Survival Rate Of Patients Research Articles

Trifluoperazine exerts anti-osteosarcoma effect by inducing mitochondria-dependent apoptosis via AKT/TXNIP signaling pathway

The survival rates for patients with osteosarcoma (OS) have stagnated over the past few decades. It is essential to find new therapies and drugs. A licensed antipsychotic medication called trifluoperazine (TFP) significantly reduces the growth of several cancers. However, the exact molecular pathways of TFP in OS remain to be discovered. Our research revealed that TFP greatly reduced OS cell migration and growth and caused the arrest of G0/G1 cell cycle. Combined with RNA-Seq data and further research, we confirmed that TFP promoted reactive oxygen species (ROS) production by elevating thioredoxin binding protein (TXNIP) expression to induce mitochondria-dependent apoptosis. Interestingly, we first demonstrated that AKT was an upstream regulatory target of TXNIP in OS cells. Dephosphorylation of AKT led to an increase in TXNIP expression, further elucidating the anticancer mechanism of TFP. In vivo, TFP inhibited subcutaneous OS cell proliferation and induced OS cell apoptosis without noticeable side effects. In conclusion, our findings imply that TFP is a potential treatment for OS.

Cells and signals of the leukemic microenvironment that support progression of T-cell acute lymphoblastic leukemia (T-ALL).

Current intensified chemotherapy regimens have significantly increased survival rates for pediatric patients with T-cell acute lymphoblastic leukemia (T-ALL), but these treatments can result in serious adverse effects; furthermore, patients who are resistant to chemotherapy or who relapse have inferior outcomes, together highlighting the need for improved therapeutic strategies. Despite recent advances in stratifying T-ALL into molecular subtypes with distinct driver mutations, efforts to target the tumor-intrinsic genomic alterations critical for T-ALL progression have yet to translate into more effective and less toxic therapies. Ample evidence now indicates that extrinsic factors in the leukemic microenvironment are critical for T-ALL growth, infiltration, and therapeutic resistance. Considering the diversity of organs infiltrated by T-ALL cells and the unique cellular components of the microenvironment encountered at each site, it is likely that there are both shared features of tumor-supportive niches across multiple organs and site-specific features that are key to leukemia cell survival. Therefore, elucidating the distinct microenvironmental cues supporting T-ALL in different anatomic locations could reveal novel therapeutic targets to improve therapies. This review summarizes the current understanding of the intricate interplay between leukemia cells and the diverse cells they encounter within their tumor microenvironments (TMEs), as well as opportunities to therapeutically target the leukemic microenvironment.

Phenotypes of patients with lupus-associated pulmonary hypertension in the Chinese Han population: a cluster analysis.

Pulmonary hypertension (PH) is a severe complication of systemic lupus erythematosus (SLE). This study investigated the clinical features of patients with SLE-PH in China based on disease manifestations and organ involvement to define precise treatment of SLE and early prevention of complications. In total, 205 SLE-PH patients were included in this study. A cluster analysis was applied according to six clinical and serological variables to define different subgroups of patients. The survival rates of SLE-PH patients and risk factors that influenced prognosis were also compared and a clinical prediction model was developed for the diagnosis of associated lupus nephritis (LN). Patients were clustered in five groups. Patients in cluster 1 had severe renal damage (all patients had LN and had the highest creatinine and urea nitrogen and the lowest eGFR levels). Patients in cluster 2 had mild renal damage (more than half of the patients had associated LN and 87.5% had increased urinary protein levels but presented a lower degree of renal damage than those in the first group. Patients in cluster 3 had low-grade proteinuria (all patients had 24h urinary protein < 0.5g). Patients in cluster 4 had hematuria or urinary tubular damage (26% of patients had associated LN, but none of the patients had proteinuria. In cluster 5, patients barely had any major organ involvement. The clinical prediction model for a diagnosis of SLE-PH-LN was anti-dsDNA antibodies > 364.64IU/mL and neutrophil-to-leukocyte ratio (NLR) > 5.55. Our findings provide evidence indicating that SLE-PH presents varying clinical phenotypes and the treatment varies accordingly, suggesting the need for individualized treatment. Key Points • Clustered grouping of patients with SLE-PH is associated with renal injury. • This may be because PH and LN share a common pathogenesis. • The clinical prediction model for a diagnosis of SLE-PH-LN was anti-dsDNA antibodies >364.64 IU/mL and NLR >5.55.

Invasive Stratified Mucin-producing Carcinoma of the Uterine Cervix: Comparison of Its Clinicopathological Characteristics and Programmed Death-ligand 1 Expression Status With Those of Other Endocervical Adenocarcinomas.

Invasive stratified mucin-producing carcinoma (ISMC) is a rare but aggressive variant of endocervical adenocarcinoma (EAC). The aim of this study was to investigate the differences in clinicopathological features, patient outcomes, and programmed death-ligand 1 (PD-L1) expression among ISMC, usual-type EAC (UEA), and gastric-type EAC (GEA). PD-L1 22C3 immunostaining was performed using 20 ISMCs, 20 UEAs, and 20 GEAs. Combined positive score (CPS) method was used to assess PD-L1 immunoreactivity. ISMC was diagnosed at a younger age and showed a more advanced stage and shorter survival than UEA. The disease-free survival (DFS) and overall survival (OS) rates of ISMC patients were lower than those of UEA but comparable to those of GEA. ISMC type was an independent prognostic factor for predicting short DFS [hazard ratio (HR)=2.790, 95% confidence interval (CI)=1.153-6.756] and OS (HR=6.071, 95%CI=1.257-29.327). All ISMCs showed PD-L1 over-expression with a mean CPS of 44.5 (range=10-100), which was higher than those of UEA (mean CPS=8.2) and GEA (mean CPS=6.5). PD-L1 positivity (CPS≥1) was also an independent prognostic factor for worse OS (HR=2.472, 95%CI=1.097-5.570). Despite PD-L1 over-expression, ISMC patients treated with pembrolizumab showed no clinical response. All examined ISMCs over-expressed PD-L1. ISMC showed higher PD-L1 expression than UEA and GEA and worse survival than UEA. PD-L1 over-expression was found to be a significant predictor for worse DFS and OS in patients with ISMC. Our data suggest that PD-L1 over-expression is associated with poor ISMC prognosis.

ASO Author Reflections: It Does Not Matter Whether Radical Prostatectomy is Performed in High-Risk Localized Disease or at the Oligometastatic Stage.

Radical prostatectomy (RP) alone has traditionally been considered insufficient for patients with high-risk localized prostate cancer (HRPC) owing to the frequent need for adjuvant salvage radiotherapy or androgen deprivation therapy (ADT) following surgery. Previously, systemic therapy, such as ADT, was the standard treatment for metastatic prostate cancer (PC) patients; RP was not considered viable for these patients. However, since 2015, there has been a recognition that metastatic PC patients can be categorized based on the extent of their metastases, leading to the consideration of RP for some metastatic cases. In recent years, the concept of cytoreductive RP has gained traction; studies suggest that it may improve survival rates in metastatic PC patients through mechanisms, such as tumor debulking and enhancement of the immune response. A meta-analysis of retrospective studies has shown that cytoreductive RP is associated with higher cancer-specific survival rates at 1-year, 3-year, and 5-year intervals compared with systemic therapy alone. In our study, which followed HRPC and oligometastatic PC patients for an average of 46 months, we observed biochemical recurrence in 17.8% of HRPC and 13% of oligometastatic patients, with overall survival rates of 96.4% and 87%, respectively. Although prospective or randomized studies are still lacking, current retrospective studies, including our own, suggest promising outcomes for RP in HRPC and oligometastatic patients. With the increasing prevalence of robotic surgery, improved pelvic anatomy observation, and growing surgical confidence, the realization of prospective randomized study results may not be far off.

XCT as a Predictor for Survival in a Population-Based Cohort of Head and Neck Squamous Cell Carcinoma.

xCT, also known as SLC7A11 (solute carrier Family 7 Member 11), is a cystine/glutamate antiporter protein that mediates regulated cell death and antioxidant defense. The aim of this study was to investigate the effect of xCT on the outcome of patients diagnosed with new head and neck squamous cell carcinoma (HNSCC). This retrospective cohort study utilized a population-based dataset, comprising all patients (n = 1033) diagnosed with new HNSCC during 2005-2015 in a population of 697,000 people. All patients (n = 585) with a tumor tissue sample available for immunohistochemical (IHC) staining were included. The follow-up rates were 97% and 81% at 3 and 5 years, respectively. Also, the specificity of the anti-xCT antibody was validated. The expression level and prognostic significance of xCT were strongly dependent on tumor location. In oropharyngeal squamous cell carcinoma (OPSCC) patients, xCT expression was a significant prognostic factor for 5-year overall survival (OAS) (HR: 2.71; 95% CI 1.67-4.39; p < 0.001), disease-specific survival (DSS) (HR: 2.58; 95% CI 1.47-4.54; p = 0.001), and disease-free survival (DFS) (HR: 2.69; 95% CI 1.55-4.64; p < 0.001). Five-year survival rates for OPSCC patients with high and low levels of xCT were OAS 34% versus 62%; DSS 51% versus 73%; DFS 43% versus 73%, respectively. According to a multivariate model adjusted for age, T-class, nodal positivity, and tobacco consumption, xCT was an independent prognostic factor for 3-year survival, in which it outperformed p16 IHC. Similar associations were not observed in squamous cell carcinomas of oral cavity or larynx. Regarding treatment modalities, xCT was most predictive in HNSCC patients who received radiotherapy. High xCT expression was associated with poor prognosis in OPSCC. Our findings suggest that joint analysis of xCT and p16 may add significant value in OPSCC treatment stratification.

Metagenomic analysis reveals effects of gut microbiome in response to neoadjuvant chemoradiotherapy in advanced rectal cancer

Neoadjuvant chemoradiotherapy can enhance survival rate of patients with advanced rectal cancer, but its effectiveness varies considerably. Previous studies have indicated that gut microbes may serve as biomarkers for predicting treatment efficacy. However, the specific roles of the gut microbiome in patients who have good response to nCRT remains unclear. In this study, shotgun metagenomic sequencing technology was used to analyze the fecal microbiome of patients with varying responses to nCRT. Our findings revealed that beneficial intestinal bacteria and genes from different metabolic pathways (carbohydrate metabolism, amino acid metabolism, and sulfur metabolism) were significantly enriched in patients with good response. Additionally, causal relationship in which microbial-derived GDP-D-rhamnose and butyrate could influence the response to nCRT was clarified. Our results offered new insights into the different response to nCRT, and provided valuable reference points for improving the effectiveness of nCRT in patients with advanced colorectal cancer.

Analysis of Prehospital Characteristics Affecting Survival Rates of Patients with Out-of-Hospital Cardiac Arrest Occurring During Work

This retrospective study analyzed survival rates of out-of-hospital acute cardiac arrest occurring during gainful work from 2013 to 2022. The survival rate at the workplace was 23.6% for patients with medical causes and 5.0% for those with non-medical causes, which was higher than the overall rate. The rate of layperson cardiopulmonary resuscitation (CPR) was 35.0% for medical causes and 11.6% for non-medical causes. Notably, cases witnessed by colleagues accounted for 72.9% of the medical cases and 76.8% of the non-medical cases, and CPR was performed in 42.7% of the medical cases and 19.6% of the non-medical cases. Survival rates were higher in both cases when there was a witness and CPR was performed. However, 45% of cardiac arrests occurring during work are still not witnessed, and the CPR performance and usage rates of automated external defibrillators (AED) remain insufficient. Enhancing the training of employees in CPR and AED usage can improve the survival rate of patients with cardiac arrest.

Unlocking vinpocetine's oncostatic potential in early-stage hepatocellular carcinoma: A new approach to oncogenic modulation by a nootropic drug.

The development of new drugs for the inhibition of hepatocellular carcinoma (HCC) development and progression is a critical and urgent need. The median survival rate for HCC patients remains disappointingly low. Vinpocetine is a safe nootropic agent that is often used to enhance cognitive function. The impact of vinpocetine on HCC development and progression has not been fully explored. Our main objective was to investigate the possible inhibitory role of vinpocetine in rats exposed to diethylnitrosamine. We observed that vinpocetine increased the survival rate of these rats and improved the ultrastructure of their livers. Additionally, vinpocetine reduced the liver weight index, mitigated liver oxidative stress, and improved liver function. In both in vitro and in vivo settings, vinpocetine demonstrated antiproliferative and apoptotic properties. It downregulated the expression of CCND1 and Ki-67 while exhibiting anti-BCL-2 effects and enhancing the levels of Bax and cleaved caspase-3. Vinpocetine also successfully deactivated NF-κB, STAT3, and HIF-1α, along with their associated transcription proteins, thereby exerting anti-inflammatory and anti-angiogenic role. Furthermore, vinpocetine showed promise in reducing the levels of ICAM-1 and TGF-β1 indicating its potential role in tissue remodeling. These findings strongly suggest that vinpocetine holds promise as a hepatoprotective agent by targeting a range of oncogenic proteins simultaneously. However, further approaches are needed to validate and establish causal links between our observed effects allowing for a more in-depth exploration of the mechanisms underlying vinpocetine's effects and identifying pivotal determinants of outcomes.

Early Diagnosis of Triple-Negative Breast Cancer Based on Dual microRNA Detection Using a Well-Defined DNA Crown-Carbon Dots Structure as an Electrochemiluminescence Sensing Platform.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer (BC). Thus, early detection and accurate diagnosis of this cancer are crucial for improving the survival rate of patients. Specific microRNAs (miRNAs) have been implicated in the occurrence, proliferation, and metastasis of TNBC. Addressing this need, our study developed a biosensor platform for early and accurate TNBC diagnosis by integrating electrochemiluminescence (ECL) technology with a DNA sensing strategy. Specifically, synthesized positively charged carbon dots (CDs) were used to neutralize the electrostatic repulsion between DNA strands and facilitate the assembly of DNA triangular prisms (DNA TP-CDs). Hairpins were then incorporated into the DNA TP-CDs to form the final DNA crown structure. The early TNBC biomarker, microRNA-93-3p (miR-93-3p), allowed for the binding between the DNA Crown and the DNA track on the electrode and initiated the ECL signal. Subsequently, microRNA-210 (miR-210) unlocked the DNA tripedal walker, and its movement on the DNA Crown eventually quenched the ECL signal, enabling accurate TNBC diagnosis and tumor stage assessment. Our proposed biosensor had satisfactory sensing efficiency due to the ordered DNA track and rapid-moving DNA walker. The data revealed a good linear relationship between the ECL signals and the logarithm of miRNA concentrations, with miR-93-3p having a detection limit of 31.04 aM and miR-210 having a detection limit of 7.69 aM. The biosensor also showed satisfactory performance in serum samples and cells. Taken together, this study hopes to provide ideas and applications for clinical diagnosis as well as the personalized treatment of TNBC.

Unveiling Tumorigenesis Mechanisms and Drug Therapy in Neuroblastoma by Mass Spectrometry Based Proteomics

Neuroblastoma (NB) is the most common type of extracranial solid tumors in children. Despite the advancements in treatment strategies over the past years, the overall survival rate in patients within the high-risk NB group remains less than 50%. Therefore, new treatment options are urgently needed for this group of patients. Compared with genomic aberrations, proteomic alterations are more dynamic and complex, as well as more directly related to pathological phenotypes and external perturbations such as environmental changes and drug treatments. This review focuses on specific examples of proteomics application in various fundamental aspects of NB research, including tumorigenesis, drug treatment, drug resistance, and highlights potential protein signatures and related signaling pathways with translational values for clinical practice. Moreover, emerging cutting-edge proteomic techniques, such as single cell and spatial proteomics, as well as mass spectrometry imaging, are discussed for their potentials to probe intratumor heterogeneity of NB.

Clinical validation of peripheral blood mononuclear cell DNA methylation markers for accurate early detection of hepatocellular carcinoma in Asian patients

BackgroundHepatocellular carcinoma (HCC), a leading cause of cancer-related deaths globally, poses significant challenges in early detection. Improved diagnostic accuracy can drastically influence patient outcomes, emphasizing the need for innovative, non-invasive biomarkers.Methods:This study utilized a cohort of 402 participants, including healthy controls, chronic hepatitis patients, and HCC patients from Bangladesh, to evaluate DNA methylation signatures in peripheral blood mononuclear cells (PBMC). We performed targeted next-generation sequencing on selected genes previously identified to assess their methylation dynamics. The development of M8 and M4 scores was based on these dynamics, using Receiver Operating Characteristic (ROC) analysis to determine their effectiveness in detecting early-stage HCC alongside existing markers such as epiLiver and alpha-fetoprotein (AFP).Results:Integration of M8 and M4 scores with epiLiver and AFP significantly enhances diagnostic sensitivity for early-stage HCC. The M4+epiLiver score achieves a sensitivity of 79.4% in Stage A HCC, while combining M4 with AFP increases sensitivity to 88.2–95.7% across all stages, indicating a superior diagnostic performance compared to each marker used alone.Conclusions:Our study confirms that combining gene methylation profiles with established diagnostic markers substantially improves the sensitivity of detecting early-stage HCC. This integrated diagnostic approach holds promise for advancing non-invasive cancer diagnostics, potentially leading to earlier treatment interventions and improved survival rates for high-risk patients.

Surgical management and outcomes of chronic mesenteric ischemia

Chronic mesenteric ischemia (CMI) is a vascular condition resulting from atherosclerotic blockage of the mesenteric arteries, which reduces blood flow to the intestines. Though rare, CMI is critical to diagnose due to the risk of progression to acute mesenteric ischemia, which can be life-threatening. This review discusses the pathophysiology, clinical presentation, and diagnostic challenges of CMI, emphasizing the need for timely revascularization to improve patient outcomes. Both endovascular and open-surgical techniques are examined, with a focus on patient selection and procedural outcomes. Endovascular interventions, preferred for their lower morbidity, have shown promising results despite a higher risk of restenosis. Comprehensive management, including aggressive medical therapy and lifestyle modifications, remains essential to address the underlying atherosclerosis. Given the complexity of CMI, a multidisciplinary approach is recommended to ensure accurate diagnosis and optimal treatment. This review emphasizes the significance of early diagnosis and customized treatments to improve the quality of life and survival rates in patients with CMI.

The Effect of Statin Usage on Survival in Metastatic Colorectal Cancer Patients Receiving Regorafenib.

Regorafenib is an oral multikinase inhibitor used in later lines for metastatic colorectal carcinoma (mCRC) treatment, but its efficacy and tolerability are low. To improve the response rates and ameliorate adverse effects, different strategies have been implemented. In our study, we examined the effect of statin usage in patients with mCRC treated with regorafenib. This single-center retrospective study included patients with mCRC who were treated with regorafenib between January 2015 and December 2023. The primary outcomes were progression-free survival (PFS) and overall survival (OS), and the secondary outcomes were adverse effects and the tolerability of regorafenib. The data of 105 patients were collected retrospectively. The median age of the patients was 66 years, and 60 patients were male. Seventeen patients (16.1%) were receiving statins. Statin-using patients were significantly older than non-users (72 years vs. 66.5 years, p=0.05). Comorbid diseases were more common in patients using statins. The median PFS was 1.9 months for statin users and 4.2 months for statin non-users (p<0.001), and the median OS was 4.7 vs. 6.7 months (p=0.01). Cox regression revealed that statin usage was significantly associated with a higher hazard ratio (HR) for PFS (2.53) and OS (2.06) (both p<0.01 and p=0.02, respectively). Statins are associated with decreased survival and response rates in patients with mCRC treated with regorafenib. However, further studies are needed to confirm these results.

Mortality and survival rate in a scottish cohort of adults with congenital heart disease

Abstract Background Adult patients with congenital heart disease (ACHD) experience higher rates of morbidity and reduced long-term survival in comparison to the general population. The care of this cohort of patients requires specialist expertise which is mainly delivered at tertiary centers. Aims We aim to report the clinical characteristics, mortality rates and causes of death in a contemporary cohort of ACHD patients followed up in a North- East Scottish Health Board. Methods We prospectively followed up ACHD patients aged ≥17 years (n=645) under review at the Regional NHS ACHD Clinic in a North- East Scottish Health Board between the years 2020 and 2023. We recorded the number and the causes of death as documented on our electronic records and on correspondence with primary care physicians. Survival analysis was performed according to the 2020 ESC Guidelines classification of congenital heart disease complexity (Table 4) classes using Kaplan-Meier method with log-rank (Mantel-Cox) test done in IBM SPSS v.24. Results Our ACHD cohort (n=645, 54% females and 46% males) included patients of all three ESC complexity classes (30% mild, 60% moderate and 10% severe). Between 2020 and 2023, 18 patients (2.8%) died, with a total incidence of 0.93 deaths/100 patient years. Median age of death was 59 years (IQR 45–71), and the majority of deceased patients were males (56%). There were 2 deaths in the mild complexity group, 11 deaths in the moderate complexity group and 5 deaths in the severe complexity group (See Table 1). This was found to correspond to an incidence of 0.34, 0.95 and 2.64 deaths/100 patient years respectively. The leading causes of death were heart failure (28%) and malignancy (22%). Using Kaplan-Meier survival analysis we found that the survival distributions for the mild, moderate and severe ACHD complexity groups were statistically significantly different by log-rank test (χ2(2) = 11.47, p &amp;lt; .005) (See Figure 1). Patients with moderate ACHD complexity had a median survival age 67 years (95% CI 58.1-75.9), patients with severe ACHD had median survival age 57 years (95% CI 44.7-69.2). Median survival could not be calculated for the mild group due to lack of data points. Conclusion The ACHD patient group is characterised for a variety of pathophysiology and clinical presentations. They require lifelong medical input and in spite of the local and national expertise, the mortality and morbidity rates are still high. Heart failure was the leading cause of death in this cohort which is similar to previous reported data. Mortality rates were proportional to the complexity of the underlying ACHD diagnosis. The survival rate of patients in the severe complexity group was ten years less than the moderate complex group. ACHD patients in the moderate and severe complexity groups have significantly reduced life expectancy and require access and clinical expertise from National ACHD Specialty Centers.

Treatment Patterns and Clinical Outcomes in Patients with Hodgkin Lymphoma from Saudi Arabia, Türkiye, and South Africa: Subgroup Analysis from the International, Multi-center, Retrospective BHOLISTIC Study.

B-HOLISTIC was a real-world, retrospective study of treatment patterns and clinical outcomes in Hodgkin lymphoma (HL) in regions outside Europe and North America. This subgroup analysis reports findings from Saudi Arabia, Türkiye, and South Africa. Patients aged ≥18 years and diagnosed with stage IIB-IV classical HL receiving frontline chemotherapy (frontline cHL) and/or relapsed/refractory HL (RRHL) from January 2010-December 2013 were assessed. The primary endpoint was progression-free survival (PFS) in patients with RRHL. Overall, 694 patients (RRHL: n=178; frontline cHL: n=653) were enrolled. Among patients with RRHL, >80% received first salvage chemotherapy. The most common first salvage regimens were etoposide, methylprednisolone, cytarabine, cisplatin (ESHAP) in Saudi Arabia (78.3%) and dexamethasone, cytarabine, cisplatin (DHAP) in Türkiye (36.1%) and South Africa (40%). Median PFS (95% confidence interval [CI]) in the RRHL group was 5.1 (3.0-15.9), 19.7 (7.5-not reached), and 5.2 (1.1- 10.1) months in Saudi Arabia, Türkiye, and South Africa, respectively. The 5-year PFS and overall survival (95% CI) rates in patients with RRHL were 33.2% (21.6-45.2) and 78.2% (65.9-86.5) in Saudi Arabia, 42.5% (29.5-54.9) and 79.4% (67.2-87.5) in Türkiye, and 13.1% (4.2-27.0) and 53% (35.5-67.8) in South Africa, respectively. This study showed that the clinical outcomes in Türkiye and Saudi Arabia were generally comparable with Western countries during the study period, although Saudi Arabia had lower PFS rates. Conversely, the clinical outcomes in South Africa were suboptimal, emphasizing the need for novel therapies and improved progression to stem cell transplantation. Additionally, these data may serve as a control group for future studies in these countries and inform clinical decision-making.

Invasive disease-free survival and brain metastasis rates in patients treated with neoadjuvant chemotherapy with trastuzumab and pertuzumab

Patients with HER2(+) early breast cancer (EBC) receiving neoadjuvant systemic therapy (NAST) have poorer outcomes if they have residual disease (RD). We analyzed IDFS and brain metastasis (BM) rates in patients with HER2(+) EBC treated with NAST and report the outcomes of patients with HER2(−) RD. Patients with HER2(+) EBC who received NAST between 1 Jan 2019 and 31 Jan 2022 were reviewed. IDFS was defined as the time from surgery until first occurrence of invasive breast cancer recurrence, distant recurrence, or death from any cause. The total cohort was 594 patients. pCR (ypT0/isN0) was achieved in 325(55%) and RD was seen in 269(45%) patients. In 269 patients with RD, 45(17%) did not have HER2 retesting and were excluded. In the remaining 224 patients, 143(64%) were HER2(+) and 81(36%) were HER2(−). With a median follow up of 24 months, 8 patients developed BM at initial recurrence, 4/325(1.2%) with pCR and 4/143(2.8%) with HER2(+) RD. IDFS events occurred in 22/594(3%) patients; 14/269(5%) in RD and 8/325(2%) in pCR (p = 0.04). There was no difference in IDFS between 9/143(6%) patients with HER2(+) RD or 5/81(6%) with HER2(−) RD (p = 0.10). Patients with RD had higher IDFS events than those with pCR. In those with RD, 36% lost HER2(+) status; IDFS events appeared similar in those with HER2(+) RD versus those with HER2(−) RD. The BM events seen in those with RD and pCR highlights the need for more effective therapy in NAST and adjuvant setting to minimize BM risk.

Survival penalty in patients undergoing transcatheter versus surgical aortic valve replacement: is it just a question of frailty? Insights from a large cohort with demographic matching

Abstract Background Transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) are the reference treatments for aortic stenosis. Conflicting data exist on late survival results of these two techniques. While randomised controlled trials (with highly selected patients) assert the non-inferiority of TAVR, real-world data from large registries (with potential uncorrected confounders) suggest the opposite. Comparing the survival rates of SAVR and TAVR with those of a matched reference population could help circumvent potential biases of direct procedural comparisons and quantify the impact of frailty on post-operative survival. Purpose Our study aims to compare the 5-year overall survival rates of SAVR, non-frail TAVR, and frail TAVR patients with the survival of their demographically matched reference population. Methods This study included all consecutive patients undergoing either SAVR or TAVR at a tertiary hospital between January 2010 and December 2021. Each patient underwent a comprehensive geriatric assessment by an experienced geriatric team, from which a Clinical Frailty Scale (CFS) was derived using a validated classification tree. Frailty was defined as a CFS ≥ 6, in accordance with ESC guidelines. The patients were stratified into 3 subgroups: SAVR, non-frail TAVR, and frail TAVR patients. For each subgroup, a corresponding reference population was generated using national actuarial tables to ensure individual-level matching based on age, gender, and year of observation. Survival of each subgroup was then compared to its corresponding reference population over a 5-year period using standardized mortality ratios (SMR) and one-sample logrank tests. Results Our cohort included 1183 SAVR, 254 non-frail TAVR, and 151 frail TAVR patients, with mean ages of 74.1, 85.4, and 85.7 years, and median EuroSCORE II of 2.0%, 4.2%, and 5.4%, respectively. Survival of SAVR patients was equivalent to the reference population (80.1 vs 80.9% survival; SMR = 1.06 [0.89 – 1.25]; p = 0.454; Figure 1A). Similarly, non-frail TAVR patients also achieved survival rates comparable to those of the reference population (50.9 vs 54.0% survival; SMR = 0.94 [0.76 – 1.18]; p = 0.549; Figure 1B). However, frail TAVR patients faced a significantly reduced survival rate (41.7% vs 54.0% survival; SMR = 1.48 [1.15 – 1.90]; p &amp;lt; 0.001; Figure 1C). The frailty of this subgroup could therefore explain a 48% increase in mortality risk compared with their reference population after 5 years. Conclusions Treating non-frail patients with aortic stenosis through TAVR or SAVR restores life expectancy to levels comparable with their reference population, challenging results from other real-world registries. In contrast, TAVR in frail patients is associated with worse survival, raising the question of treatment futility in this specific subgroup. Refining the selection of frail patients who may benefit from TAVR remains an important clinical challenge.

Study on the Predictive Value of a Pulmonary Edema Imaging Score for Delayed Extubation in Patients after Heart Valve Surgery on Cardiopulmonary Bypass.

Delayed extubation with mechanical ventilation after cardiac valve surgery is an important clinical challenge. Early extubation can improve the survival rate and prognosis of patients. The study aims to explore the predictive value of a chest X-ray pulmonary edema imaging score on the first day after surgery for delayed extubation in patients after cardiac valve surgery on cardiopulmonary bypass. Retrospective analysis of the clinical data of patients undergoing cardiac valve surgery under extracorporeal circulation admitted to the intensive care unit of Zhongshan Hospital Affiliated with Fudan University (Xiamen) from January 2020 to October 2023. The patients were divided into an early extubation group according to the postoperative mechanical ventilation time (time: <24 h) and a delayed extubation group (time: ≥24 h). The radiographic assessment of lung edema (RALE) score was performed on the chest X-ray of the patient on the first day after surgery to analyze the correlation between delayed extubation of mechanical ventilation and the chest radiograph RALE score on the first day after surgery and to verify its predictive performance. Significant differences in age, the incidence of hypertension, body mass index (BMI), left ventricular ejection fraction (LVEF), pump time, RALE score, ventilation time, oxygenation index, PaCO2, and brain natriuretic peptide (BNP) levels after the first 24 h were seen between patients who were extubated before and 24 h post operation (p = 0.013, 0.001, 0.034, <0.001, <0.001, <0.001, <0.001, <0.001, 0.014, and <0.001, respectively). No significant differences were observed in the proportion of males and the lactate level after the first 24 h between the two groups (p = 0.792 and 0.191, respectively). The time of mechanical ventilation was positively correlated with the RALE score in all patients, and the correlation coefficient was 0.419; the difference was statistically significant (p < 0.001). Multivariate binary logistic regression analysis with stepwise regression was performed on each research factor, and it was found that RALE score, pump time, oxygenation index, and postoperative BNP were independent risk factors for predicting delayed extubation in patients undergoing cardiac surgery on cardiopulmonary bypass. A 10-fold cross-validation revealed that the mean accuracy, sensitivity, specificity, and area under the curve (AUC) of the regression model were 0.737, 0.749, 0.741, and 0.825, respectively. The RALE score on the chest radiograph on the first day after surgery is an independent risk factor for predicting delayed extubation in patients after cardiac valve surgery on cardiopulmonary bypass and has good predictive value.

Neuroendocrine tumors and survival rates in MEN-1 patients: impact of gender difference.

Among 100 MEN-1patients enrolled, 59 (59%) were female and 41 (41%) male, mean age at diagnosis was 39.4 years (range 5-86). No statistically significant association was identified between MEN-1 clinical manifestations and gender (primary hyperparathyroidism PHPT p: 1.0, DP-NET p: 0.83, pituitary adenoma PA p: 0.84, lung NET p: 0.64 and thymic NET p: 0.10), similarly age at diagnosis of MEN1 and its individual manifestations was similar between genders. Survival analysis revealed no statistically significant difference between genders in DP-NET patients regarding progression disease p:1.0 and death p:1.0. Mean progression free survival (PFS) of patients with DP-NET was 98.6 months (range 3-288), mean overall survival (OS) was 130.1 months (range 3-444 months), without differences between genders (PFS p: 0.67 and OS p: 0.60). The Kaplan-Meier survival curves for PFS and OS showed no differences between genders (PFS p: 0.92; OS p: 0.87).