Prognostic Indicator Research Articles

Development and validation of nomogram to predict overall survival and disease-free survival after surgical resection in elderly patients with hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is one of the common causes of tumor death in elderly patients. However, there is a lack of individualized prognostic predictors for elderly patients with HCC after surgery.MethodWe retrospectively analyzed HCC patients over 65 years old who underwent hepatectomy from 2015 to 2018, and randomly divided them into training cohort and validation cohort in a ratio of 3:1. Univariate Cox regression was used to screen the risk factors related to prognosis. Prognostic variables were further selected by least absolute shrinkage and selection operator regression model (LASSO) and multivariate Cox regression to identify the predictors of overall survival (OS) and disease-free survival (DFS). These indicators were then used to construct a predictive nomogram. The receiver operating characteristic curve (ROC curve), calibration curve, consistency index (C-index) and decision analysis curve (DCA) were used to test the predictive value of these independent prognostic indicators.ResultA total of 188 elderly HCC patients who underwent hepatectomy were enrolled in this study. The independent prognostic indicators of OS included albumin (ALB), cancer embolus, blood loss, viral hepatitis B, total bilirubin (TB), microvascular invasion, overweight, and major resection. The independent prognostic indicators of DFS included major resection, ALB, microvascular invasion, laparoscopic surgery, blood loss, TB, and pleural effusion. In the training cohort, the ROC curve showed that the predictive values of these indicators for OS and DFS were 0.827 and 0.739, respectively, while in the validation cohort, they were 0.798 and 0.694. The calibration curve nomogram exhibited good prediction for 1-year, 2-year, and 3-year OS and DFS. Moreover, the nomogram models exhibited superior performance compared to the T-staging suggested by C-index and DCA.ConclusionThe nomogram established in this study demonstrate commendable predictive efficacy for OS and DFS in elderly patients with HCC after hepatectomy.Core Tip: The purpose of this retrospective study is to screen the risk factors of survival and recurrence in elderly patients with HCC after hepatectomy. The nomogram included cancer embolus, viral hepatitis B, overweight, major resection, ALB, microvascular invasion, laparoscopic surgery, blood loss, TB, and pleural effusion as predictors. The calibration curve of this nomogram was good, indicating credible predictive value and clinical feasibility.

The entrainment of action potential duration and contraction amplitude by recapitulation of respiratory sinus arrhythmia in isolated cardiac myocytes

Abstract Introduction Respiratory sinus arrhythmia (RSA) is the oscillation of heart rate in phase with ventilation and represents the high frequency component of heart rate variability. RSA is prevalent in the young and the endurance-trained and its loss is considered a prognostic indicator for sudden cardiac death. The recapitulation of RSA improves cardiac function in animal models of heart failure1,2. However, the precise mechanisms by which RSA affects cardiac function are unknown. Hypothesis: We examined the hypothesis that the recapitulation of RSA in isolated ventricular myocytes affects the stimulus interval-dependence of action potential duration (APD) and sarcomere shortening through mechanisms involving sarcoplasmic reticulum (SR) Ca2+ release. Methods Hearts were excised from adult male guinea pigs under general anaesthesia (140 mg/kg bodyweight euthatal, i.p.) and left ventricular myocytes isolated. Isolated myocytes were superfused with Tyrode’s solution for perforated patch whole-cell current clamp recording and action potentials and sarcomere length measured simultaneously. Sample sizes are presented as n/N (cell/animal number) and nested hierarchical analysis applied using a generalized linear mixed model (P<0.05). Results Pacing at a basic cycle length (CL, 350 ms) induced APD, Ca2+ transient amplitude (CaT) and sarcomere shortening alternans. The recapitulation of RSA through oscillatory pacing (OP), in which CL was set to 20% below and 20% above the corresponding basic CL in a 2-short, 2-long stimulus train, reduced the incidence of alternans. Furthermore, OP entrained APD, CaT and sarcomere shortening and this entrainment persisted in voltage clamp experiments with fixed APD. Using a three-step protocol to examine the dependence of APD and sarcomere shortening on both preceding (CLn-1) and anteceding (CLn-2) stimulus intervals, both APD and sarcomere shortening were found to depend directly on the preceding cycle length (CLn-1, P<0.001). In contrast, sarcomere shortening depended inversely on the anteceding CL (CLn-2, P<0.001; n/N = 24/4). Following treatment of the cells with caffeine (50 µM) to sensitise ryanodine receptors, the dependence of APD and sarcomere shortening on CLn-1 was markedly suppressed, and the inverse dependence of sarcomere shortening on CLn-2 was lost (P<0.001, n/N = 6/3). The effects of OP are akin to post-extrasystolic potentiation3 and mathematical simulation4 supports the involvement of changes in the sarcoplasmic reticulum Ca2+ content. Conclusion These data are consistent with an obligatory role for the SR in the entrainment of APD, CaT and sarcomere shortening and the suppression of alternans by the recapitulation of RSA. We hypothesise that recapitulation of RSA would be protective against ventricular tachyarrhythmia and further work is required to test this.

Predicting Unplanned Readmissions to the Intensive Care Unit in the Trauma Population.

Background: Unplanned readmission to intensive care units (UR-ICU) in trauma is associated with increased hospital length of stay and significant morbidity and mortality. We identify independent predictors of UR-ICU and construct a nomogram to estimate readmission probability. Materials and Methods: We performed an IRB-approved retrospective case-control study at a Level I trauma center between January 2019 and December 2021. Patients with UR-ICU (n = 175) were matched with patients who were not readmitted (NR-ICU) (n = 175). Univariate and multivariable binary linear regressionanalyses were performed (SPSS Version 28, IBM Corp), and a nomogram was created (Stata 18.0, StataCorp LLC). Results: Demographics, comorbidities, and injury- and hospital course-related factors were examined as potential prognostic indicators of UR-ICU. The mortality rate of UR-ICU was 22.29% vs 6.29% for NR-ICU (P < .001). Binary linear regression identified seven independent predictors that contributed to UR-ICU: shock (P < .001) or intracranial surgery (P = .015) during ICU admission, low hematocrit (P = .001) or sedation administration in the 24hours before ICU discharge (P < .001), active infection treatment (P = .192) or leukocytosis on ICU discharge (P = .01), and chronic obstructive pulmonary disease (COPD) (P = .002). A nomogram was generated to estimate the probability of UR-ICU and guide decisions on ICU discharge appropriateness. Discussion: In trauma, UR-ICU is often accompanied by poor outcomes and death. Shock, intracranial surgery, anemia, sedative administration, ongoing infection treatment, leukocytosis, and COPD are significant risk factors for UR-ICU. A predictive nomogram may help better assess readiness for ICU discharge.

May the prognostic nutritional index (PNI) play a role in predicting age-related macular degeneration?

It is known that a healthy and balanced diet plays an important role in the etiopathogenesis of age-related macular degeneration (AMD). The aim of this study is to show the possible relationship between the prognostic nutritional index (PNI) and AMD. This observational longitudinal study included 50 patients who were diagnosed with AMD and 100 participants as control group in the Ophthalmology Polyclinic of Kırşehir Ahi Evran Training and Research Hospital between December 2022 and February 2023. The PNI scores of the patients were calculated with the formula (10 × albumin (g/L) + (0.005 × total lymphocyte count), using routine hemogram and biochemical assays. One hundred fifty participants were included in the study (average age: 73.7 ± 8.6years, male: 53.3%). When adjusted for age, sex, and total comorbidity index score via multivariate logistic regression analysis, the association between AMD and PNI scores (OR = 0.3; CI: 0.2-0.4; p = 0.01) and Charlson Comorbidity Index (CCI) scores (OR = 6.8; CI: 2.8-16.6; p = 0.01) was statistically significant. The use of PNI scores may be practical and useful in routine clinical practice for predicting AMD.

The prognostic value of immune-nutritional status in metastatic colorectal cancer: Prognostic Nutritional Index (PNI)

Backround and purposeA low Prognostic Nutritional Index (PNI) value, which reflects immune nutrition and inflammation around the tumor, is associated with an unfavorable prognosis, and it was aimed to reveal its prognostic value in metastatic colorectal cancer (CRC).MethodsIn our retrospective cross-sectional study, patients with a diagnosis of metastatic colorectal disease without active infection, between January 2010 and December 2016 were included. The PNI values at the time of diagnosis were calculated according to the formula (10 × serum albumin (g/dL)) + (0.005 × total lymphocyte value).ResultsThe mean PNI value of 253 patients included in the study was 46.6. While 53.75% (n = 136) of the patients had a PNI value of 46.6 and above, 46.25% (n = 117) had a PNI value below 46.6. The overall survival (OS) of the group with a PNI of 46.6 and above was statistically significantly longer (53.06 months vs 38.80 months, p = 0.039). The PFS duration of the group with PNI below 46.6 was 25.66 months, while the PFS duration of the group with PNI above 46.6 was not reached (p = 0.265).ConclusionPNI is a simple and inexpensive index that evaluates the immunonutritional status, and it is a prognostic marker that can be easily used in patients with metastatic colorectal cancer as in other cancer types.

Relationship between altered taste and smell with malnutrition among hemodialysis patients.

Alterations in taste and smell are among the most distressing symptoms experienced by haemodialysis patients. There is limited research on the relationship between these two symptoms and malnutrition in haemodialysis patients. This study aimed to investigate alterations in taste and smell in hemodialysis patients and their relationship with malnutrition. This cross-sectional study was carried out with 149 hemodialysis patients at the dialysis centers of three state hospitals. The Taste and Smell Dysfunction Questionnaire was used to assess the changes in patients' taste and smell, and the Prognostic Nutritional Index (PNI), as well as the Controlling Nutritional Status (CONUT) tool, were utilized to evaluate their nutritional status. A substantial percentage (45.6%) of patients reported an altered sense of smell, and 40.2% reported an altered sense of taste. The aspect of taste that was most abnormal was bitterness (46.7%); 53.0% of the patients were at moderate risk of malnutrition by PNI score, and 14.8% were categorized as malnourished by CONUT score. Malnutrition was related to dialysis vintage: a 1-year increase in vintage was associated with an increased risk of malnutrition (OR: 1.17, 95% CI 1.02-1.32, p < 0.001). Altered taste was associated with malnutrition: one-unit increase in the standard deviation of the taste subdimension score was associated with a relative risk of malnutrition (OR: 6.89, 95% CI 1.67-28.39, p < 0.001). A one-unit increase in the standard deviation of the smell subdimension was associated with relative risk of malnutrition (OR: 1.35, 95% CI 1.10-1.64, p < 0.001). Malnutrition was found in a significantpercentage of hemodialysis patients. Altered taste and smell and the durationof dialysis treatment were significantly associated with malnutrition scores It isrecommended that healthcare professionals regularly assess alterations in tasteand smell in hemodialysis patients, as these alterations may be associated withmalnutrition, and manage these alterations accordingly.

#2492 The GLIM classification of malnutrition in an elderly population of patients on maintenance haemodialysis

Abstract Background and Aims The prevalence of malnutrition increases with age and is common in elderly patients on haemodialysis. Malnutrition increases complications, disability, mortality, length of hospital stay and healthcare costs. The Global Leadership Initiative on Malnutrition (GLIM) classification has been proposed to define malnutrition by the combined use of aetiological (weight loss, low body mass index and reduced muscle mass on initial bioimpedentiometry and on anthropometry if bioimpedentiometry is not feasible) and phenotypic (reduced food intake and inflammation) criteria; it is still poorly validated in CKD patients. Method Retrospective study of 121 patients on maintenance haemodialysis aged 65 years or older (mean age 77.3 ± 6.57 years, M/F 97/24, 43.1% with diabetes) who underwent routine assessment of nutritional status by anthropometric measurements and impedentiometry. Patients also received a geriatric prognostic calculator, the Multidimensional Prognostic Index (MPI, 1, low risk, 2, moderate risk, 3, high risk) and the MNA sf as an initial nutritional screening tool. According to the GLIM criteria, patients were defined as malnourished if they had at least one phenotypic criterion. By definition, haemodialysis patients fulfil the aetiological criteria of inflammation. Therefore, we added additional aetiological criteria, including loss of food intake and/or high burden of comorbidities (third tertile of CIRS): Extended HD GLIM. Results The MNAsf identified 56 (46%) patients as malnourished or at risk. However, a further 21 patients had reduced muscle mass on anthropometric measurements. Given the lack of specificity of the screening in identifying patients with malnutrition in our population, all patients were considered for GLIM characterisation. 40 out of 123 (32%) patients could not undergo impedentiometry, mainly because of cardiovascular exclusion criteria. 19 of 83 (23%) patients who underwent impedentiometry had a reduced lean tissue index (LTI). We identified 54 out of 121 (44.6%) patients who met the GLIM phenotypic criteria (4 with 3, 14 with 2 and 36 with 1 criteria). The addition of the two phenotypic GLIM criteria to the simple assessment of muscle mass allowed the identification of 17 additional patients at risk of malnutrition. Compared to patients without malnutrition, those fulfilling the GLIM criteria were more likely to have a higher KT/V (1.26 ± 1.39 vs. 1.39 ± 1.52, p = 0.008), lower PTH (286.7 ± 238.8 vs. 403.1 ± 215.0), lower triglycerides (125.8 vs. 48.91 vs. 159.51 ± 85.9, p+0.012), lower serum albumin (3.76 ± 0.32 vs. 3.92 ± 0.27 g/dl, p = 0.004). In addition, patients with GLIM criteria were more likely to have a higher MPI score (0.42 ± 0.51 vs 0.31 ± 0.37, p &amp;lt; 0.001) and to live alone or in a nursing home than with a family member or carer. Conversely, no association was found between GLIM and the presence of cognitive impairment or mobility. 38 (31.4%) patients had a loss of appetite, digestive problems, chewing or swallowing difficulties in the last 3 months. By adding this criterion and that of being in the third highest tertile of CIRS, we found that among patients fulfilling the GLIM criteria, 29/54 (37%) had enhanced aetiological criteria (Expanded HD GLIM). Conclusion A significant percentage of the elderly population on maintenance haemodialysis are malnourished or at high risk. The GLIM classification is a new classification with the potential to identify patients at risk earlier, before the development of sarcopenia. Malnutrition as defined by the GLIM criteria is related to the MPI outcome score.

#2484 Diffusion magnetic resonance imaging, a noninvasive tool to assess fibrosis level in both native and allograft kidneys

Abstract Background and Aims Renal cortical interstitial fibrosis is a well-established prognostic indicator for renal health, conventionally estimated by biopsy. Our prior research has enhanced DW-MRI sequencing, facilitating precise distinction between the renal cortex and medulla. This has enabled the measurement of the cortico-medullary apparent diffusion coefficient difference (ΔADC), which inversely correlates with the extent of histologically assessed interstitial fibrosis. The present study is designed to validate these findings, assess their reproducibility in a separate institution, and ascertain their significance in delineated subgroups, particularly between allograft recipients and native kidney patients. Method From 2014 to 2023, we orchestrated a prospective cohort study encompassing 309 patients diagnosed with chronic kidney disease (n = 106) or those with a renal allograft (n = 203). Each patient had undergone a biopsy, subsequent to which a multimodal magnetic resonance imaging (MRI) was systematically conducted in the following weeks. Initially, participants were recruited from Geneva hospitals, with subsequent inclusion of patients from Lausanne in Switzerland. The study's objective was to evaluate the correlation between ΔADC and the degree of renal fibrosis at biopsy. We performed subgroup analyses (per center, native/allograft kidneys) and applied linear regression models to investigate these associations rigorously. Results We included 270 participants in Geneva and 39 patients in Lausanne. A significant negative correlation was observed between ΔADC and the degree of fibrosis across the entire cohort (R = −0.41, p &amp;lt; 0.001). Subgroup analyses yielded consistent findings in both Geneva (R = −0.43, p &amp;lt; 0.001) and Lausanne University Hospitals (R = −0.35, p &amp;lt; 0.001). Furthermore, this association remained significant within subgroups of both native and allograft kidneys (respectively: R = −0.48, p &amp;lt; 0.001 and R = −0.38, p &amp;lt; 0.001). Conclusion Our findings reinforce the link between ΔADC and renal fibrosis, indicating that this association is consistent regardless of the center or kidney type (native or allograft). This supports the potential utility of diffusion MRI as a non-invasive tool for the assessment of renal fibrosis.

APC/C-regulated CPT1C promotes tumor progression by upregulating the energy supply and accelerating the G1/S transition

BackgroundIn addition to functioning as a precise monitoring mechanism in cell cycle, the anaphase-promoting complex/cyclosome (APC/C) is reported to be involved in regulating multiple metabolic processes by facilitating the ubiquitin-mediated degradation of key enzymes. Fatty acid oxidation is a metabolic pathway utilized by tumor cells that is crucial for malignant progression; however, its association with APC/C remains to be explored.MethodsCell cycle synchronization, immunoblotting, and propidium iodide staining were performed to investigate the carnitine palmitoyltransferase 1 C (CPT1C) expression manner. Proximity ligation assay and co-immunoprecipitation were performed to detect interactions between CPT1C and APC/C. Flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium, inner salt (MTS) assays, cell-scratch assays, and transwell assays and xenograft transplantation assays were performed to investigate the role of CPT1C in tumor progression in vitro and in vivo. Immunohistochemistry was performed on tumor tissue microarray to evaluate the expression levels of CPT1C and explore its potential clinical value.ResultsWe identified CPT1C as a novel APC/C substrate. CPT1C protein levels exhibited cell cycle-dependent fluctuations, peaking at the G1/S boundary. Elevated CPT1C accelerated the G1/S transition, facilitating tumor cell proliferation in vitro and in vivo. Furthermore, CPT1C enhanced fatty acid utilization, upregulated ATP levels, and decreased reactive oxygen species levels, thereby favoring cell survival in a harsh metabolic environment. Clinically, high CPT1C expression correlated with poor survival in patients with esophageal squamous cell carcinoma.ConclusionsOverall, our results revealed a novel interplay between fatty acid utilization and cell cycle machinery in tumor cells. Additionally, CPT1C promoted tumor cell proliferation and survival by augmenting cellular ATP levels and preserving redox homeostasis, particularly under metabolic stress. Therefore, CPT1C could be an independent prognostic indicator in esophageal squamous cell carcinoma.

#322 Are platelet-related parameters prognostic predictors of renal and cardiovascular outcomes in IgA nephropathy?

Abstract Background and Aims IgA nephropathy (IgAN) is associated with chronic inflammation. Platelet-related parameters, such as platelet (PLT) count, platelet-to-albumin ratio (PAR) and platelet-to-lymphocyte ratio (PLR), were examined as potential prognostic indicators for renal and cardiovascular (CV) outcomes in IgAN. Method 150 IgAN patients were involved and divided into two groups based on the cut-off value of PAR. All-cause mortality, major CV events and end-stage renal disease were the primary combined endpoints. Secondary endpoints, such as CV or renal endpoints, were also analyzed separately. Results Seventy-four per cent of patients were male and had a mean age of 43.7 ± 13.5 years. Mean follow-up time: 124 ± 67 months. The K-M curve showed that PLT, PLR and PAR were strongly associated with primary combined and renal outcomes, but not with cardiovascular outcomes in IgAN. In the case of combining PAR with LVH, the K-M curves showed significant differences in both the primary (p &amp;lt; 0.001) and secondary outcomes (p = 0.001 and p = 0.038). When we combined PAR with metabolic syndrome, the primary (p &amp;lt; 0.001) and secondary (p = 0.001 and p = 0.015) outcomes were also significant in the low and high PAR groups. PAR was correlated with gender (r = -0.273, p = 0.001) and segmental glomerulosclerosis on histology (r = 0.161, p = 0.047). PLR correlated with microalbuminuria (r = -0.165, p = 0.033) and left ventricular hypertrophy (r = -0.178, p = 0.025). PLT was correlated with gender (r = -0.201, p = 0.013) and eGFR (r = 0.158, p = 0.040). PLR, gender, dyslipidemia and microalbuminuria were associated with the primary composite endpoints; left ventricular hypertrophy and microalbuminuria with the secondary renal endpoints; and gender, age and diabetes with the cardiovascular endpoints by multivariate Cox regression. Conclusion Elevated PAR and PLR may predict end-stage renal disease progression, but in combination with LVH and MetS, they showed CV events also in IgAN. The determination of PAR and PLR can be useful and cost-effective parameters for assessing both cardiovascular and renal risks in CKD.

Current landscape of primary small bowel leiomyosarcoma: cases report and a decade of insights

The incidence of leiomyosarcoma (LMS) is about 4–5/100,000 individuals per year. LMSs occurring in the small bowel are even rarer, and their preoperative diagnosis is very difficult. We described two patients with pathologically confirmed small bowel LMS and analyzed their clinical and medical imaging features. Similar cases reported in English in Pubmed database over the past decade were reviewed and summarized. These tumors were categorized by the growth direction and relationship with the intestinal lumen into three types: intraluminal (n = 10), intermural (n = 3), and extraluminal (n = 7). Notably, among the three types of LMS, the intramural leiomyosarcoma stands out as a noteworthy subtype. Emerging evidence suggests that smaller tumor size (&amp;lt; 5 cm) and the intraluminal type may serve as favorable prognostic indicators, while the extraluminal type is associated with relatively poor prognosis. Furthermore, the integration of imaging features with CA125 and LDH biomarkers holds promise for potential diagnostic value in LMS.

Prognosis of isolated tumor cells and use of molecular classification in early stage endometrioid endometrial cancer

ObjectiveWe assessed the prognosis and molecular subtypes of early stage endometrioid endometrial cancer with isolated tumor cells within sentinel lymph nodes (SLNs) compared with node negative disease.MethodsPatients diagnosed with stage...

#2414 Hypertension resolution after kidney transplantation is associated with better kidney transplant outcomes in patients with pre-transplant hypertension

Abstract Background and Aims Hypertension is prevalent in patients with advanced chronic kidney disease (CKD), and kidney transplantation (KT) can potentially improve hypertension. Although hypertension is expected to be resolved after KT in many recipients with pre-transplant hypertension, little is known about the hypertension resolution rate and its prognostic role in KT outcomes. Method We retrospectively identified KT recipients (between 2006 and 2015) who had pre-transplant hypertension using Health Insurance Review &amp; Assessment Service and Korea National Health Insurance System. The recipients were categorized into two groups based on their post-KT hypertension status: “persistent hypertension” and “resolved hypertension”. Cox proportional hazard analyses were performed to assess the risk of death-censored graft failure and all-cause mortality with adjusting various clinical, immunological risk factors, and socioeconomic status. Results Among 11,342 KT recipients with pre-transplant hypertension, 8,233 (73%) remained hypertensive, while 3,109 (27%) experienced hypertension resolution after KT. Recipients with resolved hypertension had lower rates of delayed graft function and major comorbidities, including diabetes mellitus, ischemic heart disease, and stroke compared to recipients who remained hypertensive. After adjusting for multiple covariates, the resolved hypertension group had 0.59-fold (95% confidence interval [CI] 0.49–0.73) lower risk for graft failure and 0.59-fold (95% CI 0.48–0.73) lower risk for all-cause mortality compared to the persistent hypertension group. Subgroup analyses revealed that the protective effect of resolved hypertension on graft survival was more pronounced in females (P for interaction = 0.045), and on overall survival was weaker in recipients with diabetes (P for interaction = 0.033). Conclusion A significant proportion of patients experienced hypertension resolution after KT, which is associated with improved graft survival and overall patient survival. The post-KT hypertension status can be used as a prognostic indicator for predicting better outcomes in KT recipients with pre-transplant hypertension.

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.

Multi-omics prediction of lymph node metastasis status in breast cancer

Lymph node metastasis status stands as a pivotal prognostic indicator in forecasting the outlook for breast cancer patients. Consequently, precise evaluation of this status holds paramount importance in the staging, treatment, and prognosis of breast cancer. The utilization of radiomics, genomics, proteomics, transcriptomics, and histopathology methodologies has notably enhanced the precision of lymph node metastasis status prediction in breast cancer. This review provides an overview of recent advancements in omics-based lymph node metastasis prediction for breast cancer, elucidating the significance of various omics prediction models and integrated multi-omics models in this predictive endeavor. The overarching goal is to augment the accuracy of preoperative lymph node metastasis status prediction in breast cancer, thereby aiding clinicians in the selection of efficacious personalized treatment strategies, while concurrently averting undertreatment of patients with a heightened risk of metastasis.

Association of serum Spp1 levels with disease progression in ALS and SBMA.

In comparison with amyotrophic lateral sclerosis (ALS), the contribution of neuroinflammation in spinobulbar muscular atrophy (SBMA) has been less explored. We investigated the role of neuroinflammation in the pathogenesis of ALS and SBMA by analyzing systemic inflammatory markers and osteopontin (Spp1). This study involved 105 ALS, 77 SBMA, and 55 healthy controls. We measured their systemic inflammatory markers, serum Spp1, and cytokine levels (interferon-γ, interleukin [IL]-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α, and IL-17A), investigated correlations between Spp1 levels and clinical features, and evaluated ALS survival rates according to Spp1 levels. In the ALS group, systemic inflammatory markers were significantly higher than in the control and SBMA groups. Spp1 levels were observed to be higher in ALS patients, but the difference was not statistically significant among the study groups. Cytokine profiles were comparable. In ALS, higher Spp1 levels were correlated with lower ALS Functional Rating Scale-Revised (ALSFRS-R) scores (r = -0.25, p = 0.02) and faster disease progression rate (r = 0.37, p < 0.001). After adjusting for other prognostic indicators, high Spp1 levels were independently associated with shorter survival in ALS patients (hazard ratio 13.65, 95% confidence interval 2.57-72.53, p < 0.01). Neuroinflammation does not appear to be a primary contributor to the pathogenesis of SBMA. Serum Spp1 levels may serve as a reliable biomarker for disease progression and prognosis in ALS. These findings expand our understanding of these two distinct motor neuron disorders and offer a potential biomarker for future studies.

Nutritional Status as a Prognostic Factor for Survival in Palliative Care: A Retrospective Observational Analysis of Home Parenteral Nutrition in Cancer Patients with Inoperable Malignant Bowel Obstruction

Palliative care patients with malignant bowel obstruction are particularly at risk of developing malnutrition, which in turn directly shortens survival time and worsens quality of life (QoL). According to the available data, the survival time in this patient group is often less than three months. To avoid further complications related to malnutrition and poor outcomes in oncological therapy, nutritional therapy such as home parenteral nutrition (HPN) is offered. The aim of this study was to investigate whether nutritional status is a prognostic factor for survival in palliative care patients with malignant inoperable bowel obstruction qualified for home parenteral nutrition and which nutritional assessment tool has the most accurate prognostic value. This retrospective observational analysis included 200 patients with malignant bowel obstruction referred for home parenteral nutrition between January 2018 and August 2023. The analysis included laboratory test results, body mass index (BMI), Subjective Global Assessment (SGA), Nutritional Risk Index (NRI), Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI) and malnutrition as defined by the Global Leadership Initiative on Malnutrition (GLIM). The average survival time of the patients was 75 days. Patients with higher NRI and PNI scores were more likely to survive (NRI: p &lt; 0.001; PNI: p &lt; 0.001). The GLIM criteria, SGA scores and BMI values did not prove to be good prognostic factors for survival (GLIM p = 0.922, SGA p = 0.083, BMI p = 0.092). The results suggest that the use of NRI and PNI may be helpful in prognosing survival in these patients and that prevention of the development of malnutrition through earlier nutritional assessment and intervention should be considered in this patient group.

Artificial intelligence-based prognostic model accurately predicts the survival of patients with diffuse large B-cell lymphomas: analysis of a large cohort in China

BackgroundDiffuse large B-cell lymphomas (DLBCLs) display high molecular heterogeneity, but the International Prognostic Index (IPI) considers only clinical indicators and has not been updated to include molecular data. Therefore, we developed a widely applicable novel scoring system with molecular indicators screened by artificial intelligence (AI) that achieves accurate prognostic stratification and promotes individualized treatments.MethodsWe retrospectively enrolled a cohort of 401 patients with DLBCL from our hospital, covering the period from January 2015 to January 2019. We included 22 variables in our analysis and assigned them weights using the random survival forest method to establish a new predictive model combining bidirectional long-short term memory (Bi-LSTM) and logistic hazard techniques. We compared the predictive performance of our “molecular-contained prognostic model” (McPM) and the IPI. In addition, we developed a simplified version of the McPM (sMcPM) to enhance its practical applicability in clinical settings. We also demonstrated the improved risk stratification capabilities of the sMcPM.ResultsOur McPM showed superior predictive accuracy, as indicated by its high C-index and low integrated Brier score (IBS), for both overall survival (OS) and progression-free survival (PFS). The overall performance of the McPM was also better than that of the IPI based on receiver operating characteristic (ROC) curve fitting. We selected five key indicators, including extranodal involvement sites, lactate dehydrogenase (LDH), MYC gene status, absolute monocyte count (AMC), and platelet count (PLT) to establish the sMcPM, which is more suitable for clinical applications. The sMcPM showed similar OS results (P < 0.0001 for both) to the IPI and significantly better PFS stratification results (P < 0.0001 for sMcPM vs. P = 0.44 for IPI).ConclusionsOur new McPM, including both clinical and molecular variables, showed superior overall stratification performance to the IPI, rendering it more suitable for the molecular era. Moreover, our sMcPM may become a widely used and effective stratification tool to guide individual precision treatments and drive new drug development.

Exploring Inflammatory Parameters in Lung Cancer Patients: A Retrospective Analysis

Inflammation-related parameters serve as pivotal indicators in the prognosis and management of lung cancer. This retrospective investigation aimed to explore the relationship between inflammatory markers and diverse clinical variables in non-small-cell lung cancer patients. A cohort of 187 individuals undergoing elective lobectomy for lung cancer was retrospectively analyzed, spanning an 11-year data collection period. Six inflammation ratios derived from complete peripheral blood counts were assessed. Significantly elevated levels of neutrophil-to-lymphocyte ratio (NLR) (p = 0.005), platelet-to-lymphocyte ratio (PLR) (p = 0.001), Aggregate Index of Systemic Inflammation (AISI) (p = 0.015), Systemic Inflammation Response Index (SIRI) (p = 0.004), and Systemic Immune Inflammation Index (SII) (p = 0.004) were observed in patients with advanced T stages. Significantly, elevated values (p &lt; 0.05) of these parameters were observed in the study’s smoker patients compared to non-smokers. A statistically significant correlation was identified between the NLR parameter and tumor size (p = 0.07, r = 0.204), alongside a significant elevation in SIRI (p = 0.041) among patients experiencing postoperative complications. Inflammatory biomarkers emerge as invaluable prognostic indicators for patients with non-small-cell lung cancer, offering potential utility in forecasting their prognosis.

Identification and validation of a novel risk model based on cuproptosis‑associated m6A for head and neck squamous cell carcinoma

BackgroundHead and neck squamous cell carcinoma (HNSCC) is a prevalent cancer with a poor survival rate due to anatomical limitations of the head and a lack of reliable biomarkers. Cuproptosis represents a novel cellular regulated death pathway, and N6-methyladenosine (m6A) is the most common internal RNA modification in mRNA. They are intricately connected to tumor formation, progression, and prognosis. This study aimed to construct a risk model for HNSCC using a set of mRNAs associated with m6A regulators and cuproptosis genes (mcrmRNA).MethodsRNA-seq and clinical data of HNSCC patients from The Cancer Genome Atlas (TCGA) database were analyzed to develop a risk model through the least absolute shrinkage and selection operator (LASSO) analysis. Survival analysis and receiver operating characteristic (ROC) analysis were performed for the high- and low-risk groups. Additionally, the model was validated using the GSE41613 dataset from the Gene Expression Omnibus (GEO) database. GSEA and CIBERSORT were applied to investigate the immune microenvironment of HNSCC.ResultsA risk model consisting of 32 mcrmRNA was developed using the LASSO analysis. The risk score of patients was confirmed to be an independent prognostic indicator by multivariate Cox analysis. The high-risk group exhibited a higher tumor mutation burden. Additionally, CIBERSORT analysis indicated varying levels of immune cell infiltration between the two groups. Significant disparities in drug sensitivity to common medications were also observed. Enrichment analysis further unveiled significant differences in metabolic pathways and RNA processing between the two groups.ConclusionsOur risk model can predict outcomes for HNSCC patients and offers valuable insights for personalized therapeutic approaches.