Tag: pubmed

Immunotargets Ther. 2023 Dec 5;12:165-173. doi: 10.2147/ITT.S433555. eCollection 2023.

ABSTRACT

BACKGROUND: NOTCH1 is frequently mutated in non-small cell lung cancer (NSCLC), and also is a poor therapeutic target. It is of clinical importance to investigate the effects of NOTCH1 mutations on anti-tumor immunity and response to immune checkpoint blockade (ICB).

METHODS: An observational study with targeted sequencing in 963 NSCLC patients at our center were performed (FUSCC cohort). Data of the Cancer Genome Atlas Pan-Lung Cancer study (TCGA cohort) were analyzed, and gene set enrichment analysis (GSEA) was performed. The Samstein et al cohort included 350 patients with advanced NSCLC undergoing genomic profiling with the MSK-IMPACT assay, and receiving at least one dose of ICB therapy.

RESULTS: NOTCH1 mutations were more common in smokers and patients with squamous-cell carcinoma (SCC) (all P value <0.05). For patients who did not receive ICB therapy (TCGA cohort), the overall survival (OS) of NOTCH1-mutant and -WT patients were comparable (log-rank P = 0.72), while for patients who received ICB therapy in the Samstein et al cohort, NOTCH1-mutant patients had significantly superior OS than WT patients (log-rank P = 0.041). On multivariate Cox analysis, the predictive value of NOTCH1 mutations reached marginal statistical significance (HR, 0.42; 95% CI, 0.17-1.04; P = 0.059). The median of TMB for NOTCH1-mutant tumors was significantly higher than that for NOTCH1-WT tumors, and GSEA revealed that NOTCH1 mutations manifested various defects in the repair of DNA damage. NOTCH1-mutant tumors displayed an inflamed tumor microenvironment (TME), manifesting as increased PD-L1 expression and tumor-infiltrating CD8+ T cells.

CONCLUSION: NOTCH1 mutations define a molecular subtype of NSCLC, which are more common in smokers and patients with SCC, are characterized with higher TMB, inflamed TME, and display improved survival of ICB therapy for NSCLC patients.

PMID:38075489 | PMC:PMC10710100 | DOI:10.2147/ITT.S433555

World J Orthop. 2023 Nov 18;14(11):791-799. doi: 10.5312/wjo.v14.i11.791. eCollection 2023 Nov 18.

ABSTRACT

BACKGROUND: Supracondylar humerus fractures account for more than 60% of all elbow fractures and about 1/5 of all pediatric fractures. Unfortunately, these fractures can be associated with risk of complications including neurovascular injuries, malunions and limb deformities. Controversy exists regarding the effect of time of surgical intervention and/or level of surgeon performing the surgery on outcome of these fractures.

AIM: To determine whether time of surgical intervention and/or surgeon level influence the outcomes of surgically managed pediatric supracondylar humerus fractures.

METHODS: We retrospectively studied 155 pediatric patients presenting with a supracondylar humerus fracture in a level 1 trauma center from January 2006 to December 2019. The data extracted included demographic data, fracture characteristics, surgical data, and follow-up outcomes. The collected data was analyzed and P values of < 0.05 were considered statistically significant.

RESULTS: Of the cohort, 11% of patients had documented post-operative complications, of which the majority occurred in surgeries performed after day time working hours and in fractures requiring open reduction. While the lowest complication rate was found in surgeries performed by pediatric orthopaedic surgeons, this did not reach statistical significance.

CONCLUSION: In pediatric patients undergoing surgery for supracondylar fractures, we found a higher complication rate when surgeries were not performed during working hours. Surgeon level and training had no significant effect on the risk of post-operative complications.

PMID:38075474 | PMC:PMC10698341 | DOI:10.5312/wjo.v14.i11.791

World J Orthop. 2023 Nov 18;14(11):784-790. doi: 10.5312/wjo.v14.i11.784. eCollection 2023 Nov 18.

ABSTRACT

BACKGROUND: Liver transplant (LT) is becoming increasingly common with improved life expectancy. Joint replacement is usually a safe procedure; however, its safety in LT recipients remains understudied.

AIM: To evaluate the mortality, outcome, and 90-d readmission rate in LT patients undergoing hip and knee replacement surgery.

METHODS: Patients with history of LT who underwent hip and knee replacement surgery between 2016 and 2019 were identified using the National Readmission Database.

RESULTS: A total of 5046119 hip and knee replacement surgeries were identified. 3219 patients had prior LT. Mean age of patients with no history of LT was 67.51 [95% confidence interval (CI): 67.44-67.58], while it was 64.05 (95%CI: 63.55-64.54) in patients with LT. Patients with history of LT were more likely to have prolonged length of hospital stay (17.1% vs 8.4%, P < 0.001). The mortality rate for patients with no history of LT was 0.22%, while it was 0.24% for patients with LT (P = 0.792). Patients with history of LT were more likely to have re-admissions within 90 d of initial hospitalization: 11.4% as compared to 6.2% in patients without history of LT (P < 0.001). The mortality rate between both groups during readmission was not statistically different (1.9% vs 2%, P = 0.871) respectively.

CONCLUSION: Hip and knee replacements in patients with history of LT are not associated with increased mortality; increased re-admissions were more frequent in this cohort of patients. Chronic kidney disease and congestive heart failure appear to predict higher risk of readmission.

PMID:38075471 | PMC:PMC10698340 | DOI:10.5312/wjo.v14.i11.784

J Orthop. 2023 Nov 27;49:68-74. doi: 10.1016/j.jor.2023.11.060. eCollection 2024 Mar.

ABSTRACT

This systematic review was designed to compare the outcomes of the two braces against each other classified by the Graf method. The databases sources included PubMed, Embase, and Google Scholar. The keywords included “DDH Tubingen versus Pavlik” and Tubingen and Pavlik separately. Included papers provided specific data regarding success and failure rate, avascular necrosis (AVN), duration, and age of intervention. The excluded studies discussed surgeries, diagnosis and mechanism, and ones that weren’t in English. Total of 20 papers were included, resulting in 1243 Tubingen and 420 Pavlik samples. It was seen that the Tubingen splint had a statistically significant greater success rate and lower failure rate for Graf 2, D, and 3 hips, while both braces were not very successful for Graf 4 at success rates less than 60 %. Tubingen also had a lower incidence of AVN. Both braces shared similar ages of intervention, duration, and time per day. Both braces are very comparable to each other, each having better success rates for lower Graf grades, which points to the importance of bracing earlier to improve the success rates. The Tubingen splint had a higher success rate, lower failure rate, and lower AVN rate compared to the Pavlik harness. This points to the Tubingen splint potentially being the preferred option for bracing in infants.

PMID:38075458 | PMC:PMC10701362 | DOI:10.1016/j.jor.2023.11.060

Vaccine X. 2023 Nov 18;15:100407. doi: 10.1016/j.jvacx.2023.100407. eCollection 2023 Dec.

ABSTRACT

Vaccine-inducing immune thrombocytopenia, thrombosis, and bleeding emerge as infrequent and potential complications with mortality risk in healthy subjects. However, differences between survivors and non-survivors with SARS-CoV-2 vaccine-induced thrombotic thrombocytopenia (VITT) are unclear.

METHODS: According to the PRISMA statement, we conducted a systematic review and meta-analysis, and the protocol was registered in PROSPERO. The main objective is to identify differences among survivors and non-survivors of SARS-CoV-2 VITT patients. We systematically searched through PubMed, Scopus, and Web of Science. We included cohorts, case series, and case reports. We classified bleeding complications according to the ISTH definition. Statistics: unpaired Student’s t-test or one-way ANOVA, Wilcoxon, and Kruskal-Wallis.

RESULTS: We systematically searched from January 2021 to June 2021 and identified 51 studies that included 191 patients. Non-survivors had the most severe thrombocytopenia (p 0.02) and lower fibrinogen measurements (p 0.01). Subjects vaccinated with mRNA vaccines (BNT162b2 and mRNA-1273) had an earlier onset of adverse events following immunization (p 0.001). We identified a higher trend of overall thrombotic events (p 0.001) in recipients of viral mechanism-dependent vaccines (Table 2). Non-survivors with cerebral venous sinus thrombosis (CVST) had more severe thrombocytopenia (p 0.01) than survivors with CVST. Finally, 61 % of survivors and 50 % with thrombosis received heparin.

CONCLUSION: We identified more severe thrombocytopenia, lower fibrinogen measurements, and a higher trend of overall thrombotic events, including CVST and thrombotic storm, particularly with viral mechanisms-dependent vaccines in non-survivors VITT patients.

PMID:38075434 | PMC:PMC10701409 | DOI:10.1016/j.jvacx.2023.100407

Arthritis Rheumatol. 2023 Dec 10. doi: 10.1002/art.42766. Online ahead of print.

ABSTRACT

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease resulting in debilitating clinical manifestations that vary in severity by race and ethnicity with a disproportionate burden in African American, Mestizo, and Asian populations compared to populations of European descent. Differences in global and local genetic ancestry may shed light on the underlying mechanisms contributing to these disparities, including increased prevalence of lupus nephritis, younger age of symptom onset, and presence of autoantibodies.

METHODS: A total of 1,139 SLE European, African American, and Mestizos patients were genotyped using the Affymetrix LAT1 World array. Global ancestry proportions were estimated using ADMIXTURE and local ancestry was estimated using RFMIXv2.0. We investigated associations between lupus nephritis, age of onset, and autoantibody status with both global and local ancestry proportions within the MHC region.

RESULTS: Our results showed small effect sizes that did not meet the threshold for statistical significance for global or local ancestry proportions in either African American or Mestizo SLE patients who presented with the clinical manifestations of interest compared to those who did not.

CONCLUSION: These findings suggest that local genetic ancestry within the MHC region is not a major contributor to these SLE manifestations among patients with SLE from admixed populations. This article is protected by copyright. All rights reserved.

PMID:38073021 | DOI:10.1002/art.42766

Arthritis Rheumatol. 2023 Dec 10. doi: 10.1002/art.42776. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the immunologic profile associated with flares of systemic lupus erythematosus (SLE) and to investigate the clinical significance of any differences observed between patients during and following flare.

METHODS: Multi-parameter flow cytometry was used to examine 47 immune populations within the peripheral blood of 16 healthy controls, 25 clinically quiescent SLE patients and 46 SLE patients experiencing a flare, at baseline and at 6- and 12-month follow-up visits. Unsupervised clustering was used to identify subjects with similar immune profiles and to track changes over time. Parametric or non-parametric statistics were used, where appropriate, to assess the association of cellular phenotypes with clinical and laboratory parameters.

RESULTS: Five clusters of subjects were identified that variably contained active and quiescent SLE patients and that had distinct clinical phenotypes. Patients characterized by increased T peripheral helper, activated B, and age-associated B cells were the most likely to be flaring at baseline, as well as the most likely to remain active or flare over the subsequent year if they acquired or retained this phenotype at follow-up. In contrast, patients who had increased T helper cells in the absence of B cell changes, or who had increased T_h 1 cells and innate immune populations, mostly became quiescent on follow-up. A significant proportion of SLE patients had depletion of many immune populations at flare and only showed increases in these populations post-flare.

CONCLUSION: Cellular phenotyping of SLE patients reveals several distinct immunologic profiles that may help to stratify patients with regard to prognosis and treatment.

PMID:38073017 | DOI:10.1002/art.42776

J Obstet Gynaecol Res. 2023 Dec 10. doi: 10.1111/jog.15855. Online ahead of print.

ABSTRACT

AIM: The aim of this study was to investigate how the integration status of HPV in the vaginal epithelium affects the development of vaginal intraepithelial neoplasia (VaIN).

METHODS: Twenty-four vaginal tissues were collected before applying high-throughput viral integration detection (HIVID), medical records of them were documented, including age, thin-prep cytologic test (TCT) and HPV test results, colposcopic biopsy pathology, and other clinical data, such as history of total hysterectomy for cervical lesions, whether they were infected with HPV16/18 with a follow-up span of 2 years. We summarized the distribution of HPV integration on the host chromosome and HPV type, as well as the hotspot integration gene and its role in the development of VaIN.

RESULTS: In this study, 24 cases suffered from VaIN were involved. HPV integration was detected in 11 cases; furthermore, we discovered HPV 16 and 73, chromosome 1 and 2 possessed most HPV integration sites while EMBP1, CLO5A1, EHF, ELF5 as dominate hot spots. Taken clinical outcome into account, we found a significant difference between HPV integration occurrence and VaIN (p = 0.011).

CONCLUSION: (1) This study found a statistical difference between HPV integration and the occurrence of VaIN; (2) HPV integration may provide a new clinical predictor for VaIN and facilitate risk assessment and stratified management of high-risk patients.

PMID:38072997 | DOI:10.1111/jog.15855

J Orthop Surg Res. 2023 Dec 11;18(1):949. doi: 10.1186/s13018-023-04324-0.

ABSTRACT

OBJECTIVE: To evaluate three Tai Chi (TC) exercise programs as intervention measures to compare their effects on improving rate of change in bone mineral density (BMD) in elderly individuals with osteoporosis (OP) and to propose the optimal exercise duration.

METHODS: A randomized controlled trial (RCT) was conducted to identify study participants based on inclusion and exclusion criteria. Due to subject attrition, the number of participants analyzed decreased from 60 to 49. These participants were divided into four groups: 24-style TC Chuan group (24TCCG) (n = 13, 7 males/6 females), TC Kung Fu Fan group (TCKFFG) (n = 12, 5 males/7 females), TC Softball group (TCSBG) (n = 11, 6 males/5 females), and a control group (CG) (n = 13, 6 males/7 females). Except for the control group, each group received different TC exercise programs four times a week for 60 min per session, lasting for 16 weeks. BMD was measured using dual-energy X-ray absorptiometry (DXA) at the L2-L4 lumbar vertebrae, Ward’s triangle, femoral neck, and greater trochanter. The rate of change of BMD was calculated using the formula.

RESULTS: Compared with CG, all three TC groups showed significant improvements in BMD changes (P < 0.05), but their effects on the improvement of femoral neck and greater tuberosity BMD change rates were similar (P > 0.05). In addition, compared to the other exercise regimens, 24TCCG demonstrated more significant improvements in BMD at the L2-L4 lumbar vertebrae region and exhibited a more pronounced improvement in Ward’s triangle BMD after only 8 weeks (P < 0.05). Short-term (≤ 4 weeks) TCKFFG was more effective than TCSBG in enhancing femoral neck BMD (P < 0.05). However, statistical significance was not found (P > 0.05) in all other cases.

CONCLUSION: These three TC exercise programs have similar positive effects on the BMD of the femoral neck and greater trochanter. However, compared with other exercise schemes, 24TCC showed a more significant improvement in BMD of the L2-L4 lumbar vertebrae region after just 8 weeks, as well as a more pronounced improvement in BMD of Ward’s triangle. In terms of improving femoral neck BMD, TCKFF was found to be more effective than TCSB in less than 4 weeks. This study provides evidence for the effectiveness of TC exercise in improving BMD and preventing OP in the middle-aged and elderly high-risk population.

PMID:38072989 | DOI:10.1186/s13018-023-04324-0

Sci Rep. 2023 Dec 11;13(1):21881. doi: 10.1038/s41598-023-49062-9.

ABSTRACT

Postoperative desaturation is a common post-surgery pulmonary complication. The real-time prediction of postoperative desaturation can become a preventive measure, and real-time changes in spirometry data can provide valuable information on respiratory mechanics. However, there is a lack of related research, specifically on using spirometry signals as inputs to machine learning (ML) models. We developed an ML model and postoperative desaturation prediction index (DPI) by analyzing intraoperative spirometry signals in patients undergoing laparoscopic surgery. We analyzed spirometry data from patients who underwent laparoscopic, robot-assisted gynecologic, or urologic surgery, identifying postoperative desaturation as a peripheral arterial oxygen saturation level below 95%, despite facial oxygen mask usage. We fitted the ML model on two separate datasets collected during different periods. (Datasets A and B). Dataset A (Normal 133, Desaturation 74) was used for the entire experimental process, including ML model fitting, statistical analysis, and DPI determination. Dataset B (Normal 20, Desaturation 4) was only used for verify the ML model and DPI. Four feature categories-signal property, inter-/intra-position correlation, peak value/interval variability, and demographics-were incorporated into the ML models via filter and wrapper feature selection methods. In experiments, the ML model achieved an adequate predictive capacity for postoperative desaturation, and the performance of the DPI was unbiased.

PMID:38072984 | DOI:10.1038/s41598-023-49062-9