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OBJECTIVES: To explore the relationship between age and postoperative 24-hour moderate-to-severe pain after radical resection of lung cancer and the specific effect of moderate-to-severe pain in the post-anaesthesia care unit (PACU) on this relationship. DESIGN: Retrospective cohort study. SETTING: Single medical centre. PARTICIPANTS: Patients ≥18 years having radical resection of lung cancer between 2018 and 2020. MEASUREMENTS: Postoperative 24-hour moderate-to-severe pain. RESULTS: A total of 3764 patients were included in the analysis. The incidence of postoperative 24-hour moderate-to-severe pain was 28.3%. Age had a significant effect on the prediction model of postoperative 24-hour moderate-to-severe pain. Among the whole population and those without moderate-to-severe pain in the PACU, those who were younger than 58.5 years were prone to experience moderate-to-severe pain 24 hours after surgery, and in patients with moderate-to-severe pain in the PACU, the age threshold was 62.5 years. CONCLUSION: For patients who underwent elective radical resection for lung cancer, age was related to postoperative 24-hour moderate-to-severe pain, and moderate-to-severe pain in the PACU had a specific effect on this relationship. Patients among the whole population and those patients without moderate-to-severe pain in the PACU were more likely to experience postoperative 24-hour moderate-to-severe pain when they were younger than 58.5 years old, and in patients with moderate-to-severe pain in the PACU, the age threshold was 62.5 years old.
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Neoplasias Pulmonares , Dor Pós-Operatória , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Feminino , Dor Pós-Operatória/etiologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Fatores Etários , Medição da Dor , Adulto , Período de Recuperação da AnestesiaRESUMO
AIM: Choosing the initial treatment for type 2 diabetes (T2D) is pivotal, requiring consideration of solid clinical evidence and patient characteristics. Despite metformin's historical preference, its efficacy in preventing cerebrovascular events lacked empirical validation. This study aimed to evaluate the associations between first-line monotherapy (metformin or non-metformin antidiabetic medications) and cerebrovascular complications in patients with T2D without diabetic complications. METHODS: We analysed 9090 patients with T2D without complications who were prescribed either metformin or non-metformin medications as initial therapy. Propensity score matching ensured group comparability. Cox regression analyses, stratified by initial metformin use, assessed cerebrovascular disease risk, adjusting for multiple covariates and using competing risk analysis. Metformin exposure was measured using cumulative defined daily doses. RESULTS: Metformin users had a significantly lower crude incidence of cerebrovascular diseases compared with non-users (p < .0001). Adjusted hazard ratios (aHRs) consistently showed an association between metformin use and a lower risk of overall cerebrovascular diseases (aHRs: 0.67-0.69) and severe events (aHRs: 0.67-0.69). The association with reduced risk of mild cerebrovascular diseases was significant across all models (aHRs: 0.73-0.74). Higher cumulative defined daily doses of metformin correlated with reduced cerebrovascular risk (incidence rate ratio: 0.62-0.94, p < .0001), indicating a dose-dependent effect. CONCLUSION: Metformin monotherapy is associated with a reduced risk of cerebrovascular diseases in early-stage T2D, highlighting its dose-dependent efficacy. However, the observed benefits might also be influenced by baseline differences and the increased risks associated with other medications, such as sulphonylureas. These findings emphasize the need for personalized diabetes management, particularly in mitigating cerebrovascular risk in early T2D stages.
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Transtornos Cerebrovasculares , Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Metformina , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Metformina/uso terapêutico , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Transtornos Cerebrovasculares/prevenção & controle , Transtornos Cerebrovasculares/epidemiologia , Idoso , Incidência , Fatores de Risco , Angiopatias Diabéticas/prevenção & controle , Angiopatias Diabéticas/epidemiologiaRESUMO
BACKGROUND: Postoperative pancreatic fistula (POPF) remains one of the most severe complications after pancreatic surgery. The methods for predicting pancreatic fistula are limited. We aimed to investigate the predictive value of body composition parameters measured by preoperative bioelectrical impedance analysis (BIA) on the development of POPF. METHODS: A total of 168 consecutive patients undergoing pancreatic surgery from March 2022 to December 2022 at our institution were included in the study and randomly assigned at a 3:2 ratio to the training group and the validation group. All data, including previously reported risk factors for POPF and parameters measured by BIA, were collected. Risk factors were analyzed by univariable and multivariable logistic regression analysis. A prediction model was established to predict the development of POPF based on these parameters. RESULTS: POPF occurred in 41 of 168 (24.4%) patients. In the training group of 101 enrolled patients, visceral fat area (VFA) (odds ratio [OR] = 1.077, P = 0.001) and fat mass index (FMI) (OR = 0.628, P = 0.027) were found to be independently associated with POPF according to multivariable analysis. A prediction model including VFA and FMI was established to predict the development of POPF with an area under the receiver operating characteristic curve (AUC) of 0.753. The efficacy of the prediction model was also confirmed in the internal validation group (AUC 0.785, 95% CI 0.659-0.911). CONCLUSIONS: Preoperative assessment of body fat distribution by BIA can predict the risk of POPF after pancreatic surgery.
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Postoperative cognitive dysfunction (POCD) is a major concern, particularly among older adults. This study used social isolation (ISO) and multiomics analyses in aged mice to investigate potential mechanisms underlying POCD development. Aged mice were divided into two groups: ISO and paired housing (PH). Oleamide and the cannabinoid receptor type 2 (CB2R) antagonist AM630 were administered intraperitoneally, while Foxq1 adeno-associated viral (AAV) vector was injected directly into the hippocampus. Intramedullary tibial surgeries were subsequently performed to establish the POCD models. Behavioral tests comprising the Y-maze, open field test, and novel object recognition were conducted 2 days after surgery. Hippocampal and serum inflammatory cytokines were assessed. Following surgery, ISO mice demonstrated intensified cognitive impairments and escalated inflammatory markers. Integrative transcriptomic and metabolomic analysis revealed elevated oleamide concentrations in the hippocampus and serum of PH mice, with associative investigations indicating a close relationship between the Foxq1 gene and oleamide levels. While oleamide administration and Foxq1 gene overexpression substantially ameliorated postoperative cognitive performance and systemic inflammation in mice, CB2R antagonist AM630 impeded these enhancements. The Foxq1 gene and oleamide may be crucial in alleviating POCD. While potentially acting through CB2R-mediated pathways, these factors may modulate neuroinflammation and attenuate proinflammatory cytokine levels within the hippocampus, substantially improving cognitive performance postsurgery. This study lays the groundwork for future research into therapeutic approaches targeting the Foxq1-oleamide-CB2R axis, with the ultimate goal of preventing or mitigating POCD.
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BACKGROUND: The effect of preoperative natural killer (NK) cell abnormalities on postoperative pulmonary complications (PPCs) after thoracoscopic radical resection of lung cancer is still unclear. The main purpose of this study was to investigate the relationship between the preoperative NK cell ratio and PPCs. METHODS: The patients who underwent thoracoscopic radical resection for lung cancer were divided into a normal group and an abnormal group according to whether the proportion of preoperative NK cells was within the reference range. The main outcome was the incidence of PPCs during postoperative hospitalization. The demographic and perioperative data were collected. Propensity score matching was used to exclude systematic bias. Univariate logistic regression was used to test the relationship between the preoperative NK cell ratio and the incidence of PPCs. The restrictive cubic spline curve was used to analyze the dose-effect relationship between the preoperative NK cell ratio and the incidence of PPCs. RESULTS: A total of 4161 patients were included. After establishing a matching cohort, 910 patients were included in the statistical analysis. The incidence of PPCs in the abnormal group was greater than that in the normal group (55.2% vs. 31.6%). The incidence of PPCs first decreased and then increased with increasing NK cell ratio. The proportion of patients with Grade 3 or higher PPCs in the normal group was lower than that in the abnormal group [108 (23.7%) vs. 223 (49%)]. The indwelling time of the thoracic drainage tube in the abnormal group was longer than that in the normal group [3 (3, 4) vs. 3 (3, 5)]. A preoperative abnormal NK cell ratio constituted a risk factor for PPCs in each subgroup. CONCLUSION: Lung cancer patients with an abnormal proportion of peripheral blood NK cells before surgery were more likely to develop PPCs, their disease degree was more severe, and they had a prolonged duration of chest tube indwelling. Compared with those with abnormally high NK cell ratios, those with abnormally low NK cell ratios had more pronounced PPCs.
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Células Matadoras Naturais , Neoplasias Pulmonares , Complicações Pós-Operatórias , Humanos , Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/imunologia , Complicações Pós-Operatórias/etiologia , Idoso , Incidência , Período Pré-OperatórioRESUMO
AIMS: Cancer-associated fibroblasts (CAFs) have been shown to promote the metastasis of head and neck squamous cell carcinoma (HNSCC), but the underlying mechanisms remain unclear. The purpose of this study is to identify gene in CAFs that are associated with metastasis and to preliminarily validate its impact on the metastasis of HNSCC. MATERIALS AND METHODS: Scissor analysis was utilized to process single-cell and bulk RNA sequencing datasets, identifying genes associated with the metastasis of HNSCC through differential gene expression analysis. A risk model was constructed using LASSO regression analysis. Quantitative real time-PCR and Western blot were employed to measure mRNA and protein expressions, respectively. Multiplex immunohistochemistry (mIHC) was used to assess protein expression in CAFs. siRNA was utilized to achieve gene knockdown. CCK-8 and Transwell assays were employed to evaluate the biological characteristics of HNSCC cells. KEY FINDINGS: Compare to the nonmetastatic primary CAFs (nmCAFs), tissue inhibitors of metalloproteinase-1 (TIMP1) was founded to be overexpressed in the cells and tissues of metastatic primary CAFs (mCAFs). Knocking down TIMP1 in CAFs can signifucantly inhibit the proliferation, invasion, and migration of HNSCC cells. SIGNIFICANCE: CAFs facilitate HNSCC cell metastasis by upregulating TIMP1, highlighting TIMP1 as a potential therapeutic target in HNSCC metastasis management.
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Fibroblastos Associados a Câncer , Neoplasias de Cabeça e Pescoço , Análise de Célula Única , Carcinoma de Células Escamosas de Cabeça e Pescoço , Inibidor Tecidual de Metaloproteinase-1 , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genética , Análise de Célula Única/métodos , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Metástase Neoplásica/genética , Movimento Celular/genética , Análise de Sequência de RNA/métodos , Masculino , FemininoRESUMO
PURPOSE: No study has compared 30-day and 90-day adverse postoperative outcomes between old-age patients with and those without sarcopenia. PATIENTS AND METHODS: We categorize elderly patients receiving major surgery into two groups according to the presence or absence of preoperative sarcopenia that were matched at a 1:4 ratio through propensity score matching (PSM). We analyzed 30-day or 90-day adverse postoperative outcomes and mortality in patients with and without sarcopenia receiving major surgery. RESULTS: Multivariate logistic regression analyses revealed that the patients with preoperative sarcopenia were at significantly higher risk of 30-day postoperative mortality (adjusted odds ratio [aOR]. = 1.25; 95% confidence interval [CI]. = 1.03-1.52) and 30-day major complications such as postoperative pneumonia (aOR = 1.15; 95% CI = 1.00-1.40), postoperative bleeding (aOR = 2.18; 95% CI = 1.04-4.57), septicemia (aOR = 1.31; 95% CI = 1.03-1.66), and overall complications (aOR = 1.13; 95% CI = 1.00-1.46). In addition, surgical patients with sarcopenia were at significantly higher risk of 90-day postoperative mortality (aOR = 1.50; 95% CI = 1.29-1.74) and 90-day major complications such as pneumonia (aOR = 1.27; 95% CI = 1.10-1.47), postoperative bleeding (aOR = 1.90; 95% CI = 1.04-3.48), septicemia (aOR = 1.52; 95% CI = 1.28-1.82), and overall complications (aOR = 1.24; 95% CI = 1.08-1.42). CONCLUSIONS: Sarcopenia is an independent risk factor for 30-day and 90-day adverse postoperative outcomes such as pneumonia, postoperative bleeding, and septicemia and increases 30-day and 90-day postoperative mortality among patients receiving major surgery. No study has compared 30-day and 90-day adverse postoperative outcomes between patients with and those without sarcopenia. We conducted a propensity score?matched (PSM) population-based cohort study to investigate the adverse postoperative outcomes and mortality in patients undergoing major elective surgery with preoperative sarcopenia versus those without preoperative sarcopenia. We demonstrated that sarcopenia is an independent risk factor for 30-day and 90-day adverse postoperative outcomes, such as postoperative pneumonia, bleeding, septicemia, and mortality after major surgery. Therefore, surgeons and anesthesiologists should attempt to correct preoperative sarcopenia, swallowing function, and respiratory muscle training before elective surgery to reduce postoperative complications that contribute to the decrease in surgical mortality.
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Complicações Pós-Operatórias , Sarcopenia , Humanos , Sarcopenia/epidemiologia , Sarcopenia/complicações , Masculino , Idoso , Feminino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Idoso de 80 Anos ou mais , Pontuação de Propensão , Estudos Retrospectivos , Fatores de RiscoRESUMO
AIM: This cohort study aimed to explore the connection between postoperative hyperactive delirium and major complications in elderly patients undergoing emergency hip fracture surgery. METHODS: Elderly patients aged 65 years and older undergoing emergency hip fracture surgery were included in the study. The presence of postoperative hyperactive delirium was assessed, and logistic regression analysis, following propensity score matching, was conducted to investigate the association between postoperative hyperactive delirium and major complications occurring 30 and 90 days post-surgery. The analysis controlled for potential confounding factors. RESULTS: After propensity score matching, the analysis included 13 590 patients, equally distributed with 6795 in each group. The group experiencing postoperative hyperactive delirium exhibited a significantly elevated risk of 30-day postoperative complications, including acute renal failure, pneumonia, septicemia, and stroke, with adjusted odds ratios ranging from 1.64 to 2.39. Furthermore, this group displayed notably higher rates of 90-day postoperative complications, encompassing mortality, acute renal failure, pneumonia, septicemia, and stroke, with a significantly increased incidence of mortality within 90 days. CONCLUSION: Postoperative hyperactive delirium in elderly patients undergoing emergency hip fracture surgery is significantly linked to an increased risk of major complications at both 30 and 90 days post-surgery. These findings underscore the critical importance of delirium prevention and management in this patient population, offering the potential to reduce the occurrence of postoperative complications. Geriatr Gerontol Int 2024; 24: 730-736.
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Delírio , Fraturas do Quadril , Complicações Pós-Operatórias , Humanos , Fraturas do Quadril/cirurgia , Masculino , Idoso , Feminino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Idoso de 80 Anos ou mais , Delírio/epidemiologia , Delírio/etiologia , Estudos de Coortes , Pontuação de Propensão , Fatores de Risco , Incidência , Estudos RetrospectivosRESUMO
Repeated sevoflurane exposure in neonatal mice can leads to neuronal apoptosis and mitochondrial dysfunction. The mitochondria are responsible for energy production to maintain homeostasis in the central nervous system. The mitochondria-associated endoplasmic reticulum membrane (MAM) is located between the mitochondria and endoplasmic reticulum (ER), and it is critical for mitochondrial function and cell survival. MAM malfunction contributes to neurodegeneration, however, whether it is involved in sevoflurane-induced neurotoxicity remains unknown. Our study demonstrated that repeated sevoflurane exposure induced mitochondrial dysfunction and dampened the MAM structure. The upregulated ER-mitochondria tethering enhanced Ca2+ transition from the cytosol to the mitochondria. Overload of mitochondrial Ca2+ contributed to opening of the mitochondrial permeability transition pore (mPTP), which caused neuronal apoptosis. Mitofusin 2(Mfn2), a key regulator of ER-mitochondria contacts, was found to be suppressed after repeated sevoflurane exposure, while restoration of Mfn2 expression alleviated cognitive dysfunction due to repeated sevoflurane exposure in the adult mice. These evidences suggest that sevoflurane-induced MAM malfunction is vulnerable to Mfn2 suppression, and the enhanced ER-mitochondria contacts promotes mitochondrial Ca2+ overload, contributing to mPTP opening and neuronal apoptosis. This paper sheds light on a novel mechanism of sevoflurane-induced neurotoxicity. Furthermore, targeting Mfn2-mediated regulation of the MAM structure and mitochondrial function may provide a therapeutic advantage in sevoflurane-induced neurodegeneration.
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Retículo Endoplasmático , GTP Fosfo-Hidrolases , Mitocôndrias , Sevoflurano , Animais , Sevoflurano/toxicidade , Sevoflurano/farmacologia , GTP Fosfo-Hidrolases/metabolismo , Camundongos , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Camundongos Endogâmicos C57BL , Apoptose/efeitos dos fármacos , Anestésicos Inalatórios/toxicidade , Anestésicos Inalatórios/farmacologia , Masculino , Cálcio/metabolismo , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/efeitos dos fármacosRESUMO
BACKGROUND AND HYPOTHESIS: The potential role of anesthesia as an independent risk factor for childhood bipolar disorder (BD) remains unclear. To address this, we conducted a population-based cohort study employing propensity score matching to compare BD incidence between pediatric patients undergoing surgery with and without general anesthesia. STUDY DESIGN: Our study included patients aged 0-3 years who received at least 1 episode of general anesthesia and were hospitalized for over 1 day in Taiwan between January 2004 and December 2014. They were matched 1:1 with a population not receiving general anesthesia to assess pediatric BD incidence. STUDY RESULTS: The study cohort comprised 15 070 patients, equally distributed between the general anesthesia and nongeneral anesthesia groups (7535 each). Multivariate Cox regression analysis revealed adjusted hazard ratios (aHRs; 95% CIs) for pediatric BD in the general anesthesia group as 1.26 (1.04-1.54; Pâ =â .021) compared to the nongeneral anesthesia group. Moreover, the incidence rate ratio (95% CI) for the general anesthesia group was 1.26 (1.03-1.53) compared to the nongeneral anesthesia group. CONCLUSIONS: Early childhood exposure to general anesthesia is significantly associated with an increased risk of pediatric BD. This expands understanding of pediatric BD's complex development, informing preventive strategies, and enhancing mental health outcomes for vulnerable young patients and global pediatric healthcare.
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Anestesia Geral , Transtorno Bipolar , Pontuação de Propensão , Humanos , Anestesia Geral/efeitos adversos , Anestesia Geral/estatística & dados numéricos , Lactente , Transtorno Bipolar/epidemiologia , Feminino , Masculino , Taiwan/epidemiologia , Pré-Escolar , Incidência , Recém-Nascido , Estudos de Coortes , Fatores de RiscoRESUMO
OBJECTIVE: This study investigated the association between aspirin use and diabetes-associated dementia in older patients with type 2 diabetes mellitus (T2DM), assessing aspirin's potential protective effects, intensity of use, and dose-dependency against dementia. DESIGN: A cohort study evaluating the dose-dependent protective impact of aspirin against dementia in a population-based sample. SETTING AND PARTICIPANTS: Older patients with T2DM (≥60 years), comparing aspirin users with nonusers. METHODS: Used a time-varying Cox hazards model to assess dementia incidence. RESULTS: Older aspirin users exhibited a significant reduction in dementia risk (adjusted hazard ratio [aHR], 0.44; 95% CI, 0.41-0.46). The lowest aHRs for dementia were observed at a daily intensity of 0.91 defined daily doses (DDDs), and higher daily dosages (>0.91 DDD) showed gradually increasing aHRs (although still <1). Analysis of cumulative DDD revealed a dose-response relationship, with progressively lower aHRs across quartiles (0.16, 0.42, 0.57, and 0.63 for quartiles 4, 3, 2, and 1, respectively) compared with never aspirin users (P for trend < .0001). CONCLUSIONS AND IMPLICATIONS: Aspirin use in older patients with T2DM significantly reduces dementia risk. The optimal daily intensity of aspirin use (0.91 DDD) is associated with the lowest aHR for dementia. These findings suggest a dose-dependent relationship, supporting the potential benefits of higher cumulative dosages of aspirin in reducing dementia risk in this population.
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Aspirina , Demência , Diabetes Mellitus Tipo 2 , Relação Dose-Resposta a Droga , Humanos , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Demência/prevenção & controle , Demência/epidemiologia , Masculino , Feminino , Idoso , Estudos de Coortes , Idoso de 80 Anos ou mais , Modelos de Riscos Proporcionais , Pessoa de Meia-IdadeRESUMO
This study investigated the link between the adapted diabetes complication severity index at the time of type 2 diabetes mellitus diagnosis and diabetes-induced dementia risk in elderly patients. Elderly type 2 diabetes mellitus patients (age ≥ 60) were matched using propensity score matching. Cox regression was used to determine dementia hazard ratios; Kaplan-Meier method to assess cumulative incidence. The cohort included 256 214 elderly type 2 diabetes mellitus patients. Adapted diabetes complication severity index ≥ 1 showed higher dementia risk (adjusted hazard ratio: 1.30; 95% confidence interval: 1.27-1.34), increasing by 1.17-fold per adapted diabetes complication severity index point. Dementia risk rose progressively across adapted diabetes complication severity index scores (P < 0.0001). Higher adapted diabetes complication severity index scores at the time of type 2 diabetes mellitus diagnosis elevated dementia risk in elderly patients. Adapted diabetes complication severity index ≥ 1 is linked to increased dementia risk. Adapted diabetes complication severity index evaluation at the time of type 2 diabetes mellitus diagnosis could predict risk, aiding early interventions. Effective diabetes management is crucial for reducing dementia risk in this population.
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This study investigates the association between postoperative agitated delirium and the risk of dementia in patients who were cognitively intact before undergoing major inpatient surgery. The study included inpatients aged 20 years or older who underwent major surgery requiring general, epidural, or spinal anaesthesia and hospitalization for over one day in Taiwan between 2008 and 2018. Patients were categorized into two groups based on the presence or absence of postoperative agitated delirium. Propensity score matching was conducted to balance various covariates known to influence dementia risk. The final analysis included 10 932 patients (5466 in each group). Multivariate Cox regression analysis was performed to assess the risk of dementia, and incidence rates and incidence rate ratios were calculated. After Propensity score matching, the study cohort comprised 5467 patients without postoperative agitated delirium and 5467 patients with postoperative agitated delirium. In the multivariate Cox regression analysis, the adjusted hazard ratio for dementia were 1.26 (95% confidence intervals, 1.08-1.46; P = 0.003) in the postoperative agitated delirium group compared to the no postoperative agitated delirium group. The incidence rates of dementia was significantly higher in patients with postoperative agitated delirium (97.65 versus 70.85 per 10 000 person-years), with an incidence rate ratio of 1.21 (95% CI: 1.04-1.40). Our study demonstrates a substantial rise in dementia incidence linked to postoperative agitated delirium. These findings stress the need for effective prevention and management strategies. Addressing this issue emerges as a vital clinical approach to reduce subsequent dementia risk, with broad implications for enhancing overall perioperative patient outcomes.
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Introduction: This study investigates the association between chronic postsurgical pain (CPSP) and long-term postsurgical analgesic usage in patients undergoing neuraxial anesthesia, with a specific focus on the presence or absence of sarcopenia. Objectives: To assess the rate of analgesic prescription, including opioids, at 3 and 6 months postsurgery for patients with and without preoperative sarcopenia, and to determine the impact of sarcopenia on analgesic use after neuraxial anesthesia surgery. Methods: Patients undergoing surgery under neuraxial anesthesia were categorized into sarcopenic and nonsarcopenic groups based on preoperative diagnosis using the ICD-10-CM code M62.84. Propensity score matching in a 1:4 ratio was applied for group matching. Analgesic prescription rates were evaluated at 3 and 6 months postsurgery, and multivariable logistic regression was used to analyze analgesic use, comparing patients with and without preoperative sarcopenia. Results: Among 3805 surgical patients, 761 had sarcopenia, while 3044 did not. At 3 months postsurgery, 62.3% of sarcopenic patients received analgesics, with 2.9% receiving opioids, compared to 57.1% of nonsarcopenic patients receiving analgesics and 0.8% receiving opioids. At 6 months postsurgery, 30.8% of sarcopenic patients received analgesics (1.7% opioids), while 26.3% of non-sarcopenic patients received analgesics (0.3% opioids). Multivariable logistic regression analysis revealed that preoperative sarcopenia was significantly associated with higher analgesic prescription rates at both 3 months (adjusted odds ratio [aOR], 1.27; 95% confidence interval [CI], 1.05-1.53) and 6 months (aOR, 1.17; 95% CI, 1.07-1.42) postsurgery. Furthermore, sarcopenic patients exhibited significantly higher opioid prescription rates at 3 months (aOR, 1.11; 95% CI, 1.05-2.45) and 6 months (aOR, 1.89; 95% CI, 1.12-4.96) postsurgery. Conclusion: Sarcopenia emerges as an independent risk factor for prolonged analgesic use after neuraxial anesthesia surgery and significantly elevates the risk of developing CPSP.
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BACKGROUND: Sideroflexin 1 (SFXN1), a mitochondrial serine transporter implicated in one-carbon metabolism, is a prognostic biomarker in lung adenocarcinoma (LUAD). However, its role in LUAD progression remains elusive. This study aimed to investigate the functional significance of SFXN1 in LUAD and evaluate its potential as a therapeutic target. METHODS: We analyzed SFXN1 expression and its diagnostic and prognostic value in LUAD using the Pan-cancer TCGA dataset. In vitro assays (CCK-8, cell cycle, EDU, wound-healing, and transwell) were employed to assess the role of SFXN1, complemented by in vivo experiments. RNA sequencing elucidated SFXN1-mediated cellular functions and potential mechanisms. Bulk RNA-seq and scRNA-seq data from TCGA and GEO were used to investigate the correlation between SFXN1 and the tumor immune microenvironment. RT-qPCR, Western blot, and IHC assays validated SFXN1 expression and its impact on the immune microenvironment in LUAD. RESULTS: SFXN1 was upregulated in LUAD tissues and associated with poor prognosis. RNA-seq and scRNA-seq analyses revealed increased SFXN1 expression in tumor cells, accompanied by decreased infiltration of NK and cytotoxic T cells. SFXN1 knockdown significantly reduced cell proliferation and migration, and the inhibition of ERK phosphorylation and CCL20 expression may be the molecular mechanism involved. In vivo, targeting SFXN1 decreased Tregs infiltration and inhibited tumor growth. CONCLUSIONS: Our findings suggest that SFXN1 may be a potential therapeutic target for LUAD treatment.
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Adenocarcinoma de Pulmão , Sistemas de Transporte de Aminoácidos Neutros , Neoplasias Pulmonares , Linfócitos do Interstício Tumoral , Microambiente Tumoral , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinogênese/genética , Carcinogênese/imunologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Linfócitos do Interstício Tumoral/imunologia , Prognóstico , Microambiente Tumoral/imunologia , Sistemas de Transporte de Aminoácidos Neutros/genética , Sistemas de Transporte de Aminoácidos Neutros/metabolismoRESUMO
In recent years, sevoflurane and isoflurane are the most popular anesthetics in general anesthesia for their safe, rapid onset, and well tolerant. Nevertheless, many studies reported their neurotoxicity among pediatric and aged populations. This effect is usually manifested as cognitive impairment such as perioperative neurocognitive disorders. The wide application of sevoflurane and isoflurane during general anesthesia makes their safety a major health concern. Evidence indicates that iron dyshomeostasis and ferroptosis may establish a role in neurotoxicity of sevoflurane and isoflurane. However, the mechanisms of sevoflurane- and isoflurane-induced neuronal injury were not fully understood, which poses a barrier to the treatment of its neurotoxicity. We, therefore, reviewed the current knowledge on mechanisms of iron dyshomeostasis and ferroptosis and aimed to promote a better understanding of their roles in sevoflurane- and isoflurane-induced neurotoxicity.
Assuntos
Anestésicos Inalatórios , Ferroptose , Isoflurano , Éteres Metílicos , Humanos , Criança , Idoso , Isoflurano/efeitos adversos , Sevoflurano/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Transtornos Neurocognitivos , HomeostaseRESUMO
Introduction: Postoperative nausea and vomiting (PONV) is a prevalent postsurgical complication. The objective of our study was to compare the effect of different doses of dexmedetomidine on PONV in female patients undergoing radical thoracoscopic lung cancer resection. Methods: A total of 164 female patients undergoing elective thoracoscopic radical lung cancer surgery were enrolled and assigned to one of four groups. Patients received 0.2 µg/kg/h, 0.4 µg/kg/h, 0.8 µg/kg/h dexmedetomidine and normal saline in the Dex1, Dex2, Dex3 and Control groups, respectively. The primary outcome was the incidence of PONV during 48 h postoperatively. The second outcomes included the incidence of PONV and postoperative vomiting (POV) at four time points postoperatively (T1: PACU retention period; T2: PACU discharge to postoperative 12 h; T3: postoperative 12 h-postoperative 24 h; T4: postoperative 24 h-postoperative 48 h), the area under the curve of PONV grade (PONVAUC), PONV grade, POV grade and other postoperative recovery indicators. Results: The incidence of PONV differed among the four groups. The Dex2 group (29.27%) was lower than that in the Dex1 group (61.90%) and Control group (72.50%). The incidence of PONV at T2 in the Dex1 group (11.90%) and Dex2 group (9.76%) was lower than that in the Control group (42.50%). The incidence of PONV at T3 in the Dex2 group (29.27%) was lower than that in the Dex1 group (61.90%) and Control group (62.50%). The PONVAUC was lower in the Dex2 group than in the Control group. The incidence of POV at T3 in the Dex2 and Dex3 groups was lower than that in the Control group. The consumption of remifentanil, norepinephrine, PACU dwell time, VAS scores, postoperative PCA press frequency, and the time for the first postoperative oral intake were different among the four groups. The regression model shows that the Dex2 group is a protective factor for PONV. Conclusion: Dexmedetomidine can reduce the incidence of PONV and accelerate postoperative recovery in female patients undergoing radical thoracoscopic lung cancer resection. Compared with the other two dosages, 0.4 µg/kg/h dexmedetomidine is preferable. Clinical Trial Registration: chictr.org.cn, identifier ChiCTR2300071831.
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Purpose: A retrospective cohort study was performed to determine the effect of nerve block on the incidence of postoperative mortality in patients with hip replacement. Methods: According to the inclusion and exclusion criteria, patients who were undergoing hip replacement for the first time under general or intraspinal anesthesia, classified as ASA class I-IV, and aged ≥65 years were selected. We collected the general data, past medical history, preoperative laboratory test results, perioperative fluid intake and outflow data, perioperative anesthesia and related drug data, postoperative laboratory results, and correlation time index. Patients with preoperative combined nerve block were included in the N group, and those without combined nerve block were included in the NN group. The patients were followed up via telephone call to assess survival outcomes at 3 years after surgery. Propensity score matching and uni- and multivariate analyses were performed to determine the influence of nerve block and other related factors on postoperative mortality. Results: A total of 743 patients were included in this study, including 262 in the N group and 481 in the NN group. Two hundred five patients in both groups remained after propensity score matching. Main result: Preoperative nerve block was associated with reduced mortality three years after surgery. Conclusion: Nerve block reduces the incidence of 3-year postoperative mortality, and composite nerve block with general anesthesia and neuraxial anesthesia is worthy of promotion.
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This study aimed to investigate whether sarcopenia independently increases the risk of diabetes-induced dementia in elderly individuals diagnosed with type 2 diabetes mellitus. The study cohort consisted of a large sample of elderly individuals aged 60 years and above, who were diagnosed with type 2 diabetes mellitus between 2008 and 2018. To minimize potential bias and achieve covariate balance between the sarcopenia and non-sarcopenia groups, we employed propensity score matching. Various statistical analyses, including Cox regression models to assess dementia risk and associations, competing risk analysis to account for mortality and Poisson regression analysis for incidence rates, were used. Before propensity score matching, the study included 406 573 elderly type 2 diabetes mellitus patients, with 20 674 in the sarcopenia group. Following propensity score matching, the analysis included a total of 41 294 individuals, with 20 647 in the sarcopenia group and 20 647 in the non-sarcopenia group. Prior to propensity score matching, elderly type 2 diabetes mellitus patients with sarcopenia exhibited a significantly higher risk of dementia (adjusted hazard ratio: 1.12, 95% confidence interval: 1.07-1.17). After propensity score matching, the risk remained significant (adjusted hazard ratio: 1.14, 95% confidence interval: 1.07-1.21). Incidence rates of dementia were notably higher in the sarcopenia group both before and after propensity score matching, underscoring the importance of sarcopenia as an independent risk factor. Our study highlights sarcopenia as an independent risk factor for diabetes-induced dementia in elderly type 2 diabetes mellitus patients. Advanced age, female gender, lower income levels, rural residency, higher adapted diabetes complication severity index and Charlson Comorbidity Index scores and various comorbidities were associated with increased dementia risk. Notably, the use of statins was linked to a reduced risk of dementia. This research underscores the need to identify and address modifiable risk factors for dementia in elderly type 2 diabetes mellitus patients, offering valuable insights for targeted interventions and healthcare policies.
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This study aimed to investigate the controversial association between metformin use and diabetes-associated dementia in elderly patients with type 2 diabetes mellitus (T2DM) and evaluate the potential protective effects of metformin, as well as its intensity of use and dose-dependency, against dementia in this population. The study used a time-dependent Cox hazards model to evaluate the effect of metformin use on the incidence of dementia. The case group included elderly patients with T2DM (≥60 years old) who received metformin, while the control group consisted of elderly patients with T2DM who did not receive metformin during the follow-up period. Our analysis revealed a significant reduction in the risk of dementia among elderly individuals using metformin, with an adjusted hazard ratio of 0.34 (95% confidence interval: 0.33 to 0.36). Notably, metformin users with a daily intensity of 1 defined daily dose (DDD) or higher had a lower risk of dementia, with an adjusted hazard ratio (95% confidence interval) of 0.46 (0.22 to 0.6), compared to those with a daily intensity of <1 DDD. Additionally, the analysis of cumulative DDDs of metformin showed a dose-response relationship, with progressively lower adjusted hazard ratio across quartiles (0.15, 0.21, 0.28, and 0.53 for quartiles 4, 3, 2 and 1, respectively), compared to never metformin users (P for trend < 0.0001). Metformin use in elderly patients with T2DM is significantly associated with a substantial reduction in the risk of dementia. Notably, the protective effect of metformin demonstrates a dose-dependent relationship, with higher daily and cumulative dosages of metformin showing a greater risk reduction.