Association of increased participation in social activity in later life with risk of all-cause mortality and heart diseases in older people: results from the Chinese Longitudinal Healthy Longevity Survey (CLHLS).

Background: Previous studies have shown social activity is associated with reduced risk of health outcomes. However, among older people (≥65 years) who were socially inactive at baseline, limited study explored whether increased participation in social activity in later life was associated with reduced risk of health outcomes; therefore, using the data from the Chinese Longitudinal Healthy Longevity Survey, the study was performed. Methods: The study outcomes were 10-year all-cause mortality (sample number = 9,984) and 10-year heart diseases (sample number = 7,496). The exposure was the change of social activity frequency. Cox regression analysis was used for data analysis. Results: During the follow-up, there were 6,407 all-cause mortalities and 1,035 heart diseases, respectively. Kaplan-Meier analysis demonstrated that cumulative incidences of all-cause mortality were significantly lower in participants with changes into more frequent social activity (log-rank p < 0.001), while no significant difference was observed for heart diseases (log-rank p = 0.330). Compared with the subgroup who never participated in social activity at baseline, adjusted HRs of all-cause mortality were 0.79 (95% CI: 0.70-0.90, p < 0.001), 0.78 (95% CI: 0.63-0.96, p = 0.019), 0.74 (0.59-0.92, p = 0.006), and 0.70 (95% CI: 0.56-0.88, p = 0.002) for the subgroup of switching to sometimes, the subgroup of switching to once a month, the subgroup of switching to once a week, and the subgroup of switching to everyday, respectively. The corresponding HRs of heart diseases were 0.83 (95% CI: 0.65-1.08, p = 0.170), 0.82 (95% CI: 0.51-1.31, p = 0.412), 0.91 (0.58-1.42, p = 0.675) and 0.75 (95% CI: 0.47-1.20, p = 0.227), respectively. Stratified and sensitivity analyses revealed similar results. Conclusion: Among older people who never participated in social activity, increased participation in social activity in later life was associated with reduced risk of all-cause mortality, but was not associated with reduced risk of heart diseases.

Widely Targeted Metabolomic Analysis Reveals the Improvement in Panax notoginseng Triterpenoids Triggered by Arbuscular Mycorrhizal Fungi via UPLC-ESI-MS/MS.

Panax notoginseng is a highly valued perennial medicinal herb in China and is widely used in clinical treatments. The main purpose of this study was to elucidate the changes in the composition of P. notoginseng saponins (PNSs), which are the main bioactive substances, triggered by arbuscular mycorrhizal fungi (AMF) via ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). A total of 202 putative terpenoid metabolites were detected, of which 150 triterpene glycosides were identified, accounting for 74.26% of the total. Correlation analysis, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) of the metabolites revealed that the samples treated with AMF (group Ce) could be clearly separated from the CK samples. In total, 49 differential terpene metabolites were identified between the Ce and CK groups, of which 38 and 11 metabolites were upregulated and downregulated, respectively, and most of the upregulated differentially abundant metabolites were mainly triterpene glycosides. The relative abundances of the two major notoginsenosides (MNs), ginsenosides Rd and Re, and 13 rare notoginsenosides (RNs), significantly increased. The differential saponins, especially RNs, were more easily clustered into one branch and had a high positive correlation. It could be concluded that the biosynthesis and accumulation of some RNs share the same pathways as those triggered by AMF. This study provides a new way to obtain more notoginsenoside resources, particularly RNs, and sheds new light on the scientization and rationalization of the use of AMF agents in the ecological planting of medicinal plants.

Hypertension in frail older adults: current perspectives.

Hypertension is one of the most common chronic diseases in older people, and the prevalence is on the rise as the global population ages. Hypertension is closely associated with many adverse health outcomes, including cardiovascular disease, chronic kidney disease and mortality, which poses a substantial threat to global public health. Reasonable blood pressure (BP) management is very important for reducing the occurrence of adverse events. Frailty is an age-related geriatric syndrome, characterized by decreased physiological reserves of multiple organs and systems and increased sensitivity to stressors, which increases the risk of falls, hospitalization, fractures, and mortality in older people. With the aging of the global population and the important impact of frailty on clinical practice, frailty has attracted increasing attention in recent years. In older people, frailty and hypertension often coexist. Frailty has a negative impact on BP management and the prognosis of older hypertensive patients, while hypertension may increase the risk of frailty in older people. However, the causal relationship between frailty and hypertension remains unclear, and there is a paucity of research regarding the efficacious management of hypertension in frail elderly patients. The management of hypertension in frail elderly patients still faces significant challenges. The benefits of treatment, the optimal BP target, and the choice of antihypertensive drugs for older hypertensive patients with frailty remain subjects of ongoing debate. This review provides a brief overview of hypertension in frail older adults, especially for the management of BP in this population, which may help in offering valuable ideas for future research in this field.

Cardiac electrophysiology, structure and diastolic function in patients with diabetic foot versus those without diabetic foot.

AIMS/INTRODUCTION: To evaluate the differences in cardiac autonomic function, cardiac structure and diastolic function between individuals with diabetic foot (DF) and those with diabetes but without DF. MATERIALS AND METHODS: A total of 413 individuals with DF and 437 without DF who underwent a 24-h electrocardiogram Holter and a Doppler echocardiogram were included. The heart rate variability parameters to evaluate cardiac autonomic function, and the indices for the assessment of cardiac structure and left ventricular (LV) diastolic function, including left atrium, LV posterior wall thickness, interventricular septum and E/e' ratio, were measured or calculated. Propensity score matching was used for the sensitivity analysis to minimize potential imbalance. RESULTS: In both the crude and propensity score matching analyses, significant differences were observed in heart rate variability between individuals with and without DF, as evidenced by lower standard deviation of the normal sinus interval, lower low-frequency power/high-frequency power ratio, lower standard deviation of the 5-min average RR intervals, lower low-frequency power, lower percentage of normal adjacent RR interval difference >50 ms, lower root mean square of successive RR interval differences and lower high-frequency power (all P < 0.05). In multivariate analysis, DF showed an independent negative correlation with the aforementioned indices of heart rate variability (all P < 0.05). Individuals with DF showed higher left atrium, LV posterior wall thickness, interventricular septum and a higher E/e' ratio than those without DF in the crude analysis (all P < 0.05), whereas these indices were no longer associated with DF in the multivariate analysis and the propensity score matching analyses. CONCLUSIONS: Cardiac autonomic modulation was more severely impaired in individuals with DF than in their counterparts without DF. There has been insufficient evidence to demonstrate the independent association of DF and LV diastolic dysfunction.

Association of frailty status with overall survival in elderly hypertensive patients: based on the Chinese Longitudinal Healthy Longevity Survey.

BACKGROUND: Hypertension and frailty often coexist in older people. The present study aimed to evaluate the association of frailty status with overall survival in elderly hypertensive patients, using data from the Chinese Longitudinal Healthy Longevity Survey. METHODS: A total of 10,493 elderly hypertensive patients were included in the present study (median age 87.0 years, 58.3% male). Frailty status was assessed according to a 36-item frailty index (FI), which divides elderly individuals into four groups: robustness (FI ≤ 0.10), pre-frailty (0.10 < FI ≤ 0.20), mild-frailty (0.20 < FI ≤ 0.30), and moderate-severe frailty (FI > 0.30). The study outcome was overall survival time. Accelerated failure time model was used to evaluate the association of frailty status with overall survival. RESULTS: During a period of 44,616.6 person-years of follow-up, 7327 (69.8%) participants died. The overall survival time was decreased with the deterioration of frailty status. With the robust group as reference, adjusted time ratios (TRs) were 0.84 (95% confidence interval [CI]: 0.80-0.87) for the pre-frailty group, 0.68 (95% CI: 0.64-0.72) for the mild frailty group, and 0.52 (95% CI: 0.48-0.56) for the moderate-severe frailty group, respectively. In addition, restricted cubic spline analysis revealed a nearly linear relationship between FI and overall survival (p for non-linearity = 0.041), which indicated the overall survival time decreased by 17% with per standard deviation increase in FI (TR = 0.83, 95% CI: 0.82-0.85). Stratified and sensitivity analyses suggested the robustness of the results. CONCLUSIONS: The overall survival time of elderly hypertensive patients decreased with the deterioration of frailty status. Given that frailty is a dynamic and even reversible process, early identification of frailty and active intervention may improve the prognosis of elderly hypertensive patients.

The effects of initial and subsequent overweight or obesity on hypertension in the middle age.

The aims of our study were to examine whether initial or subsequent adiposity status had a greater effect on hypertension. We collected data in 1992 and again in 2007 from the same group of 597 individuals in the middle age. The subjects were classified into four groups: individuals with a normal body mass index (BMI) in 1992 and 2007 were in Group I; those with a normal BMI in 1992, but became overweight or obese in 2007 were in Group II; those who were overweight or obese in 1992, but had a normal BMI in 2007 were in Group III; and those who were overweight or obese in 1992 and 2007 were in Group IV. Their demographic data were recorded. The relationship between adiposity status and hypertension was analyzed using logistic regression model. The cumulative incidence of hypertension was 35.5%, 56.3%, 50.0%, and 65.1% for Group I to IV, respectively. Compared with Group I, after adjusted factors, the hazard ratio (HR) was 1.80 for Group II (P = .001), 1.40 for Group III (P = .150), and 2.31 for Group IV (P < .001). Adiposity status in 2007 could predict hypertension (OR = 2.5, P < .001), as opposed to the initial adiposity status (P = .148). Subsequently adiposity status could have major effects on hypertension. Our society is very short of public health resources, particularly in developing countries, we should pay more attention to current adiposity status and encourage middle-aged people to lose weight.

Improvement of Panax notoginseng saponin accumulation triggered by methyl jasmonate under arbuscular mycorrhizal fungi.

Panax notoginseng is a highly valued perennial medicinal herb plant in Yunnan Province, China, and the taproots are the main medicinal parts that are rich in active substances of P. notoginseng saponins. The main purpose of this study is to uncover the physiological and molecular mechanism of Panax notoginseng saponin accumulation triggered by methyl jasmonate (MeJA) under arbuscular mycorrhizal fungi (AMF) by determining physiological indices, high-throughput sequencing and correlation analysis. Physiological results showed that the biomass and saponin contents of P. notoginseng, the concentrations of jasmonic acids (JAs) and the key enzyme activities involved in notoginsenoside biosynthesis significantly increased under AMF or MeJA, but the interactive treatment of AMF and MeJA weakened the effect of AMF, suggesting that a high concentration of endogenous JA have inhibitory effect. Transcriptome sequencing results indicated that differential expressed genes (DEGs) involved in notoginsenoside and JA biosynthesis were significantly enriched in response to AMF induction, e.g., upregulated genes of diphosphocytidyl-2-C-methyl-d-erythritol kinases (ISPEs), cytochrome P450 monooxygenases (CYP450s)_and glycosyltransferases (GTs), while treatments AMF-MeJA and salicylhydroxamic acid (SHAM) decreased the abundance of these DEGs. Interestingly, a high correlation presented between any two of saponin contents, key enzyme activities and expression levels of DEGs. Taken together, the inoculation of AMF can improve the growth and saponin accumulation of P. notoginseng by strengthening the activities of key enzymes and the expression levels of encoding genes, in which the JA regulatory pathway is a key link. This study provides references for implementing ecological planting of P. notoginseng, improving saponin accumulation and illustrating the biosynthesis mechanism.

Disparities in overall survival by varying duration of disability in activities of daily living in older people: A population-based cohort from Chinese Longitudinal Healthy Longevity Survey (CLHLS).

OBJECTIVES: To investigate the association between duration of disability in activity of daily living (ADL) and overall survival in older individuals. DESIGN: A prospective cohort study. SETTING: Community-based data from Chinese Longitudinal Healthy Longevity Survey. PARTICIPANTS: In total, 13,560 participants without ADL disability and 2772 participants with ADL disability at baseline were included. MEASUREMENTS: ADL disability was assessed using Katz index scale, which included six essential ADLs: dressing, bathing, transferring, toileting, continence, and eating. Dependence of each item was scored on a scale of 1, the maximum total score was 6. At baseline, duration of ADL disability was defined as the maximum duration among the six items. The study outcome was overall survival. Accelerated failure time models were constructed to investigate the association between duration of ADL disability and overall survival. Subgroup analyses by sex, age, and multimorbidites, as well as sensitive analyses were conducted. RESULTS: During 81,868.7 person-years follow-up, 11,092 deaths were recorded. Overall, ADL disability was associated with lower overall survival compared to non-ADL disability. With duration of ADL disability extending, the overall survival strikingly dropped in the first 12 months, reaching its lowest point with adjusted time ratio (TR) at 0.66 (95%CI: 0.61-0.72, p < 0.001), then moderately grew until the 60th month, finally stayed constant thereafter. Participants with ADL scores of 1-3 had higher survival compared to those with scores of 4-6, and both groups followed a similar trend of varied survival to the whole cohort. Moreover, subgroup analyses and sensitivity analyses showed the robustness of these findings. CONCLUSIONS: Our findings first address a golden time window for the older individuals with ADL disability. More attention should be given to them, especially in the first 12 months since diagnosis, to reduce mortality and extend the lifespan.

Association of changes in frailty status with the risk of all-cause mortality and cardiovascular death in older people: results from the Chinese Longitudinal Healthy Longevity Survey (CLHLS).

BACKGROUND: Few studies have investigated the association between changes in frailty status and all-cause mortality, inconsistent results were reported. What's more, studies that evaluated the effect of changes of frailty on cardiovascular death in older population are scanty. Therefore, the present study aims to investigate the association of such changes with the risk of all-cause mortality and cardiovascular death in older people, using data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). METHODS: A total of 2805 older participants from two consecutive waves (i.e. 2011 and 2014) of the CLHLS were included for analysis. Based on the changes in frailty status from wave 2011 to wave 2014, participants were categorized into 4 subgroups, including sustained pre/frailty, robustness to pre/frailty, pre/frailty to robustness and sustained robustness. Study outcomes were all-cause mortality and cardiovascular death, and Cox regression analysis examined the association of changes in frailty status with outcomes. RESULTS: From wave 2011 to wave 2014, 33.2% of the participants had frailty transitions. From wave 2014 to wave 2018, there were 952 all-cause mortalities and 170 cardiovascular deaths during a follow-up of 9530.1 person-years, and Kaplan-Meier analysis demonstrated that cumulative incidences of the two outcomes were significantly lower in more robust participants (all log-rank p < 0.001). Compared with the subgroup of sustained pre/frailty, the fully adjusted HRs of all-cause mortality were 0.61 (95% CI: 0.51-0.73, p < 0.001), 0.51 (95% CI: 0.42-0.63, p < 0.001) and 0.41 (0.34-0.49, p < 0.001) in the subgroup of robustness to pre/frailty, the subgroup of pre/frailty to robustness, and the subgroup of sustained robustness, respectively. The fully adjusted HRs of cardiovascular death were 0.79 (95% CI: 0.52-1.19, p = 0.256) in the subgroup of robustness to pre/frailty, 0.45 (95% CI: 0.26-0.76, p = 0.003) in the subgroup of pre/frailty to robustness and 0.51 (0.33-0.78, p = 0.002) in the subgroup of sustained robustness when comparing to the subgroup of sustained pre/frailty, respectively. Stratified analysis and extensive sensitivity analyses revealed similar results. CONCLUSIONS: Frailty is a dynamic process, and improved frailty and remaining robust are significantly associated with lower risk of all-cause mortality and cardiovascular death in older people.

Assessing the relationship between monocyte-to-HDL cholesterol ratio and mortality in patients with hypertrophic cardiomyopathy.

OBJECTIVE: A new inflammatory marker, namely monocyte-to-high-density lipoprotein cholesterol ratio (MHR), has emerged as a useful indicator for adverse outcomes in several cardiovascular diseases; however, the relationship between MHR and the prognosis of hypertrophic cardiomyopathy (HCM) remains to be evaluated. We examined the relationship between MHR and all-cause mortality (ACM) in Chinese adult patients with HCM. METHODS: We retrospectively performed clinical evaluation in 305 patients with HCM (median age: 52.0 years, male: 54.10%). RESULTS: During a median follow-up of 4.9 years, ACM occurred in 57 (18.7%) patients. Based on the tertiles of baseline MHR, ACM increased with higher tertile. With tertile 1 as reference, adjusted ACM hazard ratios (HRs) were 2.68 for tertile 2 (95% confidence interval [CI]: 1.18-6.11, p = 0.019) and 4.85 for tertile 3 (95% CI: 2.16-10.89, p < 0.001). Stratified analysis and E-value analysis suggested the robustness of the above-mentioned results. Furthermore, adjusted smooth curve fitting exhibited a non-linear relationship between MHR and ACM (inflection point: 0.5), and the risk of ACM increased significantly with higher MHR only the value below the inflection point (HR: 4.37 per one standard deviation, 95% CI: 1.81-10.6, p = 0.001). Finally, sensitivity analysis was similar to the main findings. CONCLUSION: In Chinese adult patients with HCM, higher MHR is a strong independent predictor of ACM, and a non-linear relationship is also observed between MHR and ACM.

Triclocarban exhibits higher adipogenic activity than triclosan through peroxisome proliferator-activated receptors pathways.

Previous epidemiological and animal studies have showed the lipid metabolic disruption of antimicrobial triclocarban (TCC) and triclosan (TCS). However, the present in vivo researches were mainly devoted to the hepatic lipid metabolism, while the evidence about the impacts of TCC/TCS on the adipose tissue is very limited and the potential mechanism is unclear, especially the molecular initiation events. Moreover, little is known about the toxic difference between TCC and TCS. This study aimed to demonstrate the differential adipogenic activity of TCC/TCS as well as the potential molecular mechanism via peroxisome proliferator-activated receptors (PPARα/ß/γ). The in vitro experiment based on 3T3-L1 cells showed that TCC/TCS promoted the differentiation of preadipocytes into mature adipocytes at nanomolar to micromolar concentrations, which was approach to their human exposure levels. We revealed for the first time by reporter gene assay that TCC could activate three PPARs signaling pathways in a concentration-dependent manner, while TCS only activate PPARß. The molecular docking strategy was applied to simulate the interactions of TCC/TCS with PPARs, which explained well the different PPARs activities between TCC and TCS. TCC up-regulated the mRNA expression of three PPARs, but TCS only up-regulated PPARß and PPARγ significantly. Meanwhile, TCC/TCS also promoted the expression of adipogenic genes targeted by PPARs to different extent. The cellular and simulating studies demonstrated that TCC exerted higher adipogenic effects and PPARs activities than TCS. Our mice in vivo experiment showed that TCC could lead to adipocyte size increase, adipocyte lipid accumulation growing, fat weight and body weight gain at human-related exposure levels, and high fat diet exacerbated these effects. Moreover, male mice tended to be more susceptible to TCC induced obesogenic effect than female mice. This work highlights the potential obesogenic risks of TCC/TCS via PPARs signaling pathways, and TCC deserves more concerns for its higher activity.

Prognostic value of albumin to fibrinogen ratio for mortality in patients with hypertrophic cardiomyopathy.

BACKGROUND: Albumin to fibrinogen ratio (AFR), a new inflammatory marker, has emerged as a useful indicator to predict adverse outcomes for several diseases. However, whether AFR could be a new useful indicator to predict mortality in HCM patients remains to be evaluated. The study explored the predictive value of AFR for HCM-related death in adult HCM patients. METHODS: A total of 404 HCM patients were eventually enrolled in the study according to the inclusion criteria. Patients were divided into two groups based on the median of baseline AFR. The association between AFR and HCM-related death was analyzed. RESULTS: During a median follow-up of 4.75 years, HCM-related death was observed in 45 patients (11.1%). The incidence of HCM-related death was significantly higher in the low AFR group (log-rank p < 0.001). With the high AFR group as reference, the unadjusted hazard ratio (HR) for HCM-related death was 2.97 (95% confidence interval [CI]: 1.53-5.75, p = 0.001) in the low AFR group, and after adjusting for potentially confounding variables, the adjusted HR for low AFR group was 3.15 (95% CI: 1.56-6.37, p = 0.001). No significant interactions between AFR and other variables were observed in subgroup analysis. Sensitivity analyses in patients with normal albumin and fibrinogen showed similar results. CONCLUSION: AFR is an independent prognostic factor for HCM-related death, adult HCM patients with a lower AFR have a higher risk of HCM-related death.

Administration study of recombinant erythropoietin on the carriers of variant c.577del in EPO gene.

The issue of misjudgment in recombinant erythropoietin (rEPO) detection caused by the variant c.577del in human EPO gene has been found in recent years. Though the method of analyzing de-N-glycosylated erythropoietins (EPO) in blood samples was developed for identifying both EPO_p.Arg193AspfsTer28 (VAR-EPO) and rEPO, it cannot be applied without the evaluation of excreted samples. For this purpose, five heterozygous carriers of the variant c.577del were recruited in an administration study of rEPO. Urine and blood samples were collected at different times before and after subcutaneous injection with a single-dose of 50 IU/kg. The urine samples were analyzed for intact EPO, while the serum samples were analyzed for both intact and de-N-glycosylated EPO. A typical mixed band was detected in all blank and wash-out urine samples, which all displayed a similar result with rEPO abuse. For the analysis of intact EPO in serum samples, a typical mixed band was detected in the wash-out samples from day 1 to day 3, which could be identified as rEPO directly, while double-band was observed in other samples with inconclusive results. The result of de-N-glycosylated EPO in all serum samples showed two separated bands, and the ratioL/U decreased along with wash-out periods. Also, compared with the intact EPO analysis, a longer detection window without false positive results was obtained when analyzing de-N-glycosylated EPO. Analysis of de-N-glycosylated EPO is not only able to recognize the variant carriers directly but also able to detect rEPO abuse in the blood samples from the variant carriers with higher efficiency than the analysis of intact EPO.

HexNet: An Orientation-Aware Deep Learning Framework for Omni-Directional Input.

While omni-directional sensors provide holistic representations typical deep learning frameworks reduce the benefits by introducing distortions and discontinuities as spherical data is supplied as planar input. On the other hand, recent spherical convolutional neural networks (CNNs) often require significant memory and parameters, thus enabling execution only at very low resolutions and shallow architectures. We propose HexNet, an orientation-aware deep learning framework for spherical signals, that allows for fast computation as we exploit standard planar network operations on an efficiently arranged projection of the sphere. Furthermore, we introduce a graph-based version for partial spheres, allowing us to compete at high-resolution with planar CNNs using residual network architectures. Our kernels operate on the tangent of the sphere and thus standard feature weights, pretrained on perspective data, can be transferred, enabling spherical pretraining on ImageNet. As our design is free of distortions and discontinuity, our orientation-aware CNN becomes a new state of the art for semantic segmentation on the recent 2D3DS dataset, and the omni-directional version of SYNTHIA introduced in this work. Moreover, we experimentally show the benefit of our spherical representation over standard images on the Cityscapes dataset by reducing distortion effects of planar CNNs. We implement object detection for the spherical domain. Rotation invariant classification and segmentation tasks are additionally presented for comparison to prior art.

Physiological response mechanism of heavy metal-resistant endophytic fungi isolated from the roots of Polygonatum kingianum.

This study aims to evaluate the tolerance of endophytic fungi isolated from the fibrous roots of Polygonatum kingianum to arsenic (As) and cadmium (Cd) and their physiological response mechanisms. Five isolated strains were obtained with EC50 values for As(V) ranging from 421 to 1281 mg/L, while the other three strains tolerated Cd(II) with an EC50 range of 407-1112 mg/L. Morphological and molecular identification indicated that these eight strains were Cladosporium spp. belonging to dark septate endophytes (DSEs). The contents of metal ions in mycelium sharply increased, reaching 38.87 mg/kg for strain MZ-11 under As(V) stress and 0.33 mg/kg for fungus PR-2 under Cd(II). The physiological response revealed that the biomass decreased with increasing concentrations of As(V) or Cd(II), and the activity of superoxide dismutase significantly improved under the corresponding EC50 -concentration As/Cd of the strains, as well as the contents of antioxidant substances, including metallothionein, glutathione, malondialdehyde, melanin, and proline. Taken together, the filamentous fungi of Cladosporium spp. accounted for a high proportion of fungi isolated from the fibrous roots of P. kingianum and had a strong capacity to tolerate As(V) or Cd(II) stress by improving antioxidase activities and the content of antioxidant substances, and immobilization of metal ions in hyphae.

Snaring Self-Expanding Devices to Facilitate Transcatheter Aortic Valve Replacement in Patients with Complex Aortic Anatomies.

The snare-assisted technique has been described to facilitate transcatheter aortic valve replacement (TAVR) delivery system advancement in complex aortic anatomies. However, the evidence is limited to case reports. To evaluate the safety profile of the snare-facilitated approach and its impact on self-expanding (SE) TAVR outcomes, we collected consecutive patients who underwent transfemoral SE-TAVR for aortic stenosis, using propensity score matching (PSM) separately in tricuspid and type-0 and type-1 bicuspid aortic valve morphology between the snare and non-snare groups. In 766 patients, despite the snare group having significantly larger annulus angulation and maximal ascending aortic diameter, both groups achieved comparable 30-day device success rates, regardless of first-generation or new-generation valve use. After PSM, the snare group had a significantly lower new permanent pacemaker implantation rate among 193 type-0 patients (3.3% vs. 18.3%, p = 0.01). The ipsilateral group used new-generation valves less frequently (23.0% vs. 75.4%, p < 0.001), but there were no significant inter-group differences in procedure-related events, except for a lower incidence of PVL ≥ mild in the ipsilateral group (14.9% vs. 32.3%, p = 0.01). In conclusion, the snare-assisted technique appears useful in SE-TAVR with angulated aortic root anatomy, and the benefits were comparable between ipsilateral and contralateral snare techniques.

High accuracy epidermal growth factor receptor mutation prediction via histopathological deep learning.

BACKGROUND: The detection of epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer is critical for tyrosine kinase inhibitor therapy. EGFR detection requires tissue samples, which are difficult to obtain in some patients, costing them the opportunity for further treatment. To realize EGFR mutation prediction without molecular detection, we aimed to build a high-accuracy deep learning model with only haematoxylin and eosin (H&E)-stained slides. METHODS: We collected 326 H&E-stained non-small cell lung cancer slides from Beijing Chest Hospital, China, and used 226 slides (88 with EGFR mutations) for model training. The remaining 100 images (50 with EGFR mutations) were used for testing. We trained a convolutional neural network based on ResNet-50 to classify EGFR mutation status on the slide level. RESULTS: The sensitivity and specificity of the model were 76% and 74%, respectively, with an area under the curve of 0.82. When applying the double-threshold approach, 33% of the patients could be predicted by the deep learning model as EGFR positive or negative with a sensitivity and specificity of 100.0% and 87.5%. The remaining 67% of the patients got an uncertain result and will be recommenced to perform further examination. By incorporating adenocarcinoma subtype information, we achieved 100% sensitivity in predicting EGFR mutations in 37.3% of adenocarcinoma patients. CONCLUSIONS: Our study demonstrates the potential of a deep learning-based EGFR mutation prediction model for rapid and cost-effective pre-screening. It could serve as a high-accuracy complement to current molecular detection methods and provide treatment opportunities for non-small cell lung cancer patients from whom limited samples are available.

Deep learning-based diagnosis of histopathological patterns for invasive non-mucinous lung adenocarcinoma using semantic segmentation.

OBJECTIVES: The application of artificial intelligence (AI) to the field of pathology has facilitated the development of digital pathology, hence, making AI-assisted diagnosis possible. Due to the variety of lung cancers and the subjectivity of manual evaluation, invasive non-mucinous lung adenocarcinoma (ADC) is difficult to diagnose. We aim to offer a deep learning solution that automatically classifies invasive non-mucinous lung ADC histological subtypes. DESIGN: For this investigation, 523 whole-slide images (WSIs) were obtained. We divided 376 of the WSIs at random for model training. According to WHO diagnostic criteria, six histological components of invasive non-mucinous lung ADC, comprising lepidic, papillary, acinar, solid, micropapillary and cribriform arrangements, were annotated at the pixel level and employed as the predicting target. We constructed the deep learning model using DeepLab v3, and used 27 WSIs for model validation and the remaining 120 WSIs for testing. The predictions were analysed by senior pathologists. RESULTS: The model could accurately predict the predominant subtype and the majority of minor subtypes and has achieved good performance. Except for acinar, the area under the curve of the model was larger than 0.8 for all the subtypes. Meanwhile, the model was able to generate pathological reports. The NDCG scores were greater than 75%. Through the analysis of feature maps and incidents of model misdiagnosis, we discovered that the deep learning model was consistent with the thought process of pathologists and revealed better performance in recognising minor lesions. CONCLUSIONS: The findings of the deep learning model for predicting the major and minor subtypes of invasive non-mucinous lung ADC are favourable. Its appearance and sensitivity to tiny lesions can be of great assistance to pathologists.