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Journal of Gastrointestinal Oncology Apr 2024Multiple studies have examined the effect of perioperative blood transfusion (BTF) on postoperative complications and the prognosis of gastric cancer patients, but the...
BACKGROUND
Multiple studies have examined the effect of perioperative blood transfusion (BTF) on postoperative complications and the prognosis of gastric cancer patients, but the conclusions remain controversial, and few studies related to elderly patients are present. This study sought to examine the effect of perioperative BTF on postoperative complications and the prognosis of elderly patients who underwent radical gastrectomy.
METHODS
The clinical data of 1,666 elderly patients (aged ≥60 years) at Xijing Hospital from October 2013 to October 2021 were retrospectively analyzed. The patients were stratified into the perioperative BTF group and the perioperative non-BTF group. The clinicopathological characteristics, postoperative complications, and long-term prognoses of the patients were compared.
RESULTS
There were significant differences in terms of sex, tumor location, tumor size, gastrectomy range, tumor differentiation, T stage, N stage, tumor-node-metastasis (TNM) stage, preoperative anemia, and intraoperative blood loss between the two groups (P<0.05). The incidence of postoperative fever in the BTF group was significantly higher than that in the non-BTF group (31.6% 15.4%, P<0.001), but there were no significant differences in the other complications between the two groups (P>0.05). The survival analysis showed that in stage III patients, the prognosis of the BTF group was inferior to that of the non-BTF group [the 3-year overall survival (OS) rates of the groups were 33.7% 47.9% respectively, P<0.001], while there was no significant difference between the two groups among the stage I and stage II patients (P>0.05). There was no significant difference in the prognosis of patients with different transfusion times (preoperative/intraoperative/postoperative) (P>0.05). The multivariate analysis indicated that perioperative BTF was not an independent risk factor for prognosis in elderly patients with gastric cancer overall or elderly patients with gastric cancer in stage III (P>0.05).
CONCLUSIONS
Perioperative BTF may elevate the incidence of fever but has no significant effect on other complications in elderly patients after radical gastrectomy. Perioperative BTF is not an independent risk factor affecting the postoperative prognosis of elderly patients with gastric cancer.
PubMed: 38756647
DOI: 10.21037/jgo-23-906 -
Journal of Gastrointestinal Oncology Apr 2024While surufatinib, sunitinib, and everolimus have shown efficacy for advanced neuroendocrine neoplasms (NENs) in randomized controlled trials (RCTs), direct comparisons...
Assessing the effectiveness and safety of surufatinib versus everolimus or sunitinib in advanced neuroendocrine neoplasms: insights from a real-world, retrospective cohort study using propensity score and inverse probability treatment weighting analysis.
BACKGROUND
While surufatinib, sunitinib, and everolimus have shown efficacy for advanced neuroendocrine neoplasms (NENs) in randomized controlled trials (RCTs), direct comparisons in a real-world setting remain unexplored. This gap highlights the clinical need to understand their comparative effectiveness and safety within the diverse Chinese population. Addressing this, our study provides insights into the real-world performance of these therapies, aiming to inform treatment selection and improve patient outcomes.
METHODS
A retrospective, observational study was conducted at Fudan University Shanghai Cancer Center, including patients with advanced NENs treated with surufatinib, sunitinib, or everolimus between July 2020 and April 2023. Eligibility criteria focused on histologically confirmed, locally advanced, unresectable, or metastatic NENs, with patients having received at least one month of targeted therapy. We employed inverse probability weighting (IPW) with the propensity score (PS) matching to adjust for the bias of baseline characteristics. The assessment of covariates included age, sex, performance status, primary tumor site, functional status, genetic mutations, tumor differentiation, Ki67 index, tumor grade, metastasis site, and previous therapies. The primary outcome was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), disease control rate (DCR), and adverse events (AEs).
RESULTS
The study enrolled 123, 56, and 68 locally advanced or metastatic NEN patients treated with surufatinib, sunitinib, and everolimus, respectively. Before adjusting for confounding factors, surufatinib was used less frequently as a first-line treatment compared to sunitinib and everolimus in pancreatic NENs (pNENs) (11.1% 22.1%, P=0.057). Significant differences were noted in prior treatments and tumor characteristics between surufatinib and everolimus groups in extrapancreatic NENs (epNENs) (P<0.05). Post-IPW, these disparities were resolved (P>0.05). Surufatinib demonstrated superior median PFS (mPFS) in both pancreatic [8.30 6.33 months, hazard ratio (HR) 0.592, P<0.001] and epNENs (8.73 3.70 months, HR 0.608, P<0.001) compared to everolimus or sunitinib. Notably, male gender (HR 1.75, P=0.001), functional status (HR 2.09, P=0.01), Ki67 index >20% (HR 12.7, P=0.004), previous somatostatin analogue (SSA) treatment (HR 1.73, P=0.001), germline mutation (HR 5.62, P<0.001), poor differentiation (HR 7.45, P<0.001), liver metastasis (HR 1.72, P=0.001) and multiple treatment lines (HR 1.62 for 2 line, P=0.04; HR 1.88 for ≥3 line, P=0.01) were identified as negative prognostic factors for PFS. Conversely, dose adjustment (HR 0.63, P=0.009) and treatment with surufatinib (HR 0.58 for pNEN, P<0.001; HR 0.62 for epNEN, P=0.002) were correlated with longer PFS.
CONCLUSIONS
In a real-world Chinese cohort, surufatinib significantly outperformed sunitinib and everolimus in prolonging PFS among advanced NEN patients, with identifiable clinical features impacting survival, and conclusions regarding superiority should be interpreted with caution due to the retrospective design. Our findings underscore the need for prospective studies to further validate these results and explore additional predictive biomarkers for personalized treatment strategies.
PubMed: 38756630
DOI: 10.21037/jgo-24-218 -
Frontiers in Endocrinology 2024Syndromic autism spectrum conditions (ASC), such as Klinefelter syndrome, also manifest hypogonadism. Compared to the popular Extreme Male Brain theory, the Enhanced... (Review)
Review
Syndromic autism spectrum conditions (ASC), such as Klinefelter syndrome, also manifest hypogonadism. Compared to the popular Extreme Male Brain theory, the Enhanced Perceptual Functioning model explains the connection between ASC, savant traits, and giftedness more seamlessly, and their co-emergence with atypical sexual differentiation. Overexcitability of primary sensory inputs generates a relative enhancement of local to global processing of stimuli, hindering the abstraction of communication signals, in contrast to the extraordinary local information processing skills in some individuals. Weaker inhibitory function through gamma-aminobutyric acid type A (GABA) receptors and the atypicality of synapse formation lead to this difference, and the formation of unique neural circuits that process external information. Additionally, deficiency in monitoring inner sensory information leads to alexithymia (inability to distinguish one's own emotions), which can be caused by hypoactivity of estrogen and oxytocin in the interoceptive neural circuits, comprising the anterior insular and cingulate gyri. These areas are also part of the Salience Network, which switches between the Central Executive Network for external tasks and the Default Mode Network for self-referential mind wandering. Exploring the possibility that estrogen deficiency since early development interrupts GABA shift, causing sensory processing atypicality, it helps to evaluate the co-occurrence of ASC with attention deficit hyperactivity disorder, dyslexia, and schizophrenia based on phenotypic and physiological bases. It also provides clues for understanding the common underpinnings of these neurodevelopmental disorders and gifted populations.
Topics: Humans; Androgens; Estrogens; Autism Spectrum Disorder; Male; Sex Differentiation; Klinefelter Syndrome; Perception; Brain
PubMed: 38752176
DOI: 10.3389/fendo.2024.1343759 -
World Journal of Oncology Jun 2024Adenosquamous carcinomas (ASCs) are a very rare histology containing cancer cells with both glandular-like (adeno) and squamous cell histologies, comprising typically a...
BACKGROUND
Adenosquamous carcinomas (ASCs) are a very rare histology containing cancer cells with both glandular-like (adeno) and squamous cell histologies, comprising typically a fraction of a percent of all solid tumors. The bulk of the literature on ASCs is comprised of case reports and small series, with the general finding that ASCs tend to have worse outcomes than either of their parent histologies. However, there is a lack of pan site-comparative studies in the literature that compare ASC clinicodemographic and survival outcomes with those of conventional adenocarcinomas (ACs) and squamous cell carcinomas (SCCs).
METHODS
In this study, we summarize these outcomes in eight primary sites, comprising 92.7% of all ASC cases diagnosed from 1975 to 2020 in the Surveillance, Epidemiology, and End Results (SEER) database.
RESULTS
Lung ASCs comprise 51.5% of all ASC cases, accounting for 1.1% of all lung cancer cases, followed by uterine/cervical cancers at 29.7% of all ASC cases, translating into 1.8% of all cancers in this site. In descending order, the remaining 20% of ASCs arise in pancreatic, oral cavity, biliary, esophageal, colorectal, and gastric sites, comprising between 0.1% and 0.7% of all cancers in these sites. Apart from pancreatic and oral cavity cancers, ASC tumors tended to favor higher rates of regional or distant disease at presentation with poor tumor differentiation compared to either AC or SCC histologies. After multivariable analysis, adjusting for age, sex, detection stage, grade differentiation, surgery, chemotherapy, and radiotherapy, except for oral cavity cancers, ASCs tended to have worse overall survivals compared to ACs (hazard ratios: 1.1 - 1.6) and SCC (1.0 - 1.3), with colorectal ASCs having the worse overall survival compared to colorectal ACs, with a hazard ratio of 1.4 (95% confidence interval: 1.3 - 1.6).
CONCLUSIONS
Overall, these results suggest that ASC outcomes are site specific, and in general, tend to have worse outcomes than nonvariant ACs and SCCs even after correction for common clinical and epidemiological factors. These cancers have a poorly understood but unique tumor biology that warrants further characterization.
PubMed: 38751700
DOI: 10.14740/wjon1845 -
Journal For Immunotherapy of Cancer May 2024Only a subset of patients with gastric cancer experience long-term benefits from immune checkpoint inhibitors (ICIs). Currently, there is a deficiency in precise...
BACKGROUND
Only a subset of patients with gastric cancer experience long-term benefits from immune checkpoint inhibitors (ICIs). Currently, there is a deficiency in precise predictive biomarkers for ICI efficacy. The aim of this study was to develop and validate a pathomics-driven ensemble model for predicting the response to ICIs in gastric cancer, using H&E-stained whole slide images (WSI).
METHODS
This multicenter study retrospectively collected and analyzed H&E-stained WSIs and clinical data from 584 patients with gastric cancer. An ensemble model, integrating four classifiers: least absolute shrinkage and selection operator, k-nearest neighbors, decision trees, and random forests, was developed and validated using pathomics features, with the objective of predicting the therapeutic efficacy of immune checkpoint inhibition. Model performance was evaluated using metrics including the area under the curve (AUC), sensitivity, and specificity. Additionally, SHAP (SHapley Additive exPlanations) analysis was used to explain the model's predicted values as the sum of the attribution values for each input feature. Pathogenomics analysis was employed to explain the molecular mechanisms underlying the model's predictions.
RESULTS
Our pathomics-driven ensemble model effectively stratified the response to ICIs in training cohort (AUC 0.985 (95% CI 0.971 to 0.999)), which was further validated in internal validation cohort (AUC 0.921 (95% CI 0.839 to 0.999)), as well as in external validation cohort 1 (AUC 0.914 (95% CI 0.837 to 0.990)), and external validation cohort 2 (0.927 (95% CI 0.802 to 0.999)). The univariate Cox regression analysis revealed that the prediction signature of pathomics-driven ensemble model was a prognostic factor for progression-free survival in patients with gastric cancer who underwent immunotherapy (p<0.001, HR 0.35 (95% CI 0.24 to 0.50)), and remained an independent predictor after multivariable Cox regression adjusted for clinicopathological variables, (including sex, age, carcinoembryonic antigen, carbohydrate antigen 19-9, therapy regime, line of therapy, differentiation, location and programmed death ligand 1 (PD-L1) expression in all patients (p<0.001, HR 0.34 (95% CI 0.24 to 0.50)). Pathogenomics analysis suggested that the ensemble model is driven by molecular-level immune, cancer, metabolism-related pathways, and was correlated with the immune-related characteristics, including immune score, Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data score, and tumor purity.
CONCLUSIONS
Our pathomics-driven ensemble model exhibited high accuracy and robustness in predicting the response to ICIs using WSIs. Therefore, it could serve as a novel and valuable tool to facilitate precision immunotherapy.
Topics: Humans; Stomach Neoplasms; Male; Female; Immunotherapy; Retrospective Studies; Middle Aged; Immune Checkpoint Inhibitors; Aged
PubMed: 38749538
DOI: 10.1136/jitc-2024-008927 -
BioRxiv : the Preprint Server For... Apr 2024Epidemiological studies show that exposure to the organochlorine pesticide dieldrin is associated with increased risk of Parkinson's disease (PD). Animal studies support...
Developmental origins of Parkinson's disease risk: perinatal exposure to the organochlorine pesticide dieldrin leads to sex-specific DNA modifications in critical neurodevelopmental pathways in the mouse midbrain.
Epidemiological studies show that exposure to the organochlorine pesticide dieldrin is associated with increased risk of Parkinson's disease (PD). Animal studies support a link between developmental dieldrin exposure and increased neuronal susceptibility in the α-synuclein preformed fibril (α-syn PFF) and MPTP models in adult male C57BL/6 mice. In a previous study, we showed that developmental dieldrin exposure was associated with sex-specific changes in DNA modifications within genes related to dopaminergic neuron development and maintenance at 12 weeks of age. Here, we used capture hybridization-sequencing with custom baits to interrogate DNA modifications across the entire genetic loci of the previously identified genes at multiple time points - birth, 6 weeks, 12 weeks, and 36 weeks old. We identified largely sex-specific dieldrin-induced changes in DNA modifications at each time point that annotated to pathways important for neurodevelopment, potentially related to critical steps in early neurodevelopment, dopaminergic neuron differentiation, synaptogenesis, synaptic plasticity, and glial-neuron interactions. Despite large numbers of age-specific DNA modifications, longitudinal analysis identified a small number of DMCs with dieldrin-induced deflection of epigenetic aging. The sex-specificity of these results adds to evidence that sex-specific responses to PD-related exposures may underly sex-specific differences in disease. Overall, these data support the idea that developmental dieldrin exposure leads to changes in epigenetic patterns that persist after the exposure period and disrupt critical neurodevelopmental pathways, thereby impacting risk of late life diseases, including PD.
PubMed: 38746441
DOI: 10.1101/2024.04.26.590998 -
Supportive Care in Cancer : Official... May 2024Quality of life (QoL), appetite, cachexia, and biomarkers [albumin, hemoglobin (Hb), neutrophils, lymphocytes, platelets, C-reactive protein (CRP), tumor necrosis factor...
PURPOSE
Quality of life (QoL), appetite, cachexia, and biomarkers [albumin, hemoglobin (Hb), neutrophils, lymphocytes, platelets, C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6), interleukin 8 (IL-8), C-X-C motif chemokine ligand 5 (CXCL5) and citrullinated histoneH3 (H3Cit)] were compared for 40 cases with advanced cancer and 40 healthy controls. Baseline differences and significant relationships were explored for biomarkers with QoL, appetite, and cachexia.
METHODS
In a prospective case-control, age and sex matched study, the European Organisation for the Research and Treatment of Cancer Quality of Life-C30 questionnaire (EORTC-QLQ-C30) for QoL, the Functional Assessment of Anorexia and Cachexia Therapy assessment (FAACT A/CS-12) for appetite, and a five-factor cachexia assessment tool for cachexia assessment were performed. Routine hematological measurements and blood chemistry analyses together with ELISA procedures and a Multiplex® bead array platform, were used for biomarker analysis. Descriptive statistics and regression analyses were undertaken. P < 0.05 defined statistical significance.
RESULTS
Global health status (QL-G), functional scales (QL-FS), and symptom scales (QL-SS) differed for cases and controls (p < 0.01). In cases, differences were observed for QL-G (p < 0.01), QL-FS (p < 0.01), and QL-SS (p = 0.01) compared to standardized references values. FAACT A/CS-12 scores differed significantly between cases and controls (p < 0.01) and 30% of cases scored "poor" appetites. Cachexia was present in 60% of cases. Albumin, lymphocytes, platelets, Hb, platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), CRP, TNFα, all at p < 0.01, neutrophil to lymphocyte ratio (NLR) (p = 0.02), IL-6 (p < 0.04), and IL-8 (p = 0.02) differed significantly between cases and controls. No difference was found for CXCL5 or H3Cit. Albumin NLR, Hb, PLR, SII, TNFα, IL-8, and CRP showed significant relationships with all aspects of QoL. QL-FS was significantly related to CXCL5 (p = 0.04), significant relationships with FAACT A/CS-12 included: NLR (p = 0.002), Hb (p < 0.001), and PLR (p < 0.01). NLR, PLR, SII, TNFα, IL-6, IL-8, and CRP correlated positively to cachexia and albumin while Hb and lymphocyte count correlated negatively to cachexia.
CONCLUSION
CXCL5 and H3Cit were not reliable biomarkers for cancer cachexia, nor significantly related to QoL, appetite or cachexia. Albumin, NLR, Hb, PLR, SII, TNFα, IL-8, and CRP were reliable indicators of QoL, appetite, and cachexia. Future research should include other novel biomarkers namely growth differentiation factor-15 (GDF-15), fibroblast growth factor 21 (FGF-21), fractakline, interferon gamma (IFN-y), IL-16, macrophage colony stimulating factor (M-CSF), and macrophage procoagulant-inducing factor (MPIF).
Topics: Humans; Cachexia; Quality of Life; Male; Female; Middle Aged; Neoplasms; Case-Control Studies; Prospective Studies; Aged; Appetite; Biomarkers; Surveys and Questionnaires; Adult
PubMed: 38744744
DOI: 10.1007/s00520-024-08549-5 -
The Journal of Forensic... Apr 2024The primary step in forensic odontological analysis is sex determination. The present study is one of the few studies that evaluated the accuracy of the combination of...
The primary step in forensic odontological analysis is sex determination. The present study is one of the few studies that evaluated the accuracy of the combination of canine tooth root length and crown measurements for sex determination. The study sample comprised 196 cone-be am computed tomographic scans of individuals aged 20-80 years distributed in five age categories: 20-29, 30-39, 40-49, 50-59, and 60+ years old. Different parameters, such as width, length, and ratio measurements for the crown and root of each maxillary and mandibular canine tooth, were examined and recorded. The findings indicated that maxillary canines had greater sex dimorphism ability (87.3%) than mandibular canines (80.6%). Total tooth length and root length of maxillary canine were the most pronounced variables in the differentiation of sex groups. When the combination of the mandibular and maxillary measurements was considered, the accuracy for sex dimorphism was 85.7%. By using ratio variables, the accuracy was reduced to 68.9%. According to the findings of this study, total tooth length and root length are the most discriminant variables of canine teeth. These variables are more reliable sex indicators than crown measurements.
Topics: Humans; Cuspid; Female; Male; Middle Aged; Tooth Crown; Cone-Beam Computed Tomography; Aged; Tooth Root; Adult; Sex Characteristics; Forensic Dentistry; Aged, 80 and over; Young Adult; Odontometry; Maxilla
PubMed: 38742568
DOI: 10.5281/zenodo.11061431 -
Folia Neuropathologica 2024Human induced pluripotent stem cells (hiPSCs) are a potential source of somatic cells for cell therapies due to their ability to self-renew and differentiate into...
Human induced pluripotent stem cells (hiPSCs) are a potential source of somatic cells for cell therapies due to their ability to self-renew and differentiate into various cells of the body. To date, the clinical application of hiPSCs has been limited due to safety issues. The present study aims to standardize the safety procedure of the derivation of GMP-compliant induced pluripotent stem cell (iPSC) lines from human fibroblasts. The hiPSC lines were generated using the nonintegrative Sendai virus method to incorporate Yamanaka reprogramming factors (OCT3/4, SOX2, KLF4 and c-MYC) into cells. A constant temperature was maintained during the cell culture, including all stages of the culture after transduction with Sendai virus. Pluripotency was proved in six independently generated hiPSC lines from adult female (47 years old) and male (57 years old) donors' derived fibroblasts via alkaline phosphatase live (ALP) staining, qPCR, and immunocytochemistry. The hiPSC lines showed a gradual decrease in the presence of the virus with each subsequent passage, and this reduction was specific to the hiPSC line. The frequency and probability of chromosomal aberrations in hiPSCs were dependent on both the iPSC clone identity and sex of the donor. In summary, the generation of hiPSC for clinical applications requires safety standards application (biosafety protocol, quality control of hiPSC lines, viral and genetic integrity screening) from the first stages of the clonal selection of hiPSC from the same donor.
Topics: Induced Pluripotent Stem Cells; Humans; Sendai virus; Kruppel-Like Factor 4; Female; Male; Middle Aged; Cell Line; Fibroblasts; Cell Differentiation; Transduction, Genetic; Sex Factors
PubMed: 38741435
DOI: 10.5114/fn.2024.134026 -
Indian Journal of Dental Research :... Oct 2023Gender determination is pivotal in establishing a biological profile of human remains, where fragments of the skull persist with unidentifiable dental arch data. Owing...
OBJECTIVE
Gender determination is pivotal in establishing a biological profile of human remains, where fragments of the skull persist with unidentifiable dental arch data. Owing to the resistance and stability against external factors such as trauma and fractures, radiological assessment of the frontal sinus can be a useful indicator for sexual dimorphism. Keeping this in mind, a study was designed to analyse the efficacy of morphometric assessment of the frontal sinus for gender determination in the North Indian population.
MATERIALS AND METHOD
A total of 300 (150 males and 150 females) lateral cephalograms of the age >20 years were retrieved. The frontal sinus index (ratio of maximum height to depth), area, and perimeter of the same were calculated using Adobe Photoshop software. The results obtained were further subjected to statistical analysis.
RESULT AND CONCLUSION
The study yielded an accuracy rate of 75.3% for sex differentiation. The frontal sinus perimeter was a novel parameter which was utilised as a variable in the obtained discriminant equation for sex differentiation. Thus, this cost-effective technique might be useful as an adjunct to assess sexual dimorphism.
Topics: Humans; Frontal Sinus; Male; Female; Cross-Sectional Studies; Adult; Cephalometry; India; Young Adult; Sex Determination by Skeleton; Sex Differentiation
PubMed: 38739814
DOI: 10.4103/ijdr.ijdr_970_22