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OBJECTIVE The utility of endovascular thrombectomy (EVT) in patients with acute ischemic stroke, large vessel occlusion (LVO), and low Alberta Stroke Program Early CT Scores (ASPECTS) remains uncertain. The objective of this study was to determine the health outcomes and cost-effectiveness of EVT versus medical management in patients with ASPECTS < 6. METHODS A decision-analytical study was performed with Markov modeling to estimate the lifetime quality-adjusted life-years (QALYs) and associated costs of EVT-treated patients compared to medical management. The study was performed over a lifetime horizon with a societal perspective in the US setting. RESULTS The incremental cost-effectiveness ratios were $412,411/QALY and $1,022,985/QALY for 55- and 65-year-old groups in the short-term model. EVT was the long-term cost-effective strategy in 96.16% of the iterations and resulted in differences in health benefit of 2.21 QALYs and 0.79 QALYs in the 55- and 65-year-old age groups, respectively, equivalent to 807 days and 288 days in perfect health. EVT remained the more cost-effective strategy when the probability of good outcome with EVT was above 16.8% or as long as the good outcome associated with the procedure was at least 1.6% higher in absolute value than that of medical management. EVT remained cost-effective even when its cost exceeded $100,000 (threshold was $108,036). Although the cost-effectiveness decreased with age, EVT was cost-effective for 75-year-old patients as well. CONCLUSIONS This study suggests that EVT is the more cost-effective approach compared to medical management in patients with ASPECTS < 6 in the long term (lifetime horizon), considering the poor outcomes and significant disability associated with nonreperfusion.

Accurate prediction of topographical correlation between craniopharyngiomas (CPs) and hypothalamus is important for treatment. This study sought to develop a predicting tool based on preoperative-MRI through radiological–surgical–pathological–outcome analysis. Third ventricle floor (TVF), mammillary bodies and cerebral peduncle were evaluated through preoperative-MRI. An eagle-head-like sign named “eagle sign” was observed. Normal TVF on sagittal-MRI was defined as the baseline. Variants of the sign were analyzed by comparing with the baseline and corresponding correlations of CPs with hypothalamus were verified using intraoperative records, histopathology and outcome evaluation. A total of 146 CPs patients, who undergone endoscopic endonasal procedure were divided into four groups based on the variants of “eagle sign”. Group A: 24 patients with the upward sign; group B: 81 with the downward sign; group C: 21 with the anterior TVF upward sign and group D: 20 with the unidentifiable sign. Surgical–pathological analysis showed significant correlations between 95.8% CPs in group A and 95.2% in group C with tumor topography and tumor adherence to the hypothalamus. These CPs had their origins beneath the hypothalamus. In contrast, groups B and D, with hypothalamic origin, showed hypothalamic infiltration by tumor in 97.5% and 95% of cases in groups B and D, respectively. Outcomes of groups A and C were relatively better than groups B and D. Predictive sensitivity and specificity of “eagle sign” were more than 90%. “Eagle sign” is an accurate tool for predicting topographic correlations between CPs and hypothalamus with high sensitivity and specificity.

Background: This study aimed to evaluate the role of plasma microRNA panel (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a and miR-801) for prediction and surveillance of early tumor recurrence in hepatocellular carcinoma (HCC) patients who had undergone liver transplantation (LT). Methods: The expression of plasma microRNA panel was assayed in 193 HCC patients (training cohort, n =151; validation cohort, n = 42). Sensitivity and specificity for detecting post-transplant HCC recurrence, and the relationship of microRNA panel expression with clinical characteristics were analyzed accordingly. The prognostic value of microRNA panel was compared with that of AFP (alpha-fetoprotein) and DCP (Des-gamma-carboxyprothrombin). Cox regression analyses were used to evaluate independent prognostic factors. Results: In the training cohort, the rate of positive plasma microRNA panel status at 7-14 days after LT (late phase; 44.2%) decreased than that before (76.2%, P < 0.001) and 1-6 days after LT (early phase; 78.5%, P < 0.001). At late phase, positive microRNA panel status correlated with higher early tumor recurrence rate (one year after LT) than negative status (45.9% vs 10.7%; P < 0.001). Patients with persistent positive microRNA panel status both before and after LT had the highest early tumor recurrence rate in this cohort (54.9%, P < 0.001). The results were consistent in the validation cohort. Cox regression analysis found that positive plasma microRNA panel status at late phase was the only independent risk factor for early recurrence (HR: 4.903, 95% CI = 2.195 - 10.951; P < 0.001). Dynamic monitoring demonstrated plasma microRNA panel status changed from negative to positive earlier than AFP and DCP upon recurrence, and the median time between positivity of plasma microRNA and imaging evidence of recurrence was 2.4 (0.5-10.0) months. Conclusions: Plasma microRNA panel could be a noninvasive biomarker for prediction and surveillance of early tumor recurrence in HCC patients who have undergone LT.

Background and objective Ecological studies have suggested an association between exposure to particulate matter ≤2.5 μm (PM2.5 ) and coronavirus disease 2019 (COVID-19) severity. However, these findings are yet to be validated in individual-level studies. We aimed to determine the association of long-term PM2.5 exposure with hospitalization among individual patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We estimated the 10-year (2009-2018) PM2.5 exposure at the residential zip code of COVID-19 patients diagnosed at the University of Cincinnati healthcare system between 13 March 2020 and 30 September 2020. Logistic regression was used to determine the odds ratio (OR) and 95% CI for COVID-19 hospitalizations associated with PM2.5 , adjusting for socioeconomic characteristics and comorbidities. Results Among the 14,783 COVID-19 patients included in our study, 13.6% were hospitalized; the geometric mean (SD) PM2.5 was 10.48 (1.12) μg/m3 . In adjusted analysis, 1 μg/m3 increase in 10-year annual average PM2.5 was associated with 18% higher hospitalization (OR: 1.18, 95% CI: 1.11-1.26). Likewise, 1 μg/m3 increase in PM2.5 estimated for the year 2018 was associated with 14% higher hospitalization (OR: 1.14, 95% CI: 1.08-1.21). Conclusion Long-term PM2.5 exposure is associated with increased hospitalization in COVID-19. Therefore, more stringent COVID-19 prevention measures may be needed in areas with higher PM2.5 exposure to reduce the disease morbidity and healthcare burden.

Jianfei Pan,1,* Quanwei Zhu,1,* Xiaoqian Zhang,2 Jun Xu,1 Linlin Pan,1 Xiang Mao,3 Xiao Wu1,4,* 1Department of Emergency, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China; 3Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China; 4Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiang MaoDepartment of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of ChinaTel +86 65908477Email xiangmao1002@163.comPurpose: To explore the distribution of pathogenic bacteria in patients with intra-abdominal infection, to clarify the independent factors that affect the prognosis of patients with intra-abdominal infection and its evaluation value for prognosis.Patients and Methods: The pathogens, underlying diseases, and related clinical data of patients with intra-abdominal infection from January 2012 to December 2019 in our hospital were retrospectively collected and the APACHE II score was calculated. The patients were divided into survival group and death group according to the prognosis, and the index between the two groups was compared. Spearman correlation analysis was used to evaluate the correlation between each index and prognosis, multivariate logistic regression analysis was used to screen the independent prognostic factors.Results: Spearman correlation analysis showed that ALB level was negatively correlated with prognosis, age and APACHE II score were positively correlated with prognosis. Logistic regression analysis showed that age, ALB level, and APACHE II score were independent prognostic factors. The formula of age combined ALB level and APACHE II score was Y = X1-3.6X2 + 6.5X3 (X1 was the age, X2 was the ALB level and X3 was the APACHE II score), Y was positively correlated with poor prognosis, and the optimal cutoff value was Y = 40.96.Conclusion: Age, ALB level, and APACHE II score are independent factors that influencing the prognosis of patients with intra-abdominal infection, and the combination of age, ALB level, and APACHE II score can better assess the prognosis of patients with intra-abdominal infection.Keywords: intra-abdominal infection, formula, prognostic factors, the value of independent factors, single center

Unconventional surgical procedures may be utilized in treating complicated middle aortic syndrome (MAS), the outcome and prognosis of which remain largely undetermined due to limited numbers and significant heterogeneity of this population. Using computational fluid dynamics (CFD) analysis, this study aimed to assess the dynamic changes of postoperative aortic flow in seeking to unveil the relationship between hemodynamics and vascular remodeling and thrombotic events. One patient with middle aortic syndrome complicated with aortic rupture was treated with hybrid repair of extra-anatomic bypass and fenestrated endovascular aortic repair. The patient was followed-up for 8 months by computational tomography angiography and Doppler ultrasound. Thoracoabdominal aortic blood flow and locations with ongoing thrombosis at 1, 3, and 6 months postoperatively were simulated and analyzed. Remodeling processes, including low wall shear-mediated constrictive remodeling of non-stented aorta, neointimal hyperplasia at suture lines, and minimal thrombosis at various locations, were evident. Meanwhile, abdominal blood flow was tri-phasic at 1 month after surgery, and was reversed and stabilized at 6 months. The distribution of newly formed thrombus vary at different follow-up stages, which were in line with the numerical simulation of thrombosis from different postoperative time points. CFD-based sequential monitoring is of promising value in capturing dynamic changes of vascular outcome.

It is controversial whether there is a different risk of recurrence between two histological subtypes in craniopharyngioma (CP) patients. Some reported that adamantinomatous craniopharyngioma (ACP) had a higher risk of recurrence than papillary craniopharyngioma (PCP), but others reported that there is no significant difference between them. So, we conducted this systematic review and meta-analysis to determine the association between the histological subtype of CP and the rate of recurrence. A comprehensive literature search was undertaken in PubMed, EMBASE, and Web of Science for all English articles published up to November 2020. Recurrence data stratified by ACP and PCP were extracted from studies meeting inclusion criteria. A pooled analysis of the association between the histological subtype of craniopharyngioma and rates of recurrence was performed. Thirteen articles containing 974 patients were included. When stratified by two pathological subtypes, the total recurrence rate of ACP was 26.0% and PCP was 14.1%, which showed ACP associated with a higher risk of tumor recurrence than PCP (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.36, 3.30, P = 0.00). This is the first meta-analysis focusing on histological subtypes of CP. PCP associates with a lower risk of recurrence than ACP, indicating that ACP could act as one of recurrence risk factors for CP patients. Nevertheless, large sample size and well-designed multicenter studies in which the other clinical variables are controlled to determine the histological subtype of CP as an independent recurrence risk factor are needed.

BACKGROUND Cervical cancer is the fourth commonest malignancy in women around the world. It represents the second most commonly diagnosed cancer in South East Asian women, and an important cancer death cause in women of developing nations. Data collected in 2018 revealed 5690000 cervical cancer cases worldwide, 85% of which occurred in developing countries. AIM To assess self-perceived burden (SPB) and related influencing factors in cervical cancer patients undergoing radiotherapy. METHODS Patients were prospectively included by convenient sampling at The Fifth Affiliated Hospital of Sun Yat-Sen University, China between March 2018 and March 2019. The survey was completed using a self-designed general information questionnaire, the SPB scale for cancer patients, and the self-care self-efficacy scale, Strategies Used by People to Promote Health, which were delivered to patients with cervical cancer undergoing radiotherapy. Measurement data are expressed as the mean ± SD. Enumeration data are expressed as frequencies or percentages. Caregivers were the spouse, offspring, and other in 46.4, 40.9, and 12.7%, respectively, and the majority were male (59.1%). As for pathological type, 90 and 20 cases had squamous and adenocarcinoma/adenosquamous carcinomas, respectively. Stage IV disease was found in 12 (10.9%) patients. RESULTS A total of 115 questionnaires were released, and five patients were excluded for too long evaluation time (n = 2) and the inability to confirm the questionnaire contents (n = 3). Finally, a total of 110 questionnaires were collected. They were aged 31-79 years, with the 40-59 age group being most represented (65.4% of all cases). Most patients were married (91.8%) and an overwhelming number had no religion (92.7%). Total SPB score was 43.13 ± 16.65. SPB was associated with the place of residence, monthly family income, payment method, transfer status, the presence of radiotherapy complications, and the presence of pain (P < 0.05). The SPB and self-care self-efficacy were negatively correlated (P < 0.01). In multivariate analysis, self-care self-efficacy, place of residence, monthly family income, payment method, degree of radiation dermatitis, and radiation proctitis were influencing factors of SPB (P < 0.05). CONCLUSION Patients with cervical cancer undergoing radiotherapy often have SPB. Self-care self-efficacy scale, place of residence, monthly family income, payment method, and radiation dermatitis and proctitis are factors independently influencing SPB.

BACKGROUND Perivascular spaces (PVSs) are important component of the brain glymphatic system. While visual rating has been widely used to assess PVS, computational measures may have higher sensitivity for capturing PVS characteristics under disease conditions. PURPOSE To compute quantitative and morphological PVS features and to assess their associations with vascular risk factors and cerebral small vessel disease (CSVD). STUDY TYPE Prospective. POPULATION One hundred sixty-one middle-aged/later middle-aged subjects (age = 60.4 ± 7.3). SEQUENCE 3D T1-weighted, T2-weighted and T2-FLAIR sequences, and susceptibility-weighted multiecho gradient-echo sequence on a 3 T scanner. ASSESSMENT Automated PVS segmentation was performed on sub-millimeter T2-weighted images. Quantitative and morphological PVS features were calculated in white matter (WM) and basal ganglia (BG) regions, including volume, count, size, length (Lmaj ), width (Lmin ), and linearity. Visual PVS scores were also acquired for comparison. STATISTICAL TESTS Simple and multiple linear regression analyses were used to explore the associations among variables. RESULTS WM-PVS visual score and count were associated with hypertension (β = 0.161, P

BACKGROUND The aim of this study was to investigate the clinical effect of anti-arcuate suture in treating pernicious placenta previa. MATERIAL AND METHODS We selected 81 patients diagnosed with singleton pregnancy with pernicious placenta previa at Suzhou Municipal Hospital from January 2015 to December 2018. Among them, 41 patients treated with anti-arcuate suture were assigned to the study group, and the other 40 patients were treated with conventional suture were assigned to the control group. RESULTS Compared with traditional suture, anti-arcuate suture significantly reduced blood loss and blood transfusion, and anti-arcuate suture also reduced postoperative complications. In the control group, 7 women underwent hysterectomy, but only 1 woman underwent hysterectomy in the study group. CONCLUSIONS Anti-arcuate suture in pernicious placenta previa can reduce postpartum hemorrhage and reduce postoperative complications.

Understanding the pathophysiology of white matter hyperintensity (WMH) is necessary to reduce its harmfulness. Dilated perivascular space (PVS) had been found related to WMH. In the present study, we aimed to examine the topological connections between WMH and PVS, and to investigate whether increased interstitial fluid mediates the correlation between PVS and WMH volumes. One hundred and thirty-six healthy elder subjects were retrospectively included from a prospectively collected community cohort. Sub-millimeter T2 weighted and FLAIR images were acquired for assessing the association between PVS and WMH. Diffusion tensor imaging and free-water (FW) analytical methods were used to quantify white matter free water content, and to explore whether it mediates the PVS-WMH association. We found that most (89%) of the deep WMH lesions were spatially connected with PVS, exhibiting several interesting topological types. PVS and WMH volumes were also significantly correlated (r = 0.222, p

Background: White matter hyperintensity (WMH) is closely associated with geriatric depressive symptoms, but its underlying neural mechanism is unclear. We aim to disentangle the contribution of vascular degeneration and fiber disruption to depressive symptoms in elderly subjects at different clinical status. Methods: One hundred and thirty-three normal elderly subjects, as well as 43 patients with cerebral small vessel disease (CSVD) were included. The Hamilton Depression Rating Scale (HAMD) was used to measure depressive symptoms. Based on the diffusion tensor imaging data, a free water elimination analytical model was adopted to reflect fiber tract disruption (measure: tissue fractional anisotropy, tFA) and increased white matter water content (measure: free water fraction, FW). Results: We found that WMH severity was significantly correlated with decreased tFA and increased FW in all subjects. In normal elderly subjects, the HAMD score was correlated with mean tFA, but not FW. Compared to the traditional fractional anisotropy measure, tFA showed stronger correlation with clinical symptoms. In CSVD subjects, the correlation was only significant for FW, and marginally significant for tFA. Limitations: Most subjects had only mild to moderate depressive symptoms. Further validation in patients with major depressive disorder is needed to confirm these findings. Conclusions: The neural mechanisms of depressive symptoms may be different in elderly people with or without severe vascular damage. The free water elimination model may disentangle the effects of fiber disruption and increased free water, providing sensitive imaging markers that could potentially be used on monitoring disease treatment.

To investigate the association between white matter free water (FW) and common imaging markers of cerebral small vessel diseases (CSVD) in two groups of subjects with different clinical status. One hundred and forty-four community subjects (mean age 60.5) and 84 CSVD subjects (mean age 61.2) were retrospectively included in the present study. All subjects received multi-modal magnetic resonance imaging and clinical assessments. The association between white matter FW and common CSVD imaging markers, including white matter hyperintensities (WMH), dilated perivascular space (PVS), lacunes, and microbleeds, were assessed using simple and multiple regression analysis. The association between FW and cognitive scores were also investigated. White matter FW was positively associated with WMH volume (β = 0.270, p = 0.001), PVS volume (β = 0.290, p < 0.001), number of microbleeds (β = 0.148, p = 0.043), and age (β = 0.170, p = 0.036) in the community cohort. In the CSVD cohort, FW was positively associated with WMH volume (β = 0.648, p < 0.001), PVS score (β = 0.224, p < 0.001), number of lacunes (β = 0.140, p = 0.046), and sex (β = 0.125, p = 0.036). The associations between FW and cognitive scores were stronger than conventional CSVD markers in both datasets. White matter FW is a potential composite marker that can sensitively detect cerebral small vessel degeneration and also reflect cognitive impairments.

We performed this study to investigate the diagnostic performance of prostate-specific antigen density (PSAD) in a multicenter cohort of the Chinese Prostate Cancer Consortium. Outpatients with prostate-specific antigen (PSA) levels ≥4.0 ng ml−1 regardless of digital rectal examination (DRE) results or PSA levels

Objective The objective of this study was to describe the different components of left atrial (LA) dysfunction predictors in nonobstructive and occult obstructive hypertrophy cardiomyopathy (HCM) patients especially with preserved left ventricular (LV) ejection fraction, particularly using LA 4-dimensional (D) longitudinal and circumferential strains. Methods Twenty-eight nonobstructive HCM patients and 30 occult obstructive HCM patients according to LV outflow tract gradient at rest and after exercise were prospectively enrolled. 4D echocardiographic evaluation was performed in 58 HCM patients, both nonobstructive and occult obstructive, and 38 control subjects. LA reservoir, conduit, contractile functions were performed by 4D volume-strain with volumes and longitudinal, circumferential strains. Results Optimal correlation coefficients obtained between LV 4D mass (index) and LA 4D longitudinal/circumferential strain (r=-0.860 to 0.518, all P 0.75 and >0.85, respectively. Conclusions LA volumes were significantly increased and LA reservoir, conduit, and contractile functions were significantly impaired in HCM patients. Furthermore, different performances of LA functional analyses in nonobstruction and occult obstruction patients with 4D volume-strain echocardiography may facilitate the recognition of subtle LA dysfunctional differentiation in HCM patients.

Objectives: The most common type of noninvasive fungal rhinosinusitis is fungus ball (FB), which usually involves a solitary paranasal sinus. Multiple fungus balls (MFBs) are rarely reported in literature. The purpose of this study was to analyze and compare the clinical features of MFBs and solitary fungus ball (SFB). Methods: We retrospectively investigated consecutive cases of FB between 2001 and 2018 and compared the clinical records of SFB with MFBs with respect to demographics, clinical features, location, radiological findings, and operative outcome. Results: A total of 440 SFB and 43 MFBs cases were included in the study. The mean age was 55.3 ± 13.3 and 60.6 ± 10.9 years, respectively ( P = .011). The incidence of MFBs obviously increased from 2001 to 2018. The clinical symptoms and laboratory examination were similar. On computed tomography images, complete opacification, septal deviation, Haller cells, and obstruction of ostiomeatal complex were more common ( P < .05). The incidence of SFB on the left and right sides was similar, while MFBs were seen to involve both sides in 74.4%. Conclusions: Compared with SFB, MFBs showed some special characteristics. The MFBs affected older patients showed wide range of lesions and complex anatomy. Surgical technique is very important. Much more attention should be paid to this not so uncommon disease during the perioperative period.

BACKGROUND & AIMS Liver transplantation (LTx) is one of the most effective treatments for hepatocellular carcinoma (HCC); however, tumour recurrence after LTx often leads to poor outcomes. This study investigated the value of circulating tumour cells (CTCs) as a predictor of recurrence following LTx in patients with HCC. METHODS This analysis included 193 patients with HCC who underwent LTx at our institute and accepted pre- and post-operative CTC detection; 38 were selected for serial CTC monitoring. The predictive value of CTCs for tumour recurrence in patients with HCC following LTx was evaluated. Single-cell whole genome sequencing was used to characterize CTCs. RESULTS Overall, the CTC burden decreased after LTx (P

The precise understanding of hypothalamic injury (HI) patterns and their relationship with different craniopharyngioma (CP) classifications remains poorly addressed. Here, four HI patterns after CP resection based on endoscopic observation were introduced. A total of 131 CP cases treated with endoscopic endonasal approach (EEA) were reviewed retrospectively and divided into four HI patterns: no‐HI, mild‐HI, unilateral‐HI and bilateral‐HI, according to intraoperative findings. The outcomes were evaluated and compared between groups in terms of weight gain, endocrine status, electrolyte disturbance and neuropsychological function before and after surgery. A systematic correlation was found between CP origin and subsequent HI patterns. The majority of intrasellar and suprasellar stalk origins lead to a no‐HI pattern, the central‐type CP mainly develops a mild or bilateral HI pattern, and the majority of tumors with hypothalamic stalk origins result in unilateral HI and sometimes bilateral HI patterns. The proportion of tumors with a maximum diameter >3 cm in the no‐HI group was higher than that in the mild‐HI group, BMI and quality of life in the no‐HI group showed better results than those in the other groups. The incidence of new‐onset diabetes insipidus in the bilateral‐HI group was significantly higher than that in the other groups. Memory difficulty was observed mainly in the unilateral‐HI and bilateral‐HI groups. However, the outcomes of electrolyte disturbance, sleep, and cognitive disorder in the unilateral‐HI group were significantly better than those in the bilateral‐HI group. This study suggests the possibility of using pre‐ and intraoperative observation of CP origin to predict four HI patterns and even subsequent outcomes after tumor removal., This study provided possibility to use the pre‐ and intraoperative observation of craniopharyngiomas origin to predict the four hypothalamic injury patterns and subsequent outcomes after tumor removal.

Summary Background Accumulating evidence links fine particulate matter (PM2·5) to premature mortality, cardiovascular disease, and respiratory disease. However, less is known about the influence of PM2·5 on neurological disorders. We aimed to investigate the effect of long-term PM2·5 exposure on development of Parkinson's disease or Alzheimer's disease and related dementias. Methods We did a longitudinal cohort study in which we constructed a population-based nationwide open cohort including all fee-for-service Medicare beneficiaries (aged ≥65 years) in the contiguous United States (2000–16) with no exclusions. We assigned PM2·5 postal code (ie, ZIP code) concentrations based on mean annual predictions from a high-resolution model. To accommodate our very large dataset, we applied Cox-equivalent Poisson models with parallel computing to estimate hazard ratios (HRs) for first hospital admission for Parkinson's disease or Alzheimer's disease and related dementias, adjusting for potential confounders in the health models. Findings Between Jan 1, 2000, and Dec 31, 2016, of 63 038 019 individuals who were aged 65 years or older during the study period, we identified 1·0 million cases of Parkinson's disease and 3·4 million cases of Alzheimer's disease and related dementias based on primary and secondary diagnosis billing codes. For each 5 μg/m3 increase in annual PM2·5 concentrations, the HR was 1·13 (95% CI 1·12–1·14) for first hospital admission for Parkinson's disease and 1·13 (1·12–1·14) for first hospital admission for Alzheimer's disease and related dementias. For both outcomes, there was strong evidence of linearity at PM2·5 concentrations less than 16 μg/m3 (95th percentile of the PM2·5 distribution), followed by a plateaued association with increasingly larger confidence bands. Interpretation We provide evidence that exposure to annual mean PM2·5 in the USA is significantly associated with an increased hazard of first hospital admission with Parkinson's disease and Alzheimer's disease and related dementias. For the ageing American population, improving air quality to reduce PM2·5 concentrations to less than current national standards could yield substantial health benefits by reducing the burden of neurological disorders. Funding The Health Effects Institute, The National Institute of Environmental Health Sciences, The National Institute on Aging, and the HERCULES Center.

We try to investigate whether the values of three-dimensional principal longitudinal strain present differently between the left and right ventricles in patients with long-time follow-ups after heart transplantation (HTx).Transthoracic echocardiography with three-dimensional speckle tracking was performed at one-, five- and ten-year follow-ups in 62 "healthy" HTx patients together with routine echocardiographic evaluation in 32 control group (CG) individuals. Longitudinal strain was applied in all subjects assessing without myocardium wall motion abnormality. Firstly, left ventricular ejection fraction preserved in HTx and had no significant difference in comparison with the controls (p .05). 3D measurement showed obvious reduction in global (%: CG: -20.5 ± 3.5 vs. HT1y: -13.7 ± 4.6, HT5y: -14.4 ± 4.5, HT10y: -14.6 ± 4.7. p .01) and horizontal segmental (basal, mid, apical, CG vs. HTx: all p .01) strain values of the left compared HTx with control subjects. Secondly, tissue Doppler imaging s' velocity and tricuspid annular plane systolic excursion reduced in HTx as compared to the controls in right ventricle (p .01). Longitudinal strain presented a more distinctive reduction in global (%: CG: -24.5 ± 4.6 vs. HT1y:-14.8 ± 7.5, HT5y: -15.5 ± 6.4, HT10y: -15.9 ± 6.8. p .01) and horizontal segmental (basal, mid, apical, CG vs. HTx: all p .01) average values of the right compared HTx with control subjects. Thirdly, there weren't any significant changes between one-, five- and ten-year of all the values with HTx inter-group comparison in both the left and right ventricles (p .05). Fourthly, the global and segmental strain of the right ventricle decreased more than that of the left ventricle in all HTx groups, with the global decreased differentiation rates of 7%, 7%, 6%, respectively.Compared HTx with control subjects in both ventricles, conventional evaluation showed preserved or decreased functions in the left and right separately. Myocardial function evaluating by 3D longitudinal strain reduced after HTx, but the deformation of the right ventricle reduced more than those of the left ventricle. Additionally, 3D strain values almost remained with stable decreased differentiation rates during the long-time follow-ups.

Intramuscular hemangioma is a rare but challenging cause of pain in the lower extremities. When nonsurgical approaches have a certain possibility of post-procedural recurrence or incomplete success, surgery is a good choice. An open excision forms a long scar but allows for a wider surgical scope. Excision by arthroscopy may be a possible method for the treatment of intramuscular hemangioma with overall better results. The purpose of this study was to evaluate and compare the clinical outcomes of arthroscopic and open excisions for the treatment of intramuscular hemangioma of a lower extremity. Fifty-two patients with intramuscular hemangioma were divided into either the arthroscopic or open excision groups. Each group was compared by operative time, Lysholm score, length of the scar, the numbness of the surgery area, satisfaction of appearance, recurrence, and infection. Compared with the open excision group, the Lysholm scores mean ± standard error between the arthroscopic and open excision groups were 96.2 ± 3.7 to 93.2 ± 4.2 (P

Objectives The purpose of this study was to investigate the significance of tumor number on clinicopathologic factors and outcomes of patients with papillary thyroid carcinoma (PTC). Methods We retrospectively analyzed 667 patients with PTC. We compared clinicopathologic features of patients with a different tumor number. Cox proportional hazards model was used to analyze risk factors of recurrence. Results In papillary thyroid microcarcinoma (PTMC), the increase in the number of tumor foci was related to a higher risk of minimal extrathyroidal extension (ETE) and lymphovascular invasion (P < .05). Patients with PTMC with four or more foci had a significantly higher risk of central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM) than patients with solitary tumors (P < .05). Patients with macro-PTC with four or more foci and with three foci had a higher risk of gross ETE and lymphovascular invasion than patients with solitary tumors (P < .05). The increase in the tumor number was related to a higher risk of CLNM in macro-PTC (P < .05). The number of foci was the independent predictor of recurrence in patients with macro-PTC (P < .05). Conclusions An increase in the number of tumors was associated with an increased risk of aggressive clinicopathologic features in PTMC and macro-PTC. The number of tumor foci could influence risk of recurrence in macro-PTC.

Background The aim of this study was to investigate the potential anti-obesity effects of Camellia nitidissima Chi flower extract (Cnfe) by examining its effects in terms of the regulation of lipid levels and modulation of gut microbiota in rats with high-fat-diet-induced obesity. Results Our results demonstrated that Cnfe significantly decreased weight gain by reducing appetite and decreasing high-fat food intake. Further, Cnfe restored normal lipid metabolism and improved insulin sensitivity and glucose tolerance in rats fed a high-fat diet. Real-time reverse transcription polymerase chain reaction and western blot results showed that Cnfe significantly decreased the expression of genes and proteins involved in adipogenesis and lipogenesis, and upregulated the expression of lipolysis genes. 16S ribosomal RNA sequencing of feces showed that Cnfe dramatically reversed dysbacteriosis in rats with high-fat-diet-induced obesity by decreasing the abundance of Firmicutes and increasing that of Bacteroidetes and Verrucomicrobia at the phylum level. Conclusion The results demonstrate that Cnfe is a potential anti-obesity prebiotic nutrient that can prevent weight gain, ameliorate obesity-related dyslipidemia and hyperglycemia, inhibit liver fat accumulation, and modulate gut microbiota. © 2020 Society of Chemical Industry.

Background Adenosquamous carcinoma (ASC) is an uncommon histological subtype of lung cancer. The purpose of this study was to assess the cumulative incidences of lung cancer-specific mortality (LC-SM) and other cause-specific mortality (OCSM) in lung ASC patients, and construct a corresponding competing risk nomogram for LC-SM. Methods Data on 2705 patients with first primary lung ASC histologically diagnosed between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence function (CIF) was utilized to calculate the 3-year and 5-year probabilities of LC-SM and OCSM, and a competing risk model was built. Based on the model, we developed a competing risk nomogram to predict the 3-year and 5-year cumulative probabilities of LC-SM and the corresponding concordance indexes (C-indexes) and calibration curves were derived to assess the model performance. To evaluate the clinical usefulness of the nomogram, decision curve analysis (DCA) was conducted. Furthermore, patients were categorized into three groups according to the tertile values of the nomogram-based scores, and their survival differences were assessed using CIF curves. Results The 3-year and 5-year cumulative mortalities were 49.6 and 55.8% for LC-SM and 8.2 and 11.8% for OCSM, respectively. In multivariate analysis, increasing age, male sex, no surgery, and advanced T, N and M stages were related to a significantly higher likelihood of LC-SM. The nomogram showed good calibration, and the 3-year and 5-year C-indexes for predicting the probabilities of LC-SM in the validation cohort were both 0.79, which were almost equal to those of the ten-fold cross validation. DCA demonstrated that using the nomogram gained more benefit when the threshold probabilities were set within the ranges of 0.24–0.89 and 0.25–0.91 for 3-year and 5-year LCSM, respectively. In both the training and validation cohorts, the high-risk group had the highest probabilities of LC-SM, followed by the medium-risk and low-risk groups (both P Conclusions The competing risk nomogram displayed excellent discrimination and calibration for predicting LC-SM. With the aid of this individualized predictive tool, clinicians can more expediently devise appropriate treatment protocols and follow-up schedules.

The predominance of onychomycosis has been increasing recently. New medications and treatment modalities are being researched for better saturation of the antifungal agents through the nail plate topically because of the low resilience of some patients for the oral antifungal agents. Treatment of onychomycosis, mainly moderate to severe, can be very challenging, expensive, and time consuming. The objective of this clinical trial is to compare the efficacy and safety of a manually operated ablative CO2 laser combined with a topical antifungal agent in patients with onychomycosis. We conducted an open-label controlled prospective study of 160 eligible patients randomized into control and treatment groups with a 1:1 allocation in the department of dermatology in five different hospitals in Shanghai. It was a 6-month study where both groups were treated with a topical antifungal agent, with the treatment group also receiving ablation by the traditional CO2 laser once a month for the first 3 months. The clinical efficacy and mycological cure rate were significantly higher (p

Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 × 10 9 /L vs. 0.76 × 10 9 /L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.

Functional constipation (FC) is a chronic disease that significantly affects the life quality of patients. Acupuncture has been used for the treatment of FC for many years, but its effectiveness has not been scientifically assessed. The present study aimed to evaluate the efficacy of electro-acupuncture (EA) in relieving the symptoms, mental states and quality of life (QOL) of FC patients. A total of 96 FC patients were randomly allocated into EA, mosapride & sham EA group (MS) and mosapride control group (MC). In the EA group, patients were treated with 16 sessions of needling at Quchi (LI11) and Shangjuxu (ST37) bilaterally, 5 times a week in the first 2 weeks, and 3 times a week in the last 2 weeks. In the MC group, patients were treated with 5 mg mosapride citrate three times a day for 4 weeks. In the MS group, patients underwent sham EA and the same mosapride citrate treatment as in the MC group. The primary outcome was the number of weekly spontaneous bowel movements (SBMs). The secondary outcomes included stool consistency, intensity of defecating difficulty, 36-Item Short-Form Health Survey (SF-36), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and the validated Patient Assessment of Constipation-Quality of Life (PAC-QOL). The results showed that as compared with the baseline, EA significantly improved the weekly SBMs, stool consistency and intensity of defecating difficulty (P

Background Chronic cough is a common symptom in children and protracted bacterial bronchitis (PBB) is one of the causes of chronic cough. However, the understanding of this disease remains limited. The present study aims to update PBB in children. Methods The clinical data of children with PBB from 2014 to 2018 were retrospectively analyzed, and PBB clinical features of published studies were summarized. Electronic databases were searched in May 2019. Clinical studies were included in the present study. Reviews were undertaken in duplicate. Results Totally 712 cases were analyzed in this study, including 52 cases in our center and 660 cases from 14 studies. In the 52 cases, 88.5% of patients with PBB were less than 6 years old and all of them complained of wet cough. Three cases were confirmed with laryngomalacia, and microbiologically-based-PBB were identified in 13 cases (9 Streptococcus pneumonia, 3 Staphylococcus aureus, and 1 Pseudomonas aeruginosa). Twenty cases were completely remitted after treatment. In the 14 studies, the patients with PBB were typically younger than 3 years old, accompanying wheezing and airway malacia. Co-infection was common in most western cases, Streptococcus pneumonia, Haemophilus influenza and Moraxella catarrhalis were the top three pathogens. Symptoms were improved in most patients, whereas some cases with comorbidities required prolonged antibiotics treatment. Conclusions PBB is common in male infants with chronic wet cough and accompanied by wheezing and airway deformities. Most cases are clinically diagnosed PBB in China and microbiologically-based-PBB is common in western countries. Co-infection could be found, Streptococcus pneumoniae and Haemophilus influenza were the most frequent etiology in China and western countries, respectively. Patients with comorbidities may need extended antibiotics treatment for more than 2 weeks.

Background and Purpose— This study aims to investigate the association between the characteristics of atherosclerotic plaques of middle cerebral artery and recurrent ischemic stroke using magnetic resonance vessel wall imaging. Methods— One hundred and five patients with ischemic stroke attributed to middle cerebral artery plaque underwent high-resolution black-blood magnetic resonance vessel wall imaging. They were divided into group 1, with the first episode of acute stroke (imaging within 4 weeks of stroke, n=44); group 2, with recurrent acute stroke (n=29); and group 3, with chronic stroke (imaging after 3 months of stroke, n=32). Plaque characteristics including plaque area, plaque burden, contrast-enhancement ratio, eccentricity, and degree of stenosis were measured and compared across 3 groups. Association between plaque characteristics and recurrent strokes was investigated by multivariate analysis. Results— Plaque burden was significantly greater in recurrent stroke group than the other 2 groups (median: group 2, 82.7%, versus group 1, 76.3%, and group 3, 73.4%; P =0.001). Patients with acute stroke had higher enhancement ratio than patients with chronic stroke (median: group 1, 1.59, and group 2, 1.90, versus group 3, 1.33; P =0.014). Comparing to first-onset acute stroke patients, recurrent stroke patients were older, more likely with female sex and hypertension, and had higher plaque burden. After adjustment of clinical factors, plaque burden was the only independent imaging feature associated with recurrent stroke (odds ratio, 2.26, per 10% increase [95% CI, 1.03–4.96]; P =0.042). Conclusions— Higher plaque burden of middle cerebral artery identified on magnetic resonance vessel wall imaging is independently associated with recurrent ischemic stroke.

Objective: The purpose of this study was to evaluate the different components of left atrial (LA) dysfunction predictors in asymptomatic primary systemic hypertension patients with preserved left ventricular (LV) ejection fraction, particularly using LA 4-dimensional (4D) longitudinal and circumferential strain values. Methods and Results: Patients with no left ventricular hypertrophy (NLVH) and left ventricular hypertrophy (LVH) are all asymptomatic regarding primary blood hypertension. Thirty NLVH patients and 30 LVH patients according to LV mass index and 40 controls analyzed by 4D echocardiography were prospectively enrolled. LA volumes and longitudinal and circumferential strains were measured using 4D volume-strain echocardiography with a Vivid E95 Version 203 instrument. Correlation analysis indicated a significant relation between LV 4D mass index and LA 4D longitudinal/circumferential strain (r = –0.446 to 0.381, p = 0.000–0.042). LVH patients had a reduced LA emptying fraction compared with NLVH patients and control subjects (p < 0.01). NLVH patients had an impaired LA conduit function and increased contractile function compared with the control group (p < 0.01). LVH patients had increased LA volumes and significantly decreased reservoir, conduit and contractile functions compared with the controls (p < 0.01). LVH patients had increased LA volumes and decreased reservoir and contractile functions compared with NLVH patients (p < 0.01). The clinical utility of LA 4D volume-strain measurement was verified by receiver-operating characteristic curve analysis showing larger net benefits as evaluated with NLVH, LVH and control group comparisons. Interclass correlation coefficients of interobserver and intraobserver assessments in the LV and LA 4D value evaluations were >0.75 and >0.85, respectively. Conclusions: LVH patients showed increased LA volumes and decreased LA emptying fractions. LA reservoir, conduit and contractile functions were significantly impaired in LVH patients. Decreased LA conduit function and increased contractile function were revealed in NLVH patients. LA volumetric and functional analyses with 4D volume-strain echocardiography may facilitate the recognition of subtle LA and LV dysfunctions in asymptomatic systemic hypertension patients.

ObjectiveThe surgical management of lesions involving the lateral area of the suprasellar region, including the lateral aspect of the planum sphenoidale and the tight junction region of the optic canal (OC), anterior clinoid process (ACP), and internal carotid artery (ICA) and its dural rings, is extremely challenging. Here, these regions, namely, the “parasuprasellar” area, are described from the endonasal perspective. Moreover, the authors introduce two novels endoscopic endonasal supraoptic (EESO) and endoscopic endonasal infraoptic (EEIO) approaches to access the parasuprasellar area.MethodsSurgical simulation of the EESO and EEIO approaches to the parasuprasellar area was conducted in 5 silicon-injected specimens. The same techniques were applied in 12 patients with lesions involving the parasuprasellar area.ResultsThe EESO approach provided excellent surgical access to the lateral region of the planum sphenoidale, which corresponds to the orbital gyrus of the frontal lobe. With stepwise bone (OC, optic strut and ACP) removal, dissociation of the ophthalmic artery (OA) and optic nerve (ON), the EEIO approach enables access to the lateral region of the supraclinoidal ICA. These approaches can be used independently or in combination, but are more often employed as a complement to the endoscopic endonasal midline and transcavernous approaches. In clinical application, the EESO and EEIO approaches were successfully performed in 12 patients harboring tumors as well as multiple aneurysms involving the parasuprasellar area. Gross total and subtotal tumor resection were achieved in 9 patients and 1 patient, respectively. For two patients with multiple aneurysms, the lesions were clipped selectively according to location and size. Visual acuity improved in 7 patients, remained stable in 4, and deteriorated in only 1. No postoperative intracranial infection or ICA injury occurred in this series.ConclusionsThe EESO and EEIO approaches offer original treatment options for well-selected lesions involving the parasuprasellar area. They can be combined with the endoscopic endonasal midline and transcavernous approaches to remove extensive pathologies involving the intrasellar, suprasellar, sphenoid, and cavernous sinuses and even the bifurcation of the ICA. This work for the first time pushes the boundary of the endoscopic endonasal approach lateral to the supraclinoidal ICA and ON.

Background & Aims Early recurrence of hepatocellular carcinoma (HCC) after curative resection is common. However, the association between genetic mechanisms and early HCC recurrence, especially in Chinese patients, remains largely unknown. Methods We performed whole-genome sequencing (49 cases), whole-exome sequencing (18 cases), and deep targeted sequencing (115 cases) on 182 primary HCC samples. Focusing on WNK2, we used Sanger sequencing and qPCR to evaluate all the coding exons and copy numbers of that gene in an additional 554 HCC samples. We also explored the functional effect and mechanism of WNK2 on tumor growth and metastasis. Results We identified 5 genes (WNK2, RUNX1T1, CTNNB1, TSC1, and TP53) harboring somatic mutations that correlated with early tumor recurrence after curative resection in 182 primary HCC samples. Focusing on WNK2, the overall somatic mutation and copy number loss occurred in 5.3% (39/736) and 27.2% (200/736), respectively, of the total 736 HCC samples. Both types of variation were associated with lower WNK2 protein levels, higher rates of early tumor recurrence, and shorter overall survival. Biofunctional investigations revealed a tumor-suppressor role of WNK2: its inactivation led to ERK1/2 signaling activation in HCC cells, tumor-associated macrophage infiltration, and tumor growth and metastasis. Conclusions Our results delineate genomic events that characterize Chinese HCCs and identify WNK2 as a driver of early HCC recurrence after curative resection. Lay summary We applied next-generation sequencing and conducted an in-depth genomic analysis of hepatocellular carcinomas from a Chinese patient cohort. The results delineate the genomic events that characterize hepatocellular carcinomas in Chinese patients and identify WNK2 as a driver associated with early tumor recurrence after curative resection.

Background and Aims: Cholecystectomy is the “gold standard” for treating diseases of the gallbladder. In addition, non-alcoholic fatty liver disease (NAFLD), liver fibrosis or cirrhosis, are major causes of morbidity and mortality across the world. However, the association between cholecystectomy and these diseases is still unclear. We assessed the association among US adults and examined the possible risk factors.Methods: This cross-sectional study used data from 2017 to 2018 National Health and Nutrition Examination Survey, a population-based nationally representative sample of US. Liver fibrosis and cirrhosis were defined by median stiffness, which was assessed by transient elastography. Furthermore, patients who had undergone cholecystectomy were identified based on the questionnaire. In addition, Propensity Score Matching (PSM, 1:1) was performed based on gender, age, body mass index (BMI) and diabetes.Results: Of the 4,497 included participants, cholecystectomy was associated with 60.0% higher risk of liver fibrosis (OR:1.600;95% CI:1.278–2.002), and 73.3% higher risk of liver cirrhosis (OR:1.733, 95% CI:1.076–2.792). After PSM based on age, gender, BMI group and history of diabetes, cholecystectomy was associated with 139.3% higher risk of liver fibrosis (OR: 2.393;95% CI: 1.738–3.297), and 228.7% higher risk of liver cirrhosis (OR: 3.287, 95% CI: 1.496–7.218).Conclusions: The present study showed that cholecystectomy is positively associated with liver fibrosis and cirrhosis in US adults. The discovery of these risk factors therefore provides new insights on the prevention of NAFLD, liver fibrosis, and cirrhosis.

Background: Individualized rehabilitation based on graft maturity is necessary to optimize patient function and prevent graft re-injury. But there is a lack of studies on graft maturity in the all-inside single-bundle anterior cruciate ligament reconstruction.Hypothesis/Purpose: Compared to the difference in graft maturity, functional scores, and stability between all-inside and anatomical single-bundle anterior cruciate ligament reconstruction, it was assumed that the stability of all-inside reconstruction is relatively insufficient, and its graft maturity is worse than the anatomical reconstruction.Study Design: Randomized controlled clinical trial.Methods: Fifty-four patients were recruited in this study and randomly assigned to the all-inside reconstruction group (n = 27) and the anatomical reconstruction group (n = 27) using the same rehabilitation strategy. The Tegner, International Knee Documentation Committee, and Lysholm score were recorded at postoperative 3rd, 6th, and 12th month to assess functional recovery. Magnetic resonance imaging was conducted to measure the Signal/Noise quotient (SNQ) of the intra-articular graft to observe the maturity. Stability was assessed using GNRB relaxation measuring instrument at the postoperative 12th month.Results: The graft SNQ of the all-inside group was significantly higher than that in the anatomical group during the postoperative 6th month (p < 0.05). There was no statistical difference in graft SNQ between the two groups at postoperative 3rd and 12th month (p > 0.05). Both groups exhibited the graft’s highest SNQ in the middle region, followed by the proximal region, and the lowest was the distal region. Functional scores improved significantly in both groups and had no statistical difference (p > 0.05). The stability recovered well in both groups during the postoperative 12th month, but the GNRB relaxation was higher in the all-inside group (p < 0.05). There was no correlation between functional scores and graft maturity in the two groups (p > 0.05).Conclusions: All-inside reconstruction graft maturity is inferior to the anatomical reconstruction during postoperative 6th month, which may cause relatively insufficient stability of all-inside reconstruction compared with anatomical reconstruction under the same rehabilitation strategy. A more conservative rehabilitation strategy for all-inside reconstruction around the postoperative 6th month may achieve better stability.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or p = 0.12) or age (≥60 or p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

BackgroundIt is controversial whether adjuvant treatment could be recommended for hepatocellular carcinoma (HCC) after curative hepatectomy. Thus, we performed a network meta-analysis (NMA) to assess adjuvant treatment’s benefit and determine the optimal adjuvant regimen.MethodsWe systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials comparing adjuvant therapy versus no active treatment after curative hepatectomy among patients with HCC. Pooled data on recurrence and overall survival (OS) were analyzed within pairwise meta-analysis and NMA.ResultsTwenty-three eligible trials (3,940 patients) reporting eight treatments were included. The direct meta-analysis showed that adjuvant therapy prevented the recurrence (OR = 0.65; 95% CI: 0.55, 0.77; P = 0.177; I2 = 21.7%) and contributed to OS (HR = 0.63; 95% CI: 0.54, 0.73; P = 0.087; I2 = 31.1%) in comparison to the observation. In the NMA, internal radiotherapy (IRT; OR = 0.55; 95% CI: 0.39, 0.77; SUCRA = 87.7%) followed by hepatic artery infusion chemotherapy (HAIC; OR = 0.6; 95% CI: 0.36, 0.97; SUCRA = 77.8%), and HAIC (HR = 0.44; 95% CI: 0.21, 0.87; SUCRA = 82.6%) followed by IRT (HR 0.54; 95% CI:0.36, 0.81; SUCRA = 69.7%) were ranked superior to other treatments in terms of preventing recurrence and providing survival benefit, respectively.ConclusionsThe addition of adjuvant therapy lowers the risk of recurrence and provide survival benefit after surgical resection for HCC. HAIC and IRT are likely to be the two most effective adjuvant regimens.Systematic Review Registrationhttps://inplasy.com/inplasy-2020-11-0039/.

Assessing glymphatic function using in-vivo imaging method is of great value for understanding its contribution to major brain diseases. In the present study, we aim to validate the association between a variety of risk factors and a potential index of glymphatic function—Diffusion Tensor Image Analysis Along the Perivascular Space (ALPS index). We enrolled 142 subjects from communities and performed multi-modality magnetic resonance imaging scans. The ALPS index was calculated from diffusion tensor imaging data, and its associations with demographic factors, vascular factors were investigated using regression analyses. We found that the ALPS index was negatively associated with age (β = −0.284, p < 0.001). Compared to males, females had significantly higher ALPS index (β = −0.243, p = 0.001). Hypertensive subjects had significantly lower ALPS index compared to non-hypertensive subjects (β = −0.189, p = 0.013). Furthermore, venous disruption could decrease ALPS index (β = −0.215, p = 0.003). In general, our results are in consistent with previous conceptions and results from animal studies about the pathophysiology of glymphatic dysfunction. Future studies utilizing this method should consider introducing the above-mentioned factors as important covariates.

BackgroundIntrahepatic cholangiocarcinoma (ICC) remains one of the most intractable malignancies. The development of effective drug treatments for ICC is seriously hampered by the lack of reliable tumor models. At present, patient derived xenograft (PDX) models prove to accurately reflect the genetic and biological diversity required to decipher tumor biology and therapeutic vulnerabilities. This study was designed to investigate the establishment and potential application of PDX models for guiding personalized medicine and identifying potential biomarker for lenvatinib resistance.MethodsWe generated PDX models from 89 patients with ICC and compared the morphological and molecular similarities of parental tumors and passaged PDXs. The clinicopathologic features affecting PDX engraftment and the prognostic significance of PDX engraftment were analyzed. Drug treatment responses were analyzed in IMF-138, IMF-114 PDX models and corresponding patients. Finally, lenvatinib treatment response was examined in PDX models and potential drug resistance mechanism was revealed.ResultsForty-nine PDX models were established (take rate: 55.1%). Successful PDX engraftment was associated with negative HbsAg (P = 0.031), presence of mVI (P = 0.001), poorer tumor differentiation (P = 0.023), multiple tumor number (P = 0.003), presence of lymph node metastasis (P = 0.001), and later TNM stage (P = 0.039). Moreover, patients with tumor engraftment had significantly shorter time to recurrence (TTR) (P < 0.001) and worse overall survival (OS) (P < 0.001). Multivariate analysis indicated that PDX engraftment was an independent risk factor for shortened TTR (HR = 1.84; 95% CI, 1.05–3.23; P = 0.034) and OS (HR = 2.13; 95% CI, 1.11–4.11; P = 0.024). PDXs were histologically and genetically similar to their parental tumors. We also applied IMF-138 and IMF-114 PDX drug testing results to guide clinical treatment for patients with ICC and found similar treatment responses. PDX models also facilitated personalized medicine for patients with ICC based on drug screening results using whole exome sequencing data. Additionally, PDX models reflected the heterogeneous sensitivity to lenvatinib treatment and CDH1 might be vital to lenvatinib-resistance.ConclusionPDX models provide a powerful platform for preclinical drug discovery, and potentially facilitate the implementation of personalized medicine and improvement of survival of ICC cancer patient.

Lenticulostriate arteries (LSAs) supply blood to important subcortical areas and are, therefore, essential for maintaining the optimal functioning of the brain’s most metabolically active nuclei. Past studies have demonstrated the potential for quantifying the morphology of LSAs as biomarkers of vascular fragility or underlying arteriopathies. Thus, the current study aims to evaluate the morphological features of LSAs, their potential value in cerebrovascular risk stratification, and their concordance with other vascular risk factors in community-dwelling elderly people. A total of 125 community-dwelling elderly subjects who underwent a brain MRI scan were selected from our prospectively collected imaging database. The morphological measures of LSAs were calculated on the vascular skeletons obtained by manual tracing, and the number of LSAs was counted. Additionally, imaging biomarkers of small vessel disease were evaluated, and the diameters of major cerebral arteries were measured. The effects of vascular risk factors on LSA morphometry, as well as the relationship between LSA measures and other imaging biomarkers, were investigated. We found that smokers had shorter (p = 0.04) and straighter LSAs (p < 0.01) compared to nonsmokers, and the presence of hypertension is associated with less tortuous LSAs (p = 0.03) in community-dwelling elderly. Moreover, the middle cerebral artery diameter was positively correlated with LSA count (r = 0.278, p = 0.025) and vessel tortuosity (r = 0.257, p = 0.04). The posterior cerebral artery diameter was positively correlated with vessel tortuosity and vessel length. Considering the scarcity of noninvasive methods for measuring small artery abnormalities in the brain, the LSA morphological measures may provide valuable information to better understand cerebral small vessel degeneration during aging.

To explore the association between the primary visual cortex in the brain and optic nerve head changes, ONH, (structural thickness and microvascular changes) in neuromyelitis optica spectrum disorder (NMOSD).Nineteen patients who were aquaporin-4 (AQP-4) seropositive NMOSD patients and twenty-two healthy controls (HC) were enrolled for this cross-sectional study. Optical coherence tomographic angiography (OCT-A) was used to image and measure the capillaries density (RPC, radial peripapillary capillaries) and structural thickness (pRNFL, peripapillary retinal nerve fiber layer) around the optic nerve head. A resting-state functional magnetic resonance imaging was used to image and evaluate the gray matter volume (GMV) and functional connectivity (FC) the brain of each participant. We assessed the primary visual cortex (lingual gyrus, calcarine sulcus and thalamus) of the brain.Changes in RPC density showed a significant association (P 0.05) with FC of the right lingual gyrus, bilateral calcarine gyrus and left thalamus respectively. pRNFL thickness showed significant association with FC of the right lingual gyrus (Rho = 0.374, P = 0.016), right calcarine gyrus (Rho = 0.355, P = 0.023) and left thalamus (Rho = 0.376, P = 0.015) respectively.Visual impairment, structural and microvascular changes around optic nerve head is associated with the functional visual networks in NMOSD. Our report suggests that structural and microvascular changes around the ONH reflect the changes in the primary visual cortex of the brain.

Type 2 myocardial infarction (T2MI) refers to myocardial ischemic necrosis as a result of myocardial oxygen supply/demand mismatch, which are common comorbidities of critically ill patients. The purpose of this study was to investigate the incidence rate and risks of T2MI in critically ill elderly patients and further elucidate in-hospital prognostic factors. A total of 223 critically ill elderly patients admitted to our hospital from October 2016 to September 2018 were recruited. The clinical data and the in-hospital mortality rate were compared between the T2MI and non-T2MI groups. Multivariate linear regression analysis was used to identify independent factors related to T2MI. The clinical data and incidence of T2MI were also compared between patients who survived and those who died; multivariate regression analysis was used to identify independent risk factors for in-hospital death and survival analysis was conducted. In this study, the incidence of T2MI was 24.2% (54/223), and the mortality rate of critically ill elderly patients was 39.0% (87/223). Multivariate linear regression analysis showed that severe hypoxemia, arrhythmia, shock, and multiple organ dysfunction syndrome (MODS) were independent risk factors of T2MI. Compared to the survival patients, the use of mechanical ventilation, the incidence of T2MI, APACHE II score, troponin T, high-sensitivity C-reactive protein, and procalcitonin levels were significantly higher in patients who died, while the estimated glomerular filtration rate (eGFR) was significantly decreased (all P

Background and Purpose— Our study aims to evaluate the cost-effectiveness of computed tomography angiography (CTA) for surveillance of tiny unruptured intracranial aneurysms and the impact of CTA radiation-induced brain tumor on the overall effectiveness of CTA. Methods— A Markov decision model was constructed from a societal perspective starting with patients 30-, 40-, or 50-year-old, with incidental detection of unruptured intracranial aneurysm ≤3 mm and no prior history of subarachnoid hemorrhage. Five different management strategies were assessed (1) annual CTA surveillance, (2) biennial CTA, (3) CTA follow-up every 5 years, (4) coiling and subsequent magnetic resonance imaging follow-up, and (5) annual CTA surveillance for the first 2 years, followed by every 5-year CTA follow-up. Probabilistic, 1-way, and 2-way sensitivity analyses were performed. Results— The base case calculation shows every 5-year CTA follow-up to be the most cost-effective strategy, and the conclusion remains robust in probabilistic sensitivity analysis. It remains the dominant strategy when the annual rupture risk of nongrowing unruptured intracranial aneurysms is smaller than 2.66% or the rupture risk in growing aneurysms is Conclusions— Given the current literature, every 5-year CTA imaging follow-up is the cost-effective strategy in patients with aneurysms ≤3 mm, resulting in better health outcomes and lower healthcare spending. Patients with aneurysms at high risk of rupture might need more aggressive management.

Previous studies have identified various factors associated with the outcomes of acute ischemic stroke (AIS) but considered only 1 or 2 predictive factors. The present study aimed to use outcome-related factors derived from biochemical, imaging and clinical data to establish a logistic regression model that can predict the outcome of patients with AIS following endovascular treatment (EVT). The data of 118 patients with anterior circulation AIS (ACAIS) who underwent EVT between October 2014 and August 2018 were retrospectively analyzed. The patients were divided into 2 groups based on the modified Rankin Scale score at three months after surgery, where 0-2 points were considered to indicate a favorable outcome and 3-6 points were considered a poor outcome. Non-conditional logistic stepwise regression was used to identify independent variables that were significantly associated with patient outcome, which were subsequently used to establish a predictive statistical model, receiver operating characteristic (ROC) curve was used to show the performance of statistical model and analyze the specific association between each factor and outcome. Among the 118 patients, 47 (39.83%) exhibited a good and 71 (60.17%) exhibited a poor outcome. Multivariate analysis revealed that the predictive model was statistically significant (χ2=78.92; P

BACKGROUND AND AIMS: Intracranial atherosclerotic plaque is associated with ischemic strokes without substantial stenosis, and needs better characterization. We aim to investigate the clinical significance of intracranial plaque without substantial stenosis by high resolution vessel wall MRI (vwMRI) through a systematic review of existing studies. METHODS: Studies investigating intracranial arterial atherosclerotic plaques without substantial stenosis in acute ischemic stroke patients using vwMRI were systematically identified by searching the PubMed and Medline database and article reference lists. Study characteristics were recorded, the methodological quality of eligible studies was assessed, relevant clinical data were extracted, and collective data was analyzed. RESULTS: Twenty-one studies were identified as eligible. 463 patients were included without stenosis of the intracranial arteries, and 651 patients were included with stenosis

ObjectiveThe lack of highly sensitive and specific diagnostic biomarkers is a major contributor to the poor outcomes of patients with hepatocellular carcinoma (HCC). We sought to develop a non-invasive diagnostic approach using circulating cell-free DNA (cfDNA) for the early detection of HCC.DesignApplying the 5hmC-Seal technique, we obtained genome-wide 5-hydroxymethylcytosines (5hmC) in cfDNA samples from 2554 Chinese subjects: 1204 patients with HCC, 392 patients with chronic hepatitis B virus infection (CHB) or liver cirrhosis (LC) and 958 healthy individuals and patients with benign liver lesions. A diagnostic model for early HCC was developed through case-control analyses using the elastic net regularisation for feature selection.ResultsThe 5hmC-Seal data from patients with HCC showed a genome-wide distribution enriched with liver-derived enhancer marks. We developed a 32-gene diagnostic model that accurately distinguished early HCC (stage 0/A) based on the Barcelona Clinic Liver Cancer staging system from non-HCC (validation set: area under curve (AUC)=88.4%; (95% CI 85.8% to 91.1%)), showing superior performance over α-fetoprotein (AFP). Besides detecting patients with early stage or small tumours (eg, ≤2.0 cm) from non-HCC, the 5hmC model showed high capacity for distinguishing early HCC from high risk subjects with CHB or LC history (validation set: AUC=84.6%; (95% CI 80.6% to 88.7%)), also significantly outperforming AFP. Furthermore, the 5hmC diagnostic model appeared to be independent from potential confounders (eg, smoking/alcohol intake history).ConclusionWe have developed and validated a non-invasive approach with clinical application potential for the early detection of HCC that are still surgically resectable in high risk individuals.

Postoperative peritoneal adhesions (PPAs) constitute a common complication of abdominal surgery with a high incidence. Bletilla striata (BS) is an important hemostatic drug used in China for nearly 2000 years. The purpose of this study was to investigate the effect of Bletilla striata on postoperative intestinal adhesion in rats. PPA was induced by cecal wall abrasion, and Bletilla striata was injected to observe its effect on adhesion in rats. The adhesion and inflammation score were assessed through visual observation and histopathologic evaluation. The levels of interleukin-1 (IL-1β), tumor necrosis factor (TNF-α), and interleukin-17F (IL-17F) in abdominal cavity and interleukin-6 (IL-6) in plasma were measured by enzyme-linked immunosorbent assay (ELISA) at 6 hours, 12 hours, 24 hours, and 1 week after operation. The tissue level of transforming growth factor beta-1 (TGF-β1) was also determined by ELISA on the seventh day after surgery. The expressions of collagen and TNF-α were, respectively, detected by Masson trichrome staining and immunohistochemical staining. The expression of TGF-β1 and alpha smooth muscle actin (α-SMA) was detected by Western blot. The result showed that Bletilla striata has obvious preventive effect on PPAs and celiac inflammation of PPAs. Bletilla striata could significantly reduce the level of IL-17F abdominal cavity and IL-6 in plasma. Masson trichrome staining and immunohistochemical staining results showed that Bletilla striata also decreased the expression of TNF-α and collagen. Western blot results showed that Bletilla striata decreased the expression of α-SMA and TGF-β1. Our results suggest that Bletilla striata decreased the development of abdominal adhesion in abrasion-induced model of rats and reduced the expression of the important substance which increased in PPAs. Bletilla striata can be further studied as a new and cheaper antiadhesive substance.

Objectives Isolated perimesencephalic subarachnoid hemorrhage is an uncommon, distinct subtype of subarachnoid hemorrhage with a more benign prognosis. A negative computed tomographic angiogram has been shown to be reliable in excluding aneurysmal rupture as the underlying etiology. However, some studies continue advocating for more imaging to determine a vascular cause in perimesencephalic subarachnoid hemorrhage. The objective of this study is to evaluate the evidence for use and utility of repeat angiographic imaging after a negative computed tomographic angiogram in patients with perimesencephalic subarachnoid hemorrhage. Patients and methods Retrospective institutional analysis of patients with perimesencephalic subarachnoid hemorrhage was performed from 2014 to 2017 for number and types of follow-up angiographic imaging studies performed. Updated meta-analysis of literature was performed from 2014 onwards to assess the utility of follow-up imaging after a negative initial angiographic study. Results The institutional review revealed no utility of additional imaging after a negative computed tomographic angiogram in 6 patients with isolated perimesencephalic subarachnoid hemorrhage. Literature review and metaanalysis of 13 studies with 588 patients revealed a vascular etiology in 3 patients with isolated perimesencephalic subarachnoid hemorrhage from a single study- 2 aneurysms and 1 patient with vasculitis. Conclusions Use of repeat angiographic imaging after a negative computed tomographic angiogram for perimesencephalic subarachnoid hemorrhage patients remains not uncommon, despite previous meta-analysis. Review of the more recent literature is consistent with previously published meta-analysis and shows limited benefits despite frequent use. In patients with a strictly defined perimesencephalic subarachnoid hemorrhage pattern and clinical picture consistent with perimesencephalic subarachnoid hemorrhage, an initial negative computed tomographic angiogram should be adequate and repeated follow-up studies can be avoided.