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Frontiers in Immunology 2024Programmed cell death protein-1 (PD-1) inhibitor-based therapy has demonstrated promising results in metastatic gastric cancer (MGC). However, the previous researches...
OBJECTIVE
Programmed cell death protein-1 (PD-1) inhibitor-based therapy has demonstrated promising results in metastatic gastric cancer (MGC). However, the previous researches are mostly clinical trials and have reached various conclusions. Our objective is to investigate the efficacy of PD-1 inhibitor-based treatment as first-line therapy for MGC, utilizing real-world data from China, and further analyze predictive biomarkers for efficacy.
METHODS
This retrospective study comprised 105 patients diagnosed with MGC who underwent various PD-1 inhibitor-based treatments as first-line therapy at West China Hospital of Sichuan University from January 2018 to December 2022. Patient characteristics, treatment regimens, and tumor responses were extracted. We also conducted univariate and multivariate analyses to assess the relationship between clinical features and treatment outcomes. Additionally, we evaluated the predictive efficacy of several commonly used biomarkers for PD-1 inhibitor treatments.
RESULTS
Overall, after 28.0 months of follow-up among the 105 patients included in our study, the objective response rate (ORR) was 30.5%, and the disease control rate (DCR) was 89.5% post-treatment, with two individuals (1.9%) achieving complete response (CR). The median progression-free survival (mPFS) was 9.0 months, and the median overall survival (mOS) was 22.0 months. According to both univariate and multivariate analyses, favorable OS was associated with patients having Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1. Additionally, normal baseline levels of carcinoembryonic antigen (CEA), as well as the combination of PD-1 inhibitors with chemotherapy and trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive MGC, independently predicted longer PFS and OS. However, microsatellite instability/mismatch repair (MSI/MMR) status and Epstein-Barr virus (EBV) infection status were not significantly correlated with PFS or OS extension.
CONCLUSION
As the first-line treatment, PD-1 inhibitors, either as monotherapy or in combination therapy, are promising to prolong survival for patients with metastatic gastric cancer. Additionally, baseline level of CEA is a potential predictive biomarker for identifying patients mostly responsive to PD-1 inhibitors.
Topics: Humans; Stomach Neoplasms; Male; Female; Retrospective Studies; Middle Aged; Aged; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Adult; China; Biomarkers, Tumor; Treatment Outcome; Neoplasm Metastasis; Antineoplastic Combined Chemotherapy Protocols; East Asian People
PubMed: 38933261
DOI: 10.3389/fimmu.2024.1370860 -
Fundamental Research May 2024The sudden onset of the coronavirus disease 2019 (COVID-19) in January 2020 has affected essential global health services. Cancer-screening services that can reduce... (Review)
Review
The sudden onset of the coronavirus disease 2019 (COVID-19) in January 2020 has affected essential global health services. Cancer-screening services that can reduce cancer mortality are strongly affected. However, the specific role of COVID-19 in cancer screening is not fully understood. This study aimed to assess the efficiency of global cancer screening programs before and during the COVID-19 pandemic and to promote potential cancer-screening strategies for the next pandemic. Electronic searches in PubMed, Embase, and Web of Science, and manual searches were performed between January 1, 2020 and March 1, 2023. Cohort studies that reported the number of participants who underwent cancer screening before and during the COVID-19 pandemic were included. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Differences in cancer-screening rates were estimated using the incidence rate ratio (IRR). Fifty-five cohort studies were included in this meta-analysis. The screening rates of colorectal cancer using invasive screening methods (Pooled IRR = 0.52, 95% CI: 0.42 to 0.65, < 0.01), cervical cancer (Pooled IRR = 0.56, 95% CI: 0.47 to 0.67, < 0.01), breast cancer (Pooled IRR = 0.57, 95% CI: 0.49 to 0.66, < 0.01) and prostate cancer (Pooled IRR = 0.71, 95% CI: 0.56 to 0.90, < 0.01) during the COVID-19 pandemic were significantly lower than those before the COVID-19 pandemic. The screening rates of lung cancer (Pooled IRR = 0.77, 95% CI: 0.58 to 1.03, = 0.08) and colorectal cancer using noninvasive screening methods (Pooled IRR = 0.74, 95% CI: 0.50 to 1.09, = 0.13) were reduced with no statistical differences. The subgroup analyses revealed that the reduction in cancer-screening rates varied across economies. Our results suggest that the COVID-19 pandemic has had a noteworthy impact on colorectal, cervical, breast, and prostate cancer screening. Developing innovative cancer-screening technologies is important to promote the efficiency of cancer-screening services in the post-COVID-19 era and prepare for the next pandemic.
PubMed: 38933198
DOI: 10.1016/j.fmre.2023.12.016 -
Frontiers in Medicine 2024Infection with is associated with high rates of amputation and mortality. Alterations in the global climate have heightened the risk of atypical infections caused by...
BACKGROUND
Infection with is associated with high rates of amputation and mortality. Alterations in the global climate have heightened the risk of atypical infections caused by this pathogen.
CASE PRESENTATION
In the case report we describe, a 75-year-old man residing in a coastal city contracted secondary to an insect bite.
DISCUSSION AND CONCLUSION
This case underscores the importance for clinicians of recognizing that early administration of appropriate antibiotics in patients with non-traditional routes of infection can significantly reduce rates of amputation and mortality.
PubMed: 38933117
DOI: 10.3389/fmed.2024.1419074 -
Frontiers in Medicine 2024Bleeding following endoscopic variceal ligation (EVL) may occur as a result of numerous factors, including a diameter of esophageal varices (EV) that is too large to be...
Correlation between diameter of esophageal varices and early rebleeding following endoscopic variceal ligation: a multicenter retrospective study based on artificial intelligence-based endoscopic virtual rule.
BACKGROUND AND OBJECTIVE
Bleeding following endoscopic variceal ligation (EVL) may occur as a result of numerous factors, including a diameter of esophageal varices (EV) that is too large to be completely ligated. The present study aimed to develop an artificial intelligence-based endoscopic virtual ruler (EVR) to measure the diameter of EV with a view to finding more suitable cases for EVL.
METHODS
The present study was a multicenter retrospective study that included a total of 1,062 EVLs in 727 patients with liver cirrhosis with EV, who underwent EVL from April 2016 to March 2023. Patients were divided into early rebleeding ( = 80) and non-rebleeding groups ( = 982) according to whether postoperative bleeding occurred at 6 weeks. The characteristics of patient baseline data, the status of rebleeding at 6 weeks after surgery and the survival status at 6 weeks after rebleeding were analyzed.
RESULTS
The early rebleeding rate following 1,062 EVL procedures was 7.5%, and the mortality rate at 6 weeks after bleeding was 16.5%. Results of the one-way binary logistic regression analysis demonstrated that the risk factors for early rebleeding following EVL included: high TB ( = 0.009), low Alb ( = 0.001), high PT ( = 0.004), PVT ( = 0.026), HCC ( = 0.018), high Child-Pugh score ( < 0.001), Child-Pugh grade C( < 0.001), high MELD score( = 0.004), Japanese variceal grade F3 ( < 0.001), diameter of EV ( < 0.001), and number of ligature rings ( = 0.029). Results of the multifactorial binary logistic regression analysis demonstrated that Child-Pugh grade C ( = 0.007), Japanese variceal grade F3 ( = 0.009), and diameter of EV ( < 0.001) may exhibit potential in predicting early rebleeding following EVL. ROC analysis demonstrated that the area under curve (AUC) for EV diameter was 0.848, and the AUC for Japanese variceal grade was 0.635, which was statistically significant ( < 0.001). Thus, results of the present study demonstrated that EV diameter was more optimal in predicting early rebleeding following EVL than Japanese variceal grade criteria. The cut-off value of EV diameter was calculated to be 1.35 cm (sensitivity, 70.0%; specificity, 89.2%).
CONCLUSION
If the diameter of EV is ≥1.4 cm, there may be a high risk of early rebleeding following EVL surgery; thus, we recommend caution with EVL.
PubMed: 38933116
DOI: 10.3389/fmed.2024.1406108 -
Frontiers in Medicine 2024The objective of this research was to create a machine learning predictive model that could be easily interpreted in order to precisely determine the risk of premature...
OBJECTIVE
The objective of this research was to create a machine learning predictive model that could be easily interpreted in order to precisely determine the risk of premature death in patients receiving intensive care after pulmonary inflammation.
METHODS
In this study, information from the China intensive care units (ICU) Open Source database was used to examine data from 2790 patients who had infections between January 2019 and December 2020. A 7:3 ratio was used to randomly assign the whole patient population to training and validation groups. This study used six machine learning techniques: logistic regression, random forest, gradient boosting tree, extreme gradient boosting tree (XGBoost), multilayer perceptron, and K-nearest neighbor. A cross-validation grid search method was used to search the parameters in each model. Eight metrics were used to assess the models' performance: accuracy, precision, recall, F1 score, area under the curve (AUC) value, Brier score, Jordon's index, and calibration slope. The machine methods were ranked based on how well they performed in each of these metrics. The best-performing models were selected for interpretation using both the Shapley Additive exPlanations (SHAP) and Local interpretable model-agnostic explanations (LIME) interpretable techniques.
RESULTS
A subset of the study cohort's patients (120/1668, or 7.19%) died in the hospital following screening for inclusion and exclusion criteria. Using a cross-validated grid search to evaluate the six machine learning techniques, XGBoost showed good discriminative ability, achieving an accuracy score of 0.889 (0.874-0.904), precision score of 0.871 (0.849-0.893), recall score of 0.913 (0.890-0.936), F1 score of 0.891 (0.876-0.906), and AUC of 0.956 (0.939-0.973). Additionally, XGBoost exhibited excellent performance with a Brier score of 0.050, Jordon index of 0.947, and calibration slope of 1.074. It was also possible to create an interactive internet page using the XGBoost model.
CONCLUSION
By identifying patients at higher risk of early mortality, machine learning-based mortality risk prediction models have the potential to significantly improve patient care by directing clinical decision making and enabling early detection of survival and mortality issues in patients with pulmonary inflammation disease.
PubMed: 38933112
DOI: 10.3389/fmed.2024.1399527 -
Frontiers in Medicine 2024The fight against SARS-CoV-2 has been a major task worldwide since it was first identified in December 2019. An imperative preventive measure is the availability of...
INTRODUCTION
The fight against SARS-CoV-2 has been a major task worldwide since it was first identified in December 2019. An imperative preventive measure is the availability of efficacious vaccines while there is also a significant interest in the protective effect of a previous SARS-CoV-2 infection on a subsequent infection (natural protection rate).
METHODS
In order to compare protection rates after infection and vaccination, researchers consider different effect measures such as 1 minus hazard ratio, 1 minus odds ratio, or 1 minus risk ratio. These measures differ in a setting with competing risks. Nevertheless, as there is no unique definition, these metrics are frequently used in studies examining protection rate. Comparison of protection rates via vaccination and natural infection poses several challenges. For instance many publications consider the epidemiological definition, that a reinfection after a SARS-CoV-2 infection is only possible after 90 days, whereas there is no such constraint after vaccination. Furthermore, death is more prominent as a competing event during the first 90 days after infection compared to vaccination. In this work we discuss the statistical issues that arise when investigating protection rates comparing vaccination with infection. We explore different aspects of effect measures and provide insights drawn from different analyses, distinguishing between the first and the second 90 days post-infection or vaccination.
RESULTS
In this study, we have access to real-world data of almost two million people from Stockholm County, Sweden. For the main analysis, data of over 52.000 people is considered. The infected group is younger, includes more men, and is less morbid compared to the vaccinated group. After the first 90 days, these differences increased. Analysis of the second 90 days shows differences between analysis approaches and between age groups. There are age-related differences in mortality. Considering the outcome SARS-CoV-2 infection, the effect of vaccination versus infection varies by age, showing a disadvantage for the vaccinated in the younger population, while no significant difference was found in the elderly.
DISCUSSION
To compare the effects of immunization through infection or vaccination, we emphasize consideration of several investigations. It is crucial to examine two observation periods: The first and second 90-day intervals following infection or vaccination. Additionally, methods to address imbalances are essential and need to be used. This approach supports fair comparisons, allows for more comprehensive conclusions and helps prevent biased interpretations.
PubMed: 38933111
DOI: 10.3389/fmed.2024.1376275 -
Frontiers in Medicine 2024Intestinal ischemia/reperfusion is a prevalent pathological process that can result in intestinal dysfunction, bacterial translocation, energy metabolism disturbances,... (Review)
Review
Intestinal ischemia/reperfusion is a prevalent pathological process that can result in intestinal dysfunction, bacterial translocation, energy metabolism disturbances, and subsequent harm to distal tissues and organs via the circulatory system. Acute lung injury frequently arises as a complication of intestinal ischemia/reperfusion, exhibiting early onset and a grim prognosis. Without appropriate preventative measures and efficacious interventions, this condition may progress to acute respiratory distress syndrome and elevate mortality rates. Nonetheless, the precise mechanisms and efficacious treatments remain elusive. This paper synthesizes recent research models and pertinent injury evaluation criteria within the realm of acute lung injury induced by intestinal ischemia/reperfusion. The objective is to investigate the roles of pathophysiological mechanisms like oxidative stress, inflammatory response, apoptosis, ferroptosis, and pyroptosis; and to assess the strengths and limitations of current therapeutic approaches for acute lung injury stemming from intestinal ischemia/reperfusion. The goal is to elucidate potential targets for enhancing recovery rates, identify suitable treatment modalities, and offer insights for translating fundamental research into clinical applications.
PubMed: 38933104
DOI: 10.3389/fmed.2024.1399744 -
EClinicalMedicine Jul 2024Children in low and middle-income countries remain vulnerable following hospital-discharge. We estimated the incidence and correlates of hospital readmission among young...
BACKGROUND
Children in low and middle-income countries remain vulnerable following hospital-discharge. We estimated the incidence and correlates of hospital readmission among young children admitted to nine hospitals in sub-Saharan Africa and South Asia.
METHODS
This was a secondary analysis of the CHAIN Network prospective cohort enrolled between 20th November 2016 and 31st January 2019. Children aged 2-23 months were eligible for enrolment, if admitted for an acute illness to one of the study hospitals. Exclusions were requiring immediate resuscitation, inability to tolerate oral feeds in their normal state of health, had suspected terminal illness, suspected chromosomal abnormality, trauma, admission for surgery, or their parent/caregiver was unwilling to participate and attend follow-up visits. Data from children discharged alive from the index admission were analysed for hospital readmission within 180-days from discharge. We examined ratios of readmission to post-discharge mortality rates. Using models with death as the competing event, we evaluated demographic, nutritional, clinical, and socioeconomic associations with readmission.
FINDINGS
Of 2874 children (1239 (43%) girls, median (IQR) age 10.8 (6.8-15.6) months), 655 readmission episodes occurred among 506 (18%) children (198 (39%) girls): 391 (14%) with one, and 115 (4%) with multiple readmissions, with a rate of: 41.0 (95% CI 38.0-44.3) readmissions/1000 child-months. Median time to readmission was 42 (IQR 15-93) days. 460/655 (70%) and 195/655 (30%) readmissions occurred at index study hospital and non-study hospitals respectively. One-third (N = 213/655, 33%) of readmissions occurred within 30 days of index discharge. Sites with fewest readmissions had the highest post-discharge mortality. Most readmissions to study hospitals (371/450, 81%) were for the same illness as the index admission. Age, prior hospitalisation, chronic conditions, illness severity, and maternal mental health score, but not sex, nutritional status, or physical access to healthcare, were associated with readmission.
INTERPRETATION
Readmissions may be appropriate and necessary to reduce post-discharge mortality in high mortality settings. Social and financial support, training on recognition of serious illness for caregivers, and improving discharge procedures, continuity of care and facilitation of readmission need to be tested in intervention studies. We propose the ratio of readmission to post-discharge mortality rates as a marker of overall post-discharge access and care.
FUNDING
The Bill & Melinda Gates Foundation (OPP1131320).
PubMed: 38933099
DOI: 10.1016/j.eclinm.2024.102676 -
BMJ Neurology Open 2024Accurate outcome predictions for patients who had ischaemic stroke with successful reperfusion after endovascular thrombectomy (EVT) may improve patient treatment and...
BACKGROUND
Accurate outcome predictions for patients who had ischaemic stroke with successful reperfusion after endovascular thrombectomy (EVT) may improve patient treatment and care. Our study developed prediction models for key clinical outcomes in patients with successful reperfusion following EVT in an Australian population.
METHODS
The study included all patients who had ischaemic stroke with occlusion in the proximal anterior cerebral circulation and successful reperfusion post-EVT over a 7-year period. Multivariable logistic regression and Cox regression models, incorporating bootstrap and multiple imputation techniques, were used to identify predictors and develop models for key clinical outcomes: 3-month poor functional status; 30-day, 1-year and 3-year mortality; survival time.
RESULTS
A total of 978 patients were included in the analyses. Predictors associated with one or more poor outcomes include: older age (ORs for every 5-year increase: 1.22-1.40), higher premorbid functional modified Rankin Scale (ORs: 1.31-1.75), higher baseline National Institutes of Health Stroke Scale (ORs: 1.05-1.07) score, higher blood glucose (ORs: 1.08-1.19), larger core volume (ORs for every 10 mL increase: 1.10-1.22), pre-EVT thrombolytic therapy (ORs: 0.44-0.56), history of heart failure (outcome: 30-day mortality, OR=1.87), interhospital transfer (ORs: 1.42 to 1.53), non-rural/regional stroke onset (outcome: functional dependency, OR=0.64), longer onset-to-groin puncture time (outcome: 3-year mortality, OR=1.08) and atherosclerosis-caused stroke (outcome: functional dependency, OR=1.68). The models using these predictors demonstrated moderate predictive abilities (area under the receiver operating characteristic curve range: 0.752-0.796).
CONCLUSION
Our models using real-world predictors assessed at hospital admission showed satisfactory performance in predicting poor functional outcomes and short-term and long-term mortality for patients with successful reperfusion following EVT. These can be used to inform EVT treatment provision and consent.
PubMed: 38932996
DOI: 10.1136/bmjno-2024-000707 -
Frontiers in Cardiovascular Medicine 2024The long-term impact of type 2 diabetes mellitus (T2DM) after an acute myocardial infarction (AMI) has not been thoroughly investigated yet. This study aimed to assess...
OBJECTIVE
The long-term impact of type 2 diabetes mellitus (T2DM) after an acute myocardial infarction (AMI) has not been thoroughly investigated yet. This study aimed to assess the long-term impact of T2DM after AMI.
RESEARCH DESIGN AND METHODS
We analyzed the data of three nationwide observational studies from the French Registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) program, conducted over a 1-month period in 2005, 2010, and 2015. Patients presenting T2DM were classified as diabetic, and patients presenting type 1 diabetes mellitus were excluded. We identified factors related to all-cause death at 1-year follow-up and divided 1,897 subjects into two groups, paired based on their estimated 1-year probability of death as determined by a logistic regression model.
RESULTS
A total of 9,181 AMI patients were included in the analysis, among them 2,038 (22.2%) had T2DM. Patients with diabetes were significantly older (68.2 ± 12.0 vs. 63.8 ± 14.4, < 0.001) and had a higher prevalence of a prior history of percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or heart failure (22.5% vs. 13.0%, 7.1% vs. 3.1% and 6.7 vs. 3.8% respectively, < 0.001 for all). Even after matching two groups of 1,897 patients based on propensity score for their 1-year probability of death, diabetes remained associated with long-term mortality, with an HR of 1.30, 95%CI (1.17-1.45), < 0.001.
CONCLUSIONS
T2DM has an adverse impact on long-term survival after myocardial infarction. Independently of the risk of short-term mortality, patients with diabetes who survived an AMI have a 30% higher risk of long-term mortality.
PubMed: 38932992
DOI: 10.3389/fcvm.2024.1401569