Individual and area-level socioeconomic status, Life's Simple 7, and comorbid cardiovascular disease and cancer: a prospective analysis of the UK Biobank cohort.

OBJECTIVES: We aimed to investigate the associations of individual and area-level socioeconomic status (SES) with incident cardiovascular diseases (CVD) alone, cancer alone, and comorbid CVD and cancer, and the mediation role of cardiovascular health score in these associations. STUDY DESIGN: This was a population-based prospective cohort study. METHODS: We used data from the UK Biobank, a population-based prospective cohort study. Latent class analysis was used to create an individual-level SES index based on three indicators (household income, education level, and employment status), and the Townsend Index was defined as the area-level socioeconomic status. We used the American Heart Association's (AHA) Life's Simple 7 (smoking, body weight, physical activity, diet, blood pressure, blood glucose, and total cholesterol) to calculate the cardiovascular health score. We used Cox proportional hazard regression models to estimate the hazard ratio (HR) and 95% confidence interval (CI) adjusted for demographic, environmental, and genetic factors. RESULTS: Compared with high SES, the HRs in participants with low individual and area-level SES were 1.33 (95% confidence interval [CI] 1.29 to 1.38) and 1.24 (95% CI 1.20 to 1.29) for incident CVD, 0.96 (95% CI 0.93 to 0.99) and 0.95 (95%CI 0.92 to 0.98) for incident cancer, 1.32 (95%CI 1.24 to 1.40) and 1.15 (95%CI 1.08 to 1.22) for incident comorbid CVD and cancer, respectively. Additionally, the mediation proportion of CVD score for individual and area-level SES was 47.93% and 48.87% for incident CVD, 44.83% and 59.93% for incident comorbid CVD and cancer. The interactions between individual-level SES and CVD scores were significant on incident CVD, and comorbid CVD and cancer, and the protective associations were stronger in participants with high individual-level SES. CONCLUSIONS: Life's Simple 7 significantly mediated the associations between SES and comorbid CVD and cancer, while almost half of the associations remained unclear.

[Clinical observation of the subthreshold micropulse laser combined with ranibizumab for treatment of diabetic macular edema].

Objective: To evaluate the efficacy and safety of the subthreshold micropulse laser (SMPL) combined with ranibizumab in treating diabetic macular edema (DME). Methods: This was a prospective randomized controlled study. Patients diagnosed with DME in the Ophthalmology Department of Beijing Hospital were enrolled from January 2020 to December 2022. Patients were randomized in a ratio of 1∶1 using a table of random numbers into the ranibizumab monotherapy group and the SMPL combined with ranibizumab therapy group. We compared the changes of best-corrected visual acuity, central macular thickness measured by optical coherence tomography and optical coherence tomography angiography parameters, including the vessel density of the superficial and deep capillary plexus (DCP), foveal avascular zone size and peripapillary vessel density, at baseline, 6 and 12 months after the treatment. After 12 months of follow-up, fundus fluorescein angiography results, adverse events, and the number of injections or laser therapies were recorded. The Fisher's exact test and group t-test were used for statistical analysis. Results: Seventy-two patients (72 eyes) were enrolled, with a mean age of (61.1±8.2) years. Patients in the combination therapy group included 19 males and 17 females, while patients in the ranibizumab monotherapy group were 17 males and 19 females. There was no statistically significant difference in baseline characteristics between the two groups (P>0.05). A significant improvement in best-corrected visual acuity was shown in both groups at 6 and 12 months [(58.5±12.9) and (58.2±12.2) ETDRS letters in the combination therapy group, and (63.3±13.1) and (63.8±12.5) ETDRS letters in the ranibizumab monotherapy group]. A significant reduction in central macular thickness was shown in both groups at 6 and 12 months [(451.0±185.5) and (380.4±159.3)µm in the combination therapy group, and (387.5±135.5) and (372.8±146.1)µm in the ranibizumab monotherapy group]. However, there was no significant difference between groups at each timepoint (all P>0.05). At 12 months, the vessel density of the superficial capillary plexus showed no statistical difference compared to the baseline value in each group or between groups (42.6%±5.9% in the ranibizumab monotherapy group and 42.2%±5.5% in the combination therapy group, P>0.05). The vessel density of the DCP in the combination therapy group significantly increased to 47.5%±5.6% at 12 months, significantly different from that in the ranibizumab group (43.4%±5.1%; P<0.05). The foveal avascular zone size in the ranibizumab monotherapy group reduced to (0.32±0.13) mm2, significantly different from that in the combination therapy group [(0.34±0.16) mm2] at 12 months (P<0.05). Patients in the ranibizumab monotherapy group received (7.3±2.5) intravitreal injections, while patients in the combination therapy group received 3 injections. No unfavorable outcomes on fundus fluorescein angiography or systemic or topical severe adverse events were observed during the follow-up. Conclusions: The SMPL combined with intravitreal ranibizumab injections was effective and safe in treating DME patients. The combination treatment significantly reduced the number of injections and improved the vessel density of the DCP and macular ischemia, compared to the ranibizumab monotherapy.

[Sexual functional outcomes of vaginal dilation therapy for MRKH syndrome: a prospective study].

Objectives: To report the sexual functional outcomes of vaginal dilation therapy in Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome patients. Methods: From March 2020 to February 2023, 97 MRKH syndrome patients performed vaginal dilation therapy with guidance from Peking Union Medical College Hospital, and 45 of them engaged in penetrative intercourse and were included in this prospective cohort study. The Chinese version of female sexual function index (FSFI) was used to assess sexual function. Functional success was defined as FSFI>23.45. Forty age-matched healthy women were selected as controls. Kaplan-Meier survival analysis was used to calculate the median time to success. Pearson correlation analysis was used to explore the relationship between neovagina length and sexual function. Complications were collected using follow-up questionnaires. Results: The functional success rate of vaginal dilation therapy was 89% (40/45) with a median time to success of 4.3 months (95%CI: 3.0-6.1 months). Compared to controls, MRKH syndrome patients had significantly lower scores in the orgasm domain (4.72±1.01 vs 4.09±1.20; P=0.013) and pain domain (5.03±0.96 vs 4.26±0.83; P<0.001). However, there were no significant differences in the FSFI total score (26.77±2.70 vs 26.70±2.33; P=0.912), arousal domain (4.43±0.77 vs 4.56±0.63; P=0.422) and satisfaction domain (4.88±0.98 vs 4.65±0.86; P=0.269) between MRKH syndrome patients and controls. MRKH syndrome patients had significantly higher scores in the desire domain (3.33±0.85 vs 3.95±0.73; P<0.001) and lubrication domain (4.37±0.56 vs 5.20±0.67; P<0.001). The prevalence of sexual dysfunction in MRKH patients was non-inferior to controls: low desire [3% (1/40) vs 23% (9/40); P=0.007], arousal disorder [3% (1/40) vs 3% (1/40); P>0.999], lubrication disorder [5% (2/40) vs 25% (10/40); P=0.012], orgasm disorder [40% (16/40) vs 20% (8/40); P=0.051], sexual pain [30% (12/40) vs 15% (6/40); P=0.108]. Conclusions: MRKH syndrome patients undergoing non-invasive vaginal dilation therapy could achieve satisfactory sexual life. Given its high functional success rate and slight complication, vaginal dilation therapy should be recommended as the first-line option, reducing the need for unnecessary surgeries.

[The association between overweight/obesity and the risk of malignancy in Hürthle cell neoplasms of the thyroid].

Objective: To explore the association between obesity/overweight and the risk of malignancy in Hürthle cell neoplasms of the thyroid. Methods: The data of patients with complete data who were diagnosed with Hürthle cell neoplasms of the thyroid at the Third Hospital of Peking University from September 2016 to September 2023 were retrospectively collected. Based on postoperative pathological diagnosis, tumors were classified into thyroid Hürthle cell adenoma group and Hürthle cell carcinoma group. Multivariate logistic regression analysis was employed to explore the association between overweight/obesity and the risk of malignancy in Hürthle cell neoplasms of the thyroid. Results: A total of 102 patients (13 males and 89 females) were included, aged (48.7±13.1) years. There were 22 cases of thyroid Hürthle cell carcinoma and 80 cases of thyroid Hürthle cell adenoma. Univariate analysis showed that the rate of overweight/obesity in the Hürthle cell carcinoma group was higher than that in the adenoma group [73% (16/22) vs 46% (37/80), P=0.050]. Multivariate logistic regression analysis indicated that the overweight/obese patients had a higher risk of malignancy in Hürthle cell neoplasms of the thyroid compared with the non-overweight/obese patients (OR=3.170, 95%CI: 1.126-9.955, P=0.035). Sensitivity analysis excluding individuals with multiple tumors was consistent with the main study results (OR=2.878, 95%CI: 0.922-10.228, P=0.080). Conclusion: Overweight/obesity may be associated with a higher risk of malignancy in patients with Hürthle cell neoplasms of the thyroid.

[Prognostic value of skeletal muscle measured by CT at the T4 level in advanced EGFR-positive non-small cell lung cancer patients treated with ecotinib].

Objective: To investigate the prognostic value of skeletal muscle measured by CT at the level of the fourth thoracic vertebra (T4) in advanced epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) patients treated with ecotinib. Methods: The study retrospectively reviewed clinical and pathological characteristics of 176 patients with advanced EGFR-positive NSCLC who received ecotinib and underwent chest CT scans at Wuhan Union Hospital between January 2017 and October 2020. Among them, 70 were male and 106 were female, with ages ranging from 27 to 80 (58.6±10.6) years. As of August 21, 2021, the median follow-up duration was 19.2 months (95%CI: 15.3 to 23.7 months). The optimal cut-off value of skeletal muscle density (T4-SMD) on CT images at the T4 level were determined using X-tile software. Kaplan-Meier analysis and log-rank test were used to plot progression-free survival curves. Cox proportional hazards regression models were employed to analyze factors influencing 1-year progression-free survival (PFS), and a nomogram prognostic model was constructed accordingly. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were utilized to evaluate the predictive value of the nomogram. Results: The T4-SMD [M (Q1,Q3)] of 176 patients was 42.56 (37.05, 45.93) HU. Patients were divided into low T4-SMD group (n=122) and high T4-SMD group (n=54) based on the cut-off value (The values for males and females were 49.44 and 41.41 HU, respectively) of T4-SMD. The median PFS time and 1-year PFS rate in the low T4-SMD group were significantly lower than those in the high T4-SMD group [10.4 (95%CI: 9.3-11.8) vs 13.7 (95%CI: 11.1-18.5) months, 36.1% vs 59.3%, respectively, P=0.034]. Eastern Cooperative Oncology Group performance status (HR=3.308, 95%CI: 1.183-9.247, P=0.023), lactate dehydrogenase level (HR=1.852, 95%CI: 1.037-3.307, P=0.037), systemic immune-inflammation index (HR=1.772, 95%CI: 1.019-3.080, P=0.043), and T4-SMD (HR=0.563, 95%CI: 0.325-0.974, P=0.040) were prognostic factors for 1-year PFS in advanced EGFR-positive NSCLC patients treated with ecotinib. A nomogram for predicting 1-year PFS of advanced EGFR-positive NSCLC patients treated with ecotinib was constructed based on the four indicators selected by multivariate Cox regression analysis. The area under the ROC curve of the nomogram was 0.775 (95%CI: 0.676-0.874). The calibration curve showed good consistency between the predicted and actual 1-year PFS. DCA demonstrated good clinical prediction effectiveness of the nomogram. Conclusion: Low T4-SMD is a prognostic risk factor for patients with advanced EGFR-positive NSCLC receiving icotinib therapy.

Enhancing Quantitative Analysis of Xenobiotics in Blood Plasma through Cross-Matrix Calibration and Bayesian Hierarchical Modeling.

This study addresses the challenges of matrix effects and interspecies plasma protein binding (PPB) on measurement variability during method validation across diverse plasma types (human, rat, rabbit, and bovine). Accurate measurements of small molecules in plasma samples often require matrix-matched calibration approaches with the use of specific plasma types, which may have limited availability or affordability. To mitigate the costs associated with human plasma measurements, we explore in this work the potential of cross-matrix-matched calibration using Bayesian hierarchical modeling (BHM) to correct for matrix effects associated with PPB. We initially developed a targeted quantitative approach utilizing biocompatible solid-phase microextraction coupled with liquid chromatography-mass spectrometry for xenobiotic analysis in plasma. The method was evaluated for absolute matrix effects across human, bovine, rat, and rabbit plasma comparing pre- and postmatrix extraction standards. Absolute matrix effects from 96 to 108% for most analytes across plasma sources indicate that the biocompatibility of the extraction phase minimizes interference coextraction. However, the extent of PPB in different media can still affect the accuracy of the measurement when the extraction of small molecules is carried out via free concentration, as in the case of microextraction techniques. In fact, while matrix-matched calibration revealed high accuracy, cross-matrix calibration (e.g., using a calibration curve generated from bovine plasma) proved inadequate for precise measurements in human plasma. A BHM was used to calculate correction factors for each analyte within each plasma type, successfully mitigating the measurement bias resulting from diverse calibration curve types used to quantify human plasma samples. This work contributes to the development of cost-effective, efficient calibration strategies for biofluids. Leveraging easily accessible plasma sources, like bovine plasma, for method optimization and validation prior to analyzing costly plasma (e.g., human plasma) holds substantial advantages applicable to biomonitoring and pharmacokinetic studies.

[Different methods in predicting mortality of pediatric intensive care units sepsis in Southwest China].

Objective: To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China. Methods: This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis. Results: Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) (Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS (Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion: Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

The effect of icosapent ethyl on left atrial and left ventricular morphology.

Atrial fibrillation (AF) is a common arrhythmia associated with poor outcomes. N-3 fatty acids have been shown to provide significant cardiovascular risk reduction, but they may exacerbate the risk of AF. The pathway by which N-3 fatty acids may be arrhythmogenic is unknown. One possible mechanism involves cardiac chamber morphology alteration. The purpose of this study was to investigate the effect of icosapent ethyl (IPE) on left atrial (LA) size and left ventricular (LV) mass. This study used coronary computed tomographic angiography images gathered from the Effect of Icosapent Ethyl on Progression of Coronary Atherosclerosis (EVAPORATE) trial. EVAPORATE was a randomised, double-blind, placebo-controlled study finding a significant reduction in coronary atherosclerosis progression in patients with residually elevated triglycerides despite statin therapy on 4 g IPE daily versus 4 g placebo daily. Computed tomography images were used to measure LA size and LV mass at 0 and 18 months. Of 80 enrolled patients, 68 were included in the final analysis. Baseline demographics and risk factors were similar between IPE and placebo cohorts. LA anterior- posterior diameter measured on axial (p=0.51) and sagittal (p=0.52) orientations were not different over time. Also, there was no difference between groups in the change in LA volume (p=0.84). Change in LV mass was similar between groups (p=0.13). In conclusion, this study did not detect differences in LA size or LV mass over 18 months between patients on 4 g daily IPE versus placebo.

Recent advances in vasodilatador therapy Part 1: Physiologic correlations.

La respuesta hemodinamica obtenida de la administracion de agentes vasodilatadores a pacientes con fallo congestivo cardiaco va a depender de su efecto relativo en las arteriolas y venas. Aquellos vasodilatadores que predominantemente causan dilatacion arteriolar, aumentan el debito cardiaco sin cambios significativos en la presion de cuna pulmonar. Aquellos que son vasodilatadores venosos disminuyen la presion de cuna pulmonar sin causar cambios significativos en el debito cardiaco. Los efectos hemodinamicos en pacientes con infarto agudo del miocardio y decompensacion cardiaca van a depender del valor o nivel inicial de la presion telediastolica del ventriculo izquierdo. El rastreo hemodinamico es indispensable en situaciones agudas, para determinar los efectos hemodinamicos de este tipo de terapia