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BACKGROUND: The mechanism linking BMI and asthma remains unclear. METHOD: Mendelian Randomization (MR) analysis was conducted using summary-level GWAS data from the FinnGen Biobank and the Open GWAS project. The analysis considering potential variables as mediators, including blood cell counts, blood pressure, and blood biomarkers. Three commonly used MR methods-the inverse-variance-weighted (IVW) method, weighted median (WM) method, and MR-Egger method-were employed to infer causal links. A two-step approach was used in mediation analysis to evaluate the causal links among BMI, candidate mediators, and asthma. RESULT: Elevated BMI demonstrated a substantial correlation with increased asthma risk. Thirteen biomarkers mediated the relationship between BMI and asthma, mainly including leukocyte count (5.070%), apolipoprotein A levels (7.395%), cystatin C levels (5.345%), urate levels (9.057%), diastolic blood pressure (7.365%), and albumin levels (10.888%). These factors collectively explained over 50% of the increased asthma risk associated with BMI elevation. Additionally, eosinophil count and C-reactive protein were also identified as important mediators using the WM method. CONCLUSION: This study highlights the complex relationship between obesity, blood biomarkers, and asthma risk. Additional studies are required to validate these results and investigate causal relationships in various populations.
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BACKGROUND: Asthma is a common chronic condition with increasing prevalence. Diet, including dried fruit consumption, has been linked to asthma risk, but the mechanisms remain unclear. This study investigates how dried fruit consumption affects asthma risk, focusing on acetate as a potential mediator. METHODS: We used Mendelian Randomization (MR) to analyze the relationships between dried fruit intake, acetate levels, and asthma. We applied three MR methods-Inverse-Variance Weighted (IVW), Weighted Median (WM), and MR-Egger-to determine causal effects. RESULTS: Dried fruit intake was inversely associated with asthma risk (IVW: ß = -0.506, p = 0.0135) and positively associated with acetate levels (IVW: ß = 0.269, p < 0.0001). Higher acetate levels were also linked to lower asthma risk (IVW: ß=-0.361, p < 0.0001). Mediation analysis showed that acetate mediates approximately 19.22% of the effect of dried fruit on asthma risk. CONCLUSION: Dried fruit consumption reduces asthma risk, partly through increasing acetate levels. This acetate-mediated pathway accounts for about 20% of the effect, suggesting potential for dietary strategies in asthma prevention and management. Further research could enhance the understanding and applicability of these findings.
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This study examines the causal effects of cheese consumption on blood metabolites and essential hypertension using Mendelian Randomization (MR). GWAS data from the Open GWAS project and FinnGen Biobank were analyzed, focusing on cheese intake, 249 metabolic traits, and hypertension. Instrumental variables were selected based on strict criteria, and causal relationships were assessed using IVW, weighted-median, and MR-Egger methods. Cheese consumption significantly influenced 118 metabolic traits, including amino acids, cholesterol esters, and triglycerides. Notably, it was linked to a reduction in hypertension risk (OR = 0.652, P < 0.0001). Mediation analysis identified 50 metabolic traits as intermediaries, accounting for 0.88% to 8.25% of the total effect. These findings suggest that moderate cheese intake may benefit cardiovascular health by lowering hypertension risk, emphasizing the importance of cheese type and dietary context in health recommendations.
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PURPOSE: This study aimed to investigate the mid- to long-term benefits of high tibial osteotomy in advanced age patients. METHODS: This retrospective study was conducted in our hospital from January 2017 to January 2021 with data prospectively collected, 47 patients with knee osteoarthritis who over 65 years old were included, and a 1:1 propensity score (PS) of patients < 65 years were matched according to gender, body mass index, and side. Patient demographics, intraooperative and postoperative variables, and patient self-reported outcomes were compared. A generalized linear model was used to screen possible risk factors. RESULTS: A total of 94 consecutive patients were included; the average age of advanced age group was 69.47 + 4.26 years and 57.87 + 5.51 years in the younger group. There were no statistically difference in K-L grade, smoke, drink, comorbidity, ASA, blood loss, operative duration, length of stay, surgical site infection, hinge fracture, DVT, and preooperative and postoperative aFTA; significantly statistical difference of the eFI was found between two groups (P < 0.05). Two groups had comparable VAS and MOMAC scores at one year postoperatively (P > 0.05), while the younger group had lower VAS and WOMAC scores than the advanced age group at the end of follow-up (P < 0.05). Generalized linear model showed both age and eFI were associated with WOMAC scores; there was a statistically significant difference in the effect of eFI on WOMAC scores at different ages (P > 0.05). CONCLUSIONS: Compared with younger patients, advanced age patients have similar short-term benefits, but less long-term benefits. We recommend that patients proposed for HTO be discriminated by eFI, and patients with higher scores should be cautiously selected.
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Osteoartritis de la Rodilla , Osteotomía , Medición de Resultados Informados por el Paciente , Tibia , Humanos , Masculino , Femenino , Anciano , Osteoartritis de la Rodilla/cirugía , Estudios Retrospectivos , Osteotomía/métodos , Osteotomía/efectos adversos , Persona de Mediana Edad , Tibia/cirugía , Autoinforme , Factores de Edad , Resultado del TratamientoRESUMEN
PURPOSE: The optimal choice of distal locking modes remains a subject due to limited available data, and therefore, this study aims to investigate the relationship between distal locking mode and postoperative mechanical complications in an intertrochanteric fracture (ITF) population who underwent closed reduction and intramedullary fixation with a PFNA-II. METHODS: Patients aged 65 years or older who underwent surgery with PFNA-II fixation in a university teaching hospital between January 2020 and December 2021 were potentially eligible. Based on the distal locking mode, patients were classified into static, dynamic, and limited dynamic groups, among which the differences were tested using univariate analysis. Multivariate logistic regression was used to examine whether the distal locking mode was independently associated with the risk of postoperative one year mechanical complications, adjusting for covariates and potential confounders. Subgroup analyses were performed to evaluate the robustness of the findings. RESULT: Among 507 eligible patients, 33 (6.5%) developed postoperative mechanical complications. In the univariate analysis, sex (P = 0.007), fracture type (P = 0.020), LAT Parker ratio (P = 0.023), and lateral femoral (P = 0.003) wall showed that the differences were significant. Compared to the static group, the limited dynamic group and the dynamic group showed higher odds of postoperative mechanical complications (OR = 3.314, 95% CI: 1.215-9.041; and OR = 3.652, 95% CI: 1.451-9.191, respectively). These associations were robust across a series of analyses, including adjusting for confounders and subgroup analyses. CONCLUSION: Using a distal non-static locking mode significantly increases the risk of postoperative mechanical complications, and static locking could be a preferable option when treating an intertrochanteric fracture.
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Fijación Intramedular de Fracturas , Fracturas de Cadera , Complicaciones Posoperatorias , Humanos , Masculino , Femenino , Anciano , Fracturas de Cadera/cirugía , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Anciano de 80 o más Años , Fijación Intramedular de Fracturas/efectos adversos , Fijación Intramedular de Fracturas/métodos , Fijación Intramedular de Fracturas/instrumentación , Estudios de CohortesRESUMEN
BACKGROUND: A total of 4.5-41.2% of orthopedic surgery patients experience delirium. Until now, no formal systematic review or meta-analysis was performed to summarize the risk factors of delirium after orthopedic surgery. AIMS: The present study aimed to comprehensively and quantitatively conclude the risk factors of delirium after orthopedic surgery in elderly patients. METHODS: A search was applied to Medline, Chinese National Knowledge Infrastructure (CNKI), Embase, and Cochrane central database (all up to February 2020). All studies on the risk factors of delirium after orthopedic surgery in elderly patients without language restriction were reviewed, and qualities of included studies were assessed using the Newcastle-Ottawa Scale. Data were pooled and a meta-analysis was completed. RESULTS: A total of 15 studies altogether included 10,053 patients with orthopedic surgery, 825 cases of delirium occurred after surgery, suggesting the accumulated incidence of 8.2%. Results of meta-analyses showed that age > 70 years (odds ratio (OR) 3.78, 95% confidence interval (CI) 2.97-4.80), advanced age (standardized mean difference 0.82, 95% CI 0.54-1.09), male sex (OR 1.78, 95% CI 1.13-2.79), medical comorbidities (OR 2.18, 95% CI 1.23-3.88), malnutrition (OR 3.10, 95% CI 2.19-4.38), preoperative and postoperative haemoglobin (SMD - 0.37, 95% CI - 0.54 to - 0.19; SMD - 0.33, 95% CI - 0.55 to - 0.11), postoperative sodium (SMD - 0.52, 95% CI - 0.74 to - 0.29) and longer hospitalization after surgery (SMD 0.27, 95% CI 0.11-0.43), hearing impairment (OR 2.78, 95% CI 1.98-3.90), multiple medications (OR 1.36, 95% CI 1.21-1.52), psychotic drugs(OR 4.27, 95% CI 1.37-13.24), morphine (OR 1.97, 95% CI 1.11-3.51), cognitive impairment (OR 2.72, 95% CI 1.96-3.78), length of stay (SMD 0.26, 95% CI 0.14-0.39) and hip surgery (OR 1.63, 95% CI 1.08-2.48) were more likely to sustain delirium after hip surgery in elderly patients. ASA I and II was less likely to develop delirium after orthopedic surgery (OR 0.52, 95% CI 0.34-0.79). CONCLUSIONS: Related prophylaxis strategies should be implemented in the elderly involved with above-mentioned risk factors to prevent delirium after orthopedic surgery.
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Delirio , Procedimientos Ortopédicos , Anciano , Comorbilidad , Delirio/epidemiología , Delirio/etiología , Humanos , Incidencia , Masculino , Procedimientos Ortopédicos/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Factores de RiesgoRESUMEN
BACKGROUND: No formal systematic review or meta-analysis was performed up to now to summarize the risk factors of delirium after hip surgery. AIMS: The present study aimed to quantitatively and comprehensively conclude the risk factors of delirium after hip surgery in elderly patients. METHODS: A search was applied to CNKI, Embase, Medline, and Cochrane central database (all up to August 2015). All studies assessing the risk factors of delirium after hip surgery in elderly patients without language restriction were reviewed, and qualities of included studies were assessed using the Newcastle-Ottawa Scale. Data were pooled and a meta-analysis was completed. RESULTS: A total of 24 studies were selected, which altogether included 5364 patients with hip fracture. One thousand and ninety of them were cases of delirium occurred after surgery, suggesting the accumulated incidence of 24.0 %. Results of meta-analyses showed that elderly patients with preoperative cognitive impairment [odds ratio (OR) 3.21, 95 % confidence interval (CI) 2.26-4.56), advanced age (standardized mean difference 0.50, 95 % CI 0.33-0.67), living in an institution (OR 2.94; 95 % CI 1.65-5.23), heart failure (OR 2.46; 95 % CI 1.72-3.53), total hip arthroplasty (OR 2.21; 95 % CI 1.16-4.22), multiple comorbidities (OR 1.37; 95 % CI 1.12-1.68) and morphine usage (OR 3.01; 95 % CI 1.30-6.94) were more likely to sustain delirium after hip surgery. Females were less likely to develop delirium after hip surgery (OR 0.83; 95 % CI 0.70-0.98). CONCLUSIONS: Related prophylaxis strategies should be implemented in elderly patients involved with above-mentioned risk factors to prevent delirium after hip surgery.
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Artroplastia de Reemplazo de Cadera/efectos adversos , Delirio , Fracturas de Cadera/cirugía , Complicaciones Posoperatorias/epidemiología , Anciano , Artroplastia de Reemplazo de Cadera/métodos , Delirio/epidemiología , Delirio/etiología , Delirio/prevención & control , Humanos , Incidencia , Complicaciones Posoperatorias/prevención & control , Ajuste de Riesgo , Factores de RiesgoRESUMEN
Uncertainty exists regarding the association between diet and acute tubulointerstitial nephritis. Dietary factors served as exposures, including intake of alcohol, beef, non-oily fish, fresh fruit, oily fish, dried fruit, coffee, salad/raw vegetable, cereal, tea, water, salt, cooked vegetable, cheese, poultry, pork, Lamb/mutton, bread, and processed meat were extracted from the UK Biobank. Acute tubulointerstitial nephritis served as the outcome extracted from the FinnGen biobank. The 3 main methods of this analysis were weighted median, inverse-variance-weighted (IVW), and MR-Egger methods. The heterogeneity was measured employing Cochran Q test. The MR-PRESSO method was employed to identify possible outliers. The robustness of the IVW method was evaluated by employing the leave-one-out analysis. According to the IVW method, processed meat intake (ORâ =â 0.485; Pâ =â .00152), non-oily fish intake (ORâ =â 0.396; Pâ =â .0454), oily fish intake (ORâ =â 0.612; Pâ =â .00161), and dried fruit intake (ORâ =â 0.536; Pâ =â .00648) reduced the risk of acute tubulointerstitial nephritis. Other dietary factors were not shown to be causally related to acute tubulointerstitial nephritis. This study revealed that intake of processed meat, non-oily fish, oily fish, and dried fruit all decreased the risk of acute tubulointerstitial nephritis.
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Dieta , Nefritis Intersticial , Humanos , Nefritis Intersticial/epidemiología , Dieta/estadística & datos numéricos , Dieta/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Factores de Riesgo , Reino Unido/epidemiología , Adulto , Anciano , FrutasRESUMEN
Background: The relationship between dietary factors and hernias is currently unclear. Methods: The UK Biobank was used to extract dietary factors that were used as exposures, including intake of alcohol, non-oily fish, beef, fresh fruit, oily fish, salad/raw vegetables, dried fruit, coffee, cereal, salt, tea, water, cooked vegetables, cheese, Lamb/mutton, pork, poultry, processed meat, and bread. The FinnGen biobank was used to obtain GWAS data on hernias as outcomes. The main analysis of this study was performed using the weighted median, MR-Egger, and IVW methods. Cochran's Q test was utilized to assess heterogeneity. To find potential outliers, the MR-PRESSO method was used. Leave-one-out analysis was employed to assess the IVW method's robustness. Results: Alcoholic consumption per week (OR: 0.614; p = 0.00614) reduced the risk of inguinal hernia. Alcohol intake frequency (OR: 1.309; p = 0.0477) increased the risk of ventral hernia (mainly including incisional hernia and parastomal hernia). The intake of non-oily fish (OR: 2.945; p = 0.0214) increased the risk of inguinal hernia. Salt added to food (OR: 1.841; p = 0.00267) increased the risk of umbilical hernia. Cheese intake (OR: 0.434; p = 0.000536) and dried fruit intake (OR: 0.322; p = 0.00716) decreased the risk of ventral hernia, while cooked vegetable intake (OR: 4.475; p = 0.0380) increased the risk of ventral hernia. No causal relationships were found with hernias from other dietary factors. Conclusion: Inguinal, umbilical, and ventral hernias are all related to dietary factors.
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BACKGROUND: There is a scarcity of evidence regarding the potential relationship between the size and location of necrotic lesions, which must be understood to provide optimal joint-preserving treatment. The purpose of this study was to characterize the distribution patterns of necrotic lesions of varying sizes in early-stage osteonecrosis of femoral head (ONFH) with the use of three-dimensional mapping. METHODS: We retrospectively evaluated clinical CT images of the hips that were performed in the Third Hospital of Hebei Medical University from January 2018 to December 2022 and collected all CT images diagnosed with stage I and II ONFH. Three-dimensional structures that included both necrotic lesions and normal areas of the femoral heads were reconstructed and divided into eight regions to record their size and location. CT images for all lesions were superimposed onto a standard template, and three-dimensional mapping was created to determine the presence of concentrated areas of lesions. RESULTS: In a cohort of 143 patients with stage I and II ONFH, a total of 150 hips were reviewed. For lesions with less than 15% of the femoral head volume, necrotic lesions predominantly involve regions I, III, and V, with region I showing concentration. For lesions with volumes ranging from 15 to 30%, necrotic lesions exhibited a wider distribution across regions I, II, III, IV, V, and VII, with significant concentrations in regions I, III, and V. For lesions exceeding 30% of the femoral head volume, the necrotic lesions were extensively distributed across nearly the entire femoral head, with a notable expansion of the concentrated necrotic areas. CONCLUSIONS: The distribution of necrotic lesions varies with lesion size, with smaller lesions primarily concentrated in the anterior and medial regions of the femoral head, particularly in the anterosuperior region, while larger lesions expand to the lateral and inferior regions. These findings enhance existing classification systems and provide crucial insights for guiding hip-preserving surgical planning and approaches.
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Necrosis de la Cabeza Femoral , Imagenología Tridimensional , Tomografía Computarizada por Rayos X , Humanos , Necrosis de la Cabeza Femoral/diagnóstico por imagen , Necrosis de la Cabeza Femoral/patología , Estudios Retrospectivos , Femenino , Masculino , Imagenología Tridimensional/métodos , Adulto , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/patología , Adulto Joven , AncianoRESUMEN
Purpose: Conventional cephalomedullary nails (CMNs) are commonly employed for internal fixation in the treatment of reverse obliquity intertrochanteric (ROI) fractures. However, the limited effectiveness of conventional CMNs in addressing ROI fractures results in significant implant-related complications. To address challenges associated with internal fixation, a novel Proximal Femoral Bionic Nail (PFBN) has been developed. Methods: In this study, a finite element model was constructed using a normal femoral specimen, and biomechanical verification was conducted using the GOM non-contact optical strain measurement system. Four intramedullary fixation approaches-PFBN, Proximal Femoral Nail Antirotation InterTan nail (ITN), and Gamma nail (Gamma nail)-were employed to address three variations of ROI fractures (AO/OTA 31-A3). The biomechanical stability of the implant models was evaluated through the calculation of the von Mises stress contact pressure and displacement. Results: Compared to conventional CMNs, the PFBN group demonstrated a 9.36%-59.32% reduction in the maximum VMS at the implant. The A3.3 ROI fracture (75% bone density) was the most unstable type of fracture. In comparison to conventional CMNs, PFBN demonstrated more stable data, including VMS values (implant: 506.33 MPa, proximal fracture fragment: 34.41 MPa), contact pressure (13.28 MPa), and displacement (17.59 mm). Conclusion: Compared to the PFNA, ITN, and GN, the PFBN exhibits improvements in stress concentration, stress conduction, and overall model stability in ROI fractures. The double triangle structure aligns better with the tissue structure and biomechanical properties of the proximal femur. Consequently, the PFBN has significant potential as a new fixation strategy for the clinical treatment of ROI fractures.
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BACKGROUND: The relevance of the discovered plasma ESR1 mutations in positive metastatic breast cancer (BC) patients who had progressing disease after aromatase inhibitor (AI)-based therapy is still being debated. OBJECTIVES: We conducted this meta-analysis to explore the prognostic and predictive role of plasma ESR1 mutations in patients with progressive BC who have previously received AI therapy. MATERIAL AND METHODS: We searched for relevant studies in the PubMed, Embase and Cochrane Library databases to be included in the meta-analysis. This study was performed to compute combined hazard ratios (HRs) with 95% confidence intervals (95% CIs) for the progression-free survival (PFS) rate and overall survival (OS) rate. Subgroup and sensitivity analyses were also performed. The heterogeneity between studies was evaluated using the I2 statistic. RESULTS: In this meta-analysis, a total of 1,844 patients with metastatic BC and positive for estrogen receptors (ERs) were enrolled from 8 articles. The analysis revealed that patients with circulating ESR1 mutations had significantly worse PFS (HR: 1.34; 95% CI: 1.17-1.55; p < 0.001) and OS (HR: 1.59; 95% CI: 1.31-1.92; p < 0.001) compared to wild-type ESR1 patients. Subgroup analysis showed that the types of plasma ESR1 mutations were associated with differences in the prognosis of metastatic BC. The D538G mutation showed a statistically significant lower PFS (p = 0.03), while the Y537S mutation was not significantly correlated with PFS (p = 0.354). CONCLUSION: According to the findings of this meta-analysis, the assessment for plasma ESR1 mutations may provide prognostic and clinical guidance regarding subsequent endocrine therapy decisions for ER-positive, metastatic BC patients who had received prior therapy with AIs.
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Neoplasias de la Mama , Receptor alfa de Estrógeno , Mutación , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/sangre , Neoplasias de la Mama/mortalidad , Femenino , Receptor alfa de Estrógeno/genética , Pronóstico , Inhibidores de la Aromatasa/uso terapéutico , Metástasis de la Neoplasia , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangreRESUMEN
PURPOSE: The relationship between serum phosphorus and immunoglobulin A (IgA) nephropathy progression remains uncertain, especially normal-range serum phosphorus. Therefore, we herein examined the relationship between the normal-range serum phosphorus and the progression of IgA nephropathy. METHODS: One hundred sixty-two patients with primary IgA nephropathy were divided into three groups according to tertiles of baseline serum phosphorus (first tertile: 0.73-1.04 mmol/L; second tertile: 1.04-1.21 mmol/L; third tertile: 1.21-1.60 mmol/L). Estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration. The composite outcome was defined as a decrease of at least 50% in eGFR from baseline or end-stage kidney disease (ESKD). The association of serum phosphorus with IgA nephropathy progression was estimated using Cox proportional hazards models, adjusting for potential confounders. RESULTS: During a median 16 month follow-up period, 15 patients reached a composite outcome. In the crude Cox proportional hazard model, baseline serum phosphorus as a continuous variable was associated with increased risk for adverse renal outcomes [hazard ratio (HR) = 63.510, 95% confidence interval (CI) = 3.953-1020.284, P = 0.003], and the high tertile of serum phosphorus group had an increased risk of the composite outcome by using the low tertile group as the reference (HR = 11.895, 95% CI = 1.522-92.993, P = 0.018). After adjustment for traditional risk factors, the high tertile of serum phosphorus group was significantly related to IgA nephropathy progression compared with the low tertile group (HR = 9.424, 95% CI = 1.019-87.165, P = 0.048). CONCLUSIONS: Relatively higher serum phosphorus levels within the normal range were significantly associated with the progression of IgA nephropathy.
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Glomerulonefritis por IGA , Fallo Renal Crónico , Humanos , Glomerulonefritis por IGA/complicaciones , Estudios Retrospectivos , Progresión de la Enfermedad , Riñón , Fallo Renal Crónico/complicaciones , Tasa de Filtración Glomerular , FósforoRESUMEN
BACKGROUND: A total of 1.5% to 20.2% of total joint arthroplasty patients experience delirium. Until now, no formal systematic review or meta-analysis was performed to summarize the risk factors of delirium after primary total joint arthroplasty (TJA). METHODS: A comprehensive search encompassing Medline, Embase, and the Cochrane central database was conducted, incorporating studies available up to June 2023. We systematically reviewed research on the risk factors contributing to delirium following TJA in elderly patients, without language restrictions. The methodological quality of the included studies was evaluated using the Newcastle-Ottawa Scale. Data synthesis through pooling and a meta-analysis were performed to analyze the findings. RESULTS: A total of 23 studies altogether included 71,095 patients with primary TJA, 2142 cases of delirium occurred after surgery, suggesting the accumulated incidence of 3.0%. The results indicated that age, current smoker, heavy drinker, mini-mental state examination score, hypertension, diabetes mellitus, chronic kidney disease, history of stroke, coronary arterial disease, dementia, history of psychiatric illness, American Society of Anesthesiologists physical status III-IV, general anesthesia, anesthesia time, operative time, intraoperative blood loss, blood transfusion, ß-blockers, ACEI drugs, use of psychotropic drugs, preoperative C-reactive protein level, and preoperative albumin level were significantly associated with postoperative delirium after primary TJA. CONCLUSIONS: Related prophylaxis strategies should be implemented in the elderly involved with above-mentioned risk factors to prevent delirium after primary TJA.
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Delirio , Complicaciones Posoperatorias , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Factores de Edad , Artroplastia de Reemplazo/efectos adversos , Delirio/epidemiología , Delirio/etiología , Delirio/prevención & control , Incidencia , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Factores de RiesgoRESUMEN
Chronic kidney disease (CKD) is the 16th leading cause of mortality worldwide. Clinical studies have raised that long-term use of omeprazole (OME) is associated with the morbidity of CKD. OME is commonly used in clinical practice to treat peptic ulcers and gastroesophageal reflux disease. However, the mechanism underlying renal failure following OME treatment remains mostly unknown and the rodent model of OME-induced CKD is yet to be established. We described the process of renal injury after exposure to OME in mice; the early renal injury markers were increased in renal tubular epithelial cells (RTECs). And after long-term OME treatment, the OME-induced CKD mice model was established. Herein, aryl hydrocarbon receptor (AHR) translocation appeared after exposure to OME in HK-2 cells. Then for both in vivo and in vitro, we found that Ahr-knockout (KO) and AHR small interfering RNA (siRNA) substantially alleviated the OME-induced renal function impairment and tubular cell damage. Furthermore, our data demonstrate that antagonists of AHR and CYP1A1 could attenuate OME-induced tubular cell impairment in HK-2 cells. Taken together, these data indicate that OME induces CKD through the activation of the AHR-CYP axis in RTECs. Our findings suggest that blocking the AHR-CYP1A1 pathway acts as a potential strategy for the treatment of CKD caused by OME. KEY MESSAGES: We provide an omeprazole-induced chronic kidney disease (CKD) mice model. AHR activation and translocation process was involved in renal tubular damage and promoted the occurrence of CKD. The process of omeprazole nephrotoxicity can be ameliorated by blockade of the AHR-CYP1A1 axis.
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Citocromo P-450 CYP1A1 , Ratones Endogámicos C57BL , Ratones Noqueados , Omeprazol , Receptores de Hidrocarburo de Aril , Insuficiencia Renal Crónica , Animales , Humanos , Masculino , Ratones , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Línea Celular , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A1/genética , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Túbulos Renales/patología , Túbulos Renales/metabolismo , Túbulos Renales/efectos de los fármacos , Omeprazol/farmacología , Receptores de Hidrocarburo de Aril/metabolismo , Receptores de Hidrocarburo de Aril/genética , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/inducido químicamente , ARN Interferente Pequeño/metabolismo , ARN Interferente Pequeño/genéticaRESUMEN
Purpose: Controversy remains regarding the optimal treatment for stage III Osteonecrosis of the femoral head (ONFH). This study presents, for the first time, the precise treatment of stage III ONFH using the "substitute the beam for a pillar" technique and performs a comparative finite element analysis with other hip-preserving procedures. Methods: A formalin-preserved femur of male cadavers was selected to obtain the CT scan data of femur. The proximal femur model was reconstructed and assembled using Mimics 20.0, Geomagic, and UG-NX 12.0 software with four different implant types: simple core decompression, fibula implantation, porous tantalum rod implantation, and partial replacement prosthesis. The finite element simulations were conducted to simulate the normal walking gait, and the stress distribution and displacement data of the femur and the implant model were obtained. Results: The peak von Mises stress of the femoral head and proximal femur in the partial replacement of the femoral head (PRFH) group were 22.8 MPa and 37.4 MPa, respectively, which were 3.1%-38.6% and 12.8%-37.4% lower than those of the other three surgical methods. Conclusion: The PRFH group exhibits better mechanical performance, reducing stress and displacement in the ONFH area, thus maintaining femoral head stability. Among the four hip-preserving approaches, from a biomechanical perspective, PRFH offers a new option for treating ONFH.
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There are few studies on risk factors for frozen shoulder, and even fewer Mendelian randomization (MR) studies on frozen shoulder. Therefore, we conducted a two-sample MR study to explore whether socioeconomic status (years of schooling, average total household income before tax), obesity (body mass index and waist circumference), individual behaviors (smoking initiation, alcohol intake frequency, coffee intake, nonoily fish intake, tea intake, beef intake, bread intake, cheese intake, oily fish intake, and fresh fruit intake), and diabetes (type 1 and type 2 diabetes) are associated with frozen shoulder. The exposure datasets and the outcome dataset were extracted from the MRC Integrative Epidemiology Unit at the University of Bristol Open genome-wide association studies project (https://gwas.mrcieu.ac.uk/). We conducted MR analyses using the inverse variance weighted (primary method), MR-Egger, and weighted median methods and conducted heterogeneity and pleiotropy analyses. Type 1 diabetes (OR: 1.103; 95% CI: 1.053-1.156; Pâ =â .0000410) was associated with an increased risk of frozen shoulder. Cheese intake (OR: 0.490; 95% CI: 0.267-0.899; Pâ =â .0213), non-oily fish intake (OR: 0.0993; 95% CI: 0.0220-0.448; Pâ =â .00267), years of schooling (OR: 0.453; 95% CI: 0.349-0.588; Pâ =â .00000000277), and average total household income before tax (OR: 0.434; 95% CI: 0.253-0.743; Pâ =â .00236) were discovered as protective factors. No horizontal pleiotropy was found in all analyzes we performed (Pâ >â .05). Our study indicated that type 1 diabetes was a risk factor for frozen shoulder while cheese intake, non-oily fish intake, years of schooling, and average total household income before tax were considered as protective factors for frozen shoulder.
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Bursitis , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/epidemiología , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Obesidad/epidemiología , Humanos , DietaRESUMEN
The liver is one of the most ordinary metastatic sites of gastroesophageal junction adenocarcinoma and significantly affects its prognosis. Therefore, this study tried to construct a nomogram that can be applied to predict the likelihood of liver metastases from gastroesophageal junction adenocarcinoma. 3001 eligible patients diagnosed with gastroesophageal junction adenocarcinoma between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were involved in the analysis. Patients were randomly divided into a training cohort and an internal validation cohort using R software, with an allocation ratio of 7:3. According to the consequences of univariate and multivariate logistic regression, we constructed a nomogram for predicting the risk of liver metastases. The discrimination and calibration ability of the nomogram was appraised by the C-index, ROC curve, calibration plots, and decision curve analysis (DCA). We also used Kaplan-Meier survival curves to compare differences in overall survival in patients with gastroesophageal junction adenocarcinoma with and without liver metastases. Liver metastases developed in 281 of 3001 eligible patients. The overall survival of patients with gastroesophageal junction adenocarcinoma with liver metastases before and after propensity score matching (PSM) was obviously lower than that of patients without liver metastases. Six risk factors were finally recognized by multivariate logistic regression, and a nomogram was constructed. The C-index was 0.816 in the training cohort and 0.771 in the validation cohort, demonstrating the good predictive capacity of the nomogram. The ROC curve, calibration curve, and decision curve analysis further demonstrated the good performance of the predictive model. The nomogram can accurately predict the likelihood of liver metastases in gastroesophageal junction adenocarcinoma patients.
Asunto(s)
Adenocarcinoma , Neoplasias Hepáticas , Humanos , Nomogramas , Puntaje de Propensión , Unión EsofagogástricaRESUMEN
The principal treatment modalities for esophageal cancer are radiation, chemotherapy and surgery or a combination of them. In some sense, technological advances have tremendously heightened patients' survival rates. Nevertheless, the debate on the prognostic value of postoperative radiotherapy (PORT) has never ceased. On that account, this study made an effort to probe deep into the effects of PORT and surgery on the prognosis of stage III esophageal cancer. Our study included patients diagnosed with stage III esophageal cancer between 2004 and 2015 through the Surveillance, Epidemiology, and End Results (SEER) program. We performed propensity score matching (PSM) on the basis of whether surgery was carried out and whether PORT conducted. We identified the independent risk factors by multivariate Cox regression and constructed a nomogram model. In this research, we included 3940 patients, and the median follow-up is 14 months: 1932 cases without surgery; 2008 cases with surgery, and 322 cases of them underwent PORT. In the postPSM patient cohort, patients who underwent surgery had a median overall survival rate (OS) of 19.0 (95% confidence interval [CI] 17.2-20.8) and a median cancer-specific survival rate (CSS) of 23.0 (95% CI 20.6-25.3) months, which were remarkably higher than those without surgery (P < .001). The OSï¼P < .05ï¼and CSSï¼P < .05ï¼of the patients who underwent PORT were lower than those who did not. Similar results were obtained in the groups of N0 and N1. This study revealed surgery can heighten patients' survival rate, while PORT could not elevate patients' survival rate in stage III esophageal cancer patients.
Asunto(s)
Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/cirugía , Pronóstico , Nomogramas , Puntaje de Propensión , Factores de RiesgoRESUMEN
Background: No existing comprehensive Mendelian randomization studies have focused on how obesity affects respiratory diseases. Methods: BMI and waist circumference, mainly from the UK Biobank, and 35 respiratory diseases from the FinnGen Biobank were subjected to Mendelian randomization analyses. In this study, the inverse variance weighting method was used as the predominant analysis method and was complemented by MR-Egger and weighted median methods. Horizontal pleiotropy and potential outliers were detected by employing the MR-PRESSO method. Results: This study indicated that obesity rises the possibility of acute upper respiratory infections (BMI: OR=1.131, p<0.0001; WC: OR=1.097, p=0.00406), acute sinusitis (BMI: OR=1.161, p=0.000262; WC: OR=1.209, p=0.000263), acute pharyngitis (WC: OR=1.238, p=0.0258), acute laryngitis and tracheitis (BMI: OR=1.202, p=0.0288; WC: OR=1.381, p=0.00192), all influenza (BMI: OR=1.243, p=0.000235; WC: OR=1.206, p=0.0119), viral pneumonia (WC: OR=1.446, p=0.000870), all pneumoniae (BMI: OR=1.174, p <0.0001; WC: OR=1.272, p <0.0001), bacterial pneumoniae (BMI: OR=1.183, p=0.000290; WC: OR=1.274, p<0.0001), acute bronchitis (BMI: OR=1.252, p <0.0001; WC: OR=1.237, p=0.000268), acute unspecified lower respiratory infection (BMI: OR=1.303, p=0.000403), chronic tonsils and adenoids diseases (BMI: OR=1.236, p <0.0001; WC: OR=1.178, p=0.000157), chronic laryngotracheitis and laryngitis (WC: OR=1.300, p=0.00785), COPD (BMI: OR=1.429, p <0.0001; WC: OR=1.591, p <0.0001), asthma (BMI: OR=1.358, p <0.0001; WC: OR=1.515, p <0.0001), necrotic and suppurative conditions of lower respiratory tract (WC: OR=1.405, p=0.0427), pleural effusion (BMI: OR=1.277, p=0.00225; WC: OR=1.561, p<0.0001), pleural plaque (BMI: OR=1.245, p=0.0312), other diseases of the respiratory system (BMI: OR=1.448, p <0.0001; WC: OR=1.590, p <0.0001), and non-small cell lung cancer (BMI: OR=1.262, p=0.00576; WC: OR=1.398, p=0.00181). This study also indicated that obesity decreases the possibility of bronchiectasis (BMI: OR=0.705; p=0.00200). Conclusion: This study revealed that obesity increases the risk of the majority of respiratory diseases (including 20 of all 35 respiratory diseases) and that obesity decreases the risk of bronchiectasis.