001). In the multivariate Cox model, EGFR mutations (hazard ratio = 0.169, 95% CI = 0.042–0.675, p = 0.012; 692 days vs. 301 days) were independently associated with extended overall survival compared to the wild-type.ConclusionNon-fibrotic ILA independently predicts the presence of EGFR mutations, and the presence of EGFR mutations rather than non-fibrotic ILA serves as an independent good prognostic factor for patients with NSCLC.

Integrated analysis identified the role of three family members of ARHGAP in pancreatic adenocarcinoma

The Rho GTPase activating protein family (ARHGAPs) is expressed in pancreatic adenocarcinoma (PAAD) but its function is unclear. The aim of this study was to explore the role and potential clinical value of ARHGAPs in PAAD. Using TCGA and GEO databases to analyze expression of ARHGAPs in PAAD and normal tissues. Survival curve was drawn by Kaplan–Meier. ARHGAPs were integrated analyzed by GEPIA2, TIMER, UCLCAN, cBioPortal and R language. Protein level and prognostic value were evaluated via IHC staining or survival analysis. We totally identify 18 differentially expressed (DE) ARHGAPs in PAAD. Among the 18 DE genes, 8 were positively correlated with tumor grade; abnorrmal expression of 5 was positively correlated with copy number variation; expression of 4 was positively correlated with promoter hypomethylation. Multivariate Cox regression identified ARHGAP5, ARHGAP11A, and ARHGAP12 as independent prognostic factors of PAAD. The function of ARHGAPs was mainly related to GTPase activity and signaling, axon guidance, proteoglycans in cancer and focal adhesion. Expression of 7 ARHGAPs was strongly correlated with immune infiltration. Immunohistochemistry showed increased protein levels of ARHGAP5, ARHGAP11A, and ARHGAP12 in PAAD tissues. Survival analysis confirmed a negative correlation between ARHGAP5, ARHGAP11A, and ARHGAP12 expression and patient prognosis. Multivariate Cox regression proved ARHGAP5, ARHGAP11A, and ARHGAP12 could serve as independent prognostic indicators for PAAD. Finally, this study verified ARHGAP5, ARHGAP11A, and ARHGAP12 as independent prognostic factors in PAAD, suggesting their significance for the diagnosis and treatment of PAAD.

#1579 The effectiveness and safety of sucroferric oxyhydroxide in the treatment of hyperphosphatemia in dialysis patients: a systematic review

Abstract Background and Aims Hyperphosphatemia is an independent prognostic factor for mortality in dialysis patients. The most widely used phosphate binders are sevelamer and lanthanum carbonate. Poor compliance may be due to high pill burden and gastrointestinal adverse reactions. Some previous studies on sucroferric oxyhydroxide showed a potential reduction of phosphorus levels and pill burden. This study aims to determine the effectiveness and safety profile of sucroferric oxyhydroxide in the control of hyperphosphatemia in dialysis-dependent patients. Method A systematic search was conducted in the Cochrane Library, MEDLINE, TRIP Database, and ClinicalTrials.gov until Jan 8, 2024. All randomized controlled trials on the use of sucroferric oxyhydroxide for the treatment of hyperphosphatemia in adult dialysis patients were included. The comparator groups considered were sevelamer or lanthanum. The outcomes of interest were post-treatment serum phosphorus level, the change of serum phosphorus level from baseline, hemoglobin level, ferritin level, transferrin saturation level, adverse events, serious adverse events, and all-cause mortality. Two authors independently searched for articles, screened the articles for inclusion, and appraised the articles using the REVMAN risk of bias table. The GRADE was used to assess the certainty of evidence. In case of a disagreement, the two authors discussed until a consensus was reached. If a consensus was not reached, an independent third-party reviewer was consulted. Meta-analysis was conducted using Review Manager 5.4.1 software. Results We included 7 RCTs represented by 11 records and a total of 2031 adult dialysis patients with hyperphosphatemia. The usual dose of sucroferric oxyhydroxide is 750 mg-3000 mg/day. Sucroferric oxyhydroxide reduces serum phosphorus levels comparable to that of sevelamer (MD = −0.03 mmol/L, 95% CI −0.10 to 0.03, I2 49%) and of lanthanum (MD = −0.02 mmol/L, 95% CI −0.36 to 33, I2 0%). The decrease in serum phosphorus level from the baseline is also comparable with sevelamer (MD = −0.06 mmol/L, 95% CI −0.13 to 0.00, I2 59%). Sucroferric oxyhydroxide significantly reduces the daily number of tablet intake (MD = −7.09 tablets/day, 95% CI −10.45 to −3.73, p-value &amp;lt; 0.0001, I2 = 99%) compared to sevelamer. The use of sucroferric oxyhydroxide shows significantly higher hemoglobin level (MD = 1.15; 95% CI 0.92 to 1.39, p-value &amp;lt; 0.0001, I2 = 0%), higher transferrin saturation level (MD = 8.33; 95% CI 6.06 to 10.59, p-value &amp;lt; 0.0001, I2 = 0%) and higher ferritin level (MD = 64.16; 95% CI 31.64 to 96.68, p-value 0.0001) compared with the use of sevelamer. Pooled analysis on sucroferric oxyhydroxide showed no significant differences in adverse events (RR = 1.05, 95% CI 0.95 to 1.17, I2 = 47%); serious adverse events (RR = 1.11, 95% CI 0.84 to 1.47, I2 = 0%) and all-cause mortality (RR = 0.94; 95% CI 0.38 to 2.31, I2 = 0%) compared to sevelamer. The most common adverse events reported were nausea, diarrhea, abdominal discomfort, fecal discoloration, and hyperphosphatemia. Conclusion Sucroferric oxyhydroxide is comparable with sevelamer and lanthanum in decreasing serum phosphorus levels. It is also associated with higher hemoglobin, ferritin, and transferrin saturation levels compared with the sevelamer group. Since there are no significant differences in the risks of adverse events, serious adverse events, and all-cause mortality, the decrease in pill burden with sucroferric oxyhydroxide may help improve patient compliance.

Gender differences in lung neuroendocrine tumors: a single-center experience.

Introduction Gender difference may affect lung neuroendocrine tumors (L-NET) onset, progression and outcomes as emerged in other cancers. This study aims to analyse gender difference in L-NET to identify potential prognostic factors, to improve patient follow-up and therapeutic strategies. Methods Patients (pt) with histologically confirmed L-NEN diagnosis referred to the ENETS CoE of the Endocrinology Unit, Federico II University of Naples, from 2013 to 2023 were retrospectively evaluated. Results Among 48 pt with L-NEN, 38 (79,2%) with sporadic L-NET were enrolled: 22 typical (57,9%) and 16 atypical (42,1%) carcinoids, 22 (57,9%) female and 16 (42,1%) male, mean age at diagnosis 57,3 years (range 16-84). Median follow up was 70,5 months (range 12-305). No statistically difference resulted regardig smoking habit, body mass index (BMI), primary site (left/right and central/peripheral) and histological characteristics, between cohorts. Metastasis at diagnosis were found in 20 pt (52,3%), 10 female (10%%), 10 male (10%) (p:0,20). Progressive disease (PD) was observed in 14 (36,8%) pt, male sex developed PD more frequently 9/14 (64,3%) than female 5 (35,7%), p: 0.05. Male sex seemed to show more frequently bone metastasis without reaching statistically difference, 7male/10 (70%), p: 0.06. Among 9 deaths (23,7%), 7 (77,8%) were men and 7 died for PD, p&lt;0,03. Male had a poorer prognosis than female regarding progression free survival (p: 0,04) and overall survival (p:0,001), also when sub-groups of pt metastatic at diagnosis were compared (p: 0,02 and p:0,02). Conclusions This study showed a worse prognosis in male than female with L-NET, despite similar clinical features, tumour type, stage and treatment, with regard to PFS, OS and metastatic spread. These findings may suggest a closer follow up in men, with potential positive impact on outcomes.

Aprospective study of detection and clinical significance of bone marrow tumor cells in small cell lung cancer

Objective: To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis. Methods: A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis. Results: The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P＜0.001; 77.78% vs 16.84% for bone metastasis, P＜0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCs＜111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant (P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups (P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs＜111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage (HR=2.806, 95%CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH (HR=1.841, 95%CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS (HR=2.538, 95%CI:1.169-5.512, P=0.019). Conclusions: Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.