Background: Aggressive mature T-cell lymphoma (TCL) is a disease that carries a poor prognosis. Methods: We analyzed the expression of 22 tumor cell functional proteins in 16 randomly selected patients with TCL. Immunohistochemistry was performed in paraffin-embedded tumor tissue sections to determine the protein expression statuses in tumor cells. Results: Glucose-regulated protein 94 (GRP94), a protein that serves as a pro-survival component under endoplasmic reticulum (ER) stress in the tumor microenvironment, was significantly associated with a shortened survival. Furthermore, significant differences were observed when GRP94 was combined with six other factors. The six factors were (1) programmed cell death-ligand 1 (PD-L1); (2) programmed cell death 1 (PD-1); (3) aldo-keto reductase family 1 member C3 (AKR1C3); (4) P53, a tumor suppressor; (5) glucose-regulated protein 78 (GRP78), an ER stress protein; and (6) thymidine phosphorylase (TP). Based on the combination of GRP94 and the six other factors expressed in the tumors, we propose a new prognostic classification system for TCL (TCL Urayasu classification). Group 1 (relatively good prognosis): GRP94-negative (n = 6; median OS, 88 months; p < 0.01); Group 2 (poor prognosis): GRP94-positive, plus expression of two of the six factors mentioned above (n = 5; median OS, 25 months; p > 0.05); and Group 3 (very poor prognosis): GRP94-positive, plus expression of at least three of the six factors mentioned above (n = 5; median OS, 10 months; p < 0.01). Conclusions: Thus, the TCL Urayasu prognostic classification may be a simple, useful, and innovative classification that also explains the mechanism of resistance to treatment for each functional protein. If validated in a larger number of patients, the TCL Urayasu classification will enable a targeted treatment using selected inhibitors acting on the abnormal protein found in each patient.

Patients with cytogenetically normal acute myeloid leukemia (CN-AML) may harbor prognostically relevant gene mutations and thus be categorized into one of the three 2022 European LeukemiaNet (ELN) genetic-risk groups. Nevertheless, there remains heterogeneity with respect to relapse-free survival (RFS) within these genetic-risk groups. Our training set included 306 adults on Alliance for Clinical Trials in Oncology studies with de novo CN-AML aged < 60 years who achieved a complete remission and for whom centrally reviewed cytogenetics, RNA-sequencing, and gene mutation data from diagnostic samples were available (Alliance trial A152010). To overcome deficiencies of the Cox proportional hazards model when long-term survivors are present, we developed a penalized semi-parametric mixture cure model (MCM) to predict RFS where RNA-sequencing data comprised the predictor space. To validate model performance, we employed an independent test set from the German Acute Myeloid Leukemia Cooperative Group (AMLCG) consisting of 40 de novo CN-AML patients aged < 60 years who achieved a complete remission and had RNA-sequencing of their pre-treatment sample. For the training set, there was a significant non-zero cure fraction (p = 0.019) with 28.5% of patients estimated to be cured. Our MCM included 112 genes associated with cure, or long-term RFS, and 87 genes associated with latency, or shorter-term time-to-relapse. The area under the curve and C-statistic were respectively, 0.947 and 0.783 for our training set and 0.837 and 0.718 for our test set. We identified a novel, prognostically relevant molecular signature in CN-AML, which allows identification of patient subgroups independent of 2022 ELN genetic-risk groups.Trial registration Data from companion studies CALGB 8461, 9665 and 20202 (trials registered at www.clinicaltrials.gov as, respectively, NCT00048958, NCT00899223, and NCT00900224) were obtained from Alliance for Clinical Trials in Oncology under data sharing study A152010. Data from the AMLCG 2008 trial was registered at www.clinicaltrials.gov as NCT01382147.

BACKGROUND: Out of all cutaneous squamous cell carcinomas originating in the head and neck (HNCSCC), 2-4% are associated with parotid or cervical lymph node metastasis. The aim of this study is to analyse the prognostic factors of patients with HNCSCC with lymph node involvement treated surgically. Additionally, we aim to compare the prognostic capacity of the classification of these patients according to the 8th edition of the TNM, and an alternative classification proposed by O\'Brien et al. PATIENTS AND METHODS: Retrospective review of 65 patients with HNCSCC with lymph node metastasis treated surgically during the period 2000-2020.
RESULTS: During the study period we carried out 13 neck dissections and 52 parotidectomies + neck dissection in patients with lymph node metastases from a HNCSCC. The great majority of patients (89.2%) received post-operative radiotherapy. The 5 year disease-specific survival was 69.9%, and the overall survival it was 42.8%. The classification proposed by O\'Brien et al., based on the parotid or cervical location of the lymph node metastases, and the size and number of the metastatic lymph nodes, had a better prognostic capacity than the TNM classification.
CONCLUSIONS: The surgical treatment of lymph node metastases in patients with HNCSCC achieved a high disease control. The classification based on the location, size and number of lymph node metastases proposed by O\'Brien et al had better prognostic capacity than the TNM classification.

OBJECTIVE: To develop a machine learning algorithm with prognosis data to identify different clinical phenotypes of biliary atresia (BA) and provide instructions for choosing treatment schemes.
METHODS: Six hundred thirty-nine cases of type III BA were retrospectively collected from the Children\'s Hospital of Fudan University from Jan 1st, 2017 to Dec 1st, 2019 as a training dataset, and a survival-based forward clustering method, which can also be used to predict the subtype of a new patient was developed to identify BA subtypes.
RESULTS: A total of 2 clusters were identified (cluster 1 = 324 and cluster 2 = 315), where cluster 2 had a lower 2 y native liver survival post-Kasai rate. The infant patients in cluster 2 have higher weight, liver, and spleen volume, wider portal vein width, and older operative age; worse coagulation and liver function results; higher grade of liver fibrosis and detection rate of hepatic portal fibrous mass, and higher recent infection detection rate of herpes simplex virus type I. With the proposed prognostic classification system, the authors predicted the subtypes of the 187 cases of type III BA in a testing dataset collected from the whole year of 2020. The p-value computed from the log-rank testing for the Kaplan-Meier survival curves of the predicted two testing groups was 0.0113.
CONCLUSIONS: This classification system would be a convenient tool to choose appropriate treatment and accelerate the choice-making between clinicians and infant patients.

Ubiquitination-related genes (URGs) exerted a crucial part in a variety of human disease disorders; however, their association with pancreatic adenocarcinoma (PAAD) had yet to be clearly described. We aimed to comprehensively characterize the contributions of URGs in PAAD through in silico analysis and experimental validation, and then identified a robust mRNA-lncRNA-based molecular prognostic panel for patients with PAAD using bulk RNA-sequencing and single-cell RNA-sequencing data. Initially, we collected the multi-omics data from TCGA platform to depict a comprehensive landscape of URGs in pan-cancer. Furthermore, we were accurate to PAAD for in-depth analysis. Significant differences of the activation of ubiquitination pathways and the expression of URGs were detected between normal and malignant cells. Unsupervised hierarchical clustering determined two PAAD subtypes with distinct clinical outcomes, ubiquitination pathway activities, immune microenvironment, and functional annotation characteristics. The expression profiles of ubiquitination-associated mRNAs and lncRNAs in the training and validation datasets were utilized to develop and verify a novel ubiquitination-related mRNA-lncRNA prognostic panel, which had a satisfied prediction efficiency. Our ubiquitination-associated model could function as an effective prognostic index and outperformed four other recognized panels in evaluating PAAD patients\' survival status. Tumor immune microenvironment, mutation burden, and chemotherapy response were intensively explored to demonstrate the underlying mechanism of prognostic difference according to our panel. Our findings also revealed that FTI-277, a farnesyltransferase inhibitor, had a better curative effect in high-risk patients, while MK-2206, an Akt allosteric inhibitor, had a superior therapeutic effect in low-risk patients. The real-time PCR results uncovered the RNA expression of AC005062.1 in all the three PAAD cell lines was elevated several thousandfold. In conclusion, our URGs-based classification panel could be triumphantly served as a prediction tool for survival evaluation in patients with PAAD, and the genes in this panel could be developed as a potential target in PAAD therapy.

OBJECTIVE: Recent publications emphasized the role of dorsomedial metaphyseal extension of humeral head as predictor of ischemia after complex proximal humerus fractures (PHFs). We evaluated on preoperative 3D CT scan of PHFs the surface of this metaphyseal extension and its prognostic value on the occurrence of avascular necrosis (AVN).
METHODS: We followed a series of 25 fixations of complex PHF which had a preoperative 3D CT scan and measured the surface area of the posterior metaphyseal extension (PME) of the head. Using approximations, we calculated the ratio between the PME surface area (PMS) and the articular surface area of the head (HS). The PMS/HS ratio was analyzed against the risk of AVN.
RESULTS: The measurement of the PMS/HS ratio emphasizes the significance of PME. The incidence of AVN is correlated with the magnitude of PME. Therefore, we include the PME as a fifth element in the characterization of complex PHFs and we propose a 4-stage prognostic classification based on the number of extensions of the humeral head. The head may have 3 extensions: posteromedial (PME), lesser tuberosity (LTE) and greater tuberosity (GTE). The risk of AVN decreases with the number of extensions of the head.
CONCLUSIONS: Our study demonstrates a correlation between the occurrence of AVN and the size of PME in complex PHF cases. We propose a four-stage classification system to facilitate treatment decision-making between fixation and prosthesis.

UNASSIGNED: Several risk classifications based on various preoperative factors have been proposed to prognosticate the immediate survival of children operated for esophageal atresia. A major drawback of these classifications is that they only focus on immediate survival while ignoring the long-term morbidity and mortality in these children. Our study aims to bridge this gap in knowledge by studying the impact of one such classification (Okamoto\'s classification) on mortality and morbidity during a period of 1 year after discharge from the hospital in operated cases of esophageal atresia.
UNASSIGNED: After institutes ethical clearance, 106 children operated for esophageal atresia-tracheoesophageal fistula between 2012 and 2015 were studied prospectively for a period of 1 year after their discharge. The children were graded as per Okamoto classification. The primary objective was to determine the efficacy of this classification in predicting the survival rates in infancy and the secondary objective was to compare the complication rates in these children based on the classification.
UNASSIGNED: Sixty-nine children met the inclusion criteria. There were 40, 15, 10, and 4 children in Okamoto Classes I, II, III, and IV, respectively. Twenty-one patients (30%) died during the follow-up period with the maximum number of deaths occurring in Okamoto Class IV (75%) and the minimum in Okamoto Class I (17.5%) (P = 0.003). There was a significant correlation between the Okamoto classes with the incidence of poor weight gain (P = 0.001), lower respiratory tract infection (P = 0.007), and failure to thrive (P = 0.01) higher in Okamoto IV and III as compared to I and II.
UNASSIGNED: Okamoto prognostic classification during the initial hospitalization is relevant even at 1 year follow-up with increased mortality and morbidity in Okamoto Class IV as compared to Class I.

OBJECTIVE: This study aimed to evaluate the clinical significance of the preoperative aminotransferase to albumin ratio (AAR) in patients with hepatocellular carcinoma (HCC) after hepatectomy.
METHODS: From five hospitals, a total of 991 patients with HCC admitted between December 2014 and December 2019 were included as the primary cohort and 883 patients with HCC admitted between December 2010 and December 2014 were included as the validation cohort. The X-tile software was conducted to identify the optimal cut-off value of AAR.
RESULTS: In the primary cohort, the optimal cut-off value of the AAR was defined as 0.7 and 1.6, respectively. Compared to patients with AAR 0.7-1.6, those with AAR > 1.6 showed significantly worse overall survival (OS) and RFS, whereas those with AAR < 0.7 showed significantly better OS and RFS (all p < 0.001). Pathologically, patients with AAR > 1.6 had more aggressive tumour characteristics, such as larger tumour size, higher incidence of microvascular invasion, and severe histologic activity, and higher AFP level than patients with AAR < 0.7. Consistently, the abovementioned clinical significance of AAR was confirmed in the validation cohort.
CONCLUSIONS: A high AAR was significantly correlated with advanced tumours and severe hepatic inflammation, and a worse prognosis of HCC.

BACKGROUND: COVID-19 disease presentation is heterogeneous, from asymptomatic up to severe life-threatening forms. Getting further insights into patients with specific diseases is of particular interest. We aimed to identify profiles of hematology patients hospitalized with COVID-19 that would be associated with survival and to assess the differences between cohorts METHODS: A binational cohort of 263 patients with COVID-19 and hematological disease was studied in Paris, France and São Paulo, Brazil. Patient profiles were based on age, comorbidities, biological measurements, COVID-19 symptoms and hematological disease characteristics. A semi-supervised learning method with a survival endpoint was first used, following which, a classifier was identified to allow the classification of patients using only baseline information MAIN RESULTS: Two profiles of patients were identified, one being young patients with few comorbidities and low C-reactive protein (CRP), D-dimers, lactate dehydrogenase (LDH) and creatinine levels, and the other, older patients, with several comorbidities and high levels of the 4 biology markers. The profiles were strongly associated with survival (p < 0.0001), even after adjusting for age (p = 0.0002). The 30-day survival rate was 77.1% in the first profiles, versus 46.7% in the second. The Brazilian analysis emphasized the importance of age, while the French focused on the comorbidities CONCLUSION: This analysis showed the importance of CRP, LHD and creatinine in the COVID-19 presentation and prognosis, whatever the geographic origin of the patients.

Despite recent advancements in immunotherapy, urothelial carcinoma patients with liver metastasis have a poor response to immune checkpoint inhibitors (ICIs) and short survival durations. Here, we investigated the clinical activity and molecular correlates of resistance to ICI in patients with metastatic urothelial carcinoma (mUC), focusing on liver metastasis. In this study, 755 patients with mUC who received pembrolizumab (JUOG cohort), 144 mUC patients who were treated with atezolizumab (IMvigor210 cohort), and 59 mUC patients who had metastatic samples available were enrolled. The presence of liver metastasis was associated with increased peripheral monocytes and a reduction in lymphocytes when compared with other metastatic sites, and a poor prognosis for ICI therapy. The peripheral monocyte-to-lymphocyte ratio was significantly correlated with the CD163+M2-like tumor-associated macrophage (TAM)/CD8+ tumor-infiltrative lymphocyte (TIL) ratio in the primary and metastatic UC lesions. Exploratory molecular analyses indicated that ICI-resistant status, such as decreased tumor mutation burden, low CD8+ TILs and immune checkpoint signatures, and increased M2-like TAM markers, in primary tumors was correlated with the presence of liver metastasis. In metastatic lesions, the CD163+M2-like TAM/CD8+TIL ratio and expression of cancer-associated fibroblasts induced by the TGFβ signaling pathway were higher in the liver versus the lung metastatic tumors. This study indicated that tumor-infiltrating lymphocyte and macrophage status in primary and metastatic lesions, which correlate with peripheral monocyte and lymphocyte status, may predict immunotherapy outcomes in UC patients with liver metastasis.