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The Journal of Dermatological Treatment Dec 2024Understanding the economic value of deucravacitinib and apremilast could assist treatment decision-making for patients with moderate to severe plaque psoriasis. (Comparative Study)
Comparative Study
BACKGROUND
Understanding the economic value of deucravacitinib and apremilast could assist treatment decision-making for patients with moderate to severe plaque psoriasis.
OBJECTIVE
This study compared the cost per response (CPR) for US patients initiating deucravacitinib versus apremilast for moderate to severe plaque psoriasis.
METHODS
A CPR model using pharmacy and administration costs was developed from a US payer perspective. Response was defined as a 75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at weeks 16 and 24. Long-term response was defined as the cumulative benefit over 52 weeks, measured as area under the curve; subsequent treatment was included. Scenario analyses explored varying the efficacy measure or choices of subsequent treatments and limiting discontinuation.
RESULTS
The CPR for deucravacitinib versus apremilast was lower at 16 weeks (difference: -$3796 [95% confidence interval (CI): -$6140 to -$1659]) and 24 weeks (difference: -$12,784 [95% CI: -$16,674 to -$9369]). At 52 weeks, the cost per cumulative benefit was lower for patients who initiated deucravacitinib, regardless of initial treatment period duration (16 or 24 weeks).
CONCLUSIONS
Scenario analyses found mainly consistent results. This study showed that the CPR is lower when initiating deucravacitinib versus apremilast in moderate to severe plaque psoriasis.
Topics: Humans; Psoriasis; United States; Thalidomide; Severity of Illness Index; Cost-Benefit Analysis; Biological Products; Treatment Outcome; Drug Costs; Male; Female
PubMed: 38914425
DOI: 10.1080/09546634.2024.2366503 -
JMIR Public Health and Surveillance Jun 2024The COVID-19 pandemic has profoundly affected out-of-hospital cardiac arrest (OHCA) and disrupted the chain of survival. Even after the end of the pandemic, the risk of... (Observational Study)
Observational Study
BACKGROUND
The COVID-19 pandemic has profoundly affected out-of-hospital cardiac arrest (OHCA) and disrupted the chain of survival. Even after the end of the pandemic, the risk of new variants and surges persists. Analyzing the characteristics of OHCA during the pandemic is important to prepare for the next pandemic and to avoid repeated negative outcomes. However, previous studies have yielded somewhat varied results, depending on the health care system or the specific characteristics of social structures.
OBJECTIVE
We aimed to investigate and compare the incidence, outcomes, and characteristics of OHCA during the prepandemic and pandemic periods using data from a nationwide multicenter OHCA registry.
METHODS
We conducted a multicenter, retrospective, observational study using data from the Korean Cardiac Arrest Resuscitation Consortium (KoCARC) registry. This study included adult patients with OHCA in South Korea across 3 distinct 1-year periods: the prepandemic period (from January to December 2019), early phase pandemic period (from July 2020 to June 2021), and late phase pandemic period (from July 2021 to June 2022). We extracted and contrasted the characteristics of patients with OHCA, prehospital time factors, and outcomes for the patients across these 3 periods. The primary outcomes were survival to hospital admission and survival to hospital discharge. The secondary outcome was good neurological outcome.
RESULTS
From the 3 designated periods, a total of 9031 adult patients with OHCA were eligible for analysis (prepandemic: n=2728; early pandemic: n=2954; and late pandemic: n=3349). Witnessed arrest (P<.001) and arrest at home or residence (P=.001) were significantly more frequent during the pandemic period than during the prepandemic period, and automated external defibrillator use by bystanders was lower in the early phase of the pandemic than during other periods. As the pandemic advanced, the rates of the first monitored shockable rhythm (P=.10) and prehospital endotracheal intubation (P<.001) decreased significantly. Time from cardiac arrest cognition to emergency department arrival increased sequentially (prepandemic: 33 min; early pandemic: 35 min; and late pandemic: 36 min; P<.001). Both survival and neurological outcomes worsened as the pandemic progressed, with survival to discharge showing the largest statistical difference (prepandemic: 385/2728, 14.1%; early pandemic: 355/2954, 12%; and late pandemic: 392/3349, 11.7%; P=.01). Additionally, none of the outcomes differed significantly between the early and late phase pandemic periods (all P>.05).
CONCLUSIONS
During the pandemic, especially amid community COVID-19 surges, the incidence of OHCA increased while survival rates and good neurological outcome at discharge decreased. Prehospital OHCA factors, which are directly related to OHCA prognosis, were adversely affected by the pandemic. Ongoing discussions are needed to maintain the chain of survival in the event of a new pandemic.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03222999; https://classic.clinicaltrials.gov/ct2/show/NCT03222999.
Topics: Humans; Out-of-Hospital Cardiac Arrest; Republic of Korea; COVID-19; Registries; Female; Male; Aged; Middle Aged; Incidence; Retrospective Studies; Aged, 80 and over; Pandemics; Cardiopulmonary Resuscitation
PubMed: 38913998
DOI: 10.2196/52402 -
Aging Jun 2024The underlying mechanisms of gastric cancer (GC) remain unknown. Therefore, in this study, we employed a comprehensive approach, combining computational and experimental...
INTRODUCTION
The underlying mechanisms of gastric cancer (GC) remain unknown. Therefore, in this study, we employed a comprehensive approach, combining computational and experimental methods, to identify potential key genes and unveil the underlying pathogenesis and prognosis of GC.
METHODS
Gene expression profiles from GEO databases (GSE118916, GSE79973, and GSE29272) were analyzed to identify DEGs between GC and normal tissues. A PPI network was constructed using STRING and Cytoscape, followed by hub gene identification with CytoHubba. Investigations included expression and promoter methylation analysis, survival modeling, mutational and miRNA analysis, gene enrichment, drug prediction, and assays for cellular behaviors.
RESULTS
A total of 83 DEGs were identified in the three datasets, comprising 41 up-regulated genes and 42 down-regulated genes. Utilizing the degree and MCC methods, we identified four hub genes that were hypomethylated and up-regulated: COL1A1, COL1A2, COL3A1, and FN1. Subsequent validation of their expression and promoter methylation on clinical GC samples through targeted bisulfite sequencing and RT-qPCR analysis further confirmed the hypomethylation and overexpression of these genes in local GC patients. Furthermore, it was observed that these hub genes regulate tumor proliferation and metastasis in and exhibited mutations in GC patients.
CONCLUSION
We found four potential diagnostic and prognostic biomarkers, including COL1A1, COL1A2, COL3A1, and FN1 that may be involved in the occurrence and progression of GC.
PubMed: 38913913
DOI: 10.18632/aging.205965 -
Epigenetics Dec 2024Lung cancer is one familiar cancer that threatens the lives of humans. circCTNNB1 has been disclosed to have regulatory functions in some diseases. However, the...
Lung cancer is one familiar cancer that threatens the lives of humans. circCTNNB1 has been disclosed to have regulatory functions in some diseases. However, the functions and related regulatory mechanisms of circCTNNB1 in lung cancer remain largely indistinct. The mRNA and protein expression levels were examined through real-time polymerase chain reaction (RT-qPCR) and western blot. The cell proliferation was tested through CCK-8 assay. The cell migration and invasion were confirmed through Transwell assays. The cell senescence was evaluated through SA-β-gal assay. The binding ability between miR-186-5p and circCTNNB1 (or YY1) was verified through luciferase reporter and RIP assays. In this study, the higher expression of circCTNNB1 was discovered in lung cancer tissues and cell lines and resulted in poor prognosis. In addition, circCTNNB1 facilitated lung cancer cell proliferation, migration, invasion, and suppressed cell senescence. Knockdown of circCTNNB1 retarded the Wnt pathway. Mechanism-related experiments revealed that circCTNNB1 combined with miR-186-5p to target YY1. Through rescue assays, YY1 overexpression could rescue decreased cell proliferation, migration, invasion, increased cell senescence, and retarded Wnt pathway mediated by circCTNNB1 suppression. Furthermore, YY1 acts as a transcription factor that can transcriptionally activate circCTNNB1 to form YY1/circCTNNB1/miR-186-5p/YY1 positive loop. Through in vivo assays, circCTNNB1 accelerated tumour growth in vivo. All findings revealed that a positive loop YY1/circCTNNB1/miR-186-5p/YY1 aggravated lung cancer progression by modulating the Wnt pathway.
Topics: YY1 Transcription Factor; Humans; MicroRNAs; Lung Neoplasms; Wnt Signaling Pathway; Cell Proliferation; Animals; Cell Line, Tumor; RNA, Circular; Cell Movement; Mice; Gene Expression Regulation, Neoplastic; Mice, Nude; Male; Disease Progression; Female; A549 Cells
PubMed: 38913848
DOI: 10.1080/15592294.2024.2369006 -
PloS One 2024Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy and a major cause of blindness. RP is caused by several variants of multiple genes, and genetic...
Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy and a major cause of blindness. RP is caused by several variants of multiple genes, and genetic diagnosis by identifying these variants is important for optimizing treatment and estimating patient prognosis. Next-generation sequencing (NGS), which is currently widely used for diagnosis, is considered useful but is known to have limitations in detecting copy number variations (CNVs). In this study, we re-evaluated CNVs in EYS, the main causative gene of RP, identified via NGS using multiplex ligation-dependent probe amplification (MLPA). CNVs were identified in NGS samples of eight patients. To identify potential CNVs, MLPA was also performed on samples from 42 patients who were undiagnosed by NGS but carried one of the five major pathogenic variants reported in Japanese EYS-RP cases. All suspected CNVs based on NGS data in the eight patients were confirmed via MLPA. CNVs were found in 2 of the 42 NGS-undiagnosed RP cases. Furthermore, results showed that 121 of the 661 patients with RP had EYS as the causative gene, and 8.3% (10/121 patients with EYS-RP) had CNVs. Although NGS using the CNV calling criteria utilized in this study failed to identify CNVs in two cases, no false-positive results were detected. Collectively, these findings suggest that NGS is useful for CNV detection during clinical diagnosis of RP.
Topics: Humans; Retinitis Pigmentosa; DNA Copy Number Variations; High-Throughput Nucleotide Sequencing; Female; Male; Eye Proteins; Middle Aged; Adult; Multiplex Polymerase Chain Reaction
PubMed: 38913662
DOI: 10.1371/journal.pone.0305812 -
PloS One 2024This study aimed to evaluate the effects of sarcopenia and inflammation on the prognosis of patients with pancreatic cancer after pancreaticoduodenectomy.
BACKGROUND
This study aimed to evaluate the effects of sarcopenia and inflammation on the prognosis of patients with pancreatic cancer after pancreaticoduodenectomy.
METHODS
Eighty patients who had undergone pancreaticoduodenectomy for pancreatic cancer between July 2010 and December 2023 were included in this study. The psoas muscle index was used to assess sarcopenia. The C-reactive protein-to-albumin ratio, prognostic nutritional index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were used to calculate the preoperative inflammatory marker levels. The prognostic factors for overall survival were determined using Cox regression analysis.
RESULTS
Twenty-four patients were diagnosed with sarcopenia. Sarcopenia showed a significant association with advanced tumor stage. Univariate analysis revealed a significant reduction in overall survival in patients with a prognostic nutritional index of <45, C-reactive protein-to-albumin ratio of ≥0.047, cancer antigen 19-9 levels of ≥130 U/mL, sarcopenia, lymph node metastasis, and vascular invasion. Multivariate analysis revealed that a C-reactive protein-to-albumin ratio of ≥0.047 (hazards ratio, 3.383; 95% confidence interval: 1.384-8.689; p< 0.001), cancer antigen 19-9 levels of ≥130 U/mL (hazards ratio, 2.720; 95% confidence interval: 1.291-6.060; p = 0.008), sarcopenia (hazards ratio, 3.256; 95% confidence interval: 1.535-7.072; p = 0.002) and vascular invasion (hazards ratio, 2.092; 95% confidence interval: 1.057-4.170; p = 0.034) were independent predictors of overall survival. Overall survival in the sarcopenia and high C-reactive protein-to-albumin ratio groups was significantly poorer than that in the non-sarcopenia and low C-reactive protein-to-albumin ratio and sarcopenia or high C-reactive protein-to-albumin ratio groups.
CONCLUSION
Sarcopenia and a high C-reactive protein-to-albumin ratio are independent prognostic factors in patients with pancreatic cancer after pancreaticoduodenectomy. Thus, sarcopenia may have a better prognostic value when combined with the C-reactive protein-to-albumin ratio.
Topics: Humans; Sarcopenia; Pancreatic Neoplasms; Pancreaticoduodenectomy; Male; Female; Middle Aged; Aged; Prognosis; C-Reactive Protein; Inflammation; Retrospective Studies; Biomarkers, Tumor
PubMed: 38913646
DOI: 10.1371/journal.pone.0305844 -
Endocrine Connections Jun 2024Papillary thyroid carcinoma has become increasingly prevalent over the years. Avoiding unnecessary treatments and the risk of complications is fundamental, as well as...
BACKGROUND
Papillary thyroid carcinoma has become increasingly prevalent over the years. Avoiding unnecessary treatments and the risk of complications is fundamental, as well as understanding the mechanisms of tumor progression and conditions that indicate a worse prognosis. The evaluation of the tumor microenvironment can allow the understanding of how the immune system organizes itself to contain the neoplastic advance.
METHODS
We compared characteristics related to the lymphocytic subpopulations in the thyroid tumor microenvironment and in the lymph nodes in two groups, with and without lymph node involvement.
RESULTS
From four hundred cases followed up at a reference service in thyroid cancer, we selected thirty-two, of which thirteen cases did not present lymph node metastasis (N0 group) and nineteen had lymph node involvement (N1 group). Clinical data were collected, and immunohistochemical reactions were performed for CD4, CD8, FoxP3, CD25 and CD20 markers in lymph nodes and peritumoral infiltrate. We found that the N1 group had a larger tumor size, higher risk staging, higher frequency of extrathyroidal extension, shorter disease-free time and higher expression of CD4+ T lymphocytes in the lymph nodes; however, there was no difference in the expression of other markers or in the pattern of lymphocytic distribution in the lymph node.
CONCLUSION
In cervical lymph nodes, the higher frequency of T CD4+ lymphocytes, would be related to the presence of metastasis, while there were no differences in lymphocytic subpopulations in thyroid tumor microenvironment. The absence of changes in unaffected lymph nodes could not predict any tumor behavior.
PubMed: 38913547
DOI: 10.1530/EC-24-0135 -
BJS Open May 2024The potential benefits of robotic-assisted compared with laparoscopic surgery for locally advanced cancer have not been sufficiently proven by prospective studies. One...
BACKGROUND
The potential benefits of robotic-assisted compared with laparoscopic surgery for locally advanced cancer have not been sufficiently proven by prospective studies. One factor is speculated to be the lack of strict surgeon criteria. The aim of this study was to assess outcomes for robotic surgery in patients with locally advanced rectal cancer with strict surgeon experience criteria.
METHODS
A criterion was set requiring surgeons to have performed more than 40 robotically assisted operations for rectal cancer. Between March 2020 and May 2022, patients with rectal cancer (distance from the anal verge of 12 cm or less, cT2-T4a, cN0-N3, cM0, or cT1-T4a, cN1-N3, cM0) were registered. The primary endpoint was the rate positive circumferential resection margin (CRM) from the pathological specimen. Secondary endpoints were surgical outcomes, pathological results, postoperative complications, and longterm outcomes.
RESULTS
Of the 321 registered patients, 303 were analysed, excluding 18 that were ineligible. At diagnosis: stage I (n = 68), stage II (n = 84) and stage III (n = 151). Neoadjuvant therapy was used in 56 patients. There were no conversions to open surgery. The median console time to rectal resection was 170 min, and the median blood loss was 5 ml. Fourteen patients had a positive CRM (4.6%). Grade III-IV postoperative complications were observed in 13 patients (4.3%).
CONCLUSION
Robotic-assisted surgery is feasible for locally advanced rectal cancer when strict surgeon criteria are used.
Topics: Humans; Rectal Neoplasms; Robotic Surgical Procedures; Male; Female; Middle Aged; Aged; Prospective Studies; Feasibility Studies; Margins of Excision; Adult; Postoperative Complications; Treatment Outcome; Aged, 80 and over; Neoplasm Staging; Laparoscopy; Neoadjuvant Therapy; Operative Time
PubMed: 38913419
DOI: 10.1093/bjsopen/zrae048 -
JAMA Network Open Jun 2024Data are limited regarding the effects of intravascular imaging guidance during complex percutaneous coronary intervention (PCI) in patients with diabetes. (Randomized Controlled Trial)
Randomized Controlled Trial
Intravascular Imaging and Angiography Guidance in Complex Percutaneous Coronary Intervention Among Patients With Diabetes: A Secondary Analysis of a Randomized Clinical Trial.
IMPORTANCE
Data are limited regarding the effects of intravascular imaging guidance during complex percutaneous coronary intervention (PCI) in patients with diabetes.
OBJECTIVE
To compare the clinical outcomes of intravascular imaging-guided vs angiography-guided complex PCI in patients with or without diabetes.
DESIGN, SETTING, AND PARTICIPANTS
This prespecified secondary analysis of a subgroup of patients in RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance Versus Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention), an investigator-initiated, open-label multicenter trial, analyzed enrolled patients who underwent complex PCI at 20 sites in Korea from May 2018 through May 2021. Eligible patients were randomly assigned in a 2:1 ratio to undergo either the intravascular imaging-guided PCI or angiography-guided PCI. Data analyses were performed from June 2023 to April 2024.
INTERVENTIONS
Percutaneous coronary intervention was performed either under the guidance of intravascular imaging or angiography alone.
MAIN OUTCOMES AND MEASURES
The primary end point was target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization.
RESULTS
Among the 1639 patients included in the analysis (mean [SD] age, 65.6 [10.2] years; 1300 males [79.3%]), 617 (37.6%) had diabetes. The incidence of TVF was significantly higher in patients with diabetes than patients without diabetes (hazard ratio [HR], 1.86; 95% CI, 1.33-2.60; P < .001). Among patients without diabetes, the intravascular imaging-guided PCI group had a significantly lower incidence of TVF compared with the angiography-guided PCI group (4.7% vs 12.2%; HR, 0.41 [95% CI, 0.25-0.67]; P < .001). Conversely, in patients with diabetes, the risk of TVF was not significantly different between the 2 groups (12.9% vs 12.3%; HR, 0.97 [95% CI, 0.60-1.57]; P = .90). There was a significant interaction between the use of intravascular imaging and diabetes for the risk of TVF (P for interaction = .02). Among patients with diabetes, only those with good glycemic control (hemoglobin A1c level ≤7.5%) and who achieved stent optimization by intravascular imaging showed a lower risk of future ischemic events (HR, 0.31; 95% CI, 0.12-0.82; P = .02).
CONCLUSIONS AND RELEVANCE
In this secondary analysis of a subgroup of patients in the RENOVATE-COMPLEX-PCI trial, intravascular imaging guidance reduced the risk of TVF compared with angiography guidance in patients without diabetes (but not in patients with diabetes) during complex PCI. In patients with diabetes undergoing complex PCI, attention should be paid to stent optimization using intravascular imaging and glycemic control to improve outcomes.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03381872.
Topics: Humans; Percutaneous Coronary Intervention; Male; Female; Aged; Middle Aged; Coronary Angiography; Diabetes Mellitus; Republic of Korea; Coronary Artery Disease; Treatment Outcome
PubMed: 38913377
DOI: 10.1001/jamanetworkopen.2024.17613 -
Journal of Applied Biomedicine Jun 2024Resveratrol (RSV) is a polyphenol antioxidant that has been shown to have neuroprotective effects. We sought molecular mechanisms that emphasize the anti-inflammatory...
Resveratrol (RSV) is a polyphenol antioxidant that has been shown to have neuroprotective effects. We sought molecular mechanisms that emphasize the anti-inflammatory activity of RSV in traumatic brain injury (TBI) in mice associated with endoplasmic reticulum stress (ERS). After establishing three experimental groups (sham, TBI, and TBI+RSV), we explored the results of RSV after TBI on ERS and caspase-12 apoptotic pathways. The expression levels of C/EBP homologous protein (CHOP), glucose regulated protein 78kD (GRP78), caspase-3, and caspase-12 in cortical brain tissues were assessed by western blotting. The qPCR analysis was also performed on mRNA expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in cortical brain tissue. In addition, the expression of GRP78 in microglia (ionized calcium binding adaptor molecule 1; Iba-1) and neurons (neuronal nuclei; NeuN) was identified by immunofluorescence staining. The neurological function of mice was assessed by modified neurological severity scores (mNSS). After drug treatment, the expression of CHOP, GRP78, caspase-3 and caspase-12 decreased, and qPCR results showed that TNF-α and IL-1β were down-regulated. Immunofluorescence staining showed down-regulation of Iba-1+/GRP78+ and NeuN+/GRP78+ cells after RSV treatment. The mNSS analysis confirmed improvement after RSV treatment. RSV improved apoptosis by downregulating the ERS signaling pathway and improved neurological prognosis in mice with TBI.
Topics: Animals; Brain Injuries, Traumatic; Resveratrol; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Mice; Male; Apoptosis; Prognosis; Neuroprotective Agents; Neurons; Interleukin-1beta; Caspase 12; Heat-Shock Proteins; Tumor Necrosis Factor-alpha; Mice, Inbred C57BL; Cell Death; Microglia; Transcription Factor CHOP
PubMed: 38912865
DOI: 10.32725/jab.2024.008