Significant Difference In Survival Research Articles

Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection: How to achieve a better outcome

BACKGROUND Although the benefits of antiviral therapy for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) have been proven, researchers have not confirmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time (at least 24 wk) and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC. AIM To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC. METHODS A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2016 to June 2019 was conducted. Considering the history of antiviral therapy, patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups. RESULTS Kaplan–Meier analysis revealed significant differences in overall survival (P < 0.0001) and disease-free survival (P = 0.035) between the two groups. Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival (hazard ratio = 0.27; 95% confidence interval: 0.08-0.88; P = 0.030). CONCLUSION In patients with HBV-related HCC, it is ideal to receive preoperative long-term antiviral therapy, which helps patients tolerate more extensive hepatectomy; however, remedial antiviral therapy, which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL, can also result in improved outcomes.

CD3, CD8, IFN-γ, tumor and stroma inflammatory cells as prognostic indicators for surgically resected SCLC: evidences from a 10-year retrospective study and immunohistochemical analysis.

Current clinical guidelines limit surgical intervention to patients with cT1-2N0M0 small cell lung cancer (SCLC). Our objective was to reassess the role of surgery in SCLC management, and explore novel prognostic indicators for surgically resected SCLC. We reviewed all patients diagnosed with SCLC from January 2011 to April 2021 in our institution. Survival analysis was conducted using the Kaplan-Meier method, and independent prognostic factors were assessed through the Cox proportional hazard model. In addition, immunohistochemistry (IHC) staining was performed to evaluate the predictive value of selected indicators in the prognosis of surgically resected SCLC patients. In the study, 177 SCLC patients undergoing surgical resection were ultimately included. Both univariate and multivariate Cox analysis revealed that incomplete postoperative adjuvant therapy emerged as an independent risk factor for adverse prognosis (p < 0.001, HR 2.96). Survival analysis revealed significantly superior survival among pN0-1 patients compared to pN2 patients (p < 0.0001). No significant difference in postoperative survival was observed between pN1 and pN0 patients (p = 0.062). Patients with postoperative stable disease (SD) exhibited lower levels of tumor inflammatory cells (TIC) (p = 0.0047) and IFN-γ expression in both area and intensity (p < 0.0001 and 0.0091, respectively) compared to those with postoperative progressive disease (PD). Conversely, patients with postoperative SD showed elevated levels of stromal inflammatory cells (SIC) (p = 0.0453) and increased counts of CD3+ and CD8+ cells (p = 0.0262 and 0.0330, respectively). Survival analysis indicated that high levels of SIC, along with low levels of IFN-γ+ cell area within tumor tissue, may correlate positively with improved prognosis in surgically resected SCLC (p = 0.017 and 0.012, respectively). In conclusion, the present study revealed that the patients with pT1-2N1M0 staging were a potential subgroup of SCLC patients who may benefit from surgery. Complete postoperative adjuvant therapy remains an independent factor promoting a better prognosis for SCLC patients undergoing surgical resection. Moreover, CD3, CD8, IFN-γ, TIC, and SIC may serve as potential indicators for predicting the prognosis of surgically resected SCLC.

Outcome of Transarterial Radioembolization in the Treatment of Hepatocellular Carcinoma: Glass Versus Resin Microsphere.

To compare the treatment outcomes of glass and resin microspheres for the treatment of hepatocellular carcinoma (HCC) and evaluate the prognostic factors that influence the outcomes. We retrospectively reviewed 251 consecutive patients who underwent radioembolization for the treatment of HCC at a single tertiary center. Imaging responses after radioembolization were evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) 1.1. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard models were used to identify the prognostic factors. A total of 195 patients were included in this study (glass microsphere, n = 75; resin microsphere, n = 120). The complete and objective response rates were 16.0% and 50.7% in the glass microsphere group and 17.5% and 58.3% in the resin microsphere group, respectively. Median PFS was 241days in the glass microsphere group and 268days in the resin microsphere group (p = 0.871). Median OS was 29months in the glass microsphere group and 40months in the resin microsphere group (p = 0.669). The only significant prognostic factor was bilobar tumor distribution, which favored resin microspheres (p = 0.023). Procedure-related adverse events occurred more frequently in the resin microsphere group (glass, 2.7% vs. resin, 5.0%; p < 0.001). Glass and resin microspheres for the treatment of HCC did not show a significant difference in survival, though major adverse events occurred more frequently with the use of resin microspheres.

Long-term prognosis after endoscopic submucosal dissection for esophageal cancer in older adult patients

BackgroundThe validity of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) in older individuals with comorbidities remains unclear. Therefore, this study evaluated the safety and efficacy of ESD and additional treatment for ESCC in older adult patients.MethodsThe clinicopathological characteristics and clinical outcomes of 398 consecutive older adult patients (≥ 65 years) with 505 lesions who underwent ESD for ESCC at the Hiroshima University Hospital between September 2007 and December 2019 were retrospectively evaluated. Additionally, the prognoses of 381 patients who were followed up for > 3 years were assessed.ResultsThe mean patient age and procedure time were 73.1 ± 5.8 years and 77.1 ± 43.5 min, respectively. The histological en bloc resection rate was 98% (496/505). Postoperative stenosis, perforation, pneumonia, and delayed bleeding were conservatively treated in 82 (16%), 19 (4%), 15 (3%), and 5 (1%) patients, respectively. The 5-year overall and disease-specific survival rates were 78.9% and 98.0%, respectively (mean follow-up time: 71.1 ± 37.3 months). Multivariate analysis showed that age and the American Society of Anesthesiologists classification of physical status class ≥III (hazard ratio: 1.27; 95% confidence interval: 1.01–1.59, p = 0.0392) were independently associated with overall survival. A significantly lower overall survival rate was observed in the high-risk follow-up group than in the low-risk follow-up and high-risk additional treatment groups (p < 0.01). However, no significant difference in disease-specific survival was observed among the three groups.ConclusionsESD is safe for ESCC treatment in patients aged ≥ 65 years. However, additional treatments should be considered based on the patient’s general condition.

Integrated single-cell and bulk RNA-Seq analysis enhances prognostic accuracy of PD-1/PD-L1 immunotherapy response in lung adenocarcinoma through necroptotic anoikis gene signatures

In addition to presenting significant diagnostic and treatment challenges, lung adenocarcinoma (LUAD) is the most common form of lung cancer. Using scRNA-Seq and bulk RNA-Seq data, we identify three genes referred to as HMR, FAM83A, and KRT6A these genes are related to necroptotic anoikis-related gene expression. Initial validation, conducted on the GSE50081 dataset, demonstrated the model's ability to categorize LUAD patients into high-risk and low-risk groups with significant survival differences. This model was further applied to predict responses to PD-1/PD-L1 blockade therapies, utilizing the IMvigor210 and GSE78220 cohorts, and showed strong correlation with patient outcomes, highlighting its potential in personalized immunotherapy. Further, LUAD cell lines were analyzed using quantitative PCR (qPCR) and Western blot analysis to confirm their expression levels, further corroborating the model's relevance in LUAD pathophysiology. The mutation landscape of these genes was also explored, revealing their broad implication in various cancer types through a pan-cancer analysis. The study also delved into molecular subclustering, revealing distinct expression profiles and associations with different survival outcomes, emphasizing the model’s utility in precision oncology. Moreover, the diversity of immune cell infiltration, analyzed in relation to the necroptotic anoikis signature, suggested significant implications for immune evasion mechanisms in LUAD. While the findings present a promising stride towards personalized LUAD treatment, especially in immunotherapy, limitations such as the retrospective nature of the datasets and the need for larger sample sizes are acknowledged. Prospective clinical trials and further experimental research are essential to validate these findings and enhance the clinical applicability of our prognostic model.

PCDH11X mutation as a potential biomarker for immune checkpoint therapies in lung adenocarcinoma.

Immune checkpoint inhibitors (ICIs) have achieved impressive success in lung adenocarcinoma (LUAD). However, the response to ICIs varies among patients, and predictive biomarkers are urgently needed. PCDH11X is frequently mutated in LUAD, while its role in ICI treatment is unclear. In this study, we curated genomic and clinical data of 151 LUAD patients receiving ICIs from three independent cohorts. Relations between PCDH11X and treatment outcomes of ICIs were examined. A melanoma cohort collected from five published studies, a pan-cancer cohort, and non-ICI-treated TCGA-LUAD cohort were also examined to investigate whether PCDH11X mutation is a specific predictive biomarker for LUAD ICI treatment. Among the three ICI-treated LUAD cohorts, PCDH11X mutation (PCDH11X-MUT) was associated with better clinical response compared to wild-type PCDH11X (PCDH11X-WT). While in ICI-treated melanoma cohort, the pan-cancer cohort excluding LUAD, and the non-ICI-treated TCGA-LUAD cohort, no significant differences in overall survival (OS) were observed between the PCDH11X-MUT and PCDH11X-WT groups. PCDH11X mutation was associated with increased PD-L1 expression, tumor mutation burden (TMB), neoantigen load, DNA damage repair (DDR) mutations, and hot tumor microenvironment in TCGA-LUAD cohort. Our findings suggested that the PCDH11X mutation might serve as a specific biomarker to predict the efficacy of ICIs for LUAD patients. Considering the relatively small sample size of ICI-treated cohorts, future research with larger cohorts and prospective clinical trials will be essential for validating and further exploring the role of PCDH11X mutation in the context of immunotherapy outcomes in LUAD. KEY MESSAGES: PCDH11X mutation is associated with better clinical response compared to wild type PCDH11X in three ICIs-treated LUAD cohorts. In ICIs-treated melanoma cohort, the pan-cancer cohort excluding LUAD, and non-ICIs-treated TCGA-LUAD cohortsPCDH11X mutation is not associated with better clinical response, suggesting PCDH11X mutation might be a specific biomarker to predict the efficacy of ICIs treatment for LUAD patients. PCDH11X mutation is associated with increased PD-L1 expression, tumor mutation burden, and neoantigen load in TCGA-LUAD cohort. PCDH11X mutation is associated with hot tumor microenvironment in TCGA-LUAD cohort.

Surgical Resection in Colorectal Liver Metastasis: An Umbrella Review

Surgical resection is the gold standard for treating synchronous colorectal liver metastases (CRLM). The resection of the primary tumor and metastatic lesions can follow different sequences: “simultaneous”, “bowel-first”, and “liver-first”. Conservative approaches, such as parenchymal-sparing surgery and segmentectomy, may serve as alternatives to major hepatectomy. A comprehensive search of Medline, Epistemonikos, Scopus, and the Cochrane Library was conducted. Studies evaluating patients who underwent surgery for CRLM and reported survival results were included. Other secondary outcomes were analyzed, including disease-free survival, perioperative complications and mortality, and recurrence rates. Quality assessment was performed using the AMSTAR-2 method. No significant differences in overall survival, disease-free survival, and secondary outcomes were observed when comparing simultaneous to “bowel-first” resections, despite a higher rate of perioperative mortality in the former group. The 5-year OS was significantly higher for simultaneous resection compared to “liver-first” resection. No significant differences in OS and DFS were noted when comparing “liver-first” to “bowel-first” resection, or anatomic to non-anatomic resection. Our umbrella review validates simultaneous surgery as an effective oncological approach for treating SCRLM, though the increased risk of perioperative morbidity highlights the importance of selecting suitable patients. Non-anatomic resections might be favored to preserve liver function and enable future surgical interventions.

Controversies in minimally invasive surgery for invasive cervical cancer

Background. Determination of the feasibility of performing minimally invasive surgery for invasive cervical cancer and identification of criteria for optimal surgical access that ensures safety, effectiveness, and satisfactory immediate and long-term results remain challenging in gynecological oncology. The aim of the study was to evaluate the immediate and long-term treatment outcomes in patients with invasive cervical cancer who underwent radical hysterectomy via laparotomy compared to those who underwent minimally invasive surgery. Material and methods. Treatment outcomes of 91 patients with invasive carvical cancer were analyzed. The assessment of the objective tumor response to neoadjuvant chemotherapy using the RECIST scale (Response Evaluation Criteria in Solid Tumors) was confirmed by clinical, ultrasound and CT/ MRI findings. The Kaplan-Maier curves and the log-rank criterion were used to compare the time of relapse-free and overall survivals. Statistical analysis and visualization of the analysis results were performed using prism 9.5.1 (GraphPad, USA). Results. The presence of parametrial lymphovascular space invasion and the frequency of lymphadenopathy were comparable for both groups of patients. there were no statistically significant differences in the number of the resected lymph nodes, but there was a statistically significant difference in volume of blood loss and the duration of surgery between the groups (p=0.0001). Every third patient was diagnosed with stage IIIC after surgery (pelvic lymph node lesion). Intraoperative complications were significantly lower in the laparoscopy group than in the laparotomy group (6.7 % vs 13 %). No significant differences in the proportion of relapses of the disease between the groups were found (9.6 % in the laparotomy group vs 11.7 % in the laparoscopy group). There were no significant differences in overall and relapse-free survival between the groups. Conclusion. Minimally invasive surgery is a promising and adequate surgical technique for the treatment of cervical cancer. However, additional studies are needed to determine the indications for these surgeries.

Associated factors of mortality and morbidity in emergency and elective abdominal surgery: a two-year prospective cohort study at lacor hospital, Uganda

BackgroundThe mortality rate associated with open abdominal surgery is a significant concern for patients and healthcare providers. This is particularly worrisome in Africa due to scarce workforce resources and poor early warning systems for detecting physiological deterioration in patients who develop complications.MethodsThis prospective cohort study aimed to follow patients who underwent emergency or elective abdominal surgery at Lacor Hospital in Uganda. The participants were patients who underwent abdominal surgery at the hospital between April 27th, 2019 and July 07th, 2021. Trained research staff collected data using standardized forms, which included demographic information (age, gender, telephone contact, and location), surgical indications, surgical procedures, preoperative health status, postoperative morbidity and mortality, and length of hospital stay.ResultsThe present study involved 124 patients, mostly male, with an average age of 35 years, who presented with abdominal pain and varying underlying comorbidities. Elective cases constituted 60.2% of the total. The common reasons for emergency and elective surgery were gastroduodenal perforation and cholelithiasis respectively. The complication rate was 17.7%, with surgical site infections being the most frequent. The mortality rate was 7.3%, and several factors such as preoperative hypotension, deranged renal function, postoperative use of vasopressors, and postoperative assisted ventilation were associated with it. Elective and emergency-operated patients showed no significant difference in survival (P-value = 0.41) or length of hospital stay (P-value = 0.17). However, there was a significant difference in morbidity (p < 0.001).ConclusionCholelithiasis and gastroduodenal perforation were key surgical indications, with factors like postoperative ventilation and adrenaline infusion linked to mortality. Emergency surgeries had higher complication rates, particularly surgical site infections, despite similar hospital stay and mortality rates compared to elective surgeries.

Prediction of ovarian cancer prognosis using statistical radiomic features of ultrasound images.

Ovarian cancer is the deadliest gynecologic malignancy worldwide. Ultrasound is the most useful non-invasive test for preoperative diagnosis of ovarian cancer. In this study, by leveraging multiple ultrasound images from the same patient to generate personalized, informative statistical radiomic features, we aimed to develop improved ultrasound image-based prognostic models for ovarian cancer. A total of 2,057 ultrasound images from 514 ovarian cancer patients, including 355 patients with epithelial ovarian cancer, from two hospitals in China were collected for this study. The models were constructed using our recently developed Frequency Appearance in Multiple Univariate pre-Screening (FAMUS) feature selection algorithm and Cox proportional hazards model. The models showed high predictive performance for overall survival (OS) and recurrence-free survival (RFS) in both epithelial and nonepithelial ovarian cancer, with concordance indices (C-index) ranging from 0.773 to 0.794. Radiomic scores predicted 2-year OS and RFS risk groups with significant survival differences (log-rank test, P<1.0e-4 for both validation cohorts). OS and RFS hazard ratios between low- and high-risk groups were 15.994 and 30.692 (internal cohort) and 19.339 and 19.760 (external cohort), respectively. The improved performance of these newly developed prognostic models was mainly attributed to the use of multiple preoperative ultrasound images from the same patient to generate statistical radiomic features, rather than simply using the largest tumor ROI among them. The models also revealed that the roundness of tumor lesion shape was positively correlated with prognosis for ovarian cancer. In summary, the newly developed prognostic models based on statistical radiomic features from ultrasound images were highly predictive of the risk of cancer-related death and possible recurrence not only for patients with epithelial ovarian cancer but also for those with nonepithelial ovarian cancer. They thereby provide reliable, non-invasive markers for individualized prognosis evaluation and clinical decision-making for patients with ovarian cancer.

TOTAL KNEE ARTHROPLASTY REVISION RATES IN MOBILE- VERSUS FIXED-BEARING IMPLANTS: A NEW ZEALAND JOINT REGISTRY STUDY

IntroductionThe mobile-bearing (MB) total knee arthroplasty (TKA) design was introduced with the aim of reducing polyethylene wear and component loosening seen in the fixed-bearing (FB) design. A recent joint registry study has revealed increased risk for all-cause revision, but not revision for infection, in MB-TKA. We used the New Zealand Joint Registry (NZJR) to compare all-cause revision rates, and revision rates for aseptic loosening of MB-TKA compared with fixed bearing (FB) TKA.MethodsAll patients who underwent a primary TKA registered in the NZJR between the 1st January 1999 to 31st December 2021 were identified. Analysis compared MB to FB designs, with sub analysis of implants from a single company. We identified 135,707 primary TKAs, with 104,074 (76.7%) FB-TKAs and 31,633 (23.3%) MB-TKAs recorded. We examined all-cause revision rates, reasons for revision and performed survival analyses.ResultsFor all-comers, MB-TKA had an all-cause revision rate of 0.43/100-component-years (OCY) compared with 0.42/OCY for FB-TKA (p=0.09). The all-cause revision rate was higher for those age &lt; 65 years (MB TKA 0.60/OCY vs. FB-TKA 0.59/OCY) compared to those &gt; 65 years at time of primary TKA (MB-TKA 0.29/OCY vs. FB-TKA 0.32/OCY), however there was no statistically significant difference between implant design in either age group (p=0.16 and p=0.64; respectively). Similarly, there was no difference in revision rates for aseptic loosening between implant designs. Kaplan-Meier survival analysis demonstrates no statistically significant difference in revision-free survival of implants, with both MB-TKA and FB-TKA demonstrating ∼93% revision free survival at 23 years.ConclusionsBoth FB- and MB-TKA demonstrated excellent survivorship, with no significant difference in all-cause revision rates or revision for aseptic loosening between implant designs.

RISK FACTORS FOR MORBIDITY AND MORTALITY FOLLOWING HIP FRACTURES: AN ANZHFR STUDY

AimsUsing the Australian and New Zealand Hip Fracture Registry (ANZHFR) data, this study aimed to identify patient, fracture, and management factors associated with survival, mobility and residential status at 120 days. This will allow future interventions to target modifiable risk factors to improve the overall care of patients with hip fractures.MethodsAll NZ patients from 2018 – 2020 were included. Baseline demographics, management factors, and outcomes were recorded. Key outcomes were change in walking status, residential status and survival at 120 days. Univariate analysis was performed to compare differences in demographics, surgical and management factors for the key variables. Multivariate analysis was conducted to identify factors independently associated with outcomes.ResultsData from 9432 patients were analysed. The average age was 82.8 years (SD 9.8). 70.3% were females. 39.5% of patients were cognitively impaired on admission, 71.4% were from their own residence.At 120 days post injury, 10.9% (1029) had died 1029 (10.9%), 15.3% (1034) had a decrease in their residential status, 44.9% (2966) had a reduction in walking ability. On multivariate analysis; older age (RR1.1/yr, p&lt;0.001), male sex (RR1.7, P&lt;0.001), cognitive impairment (RR2.2, p&lt;0.001) and ASA&gt;3 (RR3.7, p=0.015) were risk factors for death. Similarly, increasing age (RR1.1 per year, p&lt;0.001), cognitive impairment (RR1.2, p=0.04) and ASA&gt;3 (RR2.9, p=0.047) were significant risk factors for worsening residential status. Decreasing mobility was associated with extracapsular fractures (RR1.4, p=0.01).After adjustment for demographics, ASA and fracture type, performing total hip arthroplasty was preventative for both worsening residential status (RR0.23, p&lt;0.001) and decreasing walking ability (RR 0.21, p&lt;0.001). There was no significant survival, functional or revision differences for other fixation types.ConclusionThere is a significant decline in walking ability post hip fracture which may be a key contributor to long-term morbidity. The benefits of THA in preserving mobility and independence should be further investigated. Additional discharge planning and multi-disciplinary team input are likely required for high-risk patients of older age, with cognitive impairment and extracapsular fractures.

The Impact of the Coexpression of MET and ESR Genes on Prognosticators and Clinical Outcomes of Breast Cancer: An Analysis for the METABRIC Dataset

Purpose. Breast cancer is a heterogeneous disease. Exploring new prognostic and therapeutic targets in patients with breast cancer is essential. This study investigated the expression of MET, ESR1, and ESR2 genes and their association with clinicopathologic characteristics and clinical outcomes in patients with breast cancer. Methods. The METABRIC dataset for breast cancer was obtained from the cBioPortal public domain. Gene expression data for MET, ESR1, and ESR2, as well as the putative copy number alterations (CNAs) for MET were retrieved. Results. The MET mRNA expression levels correlated inversely with the expression levels of ESR1 and positively with the expression levels of ESR2 (r = −0.379, p&lt;0.001 and r = 0.066, and p=0.004, respectively). The ESR1 mRNA expression was significantly different among MET CNAs groups p&lt;0.001. Patients with high MET/ESR1 coexpression had favorable clinicopathologic tumor characteristics and prognosticators compared to low MET/ESR1 coexpression in terms of greater age at diagnosis, reduced Nottingham Prognostic Index, lower tumor grade, hormone receptor positivity, HER2-negative status, and luminal subtype p&lt;0.001. In contrast, patients with high MET/ESR2 coexpression had unfavorable tumor features and advanced prognosticators compared to patients with low MET/ESR2 coexpression p&lt;0.001. No significant difference in overall survival was observed based on the MET/ESR coexpression status. However, when data were stratified based on the treatment type (chemotherapy and hormonal therapy), survival was significantly different based on the coexpression status of MET/ESR. Conclusions. Findings from our study add to the growing evidence on the potential crosstalk between MET and estrogen receptors in breast cancer. The expression of the MET/ESR genes could be a novel prognosticator and calls for future studies to evaluate the impact of combinational treatment approaches with MET inhibitors and endocrine drugs in breast cancer.

Comparison of myocardial infarction with non-obstructive coronary arteries (MINOCA) versus type 2 MI with NSTEMI presentation; an Italian observation study

Abstract Funding Acknowledgements None. Background In the last decades, NSTEMI, is the predominant phenotype of myocardial infarction (MI) and many NSTEMI patients(pts) have a non-obstructive CAD. NSTEMI, represents an umbrella for many different conditions with distinct underlying pathogenesis and exhibits significant gender discrepancies and survival differences. Further, in absence of non-obstructive CAD, pts could be wrongly comforted about their prognosis. Purpose In this study, we compared the characteristics and the prognosis of pts with MINOCA and type 2 MI with non-obstructive CAD. The primary outcome was a composite of all-cause mortality, non-fatal MI, hospitalization for heart failure (HF) and transitory ischemic attack or non-fatal stroke. Methods Were screened 18223 pts with MI, who underwent coronary angiography between 2005 and 2022. Among them, 7815 pts had NSTEMI presentation, of which 693 pts (9%) had a non-obstructive CAD. After reviewing the angiographic data and clinical presentation, 155 pts were excluded because they belonged to one of the categories known as "MINOCA mimichers" (Fig 1). Five hundred and thirty eight pts with MI, NSTEMI presentation and with non-obstructive CAD were included in the final cohort: 301 (56%) had MINOCA and 237 pts (44%) had type 2 MI (Fig 1). Results The mean age of the population was 68 years, and females were predominant in both groups. MINOCA pts were younger, more frequently had adverse events during pregnancy and endocrine disorders. Pts with type 2 MI were more likely to have typical CV risk factors and comorbidities such as CKD and HF. Pts with type 2 MI had a worse diastolic function, a more dilated left atrium and left ventricle(LV), and non-coronary distribution of regional LV wall-motion abnormalities. At initial clinical presentation, the MINOCA group had typical chest pain upon awakening or at night, responsive to nitrates, while type 2 MI were more often to present with dyspnea, palpitations, and with higher blood pressure. Coronary vasospasm and embolization were the most common identified aetiologies in MINOCA pts while tachyarrhythmias were the most common trigger of type 2 MI, followed by hypertensive crisis. The final model of the predictors of MINOCA at multivariate logistic regression analysis listed in Fig 2, yielded an AUC of 0.865, p&amp;lt;0.01 at ROC analysis(Fig 2a). These variables were used for the generation of nomogram for MINOCA prediction(Fig 2b). During the median follow-up of 61 months (IQR 34.2-100.35), pts with MINOCA had a significantly better survival rate; 135 of 538 pts (25.1%) reached the primary combined endpoint(Fig 3a). The primary end-point was mainly driven by the all-cause mortality, followed by HF hospitalization, non-fatal stroke, non-fatal MI recurrence. Results of Cox multivariable analysis are presented in Fig 3b. Conclusions MINOCA cohort was associated with unconventional risk factors and had a better prognosis compared to T2 MI, which is closer to the classical AMI-CAD.

Evaluating the utility of ZNF331 promoter methylation as a prognostic and predictive marker in stage III colon cancer: results from CALGB 89803 (Alliance)

ABSTRACT While epigenomic alterations are common in colorectal cancers (CRC), few epigenomic biomarkers that risk-stratify patients have been identified. We thus sought to determine the potential of ZNF331 promoter hypermethylation (mZNF331) as a prognostic and predictive marker in colon cancer. We examined the association of mZNF331 with clinicopathologic features, relapse, survival, and treatment efficacy in patients with stage III colon cancer treated within a randomized adjuvant chemotherapy trial (CALGB/Alliance89803). Residual tumour tissue was available for genomic DNA extraction and methylation analysis for 385 patients. ZNF331 promoter methylation status was determined by bisulphite conversion and fluorescence-based real-time polymerase chain reaction. Kaplan-Meier estimator and Cox proportional hazard models were used to assess the prognostic and predictive role of mZNF331 in this well-annotated dataset, adjusting for clinicopathologic features and standard molecular markers. mZNF331 was observed in 267/385 (69.4%) evaluable cases. Histopathologic features were largely similar between patients with mZNF331 compared to unmethylated ZNF331 (unmZNFF31). There was no significant difference in disease-free or overall survival between patients with mZNF331 versus unmZNF331 colon cancers, even when adjusting for clinicopathologic features and molecular marker status. Similarly, there was no difference in disease-free or overall survival across treatment arms when stratified by ZNF331 methylation status. While ZNF331 promoter hypermethylation is frequently observed in CRC, our current study of a small subset of patients with stage III colon cancer suggests limited applicability as a prognostic marker. Larger studies may provide more insight and clarity into the applicability of mZNF331 as a prognostic and predictive marker.

A research center’s experience of T-cell redirecting therapies in triple-class refractory multiple myeloma

The efficacies of chimeric antigen receptor T (CAR-T) cells and bispecific monoclonal antibodies (BiAbs) for triple-class refractory (TCR) myeloma have not previously been compared, and clinical data on how to rescue patients after relapse from these immunotherapies are limited. A retrospective study of 73 TCR patients included in trials was conducted: 36 received CAR-T and 37 received BiAbs. CAR-T produced a higher overall response rate (ORR) than BiAbs (97.1% vs. 56.8%, P=0.002). After a median of follow-up of 18.7 months, no significant difference in progression-free survival (PFS) was observed between the CAR-T and BiAbs groups (16.6 vs. 10.8 months; P=0.090), whereas overall survival (OS) was significantly longer in the CAR-T than in the BiAbs group (49.2 vs. 22.6 months; P=0.021). BiAbs following CAR-T yielded a higher ORR and longer PFS2 than did non-redirecting T cell therapies after CAR-T (ORR: 87.5% vs. 50.0%, PFS2: 22.9 vs. 12.4 months). By contrast, BiAbs following BiAbs resulted in an ORR of 33% and PFS2 of 8.4 months, which was similar to that produced by the non-redirecting T cell therapies (ORR: 28.6%, PFS2: 8.1 months). Even though this is a pooled analysis of different trials with different products and the patient profile is different for CAR-T and BiAbs, both were effective therapies for TCR myeloma. However, in our experience, while the PFS was similar with the two approaches, CAR-T therapy resulted in better OS, mainly because of the efficacy of BiAbs as rescue therapy. Our results highlight the importance of treatment sequence in real-word experience.

Gastric cancer molecular classification based on immunohistochemistry and in-situ hybridisation and mortality.

Gastric cancers (GC) are divided into subtypes based on molecular profile: Epstein-Barr virus (EBV)-positive, microsatellite instability (MSI), chromosomal instability (CIN) and genomically stable (GS) tumours. The prognostic impact of this classification is unclear. The aim was to evaluate whether the molecular subtypes determined using in-situ hybridisation (ISH) and immunohistochemistry (IHC) are associated with clinicopathological parameters and prognosis. The study included 503 GC patients. Based on ISH (EBV) and IHC (MSI and TP53), tumours were divided into EBV-positive, MSI, CIN (EBVneg/MSS/TP53aberrant) and GS (EBVneg/MSS/TP53wild-type) subgroups. Survival analyses with intestinal- and diffuse-type tumours were examined separately. EBV-positive tumours associated with male sex. Both EBV-positive and MSI tumours associated with intestinal type. CIN tumours associated with intestinal-type and positive lymph node status. GS tumours associated with diffuse-type and negative lymph node status. In the total cohort, no significant differences in the 5-year survival were observed. In intestinal tumours, the 5-year survival was better in EBV-positive tumours compared with GS tumours [hazard ratio (HR) = 0.57, 95% confidence interval (CI) = 0.33-0.99]. In diffuse tumours, the 5-year survival was worse in CIN tumours compared with GS tumours (HR = 1.57, 95% CI = 1.14-2.18). In radically resected diffuse tumours, the 5-year survival was worse in MSI tumours compared with GS tumours (HR = 3.26, 95% CI = 1.20-8.82). The molecular classification is associated with histological type but not prognosis in GC. As the prognostic effects of molecular subtypes in intestinal- and diffuse-type cancers may differ, combining histological and molecular information is recommended for future studies.

Comparative outcomes of trans-arterial radioembolization in patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease-induced HCC: a retrospective analysis.

Tumorigenesis in NAFLD/NASH-induced HCC is unique and may affect the effectiveness of trans-arterial radioembolization in this population. The purpose of this study was to retrospectively compare the effectiveness of trans-arterial radioembolization for the treatment of hepatocellular carcinoma (HCC) between patients with non-alcoholic steatohepatitis (NASH)/non-alcoholic fatty liver disease (NAFLD) and non-NASH/NAFLD liver disease. Consecutive patients with HCC who underwent TARE at a single academic institution were retrospectively reviewed. Outcome measures including overall survival (OS), local progression-free survival (PFS), and hepatic PFS as assessed by modified response evaluation criteria in solid tumors (mRECIST) were recorded. Kaplan-Meier and Cox proportional hazard models were utilized to compare progression-free survival and overall survival. 138 separate HCCs in patients treated with TARE between July 2013 and July 2022 were retrospectively identified. Etiologies of HCC included NASH/NAFLD (30/122, 22%), HCV (52/122, 43%), alcoholic liver disease (25/122, 21%), and combined ALD/HCV (14/122, 11%). NASH/NAFLD patients demonstrated a significantly higher incidence of type 2 diabetes mellitus (p < 0.0001). There was no significant difference in overall survival (p = 0.928), local progression-free survival (p = 0.339), or hepatic progression-free survival between the cohorts (p = 0.946) by log-rank analysis. When NASH/NAFLD patients were compared to all combined non-NASH/NAFLD patients, there was no significant difference in OS (HR 1.1, 95% C.I. 0.32-3.79, p = 0.886), local PFS (HR 1.2, 95% C.I. 0.58-2.44, p = 0.639), or hepatic PFS (HR 1.3, 95% C.I. 0.52-3.16, p = 0.595) by log-rank analysis. TARE appears to be an equally effective treatment for NASH/NAFLD-induced HCC when compared to other causes of HCC. Further studies in a larger cohort with additional subgroup analyses are warranted.

A simple risk stratification model for prostate cancer using histopathologic findings of radical prostatectomy.

To develop a simple postoperative risk stratification based on histopathologic findings from radical prostatectomy specimens. This study included 3 cohorts of patients with a preoperative diagnosis of clinically localized prostate cancer: 1 derivation cohort (n=432) and 2 validation cohorts (n=506 and n=720). First, a postoperative risk stratification model was developed in the derivation cohort using the factors extraprostatic extension, surgical margin status, seminal vesicle invasion, and lymph node involvement. Each of the first 3 factors was assigned 0 or 1 point for negative or positive results, respectively, and the sum of the points, ranging from 0 to 3, was scored. pN1 was not scored but was analyzed separately. Validation cohorts were then used to evaluate the predictive accuracy of the model. Additionally, we compared the model with the Cancer of the Prostate Risk Assessment (CAPRA) score. Because the log-rank test showed no statistically significant differences between scores 1 vs 2 or score 3 vs pN1 in the derivation cohort, the following 3-level risk stratification was created: low risk (score 0), intermediate risk (score 1-2), and high risk (score 3 or pN1). There were statistically significant differences in recurrence-free survival between any of 2 groups of 3-level risk stratification. This model similarly worked in both validation cohorts. The C indexes for the model were higher than those for the CAPRA score. This simple postoperative risk stratification model, based on radical prostatectomy findings, has a prognostic impact that has been validated in a multicenter population.

Exploring the Impact of Cytogenetic Abnormalities on Treatment Responses and Survival Outcomes in Multiple Myeloma: A Single-Centre Experience of 13 Years of Follow-Up

Exploring the Impact of Cytogenetic Abnormalities on Treatment Responses and Survival Outcomes in Multiple Myeloma: A Single-Centre Experience of 13 Years of Follow-Up