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Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Jun 2024Objective To construct a risk prediction model by integrating the molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) and immune-related genes.Methods With...
Objective To construct a risk prediction model by integrating the molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) and immune-related genes.Methods With GSE71729 data set (=145) as the training set,the differentially expressed genes and differential immune-related genes between the squamous and non-squamous subtypes of PDAC were integrated to construct a regulatory network,on the basis of which five immune marker genes regulating the squamous subtype were screened out.An integrated immune score (IIS) model was constructed based on patient survival information and immune marker genes to predict the clinical prognosis of PDAC patients,and its predictive performance was tested with 5 validation sets (=758).Results PDAC patients were assigned into high risk and low risk groups according to the IIS.In both training and validation sets,the overall survival of patients in the high risk group was shorter than that in the low risk group (both <0.001).The multivariable Cox regression showed that IIS was an independent prognostic factor for PDAC (=2.16,95%=1.50-3.10,<0.001).Conclusion IIS can be used for risk stratification of PDAC patients and may become a potential prognostic marker for PDAC.
Topics: Humans; Carcinoma, Pancreatic Ductal; Prognosis; Pancreatic Neoplasms; Female; Male; Middle Aged; Biomarkers, Tumor; Risk Assessment
PubMed: 38953259
DOI: 10.3881/j.issn.1000-503X.15736 -
Otolaryngology--head and Neck Surgery :... Jul 2024Arnold-Chiari Malformation is one possible cause of congenital vocal cord paralysis (VCP). The natural history of VCP in children with Chiari malformation has previously... (Review)
Review
OBJECTIVE
Arnold-Chiari Malformation is one possible cause of congenital vocal cord paralysis (VCP). The natural history of VCP in children with Chiari malformation has previously been limited to small case studies. This systematic review seeks to better characterize the prognostic factors that may predict symptom severity and resolution of congenital VCP in children with Arnold-Chiari malformation. We hypothesized that the onset of stridor or VCP at a younger age would be associated with a poorer prognosis and earlier intervention with posterior fossa decompression would be associated with better outcomes.
DATA SOURCES
PubMed, Web of Science, Cochrane Library, and bibliographic review.
REVIEW METHODS
A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Database search yielded 866 articles. Study abstracts were reviewed by 2 independent examiners. One hundred and seventy-six studies underwent full-text review. The following were extracted: age at onset of stridor or VCP, Chiari malformation type, laryngoscopy findings, type and timing of neurosurgical intervention, and tracheostomy history. Statistical analyses utilized χ tests.
RESULTS
Younger age at symptom onset showed statistically significant associations with decreased likelihood for symptom resolution and tracheostomy decannulation. The shorter time interval from symptom onset to neurosurgical intervention was not significantly associated with better outcomes.
CONCLUSION
This meta-analysis suggests poorer prognosis in those with earlier-onset symptoms, reinforcing prior case series findings. Additional prospective studies are needed to elucidate the natural history and utility of early intervention in children with vocal cord paralysis secondary to Chiari malformation.
PubMed: 38953205
DOI: 10.1002/ohn.884 -
Pediatric Blood & Cancer Jul 2024The molecular pathogenesis of acute myeloid leukemia (AML) was dramatically clarified over the latest two decades. Several important molecular markers were discovered in...
High DOCK1 expression identifies a distinct prognostic subgroup of pediatric acute myeloid leukemia: Results of the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 trial.
BACKGROUND
The molecular pathogenesis of acute myeloid leukemia (AML) was dramatically clarified over the latest two decades. Several important molecular markers were discovered in patients with AML that have helped to improve the risk stratification. However, developing new treatment strategies for relapsed/refractory acute myeloid leukemia (AML) is crucial due to its poor prognosis.
PROCEDURE
To overcome this difficulty, we performed an assay for transposase-accessible chromatin with sequencing (ATAC-seq) in 10 AML patients with various gene alterations. ATAC-seq is based on direct in vitro sequencing adaptor transposition into native chromatin, and is a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq analysis revealed increased accessibility of the DOCK1 gene in patients with AML harboring poor prognostic factors. Following the ATAC-seq results, quantitative reverse transcription polymerase chain reaction was used to measure DOCK1 gene expression levels in 369 pediatric patients with de novo AML.
RESULTS
High DOCK1 expression was detected in 132 (37%) patients. The overall survival (OS) and event-free survival (EFS) among patients with high DOCK1 expression were significantly worse than those patients with low DOCK1 expression (3-year EFS: 34% vs. 60%, p < .001 and 3-year OS: 60% vs. 80%, p < .001). To investigate the significance of high DOCK1 gene expression, we transduced DOCK1 into MOLM14 cells, and revealed that cytarabine in combination with DOCK1 inhibitor reduced the viability of these leukemic cells.
CONCLUSIONS
Our results indicate that a DOCK1 inhibitor might reinforce the effects of cytarabine and other anti-cancer agents in patients with AML with high DOCK1 expression.
PubMed: 38953149
DOI: 10.1002/pbc.31151 -
Indian Journal of Ophthalmology Jul 2024
Topics: Humans; Angiogenesis Inhibitors; Vascular Endothelial Growth Factor A; Visual Acuity; Intravitreal Injections; Diabetic Retinopathy; Macular Edema; Bevacizumab; Ranibizumab; Treatment Outcome; Tomography, Optical Coherence
PubMed: 38953138
DOI: 10.4103/IJO.IJO_40_24 -
Indian Journal of Ophthalmology Jul 2024Cataract surgery constitutes one of the highest volume surgeries performed worldwide approximating 10 million annually, varying from 100 to 6000 per million population....
INTRODUCTION
Cataract surgery constitutes one of the highest volume surgeries performed worldwide approximating 10 million annually, varying from 100 to 6000 per million population. Implantation of scleral fixated intra-ocular lens (SFIOL) is getting popular in managing difficult situations like aphakia, subluxated lens, and dislocated cataracts.
OBJECTIVE
This retrospective series evaluated our experience with foldable 3-piece acrylic SFIOL implantation for various challenging surgical scenarios in a tertiary care ophthalmic institute in the southern part of India.
RESULTS
The data from the first 150 patients, those operated in our hospital in the aforementioned technique, have been reviewed and analyzed. The mean age of the population was 46.43 years. The most common indication was found to be surgical aphakia (34.66%) followed by traumatic subluxated lens (8.33%). Postoperative BCVA at 3 months improved to 0.255 on the LogMAR scale from preoperative BCVA of 0.795 (P < 0.01). Intraocular pressure was found to stabilize over 3 months follow-up (P = 0.002). The various intraoperative and postoperative complications have been recorded. Ten patients required resurgery out of which eight had postoperative haptic dislocation. A detailed comparison of the role of a surgeon's experience in influencing outcomes has been evaluated.
CONCLUSION
The technique offers physiological IOL placement using minimal surgical maneuvers. We strongly recommend this as a technique of choice for the surgical management of complicated scenarios with inadequate capsular bag support.
Topics: Humans; Retrospective Studies; Sclera; Male; Female; Middle Aged; Lens Implantation, Intraocular; Lenses, Intraocular; Adult; Visual Acuity; Aged; Sutureless Surgical Procedures; Follow-Up Studies; Treatment Outcome; Prosthesis Design; Adolescent; Young Adult; Child; Suture Techniques
PubMed: 38953133
DOI: 10.4103/IJO.IJO_1698_23 -
Cureus May 2024Background Oral cancer screenings are often on the back burner in the face of other cancer screenings. In high-risk individuals, early detection of oral cancer has a...
Background Oral cancer screenings are often on the back burner in the face of other cancer screenings. In high-risk individuals, early detection of oral cancer has a better prognosis and survival. Hospitalization may offer an opportunity to target high-risk populations. This study evaluates the prevalence of women at high risk for oral cancer among hospitalized women and their preference for oral cancer screening. Design and participants Five hundred and ten cancer-free women admitted to the hospital under the internal medicine service at an academic center were enrolled to participate in the study. Three hundred and seventy women were at high risk for developing oral cancer, defined by smoking status, alcohol use, or both. High-risk women received bedside smoking cessation counseling and oral cancer informational handouts and were offered oral screening examinations during hospitalization. Six months after discharge, study participants received a follow-up phone call to determine if these women discussed oral cancer screening with their primary care physicians at the follow-up visit. Results Seventy-three percent of the hospitalized women were at high risk for developing oral cancer. Fifty-seven percent of high-risk women reported having no primary dentist. High-risk women were more likely to be younger, reported a disability, and had a lower comorbidity burden than the average-risk group. Only 41% of high-risk hospitalized women received oral cancer screening examinations during the hospital stay. Post-hospitalization, 66% of high-risk patients discussed oral cancer screening with their primary care. Conclusion Almost three-fourths of hospitalized women are at high risk for developing oral cancer. Hospitalization provides an opportunity to educate and screen high-risk populations.
PubMed: 38953068
DOI: 10.7759/cureus.61423 -
Research and Practice in Thrombosis and... May 2024Congenital fibrinogen disorders (CFDs) are rare bleeding disorders (RBDs) caused by mutations in 1 of the 3 fibrinogen genes (, , and ).
BACKGROUND
Congenital fibrinogen disorders (CFDs) are rare bleeding disorders (RBDs) caused by mutations in 1 of the 3 fibrinogen genes (, , and ).
OBJECTIVES
To investigate the clinical phenotype, laboratory features, diagnosis, treatment, and prognosis of CFDs.
METHODS
Clinical data of 93 subjects with CFDs identified from June 2018 to December 2023 were retrospectively analyzed.
RESULTS
Among the 93 patients, there were 46 males (49.5%) and 47 females (50.5%), with a median age of 23 years. Fifty-three of 93 (57%) subjects experienced bleeding, 3/93 (3.2%) experienced thrombosis, and 37/93 (39.8%) were asymptomatic. Females were more prone to experience bleeding ( < .0001). The 93 patients exhibited prolonged thrombin time, significantly decreased fibrinogen activity (Fg:C), and normal or decreased fibrinogen antigen. The 93 patients included 3 with hypofibrinogenemia, 16 with hypodysfibrinogenemia, and 74 with dysfibrinogenemia. Among the 53 patients with bleeding, bleeding episodes were identified in 3.8% (2/53), 20.8% (11/53), and 75.5% (40/53) patients with hypofibrinogenemia, hypodysfibrinogenemia, and dysfibrinogenemia, respectively. Genetic analysis was performed on 22 cases from 8 pedigrees, revealing 10 mutations, including 1 novel splice mutation. Twenty-eight (30.1%) subjects received replacement therapy to treat or prevent bleeding, consisting of 8 fresh frozen plasma transfusions, 3 packing and suture treatment, and 61 fibrinogen infusions.
CONCLUSION
Most patients with CFDs have mild or no bleeding symptoms. Fg:C combined with fibrinogen antigen and pedigree investigation can improve the feasibility and accuracy of diagnosis of CFDs. The severity of bleeding symptoms was negatively correlated with Fg:C.
PubMed: 38953055
DOI: 10.1016/j.rpth.2024.102445 -
Journal of Pathology Informatics Dec 2024The Gleason score is an important predictor of prognosis in prostate cancer. However, its subjective nature can result in over- or under-grading. Our objective was to...
The Gleason score is an important predictor of prognosis in prostate cancer. However, its subjective nature can result in over- or under-grading. Our objective was to train an artificial intelligence (AI)-based algorithm to grade prostate cancer in specimens from patients who underwent radical prostatectomy (RP) and to assess the correlation of AI-estimated proportions of different Gleason patterns with biochemical recurrence-free survival (RFS), metastasis-free survival (MFS), and overall survival (OS). Training and validation of algorithms for cancer detection and grading were completed with three large datasets containing a total of 580 whole-mount prostate slides from 191 RP patients at two centers and 6218 annotated needle biopsy slides from the publicly available Prostate Cancer Grading Assessment dataset. A cancer detection model was trained using MobileNetV3 on 0.5 mm × 0.5 mm cancer areas (tiles) captured at 10× magnification. For cancer grading, a Gleason pattern detector was trained on tiles using a ResNet50 convolutional neural network and a selective CutMix training strategy involving a mixture of real and artificial examples. This strategy resulted in improved model generalizability in the test set compared with three different control experiments when evaluated on both needle biopsy slides and whole-mount prostate slides from different centers. In an additional test cohort of RP patients who were clinically followed over 30 years, quantitative Gleason pattern AI estimates achieved concordance indexes of 0.69, 0.72, and 0.64 for predicting RFS, MFS, and OS times, outperforming the control experiments and International Society of Urological Pathology system (ISUP) grading by pathologists. Finally, unsupervised clustering of test RP patient specimens into low-, medium-, and high-risk groups based on AI-estimated proportions of each Gleason pattern resulted in significantly improved RFS and MFS stratification compared with ISUP grading. In summary, deep learning-based quantitative Gleason scoring using a selective CutMix training strategy may improve prognostication after prostate cancer surgery.
PubMed: 38953042
DOI: 10.1016/j.jpi.2024.100381 -
Transplantation Direct Jul 2024A prior single-center, retrospective cohort study identified baseline lung allograft dysfunction (BLAD) as a risk factor for death in bilateral lung transplant...
BACKGROUND
A prior single-center, retrospective cohort study identified baseline lung allograft dysfunction (BLAD) as a risk factor for death in bilateral lung transplant recipients. In this multicenter prospective cohort study, we test the association of BLAD with death in bilateral lung transplant recipients, identify clinical risk factors for BLAD, and assess its association with allograft injury on the molecular level.
METHODS
This multicenter, prospective cohort study included 173 bilateral lung transplant recipients that underwent serial pulmonary function testing and plasma collection for donor-derived cell-free DNA at prespecified time points. BLAD was defined as failure to achieve ≥80% predicted for both forced expiratory volume in 1 s and forced vital capacity after lung transplant, on 2 consecutive measurements at least 3 mo apart.
RESULTS
BLAD was associated with increased risk of death (hazard ratio, 1.97; 95% confidence interval [CI], 1.05-3.69; = 0.03) but not chronic lung allograft dysfunction alone (hazard ratio, 1.60; 95% CI, 0.87-2.95; = 0.13). Recipient obesity (odds ratio, 1.69; 95% CI, 1.15-2.80; = 0.04) and donor age (odds ratio, 1.03; 95% CI, 1.02-1.05; = 0.004) increased the risk of developing BLAD. Patients with BLAD did not demonstrate higher log(donor-derived cell-free DNA) levels compared with no BLAD (slope [SE]: -0.0095 [0.0007] versus -0.0109 [0.0007]; = 0.15).
CONCLUSIONS
BLAD is associated with an increased risk of death following lung transplantation, representing an important posttransplant outcome with valuable prognostic significance; however, early allograft specific injury on the molecular level does not increase the risk of BLAD, supporting further mechanistic insight into disease pathophysiology.
PubMed: 38953039
DOI: 10.1097/TXD.0000000000001669 -
Frontiers in Immunology 2024Unbalanced inflammatory response is a critical feature of sepsis, a life-threatening condition with significant global health burdens. Immune dysfunction, particularly... (Observational Study)
Observational Study
BACKGROUND
Unbalanced inflammatory response is a critical feature of sepsis, a life-threatening condition with significant global health burdens. Immune dysfunction, particularly that involving different immune cells in peripheral blood, plays a crucial pathophysiological role and shows early warning signs in sepsis. The objective is to explore the relationship between sepsis and immune subpopulations in peripheral blood, and to identify patients with a higher risk of 28-day mortality based on immunological subtypes with machine-learning (ML) model.
METHODS
Patients were enrolled according to the sepsis-3 criteria in this retrospective observational study, along with age- and sex-matched healthy controls (HCs). Data on clinical characteristics, laboratory tests, and lymphocyte immunophenotyping were collected. XGBoost and k-means clustering as ML approaches, were employed to analyze the immune profiles and stratify septic patients based on their immunological subtypes. Cox regression survival analysis was used to identify potential biomarkers and to assess their association with 28-day mortality. The accuracy of biomarkers for mortality was determined by the area under the receiver operating characteristic (ROC) curve (AUC) analysis.
RESULTS
The study enrolled 100 septic patients and 89 HCs, revealing distinct lymphocyte profiles between the two groups. The XGBoost model discriminated sepsis from HCs with an area under the receiver operating characteristic curve of 1.0 and 0.99 in the training and testing set, respectively. Within the model, the top three highest important contributions were the percentage of CD38CD8T cells, PD-1NK cells, HLA-DRCD8T cells. Two clusters of peripheral immunophenotyping of septic patients by k-means clustering were conducted. Cluster 1 featured higher proportions of PD1 NK cells, while cluster 2 featured higher proportions of naïve CD4T cells. Furthermore, the level of PD-1NK cells was significantly higher in the non-survivors than the survivors (15.1% vs 8.6%, <0.01). Moreover, the levels of PD1 NK cells combined with SOFA score showed good performance in predicting the 28-day mortality in sepsis (AUC=0.91,95%CI 0.82-0.99), which is superior to PD1 NK cells only(AUC=0.69, sensitivity 0.74, specificity 0.64, cut-off value of 11.25%). In the multivariate Cox regression, high expression of PD1 NK cells proportion was related to 28-day mortality (aHR=1.34, 95%CI 1.19 to 1.50; <0.001).
CONCLUSION
The study provides novel insights into the association between PD1NK cell profiles and prognosis of sepsis. Peripheral immunophenotyping could potentially stratify the septic patients and identify those with a high risk of 28-day mortality.
Topics: Humans; Sepsis; Male; Female; Programmed Cell Death 1 Receptor; Middle Aged; Aged; Killer Cells, Natural; Retrospective Studies; Biomarkers; Prognosis; Immunophenotyping; ROC Curve; Machine Learning
PubMed: 38953031
DOI: 10.3389/fimmu.2024.1426064