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1.
Surgery ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38782702

RESUMO

BACKGROUND: This study evaluated the cost-effectiveness of open, laparoscopic, and robotic liver resection. METHODS: A comprehensive literature review and Bayesian network meta-analysis were conducted. Surface under cumulative ranking area values, mean difference, odds ratio, and 95% credible intervals were calculated for all outcomes. Cluster analysis was performed to determine the most cost-effective clustering approach. Costs-morbidity, costs-mortality, and costs-efficacy were the primary outcomes assessed, with postoperative overall morbidity, mortality, and length of stay associated with total costs for open, laparoscopic, and robotic liver resection. RESULTS: Laparoscopic liver resection incurred the lowest total costs (laparoscopic liver resection versus open liver resection: mean difference -2,529.84, 95% credible intervals -4,192.69 to -884.83; laparoscopic liver resection versus robotic liver resection: mean difference -3,363.37, 95% credible intervals -5,629.24 to -1,119.38). Open liver resection had the lowest procedural costs but incurred the highest hospitalization costs compared to laparoscopic liver resection and robotic liver resection. Conversely, robotic liver resection had the highest total and procedural costs but the lowest hospitalization costs. Robotic liver resection and laparoscopic liver resection had a significantly reduced length of stay than open liver resection and showed less postoperative morbidity. Laparoscopic liver resection resulted in the lowest readmission and liver-specific complication rates. Laparoscopic liver resection and robotic liver resection demonstrated advantages in costs-morbidity efficiency. While robotic liver resection offered notable benefits in mortality and length of stay, these were balanced against its highest total costs, presenting a nuanced trade-off in the costs-mortality and costs-efficacy analyses. CONCLUSION: Laparoscopic liver resection represents a more cost-effective option for hepatectomy with superior postoperative outcomes and shorter length of stay than open liver resection. Robotic liver resection, though costlier than laparoscopic liver resection, along with laparoscopic liver resection, consistently exceeds open liver resection in surgical performance.

2.
Langenbecks Arch Surg ; 409(1): 152, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38703240

RESUMO

PURPOSE: This study evaluated the accuracy of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) calculator in predicting outcomes after hepatectomy for colorectal cancer (CRC) liver metastasis in a Southeast Asian population. METHODS: Predicted and actual outcomes were compared for 166 patients undergoing hepatectomy for CRC liver metastasis identified between 2017 and 2022, using receiver operating characteristic curves with area under the curve (AUC) and Brier score. RESULTS: The ACS-NSQIP calculator accurately predicted most postoperative complications (AUC > 0.70), except for surgical site infection (AUC = 0.678, Brier score = 0.045). It also exhibited satisfactory performance for readmission (AUC = 0.818, Brier score = 0.011), reoperation (AUC = 0.945, Brier score = 0.002), and length of stay (LOS, AUC = 0.909). The predicted LOS was close to the actual LOS (5.9 vs. 5.0 days, P = 0.985). CONCLUSION: The ACS-NSQIP calculator demonstrated generally accurate predictions for 30-day postoperative outcomes after hepatectomy for CRC liver metastasis in our patient population.


Assuntos
Neoplasias Colorretais , Hepatectomia , Neoplasias Hepáticas , Complicações Pós-Operatórias , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Masculino , Feminino , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Idoso , Medição de Risco , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Tempo de Internação , Adulto , Sudeste Asiático , População do Sudeste Asiático
3.
Surg Endosc ; 38(6): 3035-3051, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38777892

RESUMO

BACKGROUND: This study compared the cost-effectiveness of open (ODP), laparoscopic (LDP), and robotic (RDP) distal pancreatectomy (DP). METHODS: Studies reporting the costs of DP were included in a literature search until August 2023. Bayesian network meta-analysis was conducted, and surface under cumulative ranking area (SUCRA) values, mean difference (MD), odds ratio (OR), and 95% credible intervals (CrIs) were calculated for outcomes of interest. Cluster analysis was performed to examine the similarity and classification of DP approaches into homogeneous clusters. A decision model-based cost-utility analysis was conducted for the cost-effectiveness analysis of DP strategies. RESULTS: Twenty-six studies with 29,164 patients were included in the analysis. Among the three groups, LDP had the lowest overall costs, while ODP had the highest overall costs (LDP vs. ODP: MD - 3521.36, 95% CrI - 6172.91 to - 1228.59). RDP had the highest procedural costs (ODP vs. RDP: MD - 4311.15, 95% CrI - 6005.40 to - 2599.16; LDP vs. RDP: MD - 3772.25, 95% CrI - 4989.50 to - 2535.16), but incurred the lowest hospitalization costs. Both LDP (MD - 3663.82, 95% CrI - 6906.52 to - 747.69) and RDP (MD - 6678.42, 95% CrI - 11,434.30 to - 2972.89) had significantly reduced hospitalization costs compared to ODP. LDP and RDP demonstrated a superior profile regarding costs-morbidity, costs-mortality, costs-efficacy, and costs-utility compared to ODP. Compared to ODP, LDP and RDP cost $3110 and $817 less per patient, resulting in 0.03 and 0.05 additional quality-adjusted life years (QALYs), respectively, with positive incremental net monetary benefit (NMB). RDP costs $2293 more than LDP with a negative incremental NMB but generates 0.02 additional QALYs with improved postoperative morbidity and spleen preservation. Probabilistic sensitivity analysis suggests that LDP and RDP are more cost-effective options compared to ODP at various willingness-to-pay thresholds. CONCLUSION: LDP and RDP are more cost-effective than ODP, with LDP exhibiting better cost savings and RDP demonstrating superior surgical outcomes and improved QALYs.


Assuntos
Análise Custo-Benefício , Laparoscopia , Metanálise em Rede , Pancreatectomia , Procedimentos Cirúrgicos Robóticos , Pancreatectomia/economia , Pancreatectomia/métodos , Humanos , Procedimentos Cirúrgicos Robóticos/economia , Procedimentos Cirúrgicos Robóticos/métodos , Laparoscopia/economia , Laparoscopia/métodos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos
4.
Int J Neurosci ; : 1-6, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38584514

RESUMO

OBJECTIVE: To analyze the risk factors associated with postoperative stroke complications in cardiac surgery. METHODS: A retrospective analysis was conducted on the clinical data of 549 patients who underwent cardiac surgery. Among these patients, 501 did not experience a stroke postoperatively (non-stroke group), while 48 developed a postoperative stroke (stroke group). Patients who experienced a stroke postoperatively were divided into two groups based on the type of surgery: those who underwent surgery with cardiopulmonary bypass (18 patients) and those without cardiopulmonary bypass (30 patients). The clinical characteristics of the two groups of patients with postoperative strokes were compared, and the risk factors influencing the occurrence of postoperative stroke complications in cardiac surgery were analyzed. RESULTS: ① Clinical findings: Cardiopulmonary bypass group had lower cortical infarction rates but higher large-area and bilateral infarction rates compared to the non-cardiopulmonary bypass group (p < 0.05). No significant gender, age, or infarction type differences were observed (p > 0.05). ② Univariate analysis: No significant differences were found in gender, smoking, alcohol, lipids, or glucose levels (p > 0.05). However, age, education, hypertension, diabetes, hypotension, and atrial fibrillation showed significant differences (p < 0.05). ③ Multivariate Logistic regression: Age, education, hypertension, diabetes, hypotension, and atrial fibrillation were independent risk factors for postoperative stroke complications (p < 0.05). CONCLUSION: Cardiopulmonary bypass increases risk of large-area and bilateral strokes; non-bypass surgery associates with cortical strokes. Age, educational level, hypertension, diabetes, postoperative hypotension, and atrial fibrillation are all factors independently associated with the occurrence of postoperative cerebral infarctions in cardiac surgery. Early interventions may reduce postoperative strokes.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38671322

RESUMO

PURPOSE: To compare the efficacy of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) (TACE-TKI-ICI) versus TKIs plus ICIs (TKI-ICI) for unresectable hepatocellular carcinoma (HCC) with first- or lower-order portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS: A retrospective study was performed in HCC patients with first- or lower-order PVTT receiving TKIs (Lenvatinib or sorafenib) plus ICIs (camrelizumab, sintilimab, or atezolizumab) with or without TACE from four institutions between January 2019 and January 2022. Propensity score-based method was performed to minimize bias by confounding factors. Tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated and compared between the two groups. RESULTS: After inverse probability of treatment weighting, two balanced pseudopopulations were created: 106 patients in the TACE-TKI-ICI group and 109 patients in the TKI-ICI group. The objective response rate was higher in the TACE-TKI-ICI group (50.9% vs. 28.4%, P < 0.001). The median PFS and OS were significantly longer in the TACE-TKI-ICI group than in the TKI-ICI group (PFS: 9.1 vs. 5.0 months, P = 0.005; OS: 19.1 vs. 12.7 months, P = 0.002). In Cox regression, TACE-TKI-ICI treatment was an independent predictor of favorable OS. Treatment-related grade 3/4 AEs were comparable between the two groups (22.6% vs. 17.9%, P = 0.437). CONCLUSION: TACE-TKI-ICI therapy contributed to better tumor control, PFS and OS than TKI-ICI therapy in unresectable HCC patients with first- or lower-order PVTT.

6.
Knee Surg Relat Res ; 36(1): 15, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566254

RESUMO

BACKGROUND: Chat Generative Pretrained Transformer (ChatGPT), a generative artificial intelligence chatbot, may have broad applications in healthcare delivery and patient education due to its ability to provide human-like responses to a wide range of patient queries. However, there is limited evidence regarding its ability to provide reliable and useful information on orthopaedic procedures. This study seeks to evaluate the accuracy and relevance of responses provided by ChatGPT to frequently asked questions (FAQs) regarding total knee replacement (TKR). METHODS: A list of 50 clinically-relevant FAQs regarding TKR was collated. Each question was individually entered as a prompt to ChatGPT (version 3.5), and the first response generated was recorded. Responses were then reviewed by two independent orthopaedic surgeons and graded on a Likert scale for their factual accuracy and relevance. These responses were then classified into accurate versus inaccurate and relevant versus irrelevant responses using preset thresholds on the Likert scale. RESULTS: Most responses were accurate, while all responses were relevant. Of the 50 FAQs, 44/50 (88%) of ChatGPT responses were classified as accurate, achieving a mean Likert grade of 4.6/5 for factual accuracy. On the other hand, 50/50 (100%) of responses were classified as relevant, achieving a mean Likert grade of 4.9/5 for relevance. CONCLUSION: ChatGPT performed well in providing accurate and relevant responses to FAQs regarding TKR, demonstrating great potential as a tool for patient education. However, it is not infallible and can occasionally provide inaccurate medical information. Patients and clinicians intending to utilize this technology should be mindful of its limitations and ensure adequate supervision and verification of information provided.

7.
Heliyon ; 10(5): e27112, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38449592

RESUMO

Thrombotic complications of atrial fibrillation continue to pose a significant challenge in clinical practice today. Left atrial appendage occlusion (LAAO) has emerged as a promising alternative to oral anticoagulation for high-risk patients with atrial fibrillation. However, despite the potential benefits, there is still the possibility of life-threatening complications such as device dislocation. In this case study, we present a patient who experienced severe hemodynamic disturbances due to the embolization of LAAO device into the left ventricular outflow tract, resulting in a torn mitral valve and secondary massive mitral regurgitation, just 3 hours after the procedure. As a result, emergent surgical intervention was required to remove the device and repair the mitral valve. We also conducted a review of previous studies on the retrieval of dislodged left atrial appendage occluders through surgical procedures. It is crucial to maintain vigilance, foster interdisciplinary collaboration, and respond promptly to ensure the safety and efficacy of LAAO procedures.

8.
Int Arch Occup Environ Health ; 97(4): 401-412, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38480609

RESUMO

OBJECTIVE: This study investigates the associations of α1-antitrypsin, inter-α-trypsin inhibitor heavy chain (ITIH4), and 8-isoprostane with lung function in shipyard workers exposed to occupational metal fume fine particulate matter (PM2.5), which is known to be associated with adverse respiratory outcomes. METHODS: A 3-year follow-up study was conducted on 180 shipyard workers with 262 measurements. Personal exposure to welding fume PM2.5 was collected for an 8-h working day. Pre-exposure, post-exposure, and delta (∆) levels of α1-antitrypsin, ITIH4, and 8-isoprostane were determined in urine using enzyme-linked immunosorbent assays. Post-exposure urinary metals were sampled at the beginning of the next working day and analyzed by inductively coupled plasma-mass spectrometry. Lung function measurements were also conducted the next working day for post-exposure. RESULTS: An IQR increase in PM2.5 was associated with decreases of 2.157% in FEV1, 2.806% in PEF, 4.328% in FEF25%, 5.047% in FEF50%, and 7.205% in FEF75%. An IQR increase in PM2.5 led to increases of 42.155 µg/g in ∆α1-antitrypsin and 16.273 µg/g in ∆ITIH4. Notably, IQR increases in various urinary metals were associated with increases in specific biomarkers, such as post-urinary α1-antitrypsin and ITIH4. Moreover, increases in ∆ α1-antitrypsin and ∆ITIH4 were associated with decreases in FEV1/FVC by 0.008% and 0.020%, respectively, and an increase in ∆8-isoprostane resulted in a 1.538% decline in FVC. CONCLUSION: Our study suggests that urinary α1-antitrypsin and ITIH4 could indicate early lung function decline in shipyard workers exposed to metal fume PM2.5, underscoring the need for better safety and health monitoring to reduce respiratory risks.


Assuntos
Exposição Ocupacional , Soldagem , Humanos , Seguimentos , Estudos Prospectivos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Metais , Material Particulado/análise , Pulmão , Biomarcadores/urina
9.
Heliyon ; 10(6): e27461, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38515732

RESUMO

Introduction: Leeches are flesh-eating and bloodsucking parasitic worms. They are being used as a traditional Chinese medicine for centuries in activating blood and dissolving statis, dreging the meridims and tick. Hirudin, an active peptide product present in leech, has blood anticoagulant property and can assist in the treatment of thrombosis and diseases related to blood circulation. The efficacy and potential mechanism of action of leeches in such diseases should be further explored. Materials and methods: First, network pharmacology was used to screen the predicted potential targets of the active constituents of leech and AS. The common targets of the active constituents of leech and AS were obtained using Venn diagram. Further, the drug-active-constituent-target network diagram, protein-protein interaction, and GO and KEGG pathway enrichment analyses were used to construct the active-constituent-AS target-pathway network diagram. Subsequently, the protein-drug molecule docking model was drawn. Finally, the results of network pharmacology were validated using a mouse model of AS. Results: In total, 34 active constituents of leech and 1172 AS-related gene targets were selected, took the drug action targets and potential disease targets to get the common targets, and took the top 10 of degree value as the main active constituents for the treatment of atherosclerosis. There were 89 common targets and 12 core targets. The main targets included MAPK, EGFR, PIK3CB, etc. Potential regulatory pathways included cancer pathways, EGFR tyrosine kinase inhibitor resistance, Rap1 signaling pathway, PPAR signaling pathway, PI3K-Akt signaling pathway, C-type lectin receptor signaling pathway, and AGE-RAGE signaling pathway in diabetic complications. Animal experiments using mouse model of AS confirmed that AS plaques were smaller after treatment with leeches. SRC level was measured using western blotting. Expression of SRC in myocardial tissue was remarkably lower in the mice treated with leech than in the mice from model group fed on high-fat chow. Conclusions: To the best of our knowledge, this is the first study to explore the mechanism of action of the active components of leech in AS prevention. The active components of leeches play a coordinated role in preventing AS through multicomponent, multitarget, and multichannel mechanism of action related to inflammatory response, oxidative stress, and lipid metabolism. This study provided a reference for subsequent cellular and animal experiments.

10.
Support Care Cancer ; 32(3): 167, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374479

RESUMO

OBJECTIVE: In China, bladder tumors rank first for morbidity and mortality among urological and reproductive system tumors. Total radical cystectomy plus urinary flow conversion is the gold standard for the treatment of muscle-layer invasive bladder cancer. With an increasing number of radical cystectomies each year, the number of patients living with urostomy is growing. After discharge, primary care of urostomy patients is given at home, and high demands are placed on home caregivers due to issues of privacy and the complexity of replacing the urostomy device. This research explored the challenges faced by the family caregivers of urostomy patients. METHODS: We used descriptive qualitative research methods to conduct interviews with twenty-five family caregivers of patients with urostomy. Survey subjects were from five general hospitals. All interviews were recorded, transcribed, and analyzed using thematic analysis. RESULTS: Three critical challenges were identified-confusion, family crisis, and struggle psychology. Within these three themes, six sub-themes were constructed by coders. They were knowledge and skill deficiency, strong insecurities and uncertainties, role conflict, economic burden, emotional overwhelmed and calm acceptance. CONCLUSION: Family caregivers play a critical role in patient care, and especially in urostomy care. Caregiving is associated with significant challenges that hinder the family caregiver's ability to effectively care for the patient, further diminishing the caregiver's quality of life. Therefore, healthcare professionals should consider the challenges faced by family caregivers and take measures to obviate them through education, preparation, and support.


Assuntos
Cuidadores , Neoplasias da Bexiga Urinária , Humanos , Cuidadores/psicologia , Qualidade de Vida , Emoções , Família/psicologia , Pesquisa Qualitativa
11.
Cancer Metab ; 12(1): 6, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365771

RESUMO

BACKGROUND: Metastasis is the leading cause of death among prostate cancer (PCa) patients. Obesity is associated with both PCa-specific and all-cause mortality. High-fat diet (HFD) is a risk factor contributing to obesity. However, the association of HFD with PCa metastasis and its underlying mechanisms are unclear. METHODS: Tumor xenografts were conducted by intrasplenic injections. The ability of migration or invasion was detected by transwell assay. The expression levels of RPS27 were detected by QRT-PCR and western blot. RESULTS: The present study verified the increase in PCa metastasis caused by HFD in mice. Bioinformatics analysis demonstrated increased RPS27 in the experimentally induced PCa in HFD mice, indicating that it is an unfavorable prognostic factor. Intrasplenic injections were used to demonstrate that RPS27 overexpression promotes, while RPS27 knockdown significantly reduces, PCa liver metastasis. Moreover, RPS27 inhibition suppresses the effects of HFD on PCa metastasis. Further mRNA sequencing analysis revealed that RPS27 promotes PCa metastasis by selectively enhancing the expression of various genes. CONCLUSION: Our findings indicate that HFD increases the risk of PCa metastasis by elevating RPS27 expression and, subsequently, the expression of genes involved in PRAD progression. Therefore, RPS27 may serve as a novel target for the diagnosis and treatment of metastatic PCa.

12.
BMC Cancer ; 24(1): 41, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38183079

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased risk of lung cancer mortality. Nevertheless, little is known about the underlying molecular mechanisms. This research aimed to investigate differentially expressed genes (DEGs) and explore their function in Lewis lung carcinoma (LLC)-bearing mice exposed to chronic intermittent hypoxia (CIH) by transcriptome sequencing. METHODS: Lung cancer tissues in LLC-bearing mice exposed to CIH or normoxia were subjected for transcriptome sequencing to examine DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were employed to explore the function of DEGs. To evaluate the prognostic value of DEGs, the Kaplan-Meier survival analysis in combination with Cox proportional hazard model were applied based on The Cancer Genome Atlas. RESULTS: A total of 388 genes with 207 up-regulated and 181 down-regulated genes were differentially expressed between the CIH and normoxia control groups. Bioinformatics analysis revealed that the DEGs were related to various signaling pathways such as chemokine signaling pathway, IL-17 signaling pathway, TGF-ß signaling pathway, transcriptional misregulation in cancer, natural killer cell mediated cytotoxicity, PPAR signaling pathway. In addition, the DEGs including APOL1, ETFB, KLK8, PPP1R3G, PRL, SPTA1, PLA2G3, PCP4L1, NINJ2, MIR186, and KLRG1 were proven to be significantly correlated with poorer overall survival in lung adenocarcinoma. CONCLUSIONS: CIH caused a significant change of gene expression profiling in LLC-bearing mice. The DEGs were found to be involved in various physiological and pathological processes and correlated with poorer prognosis in lung cancer.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Lewis , Neoplasias Pulmonares , Animais , Camundongos , Neoplasias Pulmonares/genética , Transcriptoma , Processos Neoplásicos , Hipóxia/genética
13.
J Am Nutr Assoc ; : 1-7, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38227813

RESUMO

OBJECTIVE: Benzene is widely recognized as a potential carcinogen. Furthermore, the deficiency of specific nutrients may render individuals more vulnerable to cancer. For instance, ß-cryptoxanthin, which possesses anti-inflammatory, antioxidant, and anticancer properties, has been identified as one such nutrient. Elevated benzene levels and reduced ß-cryptoxanthin levels are reportedly correlated with an augmented susceptibility to cancer. To date, whether these 2 substances are linked with one another in the above correlation is yet to be determined. METHOD: This study included 1358 participants with data on the serum concentration of ß-cryptoxanthin as well as benzene and its derivatives. The data were sourced from the 2003-2004 National Health and Nutrition Examination Survey, a cross-sectional survey of the noninstitutionalized US population. Headspace solid-phase microextraction with gas chromatography and mass spectrometry was used to measure serum benzene and its derivatives, while high-performance liquid chromatography using multiwavelength photodiode-array absorbance detection was employed to quantify serum ß-cryptoxanthin. RESULTS: In this study, male and female participants showed average ß-cryptoxanthin levels of 9.10 ± 6.35 and 9.92 ± 8.95 ug/dL, respectively (p = 0.049). Styrene exhibited the strongest correlation with the change in ß-cryptoxanthin concentration (ß = -3.30, p for trend <0.001) upon comparing highest-quartile participants with those in the lowest quartile, followed by benzene (ß = -2.95, p for trend <0.001), toluene (ß = -2.90, p for trend <0.001), and ethylbenzene (ß = -1.43, p for trend = 0.09). Subgroup analysis by sex displayed a statistically significant negative correlation of ß-cryptoxanthin with benzene, styrene, and toluene in both the unadjusted and multivariate-adjusted models. CONCLUSIONS: The sera of noninstitutionalized US individuals exhibit a negative association of ß-cryptoxanthin levels with benzene and its derivatives. Styrene demonstrates the strongest link with a substantial decline in serum ß-cryptoxanthin levels, followed by benzene, toluene, and ethylbenzene.

14.
medRxiv ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38260438

RESUMO

Phospholipase C isozymes (PLCs) hydrolyze phosphatidylinositol 4,5-bisphosphate into inositol 1,4,5-trisphosphate and diacylglycerol, important signaling molecules involved in many cellular processes. PLCG1 encodes the PLCγ1 isozyme that is broadly expressed. Hyperactive somatic mutations of PLCG1 are observed in multiple cancers, but only one germline variant has been reported. Here we describe three unrelated individuals with de novo heterozygous missense variants in PLCG1 (p.Asp1019Gly, p.His380Arg, and p.Asp1165Gly) who exhibit variable phenotypes including hearing loss, ocular pathology and cardiac septal defects. To model these variants in vivo, we generated the analogous variants in the Drosophila ortholog, small wing (sl). We created a null allele slT2A and assessed the expression pattern. sl is broadly expressed, including in wing discs, eye discs, and a subset of neurons and glia. Loss of sl causes wing size reductions, ectopic wing veins and supernumerary photoreceptors. We document that mutant flies exhibit a reduced lifespan and age-dependent locomotor defects. Expressing wild-type sl in slT2A mutant rescues the loss-of-function phenotypes whereas expressing the variants causes lethality. Ubiquitous overexpression of the variants also reduces viability, suggesting that the variants are toxic. Ectopic expression of an established hyperactive PLCG1 variant (p.Asp1165His) in the wing pouch causes severe wing phenotypes, resembling those observed with overexpression of the p.Asp1019Gly or p.Asp1165Gly variants, further arguing that these two are gain-of-function variants. However, the wing phenotypes associated with p.His380Arg overexpression are mild. Our data suggest that the PLCG1 de novo heterozygous missense variants are pathogenic and contribute to the features observed in the probands.

15.
Surgery ; 175(2): 393-403, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38052675

RESUMO

BACKGROUND: This study aims to compare the outcomes of high-volume, medium-volume, and low-volume hospitals performing hepatic resections using a network meta-analysis. METHODS: A literature search until June 2023 was conducted across major databases to identify studies comparing outcomes in high-volume, medium-volume, and low-volume hospitals for liver resection. Bayesian network meta-analysis was conducted, and surface under cumulative ranking area values, odds ratio, and mean difference with 95% credible intervals were reported for postoperative mortality, failure-to-rescue, morbidity, length of stay, and hospital costs. RESULTS: Twenty studies comprising 248,707 patients undergoing liver resection were included. For the primary mortality outcome, overall and subgroup analyses were performed: group I: high-volume = 5 to 20 resections/year; group II: high-volume = 21 to 49 resections/year; group III: high-volume ≥50 resections/year. Results demonstrated a significant association between hospital volume and mortality (overall-high-volume versus medium-volume: odds ratio 0.66, 95% credible interval 0.49-0.87; high-volume versus low-volume: odds ratio 0.52, 95% credible interval 0.41-0.65; group I-high-volume versus low-volume: odds ratio 0.34, 95% credible interval 0.22-0.50; medium-volume versus low-volume: odds ratio 0.56, 95% credible interval 0.33-0.92; group II-high-volume versus low-volume: odds ratio 0.67, 95% credible interval 0.45-0.91), as well as length of stay (high-volume versus low-volume: mean difference -1.24, 95% credible interval -2.07 to -0.41), favoring high-volume hospitals. No significant difference was observed in failure-to-rescue, morbidity, or hospital costs across the 3 groups. CONCLUSION: This study supports a positive relationship between hospital volume and surgical outcomes in liver resection. Patients from high-volume hospitals experience superior outcomes in terms of lower postoperative mortality and shorter lengths of stay than medium-volume and low-volume hospitals.


Assuntos
Hepatectomia , Hospitais com Alto Volume de Atendimentos , Humanos , Teorema de Bayes , Hepatectomia/métodos , Mortalidade Hospitalar , Hospitais , Fígado , Metanálise em Rede
17.
Zhongguo Yi Liao Qi Xie Za Zhi ; 47(6): 617-623, 2023 Nov 30.
Artigo em Chinês | MEDLINE | ID: mdl-38086717

RESUMO

In view of the high incidence of malignant diseases such as malignant arrhythmias in the elderly population, accidental injuries such as falls, and the problem of no witnesses when danger occurs, the study developed a human vital signs and body posture monitoring and positioning alarm system. Through the collection and analysis of electrocardiogram (ECG), respiration (RESP) and acceleration (ACC) signals, the system monitors human vital signs and body posture in real time, automatically judges critical states such as malignant arrhythmias and accidental falls on the local device side, and then issues alarm information, opens the positioning function, and uploads physiological information and patient location information through 4G communication. Experiments have shown that the system can accurately determine the occurrence of ventricular fibrillation and falls, and issue position and alarm information.


Assuntos
Arritmias Cardíacas , Fibrilação Ventricular , Humanos , Idoso , Arritmias Cardíacas/diagnóstico , Eletrocardiografia , Acidentes por Quedas , Sinais Vitais , Postura , Monitorização Fisiológica
18.
Artigo em Inglês | MEDLINE | ID: mdl-38083562

RESUMO

Effective post-operative pain management requires an accurate and frequent assessment of the pain experienced by the patients. The current gold-standard of pain assessment is through patient self-evaluation (e.g., numeric rating scale, NRS) which is subjective, prone to recall-bias, and does not provide comprehensive information of the pain intensity and its trends. We conducted a study to explore the potential of wearable biosensors and machine learning-based analysis of physiological parameters to estimate the pain intensity. The results from our study of post-operative knee surgery patients monitored over a period of 30 days demonstrate the feasibility of the system in ambulatory setting, with a substantial agreement (Cohen's Kappa = 0.70, 95% CI 0.68-0.72) between the pain intensity estimation and the patient reported numerical rating scale. Therefore, the wearable biosensors coupled with the machine learning-derived pain estimation are capable of remotely assessing the pain intensity.


Assuntos
Aplicativos Móveis , Dispositivos Eletrônicos Vestíveis , Humanos , Medição da Dor/métodos , Dor/diagnóstico , Dor/etiologia , Pacientes
19.
Cancer Treat Res ; 190: 143-179, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38113001

RESUMO

RNA epigenetics, or epitranscriptome, is a growing group of RNA modifications historically classified into two categories: RNA editing and RNA modification. RNA editing is usually understood as post-transcriptional RNA processing (except capping, splicing and polyadenylation) that changes the RNA nucleotide sequence encoded by the genome. This processing can be achieved through the insertion or deletion of nucleotides or deamination of nucleobases, generating either standard nucleotides such as uridine (U) or the rare nucleotide inosine (I). Adenosine-to-inosine (A-to-I) RNA editing is the most prevalent type of RNA modification in mammals and is catalyzed by adenosine deaminase acting on the RNA (ADAR) family of enzymes that recognize double-stranded RNAs (dsRNAs). Inosine mimics guanosine (G) in base pairing with cytidine (C), thereby A-to-I RNA editing alters dsRNA secondary structure. Inosine is also recognized as guanosine by the splicing and translation machineries, resulting in mRNA alternative splicing and protein recoding. Therefore, A-to-I RNA editing is an important mechanism that causes and regulates "RNA mutations" in both normal physiology and diseases including cancer. In this chapter, we reviewed current paradigms and developments in the field of A-to-I RNA editing in the context of cancer.


Assuntos
Neoplasias , RNA , Animais , Humanos , RNA/genética , RNA/metabolismo , Edição de RNA , Neoplasias/genética , Nucleotídeos/metabolismo , Inosina/genética , Inosina/metabolismo , Adenosina/genética , Adenosina/metabolismo , Guanosina/metabolismo , Mamíferos/genética , Mamíferos/metabolismo
20.
J Appl Genet ; 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38036772

RESUMO

Phenotypical innovations during evolution are caused by novel mutations, which are usually heterozygous at the beginning. The gene expressions on two alleles of these mutation sites are not necessarily identical, leading to flexible allele-specific regulation in cell systems. We retrieve the transcriptome data of normal and non-small cell lung cancer (NSCLC) tissues from 47 African Americans (AA) and 50 European Americans (EA). We analyze the differentially expressed genes (DEGs) in NSCLC as well as the tumor-specific mutations. Expression and mutation profiles show convergent evolution in AA and EA populations. The tumor-specific mutations are poorly overlapped, but many of them are located in the same genes, mainly oncogenes and tumor suppressor genes. The DEGs in tumors are majorly caused by the mutated alleles rather than normal alleles. The relative expressions of mutated alleles are highly correlated between AA and EA. The differential expression in NSCLC is predominantly mediated by the mutated alleles on heterozygous sites. This molecular mechanism underlying NSCLC oncogenesis is conserved across different human populations, exhibiting convergent evolution. We present this novel angle that differential expression analysis should be performed separately for different alleles. Our ideas should greatly benefit the cancer community.

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