Improved Survival In Patients Research Articles

Recent Developments in Nanotechnology and Immunotherapy for the Diagnosis and Treatment of Pancreatic Cancer.

Pancreatic cancer kills millions of people worldwide each year and is one of the most prevalent causes of mortality that requires prompt therapy. A large number of people who have pancreatic cancer are detected at an advanced stage, with incurable and drug-resistant tumors. Hence the overall survival rate of pancreatic cancer is less. The advance phase of this cancer is generated because of the expression of the cancer-causing gene, inactivation of the tumorsuppressing gene, and deregulation of molecules in different cellular signalling pathways. The prompt diagnosis through the biomarkers significantly evades the progress and accelerates the survival rates. The overexpression of Mesothelin, Urokinase plasminogen activator, IGFR, Epidermal growth factor receptor, Plectin-1, Mucin-1 and Zinc transporter 4 were recognized in the diagnosis of pancreatic cancer. Nanotechnology has led to the development of nanocarriersbased formulations (lipid, polymer, inorganic, carbon-based and advanced nanocarriers) that overcome the hurdles of conventional therapy, chemotherapy and radiotherapy, which causes toxicity to adjacent healthy tissues. Biocompatibility, toxicity and large-scale manufacturing are the hurdles associated with the nanocarriers-based approaches. Currently, Immunotherapy-based techniques have emerged as an efficient therapeutic alternative for the prevention of cancer. Immunological checkpoint targeting techniques have demonstrated significant efficacy in human cancers. Recent advancements in checkpoint inhibitors, adoptive T cell therapies, and cancer vaccines have shown potential in overcoming the immune evasion mechanisms of pancreatic cancer cells. Combining these immunotherapeutic approaches with nanocarriers holds great promise in enhancing the antitumor response and improving patient survival.

Spatial profiling of endoplasmic reticulum stress markers in tumor associated cells predicts patient outcomes in pancreatic cancer.

The impact of endoplasmic reticulum (ER) stress in tumor-associated cells, such as cancer associated fibroblasts (CAFs), immune cells and endothelial cells, on patient outcomes in clinical specimens have not been examined. For the first time, we characterized the expression and spatial locations of ER stress markers, BiP and CHOP, in tumor-associated cells and assessed their prognostic significance in a panel of pancreatic ductal adenocarcinoma (PDAC) patient samples. Multiplex immunofluorescence was performed on tumor microarrays and images were analyzed using HALO AI software. BiP and CHOP were upregulated in CAFs and endothelial cells in PDAC sections relative to non-neoplastic pancreas sections. High BiP expression in CAFs and endothelial cells was associated with greater vascular invasion and in immune cells was correlated with increased tumor size. High CHOP expression in immune cells correlated with poor patient survival. CAFs and immune cells were more likely to express BiP or CHOP when located close (< 20 μm) to tumor cells. High expression of CHOP in CAFs close to tumor cells correlated with improved patient survival. For the first time, this study demonstrated that ER stress occurs in CAFs and immune cells predominantly in proximity to tumor cells in PDAC patient tissue. The correlation of high ER stress in immune cells with poor patient survival highlights the importance of the TME and the use of spatial analysis for the identification of novel biomarkers.

Chitosan and hyaluronic acid in colorectal cancer therapy: A review on EMT regulation, metastasis, and overcoming drug resistance.

Up to 90% of cancer-related fatalities could be attributed to metastasis. Therefore, understanding the mechanisms that facilitate tumor cell metastasis is beneficial for improving patient survival and results. EMT is considered the main process involved in the invasion and spread of CRC. Essential molecular components like Wnt, TGF-β, and PI3K/Akt play a role in controlling EMT in CRC, frequently triggered by various factors such as Snail, Twist, and ZEB1. These factors affect not only the spread of CRC but also determine the reaction to chemotherapy. The influence of non-coding RNAs, especially miRNAs and lncRNAs, on the regulation of EMT is clear in CRC. Exosomes, involved in cell-to-cell communication, can affect the TME and metastasis of CRC. Pharmacological substances and nanoparticles demonstrate promise as efficient modulators of EMT in CRC. Chitosan and HA are two major carbohydrate polymers with considerable potential in inhibiting CRC. Chitosan and HA can be employed to modify nanoparticles to enhance cargo transport for reducing CRC. Additionally, chitosan and HA-modified nanocarriers, which can be utilized as potential approaches in suppressing EMT and reversing drug resistance in CRC, can inhibit EMT and chemoresistance, crucial components in tumorigenesis.

Real-world outcomes of targeted therapies and local interventions in BRAF V600E–mutated metastatic colorectal cancer: A single-center retrospective study.

203 Background: Metastatic colorectal cancer (mCRC) patients with BRAF V600E mutations, especially those with microsatellite stable (MSS) tumors, have poor prognoses. Chemotherapy has limited efficacy in this subgroup, especially for second-line or subsequent-line treatments. Current research is increasingly focusing on the integration of targeted therapies and local interventions, but real-world evidence remains scarce, particularly from Asian cohorts. This study leverages real-world data to evaluate the impact of novel therapeutic combinations, including triplet and doublet targeted therapies, alongside local treatments in this high-risk patient population. Methods: This retrospective study includes MSS-type mCRC patients with BRAF V600E mutations treated at the Sixth Affiliated Hospital of Sun Yat-sen University between April 2014 and May 2024. Patients receiving targeted therapies were stratified into three groups: Triplet group (BRAF, EGFR, and MEK inhibitors, including Dabrafenib, Cetuximab and Trametinib), Doublet group (BRAF and EGFR inhibitors, including Dabrafenib and Cetuximab or Encorafenib and Cetuximab), and Doublet target-chemotherapy group (BRAF and EGFR inhibitors combined with chemotherapy, including Vemurafenib, Irinotecan, and Cetuximab). Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and objective response rate (ORR). Results: Among 239 enrolled patients, 58 received targeted therapy and 68 underwent conventional chemotherapy as second-line treatment. 63.5% (80/126) of these patients underwent local interventions, including primary tumor resection, metastasectomy, CRS±HIPEC, and liver ablation. Targeted therapy demonstrated significantly improved mPFS compared to conventional chemotherapy (5.5 vs. 4.2 months, HR = 0.44; 95% CI: 0.29-0.68, p &lt; 0.001). OS did not differ significantly between the two treatment arms (12.7 vs. 12.1 months, HR = 0.80; 95% CI: 0.50-1.25, p = 0.330). In the triplet group, ORR, mPFS, and mOS were 21%, 5.8 months and 18.0 months, respectively, showing a trend towards enhanced efficacy compared to the other targeted therapy groups, albeit without statistical significance. Patients who received targeted therapy (n=35) or chemotherapy (n=45) in combination with local interventions demonstrated significantly prolonged OS compared to those without local therapy (mOS: 22.3 vs. 9.6 months; HR = 0.19; 95% CI: 0.09-0.42; p &lt; 0.001 and 14.3 vs. 10.9 months; HR = 0.53; 95% CI: 0.29-0.98; p = 0.042, respectively). Conclusions: Optimal treatment for BRAF V600E mCRC remains under investigation. This study suggests that combining targeted therapies with selective local interventions may significantly improve patient survival in this challenging subgroup, warranting further prospective evaluation.

Cardiac resynchronization therapy in heart failure based on Strauss criteria for left bundle branch block.

The left bundle branch block (LBBB) is a strong predictor of response to cardiac resynchronization therapy (CRT). However, a significant number of patients do not respond to the treatment. The study sought to evaluate the impact of the stricter Strauss criteria for left bundle branch block (St-LBBB) on CRT response, hospitalizations, ventricular arrhythmia (VA) events and mortality. This study is a retrospective analysis of prospectively collected data on heart failure (HF) patients with LBBB admitted for CRT implantation. Patients were divided into two groups according to the fulfilment or not of St-LBBB criteria. The study included 82 patients with ischaemic (ICM) and non-ischaemic (NICM) cardiomyopathy [46 (56%) with St-LBBB and 36 (44%) with non-St-LBBB]. Patients with St-LBBB showed higher CRT response rates compared with those with non-St-LBBB (P<0.01), while the group with NICM exhibited the greatest benefit (P<0.01). St-LBBB CRT responders displayed significantly lower rates of HF hospitalization (P<0.0001) compared with the non-St-LBBB group. According to Kaplan-Meier time curves, this was primarily evident in patients with NICM (P<0.0001). CRT responders displayed significantly fewer VA events (P<0.001) and lower mortality rates (P<0.0001) than non-responders. Kaplan-Meier estimates demonstrated a significantly lower incidence of VAs in NICM patients with St-LBBB (P=0.049) compared with ICM patients with St-LBBB (P=0.25). Lower mortality rates were observed in CRT responders than non-responders (P<0.0001), with the group of NICM with St-LBBB criteria exhibiting the greatest benefit (P=0.0238). Patients with NICM and St-LBBB present the greatest benefit concerning CRT response, HF hospitalizations, VA events and mortality. Although St-LBBB criteria seem to improve patient selection for CRT, more data are needed to elucidate the role of St-LBBB criteria in this setting.

CTCs Detection Methods In Vivo and In Vitro and Their Application in Tumor Immunotherapy.

Circulating tumor cells (CTCs) are tumor cells that detach from the primary tumor site and enter the bloodstream. They hold significant value for the early detection, diagnosis, and treatment of tumors. CTC detection methods can be classified into in vivo and in vitro techniques. Compared to traditional tumor detection methods, CTC detection causes less harm to the body and allows for earlier identification of malignant tumors, thereby enabling timely treatment and improving patient survival rates. In recent years, CTC detection has been widely used to assess the effectiveness of tumor immunotherapy. Dynamic monitoring of CTCs can help optimize clinical treatment strategies. This review summarizes the latest in vivo and in vitro detection methods for CTCs and discusses their applications in immunotherapy for various common tumors, aiming to provide better guidance and support for clinical practice.

The Role of KRAS Mutations in Colorectal Cancer: Biological Insights, Clinical Implications, and Future Therapeutic Perspectives

Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer mortality globally, with KRAS mutations occurring in 30–40% of cases, contributing to poor prognosis and resistance to anti-EGFR therapy. This review explores the biological significance, clinical implications, and therapeutic targeting of KRAS mutations in CRC. Methods: A comprehensive analysis of the existing literature and clinical trials was performed, highlighting the role of KRAS mutations in CRC pathogenesis, their impact on prognosis, and recent advancements in targeted therapies. Specific attention was given to emerging therapeutic strategies and resistance mechanisms. Results: KRAS mutations drive tumor progression through persistent activation of MAPK/ERK and PI3K/AKT signaling pathways. These mutations influence the tumor microenvironment, cancer stem cell formation, macropinocytosis, and cell competition. KRAS-mutant CRC exhibits poor responsiveness to anti-EGFR monoclonal antibodies and demonstrates primary and acquired resistance to KRAS inhibitors. Recent breakthroughs include the development of KRAS G12C inhibitors (sotorasib and adagrasib) and promising agents targeting G12D mutations. However, response rates in CRC remain suboptimal compared to other cancers, necessitating combination therapies and novel approaches, such as vaccines, nucleic acid-based therapeutics, and macropinocytosis inhibitors. Conclusions: KRAS mutations are central to CRC pathogenesis and present a significant therapeutic challenge. Advances in KRAS-targeted therapies offer hope for improved outcomes, but resistance mechanisms and organ-specific differences limit efficacy. Continued efforts in personalized treatment strategies and translational research are critical for overcoming these challenges and improving patient survival.

A split-type near-infrared photoelectrochemical and colorimetric dual-mode biosensor for the high-performance determination of HepG2 cells.

Hepatocellular carcinoma (HCC) stands as a grave illness characterized by elevated death rates. Early identification plays a vital role in improving patient survival. Herein, a novel split-type dual-mode biosensor featuring with near-infrared photoelectronchemical (PEC) and colorimetric sensing characteristics was developed for the high-performance detection of HepG2 cells. Biotin labeled aptamer (Bio-Apt1) was immobilized onto 96-well plates functionalized with streptavidin to capture HepG2 cells through specific binding. HepG2 cells were then labeled with another aptamer (Apt-2) by recognizing GPC3 on the surface of HepG2 cells. Apt 2 could form DNA double strand (dsDNA-ALP) with ALP-labeled complementary DNA (cDNA-ALP). Subsequently, ALP was released to catalyze AAP to form ascorbic acid (AA), and AA reduced HAuCl4 to form gold nanoparticles (AuNPs). Then the mixture containing AuNPs was introduced onto the surface of Y-MOFs/GCE to enhance the photocurrent response. The change of photocurrent corresponding to the concentration of HepG2 cells can be used for the PEC determination. ALP can catalyze the hydrolysis of disodium phenyl phosphate to produce phenol, followed by a reaction with 4-aminoantipyrine and potassium ferricyanide, resulting in a quinone derivative for the colorimetric determination. The photoelectrochemical and colorimetric detection models show excellent selectivity and sensitivity in identifying HepG2 cells, exhibiting a linear reaction range from 1.0×102 to 1.0×106cells mL-1 and a detection limit of 13cells mL-1 and 51cells mL-1, respectively. The dual-mode split type biosensor avoided direct damage to biomolecules from high-energy light, and the independent signal transduction enabled the acquisition of reliable results.

Early identification of macrophage activation syndrome in adult-onset Still’s disease: a case report and literature review

BackgroundAdult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder characterized by high spiking fevers, evanescent rash, and polyarthritis. A serious complication of AOSD is macrophage activation syndrome (MAS), a life-threatening hyperinflammatory condition that can lead to multiorgan failure if not promptly diagnosed and treated.ObjectiveThis case report and literature review focus on the early identification of MAS in patients with AOSD, highlighting diagnostic challenges, differential diagnoses, and the utility of scoring systems like the HScore and MS score in clinical practice.Case presentationWe report the case of an 80-year-old woman who presented with a complex diagnostic challenge involving AOSD complicated by MAS and concurrent cytomegalovirus (CMV) infection. Her clinical course was marked by recurrent high fevers, cytopenias, hyperferritinemia, and liver dysfunction. Despite extensive workup, initial diagnoses of infections and autoimmune conditions were considered and ruled out. The HScore and MS score were calculated to be 210 and 1.607, respectively, both indicative of MAS. The patient was treated according to the HLH-94 protocol, with high-dose dexamethasone and etoposide, alongside broad-spectrum antimicrobial and antiviral therapy. She responded well to treatment, with resolution of fever and improvement in clinical symptoms.DiscussionThe overlap between AOSD and MAS symptoms complicates early diagnosis, making scoring systems critical in differentiating MAS from other conditions. The HScore and MS score provided a structured approach to diagnosis, guiding timely intervention and improving the patient’s prognosis. Our literature review emphasizes the importance of early recognition and integration of these scoring systems into routine clinical practice to enhance outcomes.ConclusionThis case underscores the necessity of early identification and intervention in MAS associated with AOSD. The application of diagnostic scoring systems like the HScore and MS score is essential for prompt diagnosis and effective treatment, ultimately improving patient survival rates.

Abstract B030: Novel strategy to improve response of high risk HPV+ HNSCC to radiation therapy

Abstract Background: Improving understanding of head and neck squamous cell carcinoma (HNSCC) has led to the discovery of novel molecular markers to stratify risk and guide treatment decisions. Recently, we have identified two subtypes of HPV+ OPSCC – one with good prognosis and one with poor prognosis. The subtypes are distinct in many ways – somatic genes mutated, HPV viral oncogenes expression, the physical state of the viral genome (integrated vs episomal), as well as global mutation and methylation profiles. Intriguingly, all differences converge on intrinsic tumor NF-κB activity with constitutively active NF-κB (usually arising from genetic defects in NF-κB regulators, including TRAF3 and CYLD) driving significantly elevated radiation sensitivity and improved patient survival. NF-κB-based groups define an important clinically actionable prognostic biomarker in HPV+ HNSCC: one important goal is to de-escalate therapy for patients with molecularly low-risk tumors to improve quality of life amongst survivors, while another goal is to improve the cure for of patients with a high risk of treatment failure. Material and methods: We utilized HPV+ head and neck cancer cells, HPV+ HNSCC xenografted mouse model, patient-derived xenografts (PDX), as well as our novel fully immunocompetent mouse model of high risk HPV+ HNSCC; we applied targeted fractionated radiation. To activate NF-κB, we used two clinically applicable drugs with different mechanisms of action: Toll-like receptor 5 (TLR5) agonist and mitochondria-derived activator of caspases (SMAC) mimetic. Custom NF-κB NanoString panel contains our recently developed NF-κB gene signature along with HPV genes and housekeeping genes that are used to normalize the gene expression data. Results: Both drugs activated NF-κB in HPV+ HNSCC and significantly improved response of HPV+ head and neck cancer cells and tumors to radiation. Interestingly, TLR5 agonist alone had a strong tumor suppressing effect in low NF-κB HPV+ HNSCC; this effect was significantly better than 32 Gy focused radiation given in fractions of 4 Gy. Custom NF-κB NanoString panel is robustly prognostic with NF-κB active tumors having improved outcomes after chemoradiation. Conclusions: Because of the average relatively favorable prognosis of HPV+ HNSCC, urgent need for improved therapy for patients with aggressive high risk tumors is greatly undervalued. Here, we present a clinical assay to risk stratify patients with HPV+ HNSCC and begin to explore pharmacological activation of NF-κB as a strategy to sensitize high risk HPV+ HNSCC to radiation therapy. TLR5 agonist is well known for the remarkable normal tissue protective effects against radiation and other damaging conditions; the dual effect of entolimod – sensitization of HPV+ HNSCC to radiation, while simultaneously protecting normal tissues from severe side effects - may be useful for patients with high-risk HPV+ head and neck cancer in combination with radiotherapy. Citation Format: Sri Vemulamanda, Natalia Issaeva1, Aditi Kothari, Travis Schrank, Wendell G. Yarbrough. Novel strategy to improve response of high risk HPV+ HNSCC to radiation therapy. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr B030.

How To Improve Patient Selection in Individuals With Lower Extremity Amputation Using a Bone-anchored Prosthesis.

How To Improve Patient Selection in Individuals With Lower Extremity Amputation Using a Bone-anchored Prosthesis.

Targeting Glutamine Metabolic Reprogramming in Pancreatic Cancer: Current Insights and Future Directions.

Pancreatic Cancer (PC) is a devastating malignancy with a poor prognosis and in-creasing morbidity. Current treatment strategies have limited efficacy in improving patient survival. Metabolic reprogramming is a hallmark of cancer and plays a key role in the pro-gression and maintenance of PC. PC cells exhibit a unique glutamine metabolism that is dis-tinct from other cancer types. The non-classical pathway of glutamine metabolic reprogram-ming plays a "permissive role" in the survival and proliferation of PC cells, mainly by affect-ing the redox homeostasis of the cells. In this review, we compare and contrast the canonical and non-canonical glutamine metabolic pathways and highlight recent advances in targeting non-canonical glutamine metabolism for therapeutic intervention. This may provide novel in-sights and opportunities for exploiting glutamine metabolic reprogramming in PC treatment.

Emerging Targeted Therapies in Non-Small-Cell Lung Cancer (NSCLC)

Targeted therapies have changed the treatment landscape of non-small-cell lung cancer and led to improved patient survival across all stages of lung cancer. Newer advances in common and novel oncogenic drivers continue to occur at vigorous speed, making it challenging to stay up to date with the rapidly evolving field. In this article, we review the emerging perspectives in the treatment of actionable targets in lung cancer. We focus on the development of newer KRAS-directed therapies, particularly on non-G12C mutations, pan-RAS inhibitors, and RAS-GTP inhibitors. We also describe the current standard of care for EGFR- and ALK-altered NSCLC and dive into the novel treatments expected to be in the clinic soon. A similar approach is taken toward MET, HER2, RET, ROS1, and FGFR alterations as emerging targets in non-small-cell lung cancer. Finally, we conclude this review with the current body of evidence for targeting TROP-2 as a novel target, potentially of importance in post-targeted therapy scenarios.

Association between bariatric surgery after kidney transplantation and graft and survival outcomes.

Bariatric surgery has been shown to be safe in chronic kidney disease and improves access of patients to transplantation. Whether bariatric surgery after kidney transplantation associates with improved graft or patient survival has not been examined nationally. We included adults with obesity who received a first kidney transplant according to the US Renal Data System between 2003-2019. We matched 4 controls to each case of bariatric surgery based on age at transplantation, sex, donor type, diabetes, and body mass index at transplantation (BMI). We examined the association between bariatric surgery and graft failure or death using multivariable Cox proportional hazards models and Fine-Gray models accounting for death as a competing risk. We included 770 patients, of whom 155 (20%) received bariatric surgery. Median age was 45 years and 56% were women. Receipt of bariatric surgery was associated improved graft survival (HR 0.57; 95% CI 0.34-0.98) in fully adjusted models, though findings did not consistently maintain statistical significance in competing risk analyses (SHR 0.60; 95% CI 0.35-1.02). Receipt of bariatric surgery was associated with lower risk of death (HR 0.45; 95% CI 0.26-0.76). In conclusion, bariatric surgery is associated with improved patient survival, and potentially graft survival after kidney transplantation.

Hypoxia Promotes Malignant Progression of Colorectal Cancer by Inducing POSTN+ Cancer-Associated Fibroblast Formation.

Colorectal cancer (CRC) is one of the most common malignancies. Hypoxia can promote the occurrence and development of CRC. However, how hypoxia regulates the CRC immune microenvironment needs to be further explored. The bulk RNA sequencing data and clinicopathological information of CRC patients were enrolled from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The single-cell RNA sequencing (scRNA-seq) datasets of CRC were collected from and analyzed from the GEO database and the ArrayExpress database. The score of the hypoxia gene set was estimated using the "ssGSEA" algorithm in the "GSVA" R package. The functional characteristics of CAF subtypes were studied by bioinformatics analysis and in vitro experiments, and a prognostic model was constructed based on machine learning correlation. Hypoxia is associated with poor prognosis in CRC patients. Periostin (POSTN) + Fib is a cancer-associated fibroblast (CAF) closely associated with hypoxia, and high infiltration of POSTN + Fib is associated with adverse outcomes in overall survival (OS) and relapse-free survival (RFS) in CRC patients. Hypoxia can induce POSTN expression and secretion in CAFs. Hypoxia-induced increase of POSTN expression in CAFs can significantly promote the migration and proliferation of CRC cells. Hypoxia-induced increase of POSTN expression in CAFs can significantly promote the proliferation and migration of CRC cells. The POSTN+Fib Hypoxia-Related Risk Model (PFHRM) can predict the survival and immunotherapy response of CRC patients. Our study identified a POSTN+Fib cell subpopulation closely associated with hypoxia, which promotes the malignant progression of CRC. The development of PFHRM provides a theoretical basis for improving patient survival and prognosis.

Pneumonia and COVID-19 Classification and Detection Based on Convolutional Neural Network: A Review

Pneumonia diseases are considered one of the most pandemic diseases by the WHO, claiming the lives of millions across the world. Therefore, the necessity of having mechanisms for early diagnosis and detection of these epidemic diseases to preserve people's lives. On the other hand, the increase in cases requires not relying on traditional means of detecting diseases due to these tests' limitations and high costs like RT-PCR and errors in interpretation by humans. Among the available methods for diagnosing Pneumonia diseases are X-rays and CT scans. For accurate and highly efficient diagnosis, computer-aided diagnosis (CAD) is required. Deep learning has been suggested as the best solution to enhance the prognosis for many lung diseases using CAD systems. The ability of machine learning algorithms was not sufficient to diagnose with high accuracy due to several challenges, like: limited dataset, high computational, and less robustness because of huge numbers of features in the images. The aspiration to deep learning to solve the problems of diagnosis more accurate, especially convolution neural networks, showed impressive results in the classification of images. The convolutions layer in the network with filters automatically discover the critical spatial and temporal features in an image. Hierarchical representations were used in human brains in designing the learning process of CNN. Several deep learning architectures have been used to detect pneumonia diseases, the most popular such as AlexNet, VGG-16, Inception-v1, Inception-v3, ResNet-50, Inception-ResNet-V2, and ResNet201. The strength of CNNs lies in the size of data to be trained. Previous algorithms have been used to pre-train on a vast dataset. An augmentation strategy has been used in the model design to increase the dataset's size and quality artificially. This review aims to pave the way for better, more accurate, and efficient models for early detection and classification of lung diseases to improve patient survival.

Response to neoadjuvant chemotherapy leads to better survival outcomes in upper tract urothelial carcinoma.

To evaluate the benefit of neoadjuvant chemotherapy (NAC) for patients with high-risk upper tract urothelial carcinoma (UTUC) using a large, well-curated multi-institutional database. This study was a multi-institutional retrospective analysis conducted by the UTUC Collaborative Network (UCAN), combining data from 2276 patients with UTUC who underwent radical nephroureterectomy at seven high-volume tertiary care centres in the United States. The UCAN data were analysed to evaluate the impact of response to NAC on survival outcomes in patients with UTUC. A total of 378 patients in the UCAN database underwent NAC. On final surgical pathology, 101 patients (26.8%) had ≤ypT1N0 disease and were defined as NAC treatment responders. Patients who responded to NAC had significantly longer overall survival (OS) and progression-free survival (PFS) compared to non-responders. At 5 years post-surgery, 81.5% of responders were alive compared to 59.8% of non-responders. The median OS and PFS times among non-responders were 7.0 years (95% confidence interval [CI] 5.6-9.7) and 6.0 years (95% CI 4.6-9.3) respectively, while the median OS and PFS were not reached among responders. Limitations of this study include its retrospective design, heterogeneity in chemotherapy regimens, and the absence of clearly defined patient selection criteria for treatment. These data suggest that NAC can play a pivotal role in the treatment of well-selected UTUC patients who respond positively. Non-responders had clearly inferior outcomes. More work is needed to find predictors of response which can improve patient selection.

Prioritizing Patient Selection in Clinical Trials: A Machine Learning Algorithm for Dynamic Prediction of In-Hospital Mortality for ICU Admitted Patients Using Repeated Measurement Data.

Background: A machine learning prognostic mortality scoring system was developed to address challenges in patient selection for clinical trials within the Intensive Care Unit (ICU) environment. The algorithm incorporates Red blood cell Distribution Width (RDW) data and other demographic characteristics to predict ICU mortality alongside existing ICU mortality scoring systems like Simplified Acute Physiology Score (SAPS). Methods: The developed algorithm, defined as a Mixed-effects logistic Random Forest for binary data (MixRFb), integrates a Random Forest (RF) classification with a mixed-effects model for binary outcomes, accounting for repeated measurement data. Performance comparisons were conducted with RF and the proposed MixRFb algorithms based solely on SAPS scoring, with additional evaluation using a descriptive receiver operating characteristic curve incorporating RDW's predictive mortality ability. Results: MixRFb, incorporating RDW and other covariates, outperforms the SAPS-based variant, achieving an area under the curve of 0.882 compared to 0.814. Age and RDW were identified as the most significant predictors of ICU mortality, as reported by the variable importance plot analysis. Conclusions: The MixRFb algorithm demonstrates superior efficacy in predicting in-hospital mortality and identifies age and RDW as primary predictors. Implementation of this algorithm could facilitate patient selection for clinical trials, thereby improving trial outcomes and strengthening ethical standards. Future research should focus on enriching algorithm robustness, expanding its applicability across diverse clinical settings and patient demographics, and integrating additional predictive markers to improve patient selection capabilities.

Inflammatory Markers and Severity in COVID-19 Patients with Clostridioides Difficile Co-Infection: A Retrospective Analysis Including Subgroups with Diabetes, Cancer, and Elderly.

The interplay of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and Clostridioides difficile infection (CDI) poses a critical clinical challenge. The resultant inflammatory milieu and its impact on outcomes remain incompletely understood, especially among vulnerable subgroups such as elderly patients, those with diabetes, and individuals with cancer. This study aimed to characterize inflammatory markers and composite inflammatory severity scores-such as Acute Physiology and Chronic Health Evaluation II (APACHE II), Confusion, Urea, Respiratory rate, Blood pressure, and age ≥ 65 years (CURB-65), National Early Warning Score (NEWS), and the Systemic Immune-Inflammation Index (SII)-in hospitalized Coronavirus Disease 2019 (COVID-19) patients with and without CDI, and to evaluate their prognostic implications across key clinical subgroups. We conducted a retrospective, single-center study of 240 hospitalized adults with Reverse Transcription Polymerase Chain Reaction (RT-PCR)-confirmed COVID-19 between February 2021 and March 2023. Of these, 98 had concurrent CDI. We collected baseline demographics, comorbidities, and laboratory parameters including C-reactive protein (CRP), Interleukin-6 (IL-6), ferritin, neutrophil and lymphocyte counts, albumin, platelet counts, and calculated indices (C-reactive protein to Albumin Ratio (CAR), Neutrophil-to-Lymphocyte Ratio (NLR), Prognostic Nutritional Index (PNI), SII). Patients were stratified by CDI status and analyzed for inflammatory marker distributions, severity scores (APACHE II, CURB-65, NEWS), and outcomes (Intensive Care Unit (ICU) admission, mechanical ventilation, mortality). Subgroup analyses included diabetes, elderly (≥65 years), and cancer patients. Statistical comparisons employed t-tests, chi-square tests, and logistic regression models. Patients with CDI demonstrated significantly higher CRP, IL-6, SII, and CAR, coupled with lower albumin and PNI (p < 0.05). They also had elevated APACHE II, CURB-65, and NEWS scores. CDI-positive patients experienced increased ICU admission (38.8% vs. 20.5%), mechanical ventilation (24.5% vs. 12.9%), and mortality (22.4% vs. 10.6%, all p < 0.05). Subgroup analyses revealed more pronounced inflammatory derangements and worse outcomes in elderly, diabetic, and cancer patients with CDI. Concurrent CDI intensifies systemic inflammation and adverse clinical trajectories in hospitalized COVID-19 patients. Elevations in inflammatory markers and severity scores predict worse outcomes, especially in high-risk subgroups. Early recognition and targeted interventions, including infection control and supportive measures, may attenuate disease severity and improve patient survival.

Real-World Experience in Tricuspid Transcatheter Edge-to-Edge Repair: Transcatheter Tricuspid Valve Repair in Spain Registry.

Significant tricuspid regurgitation (TR) is associated with increased morbidity and mortality. The development of transcatheter valve repair therapies has opened a wide range of opportunities for treatment of patients with high surgical risk. Real-world data might improve patient selection and outcome. The authors sought to investigate acute and short-term cardiovascular outcomes of tricuspid transcatheter edge-to-edge repair (T-TEER) with dedicated devices in a real-world setting. This is a retrospective, single-arm, multicenter registry conducted at 15 sites in Spain. The primary end point was a composite of all-cause death, rehospitalization for heart failure, and tricuspid valve re-intervention. Patients included (n=283) were older (76±9 years, 70% female), and showed significant comorbidities. Massive or torrential TR was present in 55% of subjects, with secondary cause being the main mechanism of regurgitation in ≈80% of individuals. Intraprocedural success was achieved in 79% of patients. At 1-year follow-up, significant improvements in TR grade (≥3+, 100% to 25%, P <0.001) and New York Heart Association functional class (I/II, 33%-86%, P <0.001) were observed. Lead-induced cause and single leaflet device attachment emerged as independent predictors of at least severe predischarge residual TR. In-hospital mortality occurred in 4 (1.4%) patients, whereas the Kaplan-Meier estimated 1-year primary end point occurrence rate was 21%. Intraprocedural success (hazard ratio, 0.353 [95% CI, 0.156-0.798]; P=0.012), was found to be an independent predictor of primary end point. In a real-world contemporary setting, tricuspid transcatheter edge-to-edge repair with dedicated devices emerged as effective therapeutic option for patients with severe TR.