Independent Predictor Of Poor Prognosis Research Articles

Sarcopenia in liver cirrhosis and its sequential changes after liver transplantation

Background and Aim: Sarcopenia in liver cirrhosis has emerged as an independent predictor of poor prognosis with increased likelihood of adverse outcomes including falls, fractures, physical disability and mortality. Pre-transplant sarcopenia is associated with a longer hospitalization, longer ICU stay and increased risk of mortality even after transplant. Data on sarcopenia diagnosed with Psoas Muscle Thickness/Height (PMTH) is absent in India, hence we indented to study PMTH in sarcopenia using sex specific cut-offs and prospectively observe sarcopenia changes after liver transplant. Methods: We did a cross sectional study from November 2019 to November 2021 in Gleneagles global health city, Chennai. 378 patients with cirrhosis of liver who underwent CT abdomen were enrolled for assessing prevalence of sarcopenia in liver cirrhosis using hand grip strength and psoas muscle thickness/height (PMTH) and among those 25 patients who underwent CT abdomen 6 to 12 months after liver transplant were included into subgroup analysis to study post-transplant changes in sarcopenia. Results: Prevalence of sarcopenia was 70.1% which is more common in males than females (73.35% vs 56.75%). Sarcopenia was seen in 46.6%, 86.8% and 82.5% of patients with CTP A, B and C classes respectively. Only high MELD score and presence of ascites independently predicted sarcopenia (P<0.05). Sarcopenia was present in 76% of patients before and after transplant at 6-12 months. De novo sarcopenia developed in 2 patients after transplantation. There was a significant association between sarcopenia and post-operative length of hospital stay (20.73% vs 13.83%; P<0.05) Conclusions: In this single centre study, sarcopenia is highly prevalent in cirrhosis, more common in males and worsen with the severity of cirrhosis. Presence of ascites and high MELD score were independently associated with sarcopenia. Pre-transplant sarcopenia is associated with increased risk of infectious, vascular complications and prolonged hospital stay in the immediate postoperative period.

The Role of DBR1 as a Candidate Prognosis Biomarker in Esophageal Squamous Cell Carcinoma.

Aims: Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent malignancies with unfavorable clinical outcomes and limited therapeutic methods. As a key enzyme in RNA metabolism, debranching RNA Lariats 1 (DBR1) is involved in intron turnover and biogenesis of noncoding RNA. Although cancer cells often show disorder of nucleic acid metabolism, it is unclear whether DBR1 has any effect on the carcinogenesis and progression of ESCC. Methods: Here we detected DBR1 expression in 112 ESCC samples by immunohistochemistry and analyzed its correlation with clinical parameters and survival. Results: DBR1 is mainly located in the nucleus of ESCC tissue. And DBR1 was associated with several malignant clinical features in patients, including tumor location (χ2 = 9.687, P = .021), pathologic T stage (χ2 = 5.771, P = .016), lymph node metastasis (χ2 = 8.215, P = .004) and N classification (χ2 = 10.066, P = .018). Moreover, Kaplan-Meier analysis showed that ESCC patients harboring lower DBR1 expression had a worse prognosis in comparison with those with higher DBR1 expression (P = .005). Univariate and multivariate Cox proportional hazards regression analyses indicated that decreased DBR1 might act as an independent predictor of poor prognosis for ESCC patients. Conclusion: Abnormal RNA metabolism might play a critical role in promoting the progression of ESCC, and DBR1 may be a promising potential biomarker for predicting the prognosis of ESCC patients.

Early Application of Palbociclib Plus Endocrine Therapy in HR+/HER2- Metastatic Breast Cancer: A Better Choice Based on Data From the Chinese Population.

Background: Palbociclib is the most widely used cyclin-dependent kinase 4/6 inhibitor in China, but its early application efficacy on Chinese metastatic breast cancer (MBC) patients was reported deficiently. Methods: Between February 2019 to December 2021, 95 female hormone receptor-positive (HR+)/human epidermal growth factor receptor-2 negative (HER2-) patients with MBC received palbociclib combined with AI or fulvestrant were retrospectively analyzed in our center. The primary outcome was progression-free survival (PFS). The objective response rate and clinical benefit rate (CBR) were evaluated. Results: The median follow-up period was 15 months (range from 2 to 37). Palbociclib performed superiorly when applicated in first-and-second line therapy than in later lines (P = .002). Palbociclib combined with AI or fulvestrant had a median PFS of 34 months (95% confidence interval [CI] = 6.87-61.13) and 12 months (95%CI = 7.76-16.24), respectively. Univariate subgroup analysis showed that the previous history of salvage chemotherapy (P = .015) and the presence of liver metastases (P < .001) significantly affected the efficacy of palbociclib. Despite the existence of liver metastases and primary endocrine resistance, which are two independent predictors of poor prognosis, early application of palbociclib in advanced stage can bring further benefits to these two groups of patients, rather than choosing salvage chemotherapy in the first place. Conclusion: Palbociclib combined with endocrine therapy has a favorable efficacy and acceptable toxicity in HR+/HER2- Chinese MBC patients. Better performance can be seen when palbociclib was applicated in the early stage.

Identification of MICALL2 as a Novel Prognostic Biomarker Correlating with Inflammation and T Cell Exhaustion of Kidney Renal Clear Cell Carcinoma.

Purpose: The interplay of inflammation and immunity affects all stages from tumorigenesis to progression, and even tumor response to therapy. A growing interest has been attracted from the biological function of MICALL2 to its effects on tumor progression. This study was designed to verify whether MICALL2 could be a prognostic biomarker to predict kidney renal clear cell carcinoma (KIRC) progression, inflammation, and immune infiltration within tumor microenvironment (TME).Methods: We firstly analyzed MICALL2 expressions across 33 cancer types from the UCSC Xena database and verified its expression in KIRC through GEPIA platform and GEO datasets. The clinicopathological characteristics were further analyzed based on the median expression. Kaplan-Meier method, univariate and multivariate analyses were applied to compare survival outcomes. ESTIMATE and CIBERSORT algorithms were performed to assess immune infiltration, and a co-expression analysis was conducted to evaluate the correlation between MICALL2 and immunoregulatory genes. Enrichment analysis was finally performed to explore the biological significance of MICALL2.Results: MICALL2 was highly expressed in 16 types of cancers compared with normal tissues. MICALL2 expression increased with advanced clinicopathological parameters and was an independent predictor for poor prognosis in KIRC. Moreover, MICALL2 closely correlated with inflammation-promoting signatures and immune infiltration including T cell exhaustion markers. Consistently, MICALL2 involved in the regulation of signaling pathways associated with tumor immunity, tumor progression, and impaired metabolic activities.Conclusion: MICALL2 can function as a prognostic biomarker mediating inflammation, immune infiltration, and T cell exhaustion within the microenvironment of KIRC.

Paraneoplastic syndrome frequency and prognostic effect in hepatocellular carcinoma patients.

Symptomatic hepatocellular carcinoma (HCC) patients may generally display constitutional symptoms such as abdominal pain, weight loss, anorexia and localized mass, or atypical clinical features of paraneoplastic syndrome (PNS) such as hypercholesterolemia, hypercalcemia, hypoglycemia, erythrocytosis and thrombocytosis. The most common PNS in HCC is hypercholesterolemia, hypercalcemia, hypoglycemia and erythrocytosis. The aim of this study isto evaluate the relationship of PNS in HCC patients. In this study, the data of 534 patients who were followed up with the diagnosis of HCC between January 2010 and December 2020 in the Gastroenterology clinic were evaluated retrospectively. Clinical data, age, gender, complete blood count of patients with and without PNS, liver biochemistry, alpha-fetoprotein (AFP) level, hepatitis B surface antigen, anti-hepatitis B virus, Child-Pugh score, model for end-stage liver disease score, tumor volume, portal vein thrombosis, liver biopsy histology and radiologic images were taken from the hospital data system and analyzed. Out of the 534 HCC patients, 120 (22.3%) were PNS-positive patients. There was a significant difference between the ages of PNS-positive and PNS-negative patients, and PNS-positive patients were older (64.60±12.97) (P=0.02). PNS-positive HCC was determined as hypoglycemia 5.8%, hypercalcemia 6.3%, erythrocytosis 3.9%, hypercholesterolemia 2.4% and thrombocytosis 3.9%. AFP level (22908 ± 60 ng/ml) and tumor diameter (>10 cm) were higher in the PNS-positive group. Multivariate analysis showed that stage C according to Child-Pugh score and tumor diameter >10 cm were independent predictors of poor prognosis, whereas PNS erythrocytosis and thrombocytosis were independent predictors of better prognosis. In PNS-positive HCC patients, hypoglycemia and hypercalcemia were associated with poor prognosis according to Child-Pugh score, whereas erythrocytosis and thrombocytosis were associated with good prognosis.

Prognostic Value of Squamous Differentiation in Upper Tract Urothelial Carcinoma Treated With Radical Nephroureterectomy.

This study retrospectively investigated the impact of squamous differentiation on the prognosis of patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Among the 244 consecutive patients who underwent RNU at our Institution from May 2005 to October 2019, 224 were analysed. Metastasis-free (MFS) and overall (OS) survival rates were evaluated using Kaplan-Meier analysis and Cox regression analysis. With a median follow-up time of 58 months, the groups with pure UTUC (n=197) and UTUC with squamous differentiation (n=27) had 5-year MFS rates of 65.2% and 40.9% (p=0.005) and 5-year OS rates of 74.4% and 49.0% (p=0.002), respectively. Multivariate analyses revealed that the presence of squamous differentiation was significantly associated with poor MFS (hazard ratio=1.88; p=0.027) and OS (hazard ratio=1.70; p=0.048). Squamous differentiation in UTUC appears to be an independent predictor of poor prognosis after RNU for UTUC.

Prognostic Analysis of Different Metastatic Patterns in Invasive Intraductal Papillary Mucinous Neoplasm: A Surveillance, Epidemiology, and End Results Database Analysis.

Objective To evaluate the impacts of different metastatic patterns on the prognosis of patients with invasive intraductal papillary mucinous neoplasm (IPMN). Materials and Methods All patients who were diagnosed with invasive IPMN in the Surveillance, Epidemiology, and End Results SEER database (2010–2015) were included in this study. They were grouped according to different metastatic patterns. Kaplan–Meier analysis and log-rank test were used for the comparison of their survival rates. The hazard ratio (HR) with 95% confidence interval (CI) was analyzed using the Cox proportional-hazards model. Results A total of 2264 cases were included in this study. The most common metastatic site was the liver. The patients with the nonorgan metastasis demonstrated the best survival outcomes, while those with multiple metastases showed the worst survival outcomes. As compared to the patients with isolated liver metastasis, those with isolated lung and other organ metastases showed better overall survival rates and tumor-specific survival rates. The patients with liver, lung, multiple, and other organ metastases or of age >60 years were the independent predictors of poor prognosis. Conclusions The patients with isolated lung and other organ metastases demonstrated better survival outcomes as compared to those with isolated liver metastasis. The patients with nonorgan metastasis demonstrated the best survival outcomes, while those with multiple metastases showed the worst survival outcomes. Further studies are needed to determine a highly selected subset of patients, who might benefit from surgery or chemotherapy.

N-terminal prohormone B-type natriuretic peptide variability acts as a predictor of poor prognosis in patients with cardiorenal syndrome type 2

ABSTRACT This study aims to explore the effect of N-terminal pro-brain natriuretic peptide (NT-proBNP) variability (mean absolute difference of the log2 NT-proBNP level measured in hospital) on the prognosis of patients with cardiorenal syndrome (CRS) type 2. Patients with CRS type 2 were retrospectively included. The varied NT-proBNP indications were analyzed. They were NT-proBNP I(pre-treatment), NT-proBNP II(post-treatment), NT-proBNP II/I, ΔNT-proBNP, log2 (NT-proBNP) variability and mean log2 (NT-proBNP). A logistic regression model and survival curves (Kaplan–Meier analysis) were built to identify independent predictors associated with poor prognosis. The primary outcomes were major adverse renal and cardiac events. The secondary outcome was all-cause mortality. From 2012 to 2016, 136 patients were included in this study with 69 (50.7%) had high log2 (NT-proBNP) variability level. The optimal cutoff level for each NT-proBNP indication that predicts poor prognosis was calculated, and the area under curves ranged from 0.668 to 0.891 with different indications. Kaplan–Meier analysis revealed that there was significantly correlated with prevalence of primary outcomes and NT-proBNP variability. The hazard ratios (HRs) ranged from 1.67 to 6.61 with different indications. The multivariate regression analyses also identified the risk of the primary outcomes were associated with elevated NT-proBNP values, except NT-proBNP I. The odds ratio (ORs) ranged from 1.83 to 6.61 with different indications. When analyzing the relationship between NT-proBNP variability and all-cause mortality, the results were the same. NT-proBNP variability might serve as an independent predictor for poor prognosis and all-cause mortality in patients with CRS type 2.

Spread through air spaces is a common phenomenon of pulmonary metastasized tumours regardless of origins.

Spread through air spaces (STAS) is a unique pattern of invasion in primary lung cancers. However, little is known about STAS in pulmonary metastases (PMs). This study was to investigate the incidence of STAS among PMs and the association between STAS and clinicopathological characteristics of PMs. A total of 127 patients who underwent metastasectomy at our institution from June 2009 to December 2019 were retrospectively analysed. Survival analysis was performed in 40 patients with PM from colorectal cancer (CRC). STAS was identified in 33.1% of patients (42 of 127) with PMs. STAS was found in PMs of various primary cancers, including CRC, breast cancer, renal cell carcinoma, cholangiocarcinoma and osteogenic and soft tissue sarcoma, but the incidence varies. PMs originating from epithelial tissue showed higher incidence of STAS than those from mesenchymal tissue (45% vs 11%, P < 0.001). Elder age (P = 0.006) and primary sites (P < 0.001) were significantly correlated with STAS. In patients with PMs from CRC, the presence of STAS was an independent predictor of shorter recurrence-free survival (hazard ratio = 10.25, P = 0.002) and poor overall survival (hazard ratio = 4.75, P = 0.047) by multivariable analysis. STAS might be a lung-specific tumour invasion pattern and STAS is commonly observed in PMs of different origins. The incidence of STAS was significantly higher in PMs originating from epithelial tissues than those from mesenchymal tissues. Presence of STAS was an independent predictor of poor prognosis in patients with PM from CRC.

Distribution pattern and pathologic analysis of metastatic sentinel and non-sentinel lymph nodes in lymphatic basin dissection for clinical T2/T3 oral cancer with clinical N0 status

ObjectiveThe localization pattern of metastatic sentinel lymph node (SN) and non-SNs and pathologic analysis of metastatic lymph nodes in SN lymphatic basin dissection (SLBD) were investigated in patients with cT2/T3cN0 oral squamous cell carcinoma (OSCC). MethodsThis prospective multicenter trial involved 10 institutions nationwide in Japan. A total of 57 patients were enrolled. The lateral neck was divided into 5 lymphatic basins. The lymphatic basin containing SNs was defined as the SN lymphatic basin.All patients underwent SLBD with backup selective neck dissection (I-III) combined with primary tumor removal. When SNs were found outside of levels I-III, including in the contralateral neck, SLBD was performed by removing the compartments containing SNs separately. SN metastasis was classified as isolated tumor cells (ITCs), micrometastasis, or macrometastasis. ITCs are defined as a lesion no larger than 0.2 mm in largest dimension and are classified as pN0. ResultsSN metastasis was observed in 22 cases. All metastatic lymph nodes, including false-negative cases, were detected in the SN lymphatic basin. Isolated tumor cells in the SNs did not affect prognosis, whereas micrometastasis tended to have poor prognosis.After adjusting for other risk factors, a positive SN remained a significant predictor of poor 5-year overall survival in pT2-4 OSCC. ConclusionSLBD for intraoperative SN biopsy is a sufficient therapeutic procedure and is valuable for determining pathologic nodal stage in OSCC. SN positivity was demonstrated to be an independent predictor of poor prognosis in patients with pT2-4 disease undergoing SLBD with backup selective neck dissection (I-III).

Identification of MATN3 as a Novel Prognostic Biomarker for Gastric Cancer through Comprehensive TCGA and GEO Data Mining.

Gastric cancer (GC) is still a vital malignant cancer across the world with unsatisfactory prognostic results. Matrilin-3 (MATN3) is a member of the extracellular matrix (ECM) protein family. The present research intends to explore the expression level of MATN3 in patients with GC and to explore the prognosis significance of MATN3. In this study, we observed that the MATN3 expression was remarkably upregulated in GC samples in contrast to noncancer samples. Clinical analyses unveiled that high MATN3 expression was related to age, tumor status, and clinical stages. Survival analyses unveiled that patients with high MATN3 expression displayed a poorer overall survival and progression-free survival than those with low MATN3 expression. The AUC of the relevant ROC curve for 1 year, 3 years, and 5 years of survival is 0.571, 0.596, and 0.720, separately. Multivariate assays revealed that MATN3 expression and stage were independent predictors of poor prognosis of GC patients. A meta-analysis unveiled that high MATN3 expression was tightly associated with better overall survival. Overall, our data indicated that MATN3 may have a diagnostic and prognostic value for patients with advanced gastric cancer and assist to improve clinical outcomes for GC patients.

H19- and hsa-miR-338-3p-mediated NRP1 expression is an independent predictor of poor prognosis in glioblastoma.

Glioblastoma multiforme (GBM) is the most common and also the most invasive brain cancer. GBM progression is rapid and its prognosis is poor. Therefore, finding molecular targets in GBM is a critical goal that could also play important roles in clinical diagnostics and treatments to improve patient prognosis. We jointly analyzed the GSE103227, GSE103229, and TCGA databases for differentially expressed RNA species, obtaining 52 long non-coding RNAs (lncRNAs), 31 microRNAs (miRNAs), and 186 mRNAs, which were used to build a competing endogenous RNA network. Kaplan–Meier and receiver operating characteristic (ROC) analyses revealed five survival-related lncRNAs: H19, LINC01574, LINC01614, RNF144A-AS1, and OSMR-AS1. With multiple optimization mRNAs, we found the H19-hsa-miR-338-3P-NRP1 regulatory pathway. Additionally, we noted high NRP1 expression in GBM patients, and Kaplan–Meier and ROC analyses showed that NRP1 expression was associated with GBM prognosis. Cox analysis indicated that NRP1 is an independent prognostic factor in GBM patients. In conclusion, H19 and hsa-miR-338-3P regulate NRP1 expression, and this pathway plays an important role in GBM.

Establishment and validation of prognosis model for patients with cerebral contusion

Background And ObjectiveCerebral Contusion (CC) is one of the most serious injury types in patients with traumatic brain injury (TBI). In this study, the baseline data, imaging features and laboratory examinations of patients with CC were summarized and analyzed to develop and validate a prediction model of nomogram to evaluate the clinical outcomes of patients.MethodsA total of 426 patients with cerebral contusion (CC) admitted to the People’s Hospital of Qinghai Province and Affiliated Hospital of Qingdao University from January 2018 to January 2021 were included in this study, We randomly divided the cohort into a training cohort (n = 284) and a validation cohort (n = 142) with a ratio of 2:1.At Least absolute shrinkage and selection operator (Lasso) regression were used for screening high-risk factors affecting patient prognosis and development of the predictive model. The identification ability and clinical application value of the prediction model were analyzed through the analysis of receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA).ResultsTwelve independent prognostic factors, including age, Glasgow Coma Score (GCS), Basal cistern status, Midline shift (MLS), Third ventricle status, intracranial pressure (ICP) and CT grade of cerebral edema,etc., were selected by Lasso regression analysis and included in the nomogram. The model showed good predictive performance, with a C index of (0.87, 95% CI, 0.026–0.952) in the training cohort and (0.93, 95% CI, 0.032–0.965) in the validation cohort. Clinical decision curve analysis (DCA) also showed that the model brought high clinical benefits to patients.ConclusionThis study established a high accuracy of nomogram model to predict the prognosis of patients with CC, its low cost, easy to promote, is especially applicable in the acute environment, at the same time, CSF-glucose/lactate ratio(C-G/L), volume of contusion, and mean CT values of edema zone, which were included for the first time in this study, were independent predictors of poor prognosis in patients with CC. However, this model still has some limitations and deficiencies, which require large sample and multi-center prospective studies to verify and improve our results.

Risk of station 12a lymph node metastasis in patients with lower-third gastric cancer.

BACKGROUNDControversy over the issue that No. 12a lymph node involvement is distant or regional metastasis remains, and the possible inclusion of 12a lymph nodes in D2 lymphadenectomy is unclear. As reported, gastric cancer (GC) located in the lower third is highly related to the metastasis of station 12a lymph nodes.AIMTo investigate whether the clinicopathological factors and metastasis status of other perigastric nodes can predict station 12a lymph node metastasis and evaluate the prognostic significance of station 12a lymph node dissection in patients with lower-third GC.METHODSA total of 147 patients with lower-third GC who underwent D2 or D2+ lymphadenectomy, including station 12a lymph node dissection, were included in this retrospective study from June 2003 to March 2011. Survival prognoses were compared between patients with or without station 12a lymph node metastasis. Logistic regression analyses were used to clarify the association between station 12a lymph node metastasis and clinicopathological factors or metastasis status of other perigastric nodes. The metastasis status of each regional lymph node was evaluated to identify the possible predictors of station 12a lymph node metastasis.RESULTSMetastasis to station 12a lymph nodes was observed in 18 patients with lower-third GC, but not in 129 patients. The incidence of station 12a lymph node involvement was reported as 12.2% in patients with lower-third GC. The overall survival of patients without station 12a lymph node metastasis was significantly better than that of patients with station 12a metastasis (P < 0.001), which could also be seen in patients with or without extranodal soft tissue invasion. Station 12a lymph node metastasis and extranodal soft tissue invasion were identified as independent predictors of poor prognosis in patients with lower-third GC. Advanced pN stage was defined as independent risk factor significantly correlated with station 12a lymph node positivity. Station 3 lymph node staus was also proven to be significantly correlated with station 12a lymph node involvement.CONCLUSIONMetastasis of station 12a lymph nodes could be considered an independent prognosis factor for patients with lower-third GC. The dissection of station 12a lymph nodes may not be ignored in D2 or D2+ lymphadenectomy due to difficulties in predicting station 12a lymph node metastasis.

Multimorbidity, polypharmacy, and mortality in older patients with pacemakers.

BackgroundThe prevalence of multimorbidity and polypharmacy and its association with all‐cause mortality in older patients with pacemakers are largely unknown. We aimed to clarify the prevalence of multimorbidity and polypharmacy, and its association with all‐cause mortality in patients ≥75 years of age with pacemakers.MethodsWe retrospectively investigated 256 patients aged ≥75 years (mean age 84.0 ± 5.3 years; 45.7% male) with newly implanted pacemakers. The study endpoint was all‐cause mortality (“with events”). Multimorbidity was defined as a Charlson Comorbidity Index ≥3. Polypharmacy was defined as the use of ≥5 medications.ResultsDuring the follow‐up period (median, 3.1 years), 60 all‐cause deaths were reported. The Charlson Comorbidity Index (2.9 ± 1.9 vs. 1.7 ± 1.7, p < .001) and prevalence of multimorbidity (56.7% vs. 26.0%, p < .001) were significantly higher in deceased patients than in survivors. The number of drugs (6.9 ± 3.0 vs. 5.9 ± 3.3, p = .03) and the prevalence of polypharmacy (78.3% vs. 63.8%, p = .04) were significantly higher in patients with events than in those without events. The event‐free survival rate was significantly higher among patients without multimorbidity than in those with multimorbidity (log‐rank, p < .001), and was also significantly higher among patients without polypharmacy than in those with polypharmacy (log‐rank, p < .001). Multimorbidity (hazard ratio [HR]: 3.21; 95% confidence interval [CI]: 1.85–5.58; p < .001) and polypharmacy (HR: 1.97; 95% CI: 1.03–3.77; p = .04) were independent predictors of all‐cause mortality.ConclusionsMultimorbidity and its associated polypharmacy, which are common in the older population, are prevalent in patients with pacemakers and are independent predictors of poor prognosis.

Influencia de la historia de tabaquismo en la evolución de la hospitalización en pacientes COVID-19 positivos: datos del registro SEMI-COVID-19

IntroducciónEl tabaquismo puede tener un papel importante en la infección por SARS-CoV-2 y en el curso de la enfermedad. Los estudios previos muestran resultados contradictorios o no concluyentes sobre la prevalencia de fumar y la severidad en la enfermedad por coronavirus (COVID-19).Material y métodosEstudio de cohortes observacional, multicéntrico y retrospectivo de 14.260 pacientes que ingresaron por COVID-19 en hospitales españoles desde febrero hasta septiembre de 2020. Se registraron sus características clínicas y se clasificaron en el grupo con tabaquismo si tabaquismo activo o previo, o en el grupo sin tabaquismo si nunca habían fumado. Se realizó un seguimiento hasta un mes después del alta. Se analizaron las diferencias entre grupos. La relación entre tabaquismo y mortalidad intrahospitalaria se valoró mediante una regresión logística multivariante y curvas de Kapplan Meier.ResultadosLa mediana de edad fue 68,6 (55,8-79,1) años, con un 57,7% de varones. El grupo con tabaquismo presentó mayor edad (69,9 [59,6-78,0 años]), predominio masculino (80,3%) y mayor índice de Charlson (4 [2-6]). La evolución fue peor en estos pacientes, con una mayor tasa de ingreso en UCI (10,4 vs. 8,1%), mayor mortalidad intrahospitalaria (22,5 vs. 16,4%) y reingreso al mes (5,8 vs. 4,0%) que el grupo sin tabaquismo. Tras el análisis multivariante, el tabaquismo permanecía asociado a estos eventos.ConclusionesEl tabaquismo de forma activa o pasada es un factor predictor independiente de mal pronóstico en los pacientes con COVID-19, estando asociado a mayor probabilidad de ingreso en UCI y a mayor mortalidad intrahospitalaria.

First-Line Treatment and Survival of Stage I(E) Peripheral T-Cell Lymphoma in the Netherlands; A Nationwide Population-Based Cohort Study

Introduction: Peripheral T-cell lymphomas (PTCL) comprise a heterogenous group of mature T-cell neoplasms with generally an unfavorable prognosis. Presentation of PTCL with stage I(E) disease, according to the Ann Arbor classification, is uncommon. Clinical trials in diffuse large B-cell lymphoma (DLBCL) support the use of an abbreviated treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone combined with radiotherapy (combined modality therapy (CMT)) in case of stage I(E) disease. CMT in stage I(E) PTCL has been adapted in daily practice, but clinical trials are lacking. A recent population-based study conducted in Scandinavia indicated that the outcome in patients with limited stage PTCL is as poor as in patients with extensive disease. However, the outcomes of different treatment modalities were not analyzed.Aim: The aim of this nationwide population-based cohort study is to describe first-line treatment and outcome of patients with stage I(E) PTCL in comparison to advanced stage PTCL.Methods: All newly diagnosed patients ≥ 18 years with stage I(E) PTCL who were diagnosed in 1989-2018 were identified in the Netherlands Cancer Registry (NCR). Survival follow-up was available through February 1, 2021. The PTCL subgroups analyzed included anaplastic large cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AITL), enteropathy associated T-cell lymphoma (EATL) and peripheral T-cell lymphoma NOS (PTCL NOS). Patients were categorized according to treatment regimen, i.e. chemotherapy, chemotherapy followed by autologous stem cell transplantation (ASCT), radiotherapy, CMT, and no/other therapy. Calendar period analyses (1989-1999 and 2000-2018) were conducted to assess trends in primary therapy and overall survival (OS) over time. The calendar periods were defined according to the implementation of CMT in patients with limited stage DLBCL from approximately 2000 onward in the Netherlands. The primary endpoint was OS, defined as all-cause-death post-diagnosis.Results: From 1989 to 2018, 854 patients with a median age of 62 years were diagnosed with stage I(E) PTCL, accounting for 19% of all PTCL diagnoses. In stage I(E), the predominant PTCL subtype was PTCL NOS (40%, n=343). Furthermore, 26% (n=222) of patients were diagnosed with ALCL, 3% (n=28) with AITL, 11% (n=93) with EATL and 20% (n=168) with other histological subtypes. In contrast, for patients with advanced stage disease, 42% was diagnosed with PTCL NOS, 23% with ALCL, 24% with AITL, 6% with EATL and 5% with other histological subtypes .To evaluate treatment and survival outcome in patients with stage I(E) PTCL, patients with ALCL, AITL, PTCL NOS and EATL were included for further analyses (n=686). Patients with ALCL, AITL and PTCL NOS were most commonly treated with CMT (n=164; 28%) or chemotherapy only (n=154; 26%). Only 10 patients (1%) received chemotherapy followed by ASCT. The remaining patients were treated with either radiotherapy only (n=116; 20%) or received other/no therapy (n=149; 25%). More patients were treated with CMT in 2000-2018 as compared to 1989-1999 (36% versus 17%, p<0.01). Patients with EATL were most commonly treated with either chemotherapy only or other/no treatment (both n=45; 48%), while 3 patients (4%) received chemotherapy in combination with ASCT (n=2) or CMT (n=1). In EATL, no differences in treatment strategy were observed over time.Overall, 5-year OS for all stage I(E) PTCL was 52%. There was no significant difference in outcome between the two time periods (53% vs. 52%, p=0.92). EATL had a worse prognosis when compared to ALCL, AITL and PTCL NOS (5-year OS 15% vs. 58%, respectively; p<0.01). Five-year OS was significantly higher for patients with ALCL, AITL and PTCL NOS treated with CMT (71%) as compared to patients treated with either chemotherapy alone or with radiotherapy alone (52%, and 53%, respectively; p<0.01). Independent predictors for poor prognosis were higher age, male gender and EATL subtype whereas CMT was associated with a lower risk of mortality when evaluated for in multivariable analysis.Conclusions: For stage I(E) ALCL, AITL and PTCL NOS, 5-year OS is 58%. This compares favorably to the reported outcomes in advanced stage disease. EATL, even when presenting with limited stage disease, is associated with a very poor prognosis. CMT is associated with superior OS when compared to either chemotherapy or radiotherapy alone. DisclosuresVan Der Poel: Roche, Janssen, Abbvie: Honoraria. Kersten: Kite/Gilead: Consultancy, Honoraria, Research Funding; BMS/Celgene: Consultancy; Miltenyi Biotech: Consultancy; Novartis: Consultancy, Honoraria; Roche: Honoraria; Takeda: Consultancy. Mutsaers: BMS: Consultancy; AstraZeneca: Research Funding. Woei-a-Jin: University Hospitals Leuven, Belgium: Current Employment; Recordati: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Kyowa Kirin: Research Funding.

CSMD1 Mutation Related to Immunity Can Be Used as a Marker to Evaluate the Clinical Therapeutic Effect and Prognosis of Patients with Esophageal Cancer.

IntroductionAs a highly aggressive tumor with a poor prognosis, esophageal cancer (ESCA)’s relationship with gene mutations is unclear. Therefore, we tried to explore the role of gene mutation in ESCA progression and its relationship with immune response, clinical treatment, and prognosis.MethodsIn addition to copy number variation (CNV) situations of common genes obtained from 2 public databases, the relationship between mutations and prognosis/tumor mutational burden (TMB) was also analyzed. Kaplan–Meier survival and Cox regression analysis were used to identify the CSMD1 mutation status as an independent predictor of prognosis. We also enriched related functions and pathways. Next, the relationship between 22 immune cells and CSMD1 mutation status was analyzed. In addition to the differences in the expression levels of immune checkpoint inhibitors (ICIs)-related genes between the high TMB and low TMB groups, the differences in the expression levels of ICIs/m6a/multi-drug resistance-related genes and the sensitivity of three chemotherapeutic drugs between CSMD1 mutant and the wild group were also compared. In addition to differences and prognostic analysis of CSMD1 expression, the correlation analysis between the expression of these genes/immune cells and the expression of CSMD1 was also performed. Finally, a nomogram that could efficiently and conveniently predict the survival probability of ESCA patients was constructed and verified.ResultsWe obtained 17 frequently mutated genes distribution. Mutation and loss of CSMD1 are frequent in ESCA. Only CSMD1 mutation can be used as an independent predictor of poor prognosis. Patients in the high TMB group have a lower survival probability. Wild CSMD1 may be involved in immune-related pathways. More helper T cells and fewer resting state dendritic cells were found in the CSMD1 mutant group. The PD-1 expression in the high TMB group showed higher. Paclitaxel sensitivity and ABCC1 expression were higher in the wild CSMD1 group. Most cancers show differential expression of CSMD1. Except for the prognosis of ESCA, the expression of CSMD1 is related to immune cell content and the expression of ICIs/m6a/multi-drug resistance related genes.DiscussionCSMD1 mutation could be used as an immune-related biomarker to predict prognosis and treatment effect of paclitaxel. Mutation and loss of CSMD1 may promote the progression of ESCA.

Adenocarcinoma with Mixed Subtypes in the Early and Advanced Gastric Cancer.

Objective Adenocarcinoma with mixed subtypes (AM) is a histological classification based on the WHO classification. We aimed to compare the prognosis among AM, classic adenocarcinoma (CA), mucinous adenocarcinoma (MAC), and signet-ring cell carcinoma (SRCC) in early and advanced gastric cancer (EGC and AGC), respectively. Methods The Surveillance, Epidemiology, and End Results (SEER) database was queried from 2001 to 2016. Univariate and multivariate Cox analyses were performed to compare prognosis between AM and histologic subtypes of CA, SRCC, and MAC in ECG and ACG. A nomogram was established to predict the cancer-specific survival (CSS) of gastric cancer (GC) patients with AM. C-index, calibration curves, and receiver operating characteristic (ROC) and decision curve analysis (DCA) curves were applied to examine the accuracy and clinical benefits. Results In the prognosis among these four histological subtypes in EGC patients, there are no differences. For AGC patients, AM had a significantly poorer prognosis compared with CA and MAC (P=0.003, 0.029) but similar prognosis to SRCC. A nomogram based on race, T stage, N stage, M stage, and surgical modalities was proposed to predict 1- and 3-year CSS for GC patients with AM (C-index: training cohort: 0.804, validation cohort: 0.748. 1- and 3-year CSS AUC: training cohort: 0.871 and 0.914, validation cohort: 0.810 and 0.798). 1- and 3-year CSS DCA curves showed good net benefits. Conclusions EGC patients with AM had similar survival to those with CA, MAC, and SRCC. AM was an independent predictor of poor prognosis in AGC. A nomogram for predicting the prognosis of GC patients with AM was proposed to quantitatively assess the long-term survival.

Neutrophil-to-lymphocyte Ratio Predicts the Outcome of Cerebral Venous Thrombosis.

Increasing evidences suggest that Neutrophil-to-Lymphocyte Ratio (NLR) is an independent predictor of poor prognosis in patients with cardiovascular disease. However, the relationship between NLR and prognosis in patients with Cerebral Venous Thrombosis (CVT) has not been studied. Consecutive CVT patients from November 2011 through April 2019 were retrospectively identified. Poor outcome was defined as a modified Rankin Scale (mRS) of 3-6. Multivariate regression analysis was conducted to assess the relationship between total and differential leukocyte counts, NLR and clinical outcome in CVT patients. The Receiver Operating Characteristic (ROC) analysis was further performed to evaluate the ability to predict mortality, and subgroup analysis was conducted to explore the potential interaction effects. A total of 360 CVT patients were included, and the median duration of follow-up was 9.0 months. Multivariate logistic regression analysis suggested that NLR value, as a continuous variable, was significantly associated with a high risk of poor outcome (adjusted odds ratio [OR]=1.06, 95% confidence intervals [CI] 1.01-1.11, P = 0.013) and mortality (adjusted OR = 1.08; 95% CI, 1.03-1.14; P = 0.002). Compared with the total and differential leukocyte counts, the best discriminating variable to predict the risk of mortality was NLR, and the area under the receiver operating curve was 0.81. The optimal cut-off value of NLR to predict mortality was 5.6 (sensitivity 84.2%, specificity 69.9%). Multivariate Cox regression analysis indicated that the mortality rate was significantly higher in patients with a high NLR level group (>5.6) (adjust hazard ratio=5.65, 95% CI 2.33-12.73, P<0.001). There was no potential heterogeneity in the further subgroup analysis across age (above vs. below 45 years old), sex, history of infections and pregnancy/postpartum, presence of coma and intracerebral hemorrhage. Elevated NLR value is associated with a high risk of poor outcomes in CVT patients.