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Objective Experimental studies of head-up positioning (HUP) during cardiopulmonary resuscitation (CPR) have had some degree of conflicting published results. The current study aim was to analyze and reconcile those discrepancies in order to better clarify the effects of HUP CPR compared to conventional supine (SUP) CPR. Methods Three databases (PubMed, EMBASE and Cochrane Library) were searched comprehensively (from each respective database's inception to May 2021) for articles addressing HUP CPR. The primary outcome to be observed was cerebral perfusion pressure (CerPP), and secondary outcomes were mean intracranial pressure (ICP), mean arterial pressure (MAP), coronary perfusion pressure (CoPP) and frequencies of return of spontaneous circulation (ROSC). Results Seven key studies involving 131 animals were included for analysis. Compared to SUP CPR, CerPP (MD 10.37; 95% CI 7.11–13.64; p I2 = 58%) and CoPP (MD 7.56; 95% CI 1.84–13.27, p = 0.01; I2 = 75%) increased significantly with HUP CPR, while ICP (MD − 13.66; 95% CI − 18.6 to –8.71; p I2 = 96%) decreased significantly. Combining all study methodologies, there were no significant differences detected in MAP (MD − 1.63; 95% CI − 10.77–7.52; p = 0.73; I2 = 93%) or frequency of ROSC (RR 0.9; 95% CI 0.31–2.60; p = 0.84; I2 = 65%). However, in contrast to worse outcomes in studies using immediate elevation of the head in a reverse Trendelenburg position, study outcomes were significantly improved when HUP (head and chest only) was introduced in a steady, graduated manner following a brief period of basic CPR augmented by active compression–decompression (ACD) and impedance threshold (ITD) devices. Conclusion In experimental models, gradually elevating the head and chest following a brief interval of circulatory priming with ACD and ITD devices can enhance CoPP, lower ICP and improve CerPP significantly while maintaining MAP. This effect is immediate, remains sustained and is associated with improved outcomes.

Background We aimed to evaluate the efficacy and safety of phacoemulsification with intravitreal 3 mg triamcinolone acetonide injection in preventing postoperative inflammation and complications in patients with non-infectious anterior uveitis and panuveitis complicated cataract. Method In this retrospective cohort study, 140 uveitic cataract patients who received phacoemulsification and intraocular lens implantation in Shanxi Eye hospital from January 2018 to January 2020 were reviewed. The IVTA group (51 eyes of 41 patients) received intravitreal injection of 3 mg triamcinolone acetonide (TA) at the end of surgery, and the control group (51 eyes of 41 patients) without injection matched by propensity score matching were enrolled. Outcome measures were best corrected visual acuity (BCVA), anterior chamber inflammation, intraocular pressure, corneal endothelial cell density, central macular thickness and complications within 3 months follow-up. Results The degree of postoperative anterior chamber inflammation in the IVTA group was lighter than that in the control group (P P P P P > 0.05). Two of 51 eyes (3.9%) in the IVTA group and 8 of 51 eyes (15.7%) in the control group had recurrence of uveitis; 6 of 45 eyes (13.3%) in the control group developed cystoid macular edema but none in the IVTA group; 11 of 51 eyes (21.6%) in the IVTA group and 22 of 51 eyes (43.1%) in the control group developed posterior synechiae postoperatively. Conclusions Intraoperative Intravitreal injection of 3 mg TA is an effective and safe adjunctive therapy for preventing postoperative inflammation and complications to promote early recovery for anterior uveitis or panuveitis complicated cataract patients following phacoemulsification. Trial registration This retrospective cohort study was in accordance with the tenets of the Helsinki Declaration and was approved by the Shanxi Eye Hospital Ethics Committee. Written informed consent was obtained from all participants for their clinical records to be used in this study.

Background The aim of this study is to explore the characteristics of Kawasaki disease (KD) and concurrent pathogens due to a stay-at-home isolation policy during coronavirus disease 2019 (COVID-19) epidemic. Methods All patients with KD admitted between February and April in 2015–2020, were classified into before (group 1, in 2015–2019) and after (group 2, in 2020) isolation groups. A total of 4742 patients [with KD (n = 98) and non-KD (n = 4644)] referred to Mycoplasma pneumoniae (MP) and virus detection were analyzed in 2020. Clinical characteristics, laboratory data, and 13 pathogens were analyzed retrospectively. Results Group 2 had a significantly increased incidence of KD (0.11%) with 107 patients compared to that of group 1 (0.03%) with 493 patients. The comparisons of oral mucosal change, strawberry tongue, desquamation of the fingertips, cervical lymphadenopathy and neutrophil percentage decreased in group 2 compared to group 1. The infection rate of MP increased significantly in group 2 (34.7%) compared to group 1 (19.3%), while the positive rate of viruses decreased significantly in group 2 (5.3%) compared to group 1 (14.3%). In 2020, the positive rate of MP infection increased significantly in patients with KD compared to the increase in patients with non-KD. The infection rate of MP for younger children aged less than 3 years old was higher in group 2 than in group 1. Conclusion Compared with the characteristics of KD from 2015 to 2019 years, the incidence of KD was increased in 2020 and was accompanied by a high incidence of MP infection, especially in younger children (less than 3 years old) during the isolation due to COVID-19 pandemic.

Background Management of primary aldosteronism (PA) has become a research hotspot in the field of endocrinology. To obtain reliable research evidence, it is necessary to establish a high-quality PA research database. Methods The establishment of PA research database involved two steps. Firstly, patients with confirmation of PA diagnosis between 1 Jan 2009 to 31 Aug 2019 at West China Hospital were identified and data were extracted. Secondly, patients with confirmatory testing for PA will be enrolled into a prospective cohort. Data will be prospectively collected based on the case report forms since 1 Sep 2019. We evaluated the quality of research database through assessment of quality of key variables. Results Totally, 862 patients diagnosed as PA were identified, of which 507 patients who had positive confirmatory testing for PA were included into the retrospective database. Among 862 patients diagnosed as PA, the mean systolic blood pressure (SBP) was 156.1 (21.7) mmHg, mean diastolic blood pressure (DBP) was 97.2 (14.5) mmHg. Among included patients, the mean serum potassium level was 2.85 (IQR, (2.47–3.36) mmol/L, and the mean plasma aldosterone concentration (PAC) was 28.1 (IQR, 20.0–40.4) ng/dL. The characteristics of patients with positive confirmatory testing for PA were similar. Validation of data extracting and linking showed the accuracy were 100%. Evaluation of missing data showed that the completeness of BMI (95.9%), SBP (99.4%) and DBP (99.4%) were high. Conclusion Through integrating retrospective and prospective cohort of PA, a research database of PA with high quality and comprehensive data can be established. We anticipate that the research database will provide a high level of feasibility for management of PA in China.

Background Sepsis is a common disease in intensive care units, with high morbidity and mortality. Intestinal microecology plays a vital part in the development and progression of this disease, possibly because sepsis and its treatment cause specific changes in the composition of the intestinal flora. Aim To investigate the characteristics of intestinal flora disturbance in sepsis patients treated with antibiotics. Methods In this prospective comparative study, we enrolled ten patients with sepsis (sepsis group), hospitalized in the Department of Critical Care Medicine of the General Hospital, Ningxia Medical University, China (a class IIIa general hospital) from February 2017 to June 2017; ten patients without sepsis hospitalized in the same period (non-sepsis group) and ten healthy individuals (control group) were also enrolled. Fecal samples collected from the three groups were subjected to 16S rRNA gene sequencing and the intestinal flora diversity, structure, and composition were determined. Additionally, the dynamics of the intestinal flora diversity, structure, and composition in sepsis patients were investigated via 16S rRNA gene sequencing of samples collected 0 d, 3 d, and 7 d after admittance to the intensive care unit. Correlations between the serum levels of procalcitonin, endotoxin, diamine oxidase, and D-lactic acid and the intestinal flora composition of sepsis patients were also investigated. Results Compared with the healthy control group, sepsis and non-sepsis patients showed reduced intestinal flora α-diversity and a distinct flora structure, with Firmicutes as the dominant phylum, and significantly decreased proportions of Bacteroidetes, as well as Prevotella and Lachnospira, among other genera. Of note, the proportion of Enterococcus was significantly increased in the intestinal tract of sepsis patients. Interestingly, the α-diversity in the sepsis group decreased gradually, from days 1 to 7 of treatment. However, pairwise comparisons showed that both the diversity and structure of the intestinal flora were not significantly different considering the three different time points studied. Curiously, the serum levels of procalcitonin, endotoxin, diamine oxidase, and D-lactic acid in sepsis patients correlated with the prevalence of various bacterial genera. For example, the prevalence of Ruminococcus was positively correlated with serum procalcitonin, endotoxins, and diamine oxidase; similarly, the prevalence of Roseburia was positively correlated with serum procalcitonin, endotoxins, and D-lactic acid. Conclusion Sepsis patients in intensive care units show dysbiosis, lasting for at least 1 wk.

Background Liberal oxygen therapy might increase the mortality rate of patients. Non-rebreathing masks (NRM) are a high-flow, non-invasive oxygen device that can provide oxygen concentration up to 95%. This study aimed to determine the impact of using NRM in patients with respiratory failure. Methods This retrospective cohort study was conducted in four medical institutions in Taiwan from January 2010 to December 2016. The association between mortality and NRM use before receiving ventilator support in patients with respiratory failure in the emergency department was analyzed. Patients were divided into the NRM treatment and no NRM treatment groups. A 1:4 propensity score matching was conducted. Regarding the duration of NRM use, treatments were grouped as 0 h, 0–1 h, 1–2 h, and >2 h. Results A total of 18,749 patients were included, with 1074 using NRM. After propensity score matching, 1028 patients using NRM (0–1 h: 508, 1–2 h: 193, and >2 h: 327) and 4112 patients not using NRM were analyzed. The 30-day mortality rates were 29.1%, 28.5%, 27.5%, and 35.5% in the 0 h, 0–1 h, 1–2 h, and >2 h treatment groups, respectively. Patients with respiratory failure due to pulmonary disease using NRM over 2 h had a higher mortality rate than patients not using NRM (hazard ratio: 1.3, 95% CI: 1.01–1.66). Conclusions Prolonged use of NRM in patients with respiratory failure due to pulmonary disease possibly increases mortality.

To examine to what degree guidelines for PET and PET/CT used systematic review evidence. The latest version of guidelines for PET, PET/CT or PET/MRI published in English in PubMed until December 2019 was analysed in two categories: (1) for indications, if mainly discussing the appropriate use of PET in diverse conditions; (2) for procedures, if providing step-by-step instructions for imaging. We surveyed the general characteristics and the use of systematic review evidence for developing recommendations across all guidelines, and surveyed the citation of evidence for five recommendation topics in guidelines for procedures. Forty-seven guidelines, published between 2004 and 2020, were included. Guidelines for indications were developed mainly on systematic reviews (13 of 19, 68.4%). Among those, 12 (63.2%) reported the level of evidence, 4 (21.1%) reported the strength of recommendations, 3 (15.8%) described external review and 7 (36.8%) involved methodologists. Guidelines for procedures were seldom developed on systematic reviews (1 of 27, 3.7%). Among those, 1 (3.7%) reported the level of evidence, 1 (3.7%) reported the strength of recommendations, 3 (11.1%) described external review and 1 (3.7%) involved methodologists. Systematic review evidence was cited by 2 (7.4%) procedure guidelines per recommendation topic in median. The use of systematic review evidence for developing recommendations among PET or PET/CT guidelines was suboptimal. While our survey is an icebreaking attempt to explore a key element (i.e. use of systematic review evidence) for developing nuclear medicine guidelines, assessments of other domains of guideline quality may help capture the entire picture. • The use of systematic review evidence for developing recommendations among guidelines for PET or PET/CT was suboptimal. • Only 13 (68.4%) guidelines for indications and 1 (3.7%) guideline for procedures systematically reviewed the literature during guideline development. • For each recommendation topic we examined, only a median of 2 (7.4%) procedure guidelines cited systematic review evidence.

Purpose Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial arteriopathy characterized by recurrent lacunar stroke, migraine, and depression. The mechanism of cognitive dysfunction in CADASIL is still uncertain. The aim of this study was to use tract-based spatial statistics (TBSS) to map voxelwise the spatial distribution of brain microstructural change revealed by DTI-derived indices in patients with CADASIL to further study the underlying neuropsychopathological mechanism of CADASIL. Method Twelve patients with CADASIL and 11 age-, sex-matched healthy controls underwent magnetic resonance imaging at 3 T. Then we evaluated DTI-derived indices (fractional anisotropy [FA], mode of anisotropy [MO], mean diffusivity [MD], axial diffusivity [AD] and radial diffusivity [RD]) of brain white matter (WM) between CADASIL patients and healthy subjects through TBSS. Results Compared with healthy controls, patients with CADASIL showed extensive decreased FA, MO and increased RD, AD, and MD throughout the entire brain (mainly the WM of the temporal poles, inferior and superior longitudinal fasciculus, inferior fronto-occipital fasciculus, corpus callosum, uncinate fasciculus, internal capsule, external capsule, corona radiata, thalamic radiation, and cingulum). Furthermore, these WM microstructural alterations were significantly correlated with cognitive scores and Scheltens scores. Decreased FA values and MO values were positively correlated with Montreal Cognitive Assessment scores in CADASIL patients. Increased AD, RD, and MD values were significantly negatively correlated with Montreal Cognitive Assessment scores. Conclusions Widespread WM abnormalities were clearly shown in CADASIL by using TBSS. Severity of microstructural changes correlates significantly with extension of T2 hyperintensity. Moreover, WM microstructural damage and cognitive impairment were significantly correlated. This study indicated that WM tract damage plays an important role in cognitive impairment in CADASIL.

Primitive neuroectodermal tumors (PNETs) arising from the lung without thoracic wall involvement are extremely rare and particularly aggressive neoplasms. Herein, we present the case of a 41-year-old woman with pulmonary PNET diagnosed following histopathological, immunohistochemical, and molecular pathological examination of a surgical biopsy specimen. The case report is accompanied by a literature review of primary pulmonary PNETs.

Objective. In this study, we aimed to analyze thyroid function and related risk factors for thyroid dysfunction in 35 patients with Gitelman syndrome (GS). Methods. This study included 35 patients with GS who were referred to West China Hospital of Sichuan University from Aug 2013 to Jan 2018. General patient characteristics were collected, and thyroid function was assessed. To evaluate the potential contribution of hypokalemia to thyroid dysfunction, 636 patients who were clinically diagnosed with primary aldosteronism (PA) during the same period were included as the control group; these patients were divided into a hypokalemia group ( N = 528 ) and a normokalemia group ( N = 108 ). Logistic regression was used to screen for significant determinants of thyroid dysfunction in the GS patients. Results. Patients with GS had a significantly different prevalence of subclinical hypothyroidism, hypothyroidism, and hyperthyroidism than patients with hypokalemic PA and normokalemic PA (28.6%, 2.9%, and 11.4% vs. 15.5%, 6.1%, and 0.7% vs. 8.3%, 4.6%, and 2.8%, P < 0.001 ). No significant difference was observed in the distribution of thyroid function between the hypokalemic PA group and the normokalemic PA group ( P > 0.05 ). No significant differences were seen in the positive rates of thyrotropin receptor antibody (TRAb), thyroglobulin antibody (TGAb), and thyroid peroxidase antibody (TPOAb) among the three groups ( P > 0.05 ). In the logistic regression, only sex (OR, 7.4; 95% CI, 1.555-35.479; P = 0.012 ) was significantly correlated with thyroid dysfunction in GS patients. Conclusion. GS is complicated with a greater rate of thyroid dysfunction than primary aldosteronism. The risk of thyroid dysfunction in female patients with GS is higher than that in male patients.

Evaluating patients with chronic venous leg ulcers (CVLUs) is essential to find the underlying etiology. The basic tenets in managing CVLUs are to remove the etiological causes, to address systemic and metabolic conditions, to examine the ulcers and artery pulses, and to control wound infection with debridement and eliminating excessive pressure on the wound. The first-line treatments of CVLUs remain wound care, debridement, bed rest with leg elevation, and compression. Evidence to support the efficacy of silver-based dressings in healing CVLUs is unavailable. Hydrogen peroxide is harmful to the growth of granulation tissue in the wound. Surgery options include a high ligation with or without stripping or ablation of the GSVs depending on venous reflux or insufficiency. Yet, not all CVLUs are candidates for surgical treatment because of comorbidities. When standard care of wound for 4 wk failed to heal CVLUs effectively, use of advanced wound care should be considered based on the available evidence. Negative pressure wound therapy facilitates granulation tissue development, thereby helping closure of CVLUs. Autologous split-thickness skin grafting is still the gold standard approach to close huge CVLUs. Hair punch graft appears to have a better result than traditional hairless punch graft for CVLUs. Application of adipose tissue or placenta-derived mesenchymal stem cells is a promising therapy for wound healing. Autologous platelet-rich plasma provides an alternative strategy for surgery for safe and natural healing of the ulcer. The confirmative efficacy of current advanced ulcer therapies needs more robust evidence.

Background Knee osteoarthritis (OA) is a common disease condition associated with aging and a frequent cause of primary care consultations. Few longitudinal studies have been conducted to investigate the incidence of symptomatic knee osteoarthritis (OA) and to identify its risk factors among the Chinese population. Methods The China Health and Retirement Longitudinal Study (CHARLS) is a nationwide longitudinal survey of persons aged ≥45 years. Symptomatic knee OA was diagnosed when both self-reported knee pain and self-reported physician-diagnosis arthritis existed. Using the national survey data collected from the CHARLS, we estimated the incidence of symptomatic knee OA, taking into account the complex survey design and response rate. We applied weighted logistic regression analysis to identify its risk factors. Results In the 4-year follow-up, the cumulative incidence of symptomatic knee OA among middle-aged and older Chinese adults was 8.5%; the incidence was higher among females (11.2%) than males (5.6%). Female (odds ratio (OR) 1.98 [95% confidence interval (CI) 1.65–2.37]), rural area (OR 1.32 [95% CI 1.08–1.60]), and West region (OR 2.33 [95% CI 1.89–2.87]) were associated with a higher risk of incident symptomatic knee OA. Physical activities (OR 0.47 [95% CI 0.29–0.76]) and high education level (OR 0.60 [95% CI 0.41–0.88]) was associated with a lower risk of incident symptomatic knee OA, while histories of heart disease (OR 1.40 [95% CI 1.07–1.82]), kidney disease (OR 1.80 [95% CI 1.35–2.39]), and digestive disease (OR 1.54 [95% CI 1.30–1.82]) were associated with a higher risk of incident symptomatic knee OA. Conclusion The cumulative incidence of symptomatic knee OA over 4 years was relatively high, and varied by province and region. Lack of physical activities was confirmed to be risk factors of incident symptomatic knee OA. The presence of heart disease, kidney disease, and digestive disease may be associated with a higher risk of incident symptomatic knee OA, further research need to confirm these findings.

Introduction This study was to develop a simple model for predicting malignancy of peripheral pulmonary lesions (PPLs) based on endobronchial ultrasonography (EBUS) and clinical findings. Methods Patients who had EBUS for PPLs were analyzed and compared on the EBUS imaging characteristics and clinical data. The malignancy prediction model was established by the logistic equation of probability of malignant PPL based on the data of 135 patients. The model was tested on an additional 50 patients for efficiency. Results Among 135 prospectively enrolled patients, 77 (57%) patients had malignant and 58 (43%) had benign lesions with the size of 36.5±19.9 mm. Univariate analysis demonstrated a significant (P 0.05) difference in age (50 years as the cutoff value) and history of extra-thoracic malignancies. Logistic analysis of multiple factors showed that smoking history, serum CEA, borderline, air bronchogram, heterogeneous echo, and anechoic areas were significant (P

To quantify the global and regional left ventricular (LV) myocardial strain in type 2 diabetes mellitus (T2DM) patients using cardiac magnetic resonance (CMR) tissue-tracking techniques and to determine the ability of myocardial strain parameters to assessment the LV deformation. Our study included 98 adult T2DM patients (preserved LV ejection fraction [LVEF], 72; reduced LVEF, 26) and 35 healthy controls. Conventional LV function, volume-time curve parameters and LV remodeling index were measured using CMR. Global and regional LV myocardial strain parameters were measured using CMR tissue tracking and compared between the different sub-groups. Receiver operating characteristic analysis was used to assess the diagnostic accuracy. Regression analyses were conducted to determine the relationship between strain parameters and the LV remodeling index. The results show that global radial peak strain (PS) and circumferential PS were not significantly different between the preserved-LVEF group and control group (P > 0.05). However, longitudinal PS was significantly lower in the preserved-LVEF group than in the control group (P = 0.005). Multivariate linear and logistic regression analyses showed that global longitudinal PS was independently associated (β = 0.385, P

This study aimed to examine the design, conduct, and analysis of systematic reviews assessing drug safety through a cross-sectional survey.We searched PubMed to identity systematic reviews published in the Cochrane Database of Systematic Reviews and Core Clinical Journals indexed in 2015 and randomly sampled systematic reviews assessing drug effects at a 1:1 ratio of Cochrane and non-Cochrane reviews. Teams of two investigators independently conducted study screening and collected data, using prespecified, standardized questionnaires. In addition to general information, we collected details about the planning and analyses of safety outcomes.We included 120 systematic reviews, including 60 Cochrane and 60 non-Cochrane reviews. Most reviews searched PubMed/MEDLINE (n = 117, 97.5%), EMBASE (n = 105, 87.5%), and Cochrane CENTRAL (n = 110, 91.7%) and conducted independent and duplicate study selection (n = 98, 81.7%), risk of bias assessment (n = 105, 87.5%), and data collection (n = 105, 87.5%). Only nine (7.5%) reviews clearly defined safety outcomes, and seven (5.8%) defined a primary safety outcome; none stated whether the primary safety outcome was predefined. Among the 80 reviews that pooled the primary dichotomous safety data across studies, less than half (41%, n = 33) conducted subgroup analysis to explore for sources of heterogeneity or reported a GRADE assessment for the overall quality of evidence. Cochrane reviews were more likely to provide a study protocol (100% vs. 23.3%; P 0.001), involve methodologists (53.3% vs. 20.0%; P 0.001), and report a GRADE assessment for the primary safety outcome (70.6% vs. 19.6%; P 0.001).Our findings highlighted areas for improved planning and analysis in the assessment of drug safety among systematic reviews. Cochrane reviews were superior to non-Cochrane reviews; however, most reviews did not prespecify their safety outcomes or methods for analysis, explore sources of heterogeneity among pooled effects, or assess the overall quality of evidence with the GRADE approach.

This study aimed to investigate the association of obesity with adrenal gland volume (AGV) and the effects of weight loss on AGV. This study included obese patients (N = 25) who underwent sleeve gastrectomy and age- and sex-matched healthy volunteers (HVs) (N = 25) and overweight healthy volunteers (overweight-HVs) (N = 21). Thin-slice computed tomography was used to evaluate adrenal morphological changes. AGV was measured semiautomatically based on the digital imaging and communications in medicine (DICOM) image. The effects of weight loss on AGV and adrenal gland density were evaluated in patients for 1 year or more after sleeve gastrectomy. Left, right, and total AGV were 6.77 ± 0.36, 5.76 ± 0.31, and 12.53 ± 0.64 cm3 in obese patients, which were significantly higher than those in the overweight-HVs (3.88 ± 0.14, 3.09 ± 0.13, and 6.97 ± 0.24 cm3) and HVs (3.38 ± 0.23, 2.67 ± 0.15, and 6.04 ± 0.36 cm3). AGV was larger in overweight-HVs than in HVs, but no statistically significant difference was identified. Sleeve gastrectomy significantly reduced body weight (− 27.1 ± 2.5 kg), left AGV (− 0.80 ± 0.26 cm3), and right AGV (− 0.88 ± 0.20 cm2). The adrenal volume in five patients was not reduced, despite significant weight loss postsurgery. The mean density of adrenal glands was lower in obese patients (P = 0.025) but were not significantly increased postsurgery. Obesity leads to increased AGV, and in some cases, this effect seems to be irreversible. The clinical implication of obesity-induced adrenal morphological changes needs to be studied further.

Background The microvascular effects of obesity should be considered in diabetic individuals for elucidating underlying mechanisms and developing targeted therapies. This study aims to determine the effect of obesity on myocardial microvascular function in type 2 diabetes mellitus (T2DM) patients using cardiac magnetic resonance (CMR) first-pass perfusion imaging and assessed significant risk factors for microvascular dysfunction. Materials and methods Between September 2016 and May 2018, 120 patients with T2DM (45.8% women [55 of 120]; mean age, 56.45 ± 11.97 years) and 79 controls (44.3% women [35 of 79]; mean age, 54.50 ± 7.79 years) with different body mass index (BMI) scales were prospectively enrolled and underwent CMR examination. CMR-derived perfusion parameters, including upslope, time to maximum signal intensity (TTM), maximum signal intensity (MaxSI), MaxSI (-baseline), and SI (baseline), and T2DM related risk factors were analyzed among groups/subgroups both in T2DM patients and controls. Univariable and multivariable linear and logistic regression analyses were performed to assess the potential additive effect of obesity on microvascular dysfunction in diabetic individuals. Results Compared with controls with comparable BMIs, patients with T2DM showed reduced upslope and MaxSI and increased TTM. For both T2DM and control subgroups, perfusion function gradually declined with increasing BMI, which was confirmed by all perfusion parameters, except for TTM (all P P P P = 0.022) and glycated haemoglobin (β = − 0.184; 95% CI, − 0.281 to − 0.039; P = 0.010) were significantly associated with global upslope in the T2DM group. Multivariable logistic regression analysis indicated that T2DM was an independent predictor of microvascular dysfunction in normal-weight (odds ratio[OR], 6.46; 95% CI, 2.08 to 20.10; P = 0.001), overweight (OR, 7.19; 95% CI, 1.67 to 31.07; P = 0.008) and obese participants (OR, 11.21; 95% CI, 2.38 to 52.75; P = 0.002). Conclusions Myocardial microvascular function gradually declined with increasing BMI in both diabetes and non-diabetes status. T2DM was associated with an increased risk of microvascular dysfunction, and obesity exacerbated the adverse effect of T2DM.

Objective. The aim of this study was to investigate the expression of Snail, galectin-3, and IGF1R in benign and malignant pheochromocytoma and paraganglioma (PPGL) and explore their role in the diagnosis of malignant PPGL. Methods. We retrospectively collected and analyzed surgical tumor tissue from 226 patients initially diagnosed with PPGL who underwent surgery from Jan. 2009 to Jan. 2016 at West China Hospital, Sichuan University. We observed and quantified the expression of Snail, galectin-3, and IGF1R in paraffin-embedded samples by immunohistochemical staining. Results. The significant difference in survival time among the three groups (benign PHEO, benign PGL, and potentially malignant PPGL) was compared by Kaplan-Meier survival analysis. The positive staining of Snail, galectin-3, and IGF1R in the benign PHEO group was significantly lower than that in the other three groups (P<0.001). The Kaplan-Meier survival plots indicated that the survival time of the patients with intense positive staining was significantly lower than that of the patients with weak positive staining. Conclusion. The intense expression of Snail, galectin-3, and IGF1R may be valuable indicators for the diagnosis of malignant PPGL.

Objectives The current study aimed to investigate the value of the computed tomography-based left-versus-right adrenal gland volume ratio (L/Rv) in screening patients with unilateral primary aldosteronism. Methods The current study recruited 114 patients who underwent successful adrenal venous sampling (AVS) and adrenal computed tomography at West China Hospital of Sichuan University. The patients were divided into three groups according to the AVS results: AVS-left, AVS-bilateral, and AVS-right primary aldosteronism. The volumes of the left and right adrenal glands were semiautomatically calculated. The L/Rv of each patient was computed, and its value in identifying unilateral primary aldosteronism was analyzed. Results The mean value of the L/Rv was larger in AVS-left patients and smaller in AVS-right patients than that in AVS-bilateral patients. In AVS-left primary aldosteronism patients, the cutoff value of the L/Rv with the highest Youden index was 1.344 [area under the curve (AUC) 0.851, sensitivity 80.0%, specificity 78.1%]. The optimal cutoff value was 1.908, of which 46.0% (23/50) of AVS-left primary aldosteronism patients could be identified (specificity 100.0%). In AVS-right primary aldosteronism patients, the cutoff value of the L/Rv with the highest Youden index was 1.267 (AUC 0.868, specificity 72.8%, sensitivity 87.9%). The optimal cutoff value was 0.765, of which 27.3% (9/33) of AVS-right primary aldosteronism patients could be identified (specificity 100.0%). Patients with L/Rv more than 1.908 or less than 0.765 had higher complete success rate postsurgery. Conclusion Although not perfect, the L/Rv is an applicable index to screen unilateral primary aldosteronism patients for surgery. Primary aldosteronism patients, even those aged more than 35 years, with an L/Rv more than 1.908 or less than 0.765 can be spared AVS before surgery.

Objective Aim of the study was to evaluate the clinical efficacy and safety of major uterine wall resection and reconstruction of the uterus (MURU) combined with a levonorgestrel-releasing intrauterine system (LNG-IUS) for the treatment of adenomyosis. Methods Ninety patients diagnosed with adenomyosis were enrolled in this study. All participants were examined by transvaginal ultrasound (TVU) or magnetic resonance imaging (MRI). Serum levels of cancer antigen 125 (CA 125) were quantitatively measured. All patients underwent MURU in combination with LNG-IUS. The therapeutic safety of MURU was assessed during surgery and the patientsʼ stay in hospital. The clinical efficacy was evaluated by comparatively analyzing changes in dysmenorrhea, volume of menstrual blood, uterine volume and serum levels of CA 125 before, and at 3, 6 and 12 months following MURU. Results All 90 patients enrolled in the study were successfully treated with MURU combined with LNG-IUS. No significant complications were observed during surgery and hospital stay. The mean operation time, intraoperative blood loss and length of hospital stay were 82.4 ± 13.8 min, 53.3 ± 20.3 ml, and 4.3 ± 0.8 days, respectively. Dysmenorrhea completely disappeared in all patients. Uterine volume and serum levels of CA 125 were restored to normal ranges. No recurrence of adenomyosis was observed during postoperative follow-up. Conclusion MURU combined with LNG-IUS is an efficacious and safe treatment for severe adenomyosis. This combined technique is not only effective to manage severe adenomyosis but also preserves as much of the uterus as possible.

Summary: Objective: To explore the likelihood of resolution of diabetes postoperatively. Besides, we would like to determine the risk factors associated with development and prognosis of diabetes. Methods: All patients in our hospital undergoing surgical removal of pheochromocytoma (PHEO) from 10 October 2010 to 21 July 2017 were retrospectively analyzed to determine those with preoperative diabetes. Preoperatively demographic data and information on diabetes were recorded. The median follow-up was 45.2 months. Results: Finally, 67 (36.2%) patients were with diabetes among 185 patients undergoing surgery. Furthermore, 47 patients had complete follow-up. And 37 (78.7%) patients had improvement of diabetes after resection of PHEO. In details, 29 (61.7%) patients had complete resolution. Older patients were more likely to develop diabetes, and symptomatic patients with longer course of PHEO were also more susceptible to preoperative diabetes. Elevated body mass index (BMI) was a risk factor of persistent diabetes postoperatively after surgery. Conclusions: 36.2% of PHEO patients might be with preoperative diabetes mellitus. Older patients were more likely to present diabetes preoperatively. And the increasing length of PHEO course might be another risk factor on developing diabetes preoperatively. Resection of tumors improved diabetes in 78.7% of patients, with resolution in 61.7%. Patients with higher BMI might need treatment for diabetes postoperatively. Keywords: Diabetes mellitus, Development, Pheochromocytoma, Risk factor

Background The initial episode of angioedema in children can be potential life-threatening due to the lack of prompt identification and treatment. We aimed to analyze the factors predicting the severity and outcomes of the first attack of acute angioedema in children. Methods This was a retrospective study with 406 children ( Result In total, 109 (26.8%) children had severe angioedema, and the majority of those children were male (65.1%). Most of the children were of preschool age (56.4%), and only 6.4% were adolescents. The co-occurrence of pyrexia or urticaria, etiologies of the angioedema related to medications or infections, the presence of respiratory symptoms, and a history of allergies (asthma, allergic rhinitis) were predictors of severe angioedema (all p p Conclusion The co-occurrence of pyrexia or urticaria, etiologies related to medications or infections, the presence of respiratory symptoms, and a history of allergies were predictors of severe angioedema. More importantly, short-term POU observation and prompt treatment might be benefit for patients who did not require hospital admission.

Background Adrenal venous sampling (AVS) is the gold standard for preoperative differentiation between unilateral and bilateral primary aldosteronism (PA). However, results are sometimes vitiated by failing to access the right adrenal vein. Materials and methods The present study assumed that clinical decisions can be made with incomplete AVS data, by comparing aldosterone/cortisol (A/C) ratio in both left and right adrenal veins with that in the inferior vena cava (LAV/IVC and RAV/IVC). Receiver operation characteristic (ROC) curve and scatterplot were used to certify the upper and lower cutoffs and to analyze the significance of discrimination. One hundred and sixty patients diagnosed with PA from April 2017 to June 2018 underwent AVS in the Urology Department of West China Hospital, Chengdu, China. One hundred and eleven with complete AVS data were divided into 3 groups: left-sided (N = 40), right-sided (N = 29) and bilateral (N = 42). We also collected patients from September 2018 to April 2019 in our department as validation cohort to test our hypothesis. Results On the basis of LAV/IVC, RAV/IVC and diagnostic category, upper cutoff was 1.14 (50% sensitivity and 100% specificity) and lower cutoff 0.07 (27.5% sensitivity and 100% specificity) for LAV/IVC, and 1.04 (55% sensitivity and 100% specificity) and 0.08 (40% sensitivity and 100% specificity), respectively, for RAV/IVC. Conclusion The diagnostic model in this study contributes to clinical decision-making in patients with only partial PA with incomplete AVS data.

8-oxoguanine (8-oxoG) is one of the most prevalent genotoxic lesions, and it is generated in DNA attacked by reactive oxygen species (ROS). Adenine misincorporated opposite to 8-oxoG during replication is excised by MutY homolog (MUTYH), an important protein of the base excision repair (BER) system. Mutyh plays an important role in the maintenance of genomic integrity, but the functional consequences of Mutyh deficiency are not fully understood. In the current study, we investigated the histological and functional changes of five tissues (hippocampus, heart, liver, kidney and lung) and their molecular basis in Mutyh-/- and wild-type mice exposed to D-galactose (D-gal). Our data indicated that Mutyh deficiency hindered the weight gain of experimental mice and induced substantial alterations of 8-oxoG content and superoxide dismutase (SOD) activity, but no significant histological and functional impairment appeared in the investigated tissues of Mutyh- deficient mice without D-gal exposure. Under low-dose D-gal exposure, Mutyh deficiency altered expression of genes involved in mitochondrial unfolded protein response (UPRmt) in the heart, liver and lung, and caused an enhanced expression of mitochondrial dynamics proteins (MDPs) in hippocampus and liver. The stress responses could maintain mitochondrial proteostasis and function. However, such responses were not noted when experiencing excessive damage burden induced by high-dose D-gal exposure, in which Mutyh deficiency increased accumulation of 8-oxoG and aggravated mitonuclear protein imbalance, as well as histological lesions in heart, liver and kidney. A higher sensitivity to ROS-induced cardiotoxicity with high-dose D-gal exposure was noticed in Mutyh-/- mice. However, no differences in learning and memory impairments were observed between Mutyh-/- and wild-type mice with high-dose D-gal exposure. In conclusion, our data demonstrated that Mutyh deficiency has different impacts on various tissues based on the degree of oxidative stress.

Background: We aim to investigate the guideline adherence of β-blocker (BB) initiating dose in Chinese hospitalized patients with heart failure with reduced ejection fraction (HFrEF) and whether the adherence affected the in-hospital outcomes.Methods: This was a retrospective study of patients hospitalized with HFrEF who had initiated BBs during their hospitalization. We defined adherence to clinical practice guidelines as initiating BB with standard dose and non-adherence to guidelines if otherwise, and examined the association between adherence to guidelines and in-hospital BB-related adverse events. Subgroup analyses based on sex, age, coronary heart disease, and hypertension were performed.Results: Among 1,104 patients with HFrEF initiating BBs during hospitalization (median length of hospitalization, 12 days), 304 (27.5%) patients received BB with non-adherent initiating dose. This non-adherence was related to a higher risk (hazard ratio [95% confidence interval]) of BB dose reduction or withdrawal (1.78 [1.42 to 2.22], P < 0.001), but not significantly associated with risks of profound bradycardia, hypotension, cardiogenic shock requiring intravenous inotropes, and severe bronchospasm requiring intravenous steroid during hospitalization.Conclusion: This study identified that over a fourth of patients had received BBs with an initiating dose that was not adherent to guidelines in Chinese hospitalized patients with HFrEF, and this non-adherence was associated with BB dose reduction or withdrawal during hospitalization.

Aim: The aim of this study was to identify the long noncoding RNAs (lncRNAs) associated with schizophrenia (SZ) and the relationships among their expression, antipsychotic efficacy and SZ severity. Method: The diagnostic and predictive value of nine lncRNAs, Gomafu, DISC2, PSZA11, AK096174, AK123097, DB340248, uc011dma.1, ENST00000509804-1 and ENST00000509804-2, was investigated in 48 patients with SZ before and after antipsychotic treatment. Results: Gomafu, AK096174, AK123097, DB340248, uc011dma.1, ENST00000509804-1 and ENST00000509804-2 were individually and collectively associated with, and predictive of, SZ pathogenesis. Moreover, increased expression of plasma AK123097, uc011dma.1 and ENST00000509804-1 levels was reversed after 12 weeks of antipsychotic treatment, which was associated with SZ severity. Conclusion: Seven lncRNAs serve as novel biomarkers for SZ diagnosis and prognosis and three lncRNAs are potential therapeutic targets.

Background The development of sarcopenia is attributed to normal aging and factors like type 2 diabetes, obesity, inactivity, reduced testosterone levels, and malnutrition, which are factors of poor prognosis in patients with coronary artery disease (CAD). This study aimed to perform a meta-analysis to assess whether preoperative sarcopenia can be used to predict the outcomes after cardiac surgery in elderly patients with CAD. Methods PubMed, Embase, the Cochrane library, and Web of Science were searched for available papers published up to December 2020. The primary outcome was major adverse cardiovascular outcomes (MACE). The secondary outcomes were mortality and heart failure (HF)-related hospitalization. The random-effects model was used. Hazard ratios (HRs) with 95% confidence intervals (95%CIs) were estimated. Results Ten studies were included, with 3707 patients followed for 6 months to 4.5 ± 2.3 years. The sarcopenia population had a higher rate of MACE compared to the non-sarcopenia population (HR = 2.27, 95%CI: 1.58–3.27, P 2 = 60.0%, Pheterogeneity = 0.02). The association between sarcopenia and MACE was significant when using the psoas muscle area index (PMI) to define sarcopenia (HR = 2.86, 95%CI: 1.84–4.46, P 2 = 0%, Pheterogeneity = 0.604). Sarcopenia was not associated with higher late mortality (HR = 2.15, 95%CI: 0.89–5.22, P = 0.090; I2 = 91.0%, Pheterogeneity P = 0.792; I2 = 90.5%, Pheterogeneity = 0.001), and death, HF-related hospitalization (HR = 1.37, 95%CI: 0.59–3.16, P = 0.459; I2 = 62.0%, Pheterogeneity = 0.105). The sensitivity analysis revealed no outlying study in the analysis of the association between sarcopenia and MACE after coronary intervention. Conclusion Sarcopenia is associated with poor MACE outcomes in patients with CAD. The results could help determine subpopulations of patients needing special monitoring after CAD surgery. The present study included several kinds of participants; although non-heterogeneity was found, interpretation should be cautious.

Background The tumor microenvironment (TME) is increasingly appreciated as an important determinant of cancer outcome, including in multiple myeloma (MM). However, most myeloma microenvironment studies have been based on bone marrow (BM) aspirates, which often do not fully reflect the cellular content of BM tissue itself. To address this limitation in myeloma research, we systematically characterized the whole bone marrow (WBM) microenvironment during premalignant, baseline, on treatment, and post-treatment phases. Methods and findings Between 2004 and 2019, 998 BM samples were taken from 436 patients with newly diagnosed MM (NDMM) at the University of Arkansas for Medical Sciences in Little Rock, Arkansas, United States of America. These patients were 61% male and 39% female, 89% White, 8% Black, and 3% other/refused, with a mean age of 58 years. Using WBM and matched cluster of differentiation (CD)138-selected tumor gene expression to control for tumor burden, we identified a subgroup of patients with an adverse TME associated with 17 fewer months of progression-free survival (PFS) (95% confidence interval [CI] 5–29, 49–69 versus 70–82 months, χ2 p = 0.001) and 15 fewer months of overall survival (OS; 95% CI –1 to 31, 92–120 versus 113–129 months, χ2 p = 0.036). Using immunohistochemistry-validated computational tools that identify distinct cell types from bulk gene expression, we showed that the adverse outcome was correlated with elevated CD8+ T cell and reduced granulocytic cell proportions. This microenvironment develops during the progression of premalignant to malignant disease and becomes less prevalent after therapy, in which it is associated with improved outcomes. In patients with quantified International Staging System (ISS) stage and 70-gene Prognostic Risk Score (GEP-70) scores, taking the microenvironment into consideration would have identified an additional 40 out of 290 patients (14%, premutation p = 0.001) with significantly worse outcomes (PFS, 95% CI 6–36, 49–73 versus 74–90 months) who were not identified by existing clinical (ISS stage III) and tumor (GEP-70) criteria as high risk. The main limitations of this study are that it relies on computationally identified cell types and that patients were treated with thalidomide rather than current therapies. Conclusions In this study, we observe that granulocyte signatures in the MM TME contribute to a more accurate prognosis. This implies that future researchers and clinicians treating patients should quantify TME components, in particular monocytes and granulocytes, which are often ignored in microenvironment studies., Author summary Why was this study done? The cells around a tumor, also known as the tumor microenvironment (TME), can help a tumor grow by suppressing the immune system or fight a tumor by mounting an immune response. Most studies of multiple myeloma (MM) have focused on the tumor itself, rather than the bone marrow (BM) TME in which the tumor is growing. We hypothesized that the MM TME held clues that could help us better treat patients. What did the researchers do and find? We used a gene-expression–based computational technique to determine which cell types were present in patient BM. Patients with BM lacking a family of innate immune cells called granulocytes presented with worse outcomes compared to other patients. As MM progresses from a predisease to a cancerous state, the percentage of granulocytes decreases; the patients with the fewest granulocytes had more serious diseases. What do these findings mean? If granulocytes help myeloma patients respond to therapy, then addressing the decline in granulocytes may improve MM treatment. Patients with MM and few granulocytes in their BM should be watched for worse outcomes.

Wrist guards are widely used for preventing distal radius fracture during in-line skating and snowboard-related activities. However, more than half of people wearing wrist guards nonetheless sustain a fracture of the wrist in forward falls. Accordingly, this study evaluates the effects of three factors, namely the wrist guard design, the fall height and the arrest strategy, on the impact force during a forward fall onto a single outstretched hand. Fifteen physically healthy male participants volunteered for the biomechanical investigation. None of the participants had a previous history of upper extremity injuries or disorders. A 1000[Formula: see text]Hz AMTI force plate was used to measure the ground reaction force (GRF) in forward falls performed using a self-built release system onto a single hand. The GRF and impact time were analyzed in terms of three factors, namely (1) the wrist guard design, including bare hand (BH), conventional wrist guard (WG), wrist guard pad on palm (WG+), and WG+ with no lower splint (WG[Formula: see text]; (2) the elbow arrest strategy, including elbow extended and elbow flexed; and (3) the fall height, including 4[Formula: see text]cm and 8[Formula: see text]cm. The impact force and loading rate significantly increased with an increasing fall height. However, the elbow flexed strategy attenuated the GRF peak force and delayed the point of peak impact force. The GRF in the WG, WG+ and WG− conditions was significantly lower than that in the BH condition. Overall, a lower fall height, a wrist guard with a compliant pad (WG+ or WG[Formula: see text], and an elbow flexed strategy reduced the impact force, delayed the peak impact force, and reduced the loading rate in forward falls.

OBJECTIVE To explore the value of magnetic resonance imaging (MRI) textures and its correlation with histopathological malignancy of gliomas by magnetic resonance (MR) navigated stereotactic biopsy. METHODS A total of 36 diffuse glioma cases and 64 puncture targets were included. All patients underwent a preoperative MR scan and intraoperative MR-navigated stereotactic biopsy. The histopathological diagnosis was grade II or grade III diffuse glioma. Regions of interest consistent with puncture targets were delineated on T1-weighted brain volume with gadolinium contrast enhancement images, and textures were extracted using Omni Kinetics software. Mann-Whitney rank sum test was used to analyze texture differences between grade II and grade III samples. False discovery rate (FDR) correction was applied to correct for multiple comparisons. Receiver operating characteristic curves evaluated the diagnostic value of textural analysis for grading gliomas. Correlation between MRI textures and histopathology was examined by Spearman correlation test. RESULTS Texture features, including max intensity, 95th quantile, range, variance, standard deviation, sum variance, and cluster prominence were higher in grade III glioma targets than grade IIs, grade II gliomas showed increased uniformity and short run low gray-level emphasis values (P and qFDRcorr < 0.05). Area under the curve was 0.887 (95% confidence interval, 0.805-0.969; P < 0.001) with combined textures in glioma grading. The listed first-order and gray-level cooccurrence matrix textures were correlated with Ki-67 labeling index. Gray-level cooccurrence matrix and gray-level run length matrix textures were correlated with isocitrate dehydrogenase 1 mutation. CONCLUSIONS Textures on T1-weighted brain volume with gadolinium contrast enhancement images differ between grade III and II gliomas and are correlated with Ki-67 labeling index and isocitrate dehydrogenase 1 mutation.

This study investigated the gut microbiota and short chain fatty acids (SCFAs) characteristics of subjects with obesity from Xinjiang in northwestern China, a region with a multiethnic culture and characteristic lifestyle, and to explore the potential microbes that respond to a 12-wk medication of orlistat and ezetimibe with a randomized controlled open-label trial manner. The gut microbiota profile of patients with overweight and obesity with dyslipidemia in Xinjiang was distinctive and characterized by enrichment of Lactobacillus and the reduction of the diversity and the depletion of Actinobacteria, Bacteroides, Bifidobacterium, and Bacteroides fragilis. Prevotella-type, Gemmiger-type, and Escherichia/Shigella-type were the gut microbial patterns of the Xinjiang population. However, the fecal SCFAs levels and enterotypes were similar between healthy individuals and patients. These results indicated that the contribution of the gut microbiota to obesity was highly dependent on geography and dietary habits. Waist circumference, total triglyceride (TG), and fasting blood glucose (FBG) were significantly decreased after orlistat therapy, whereas TG, total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C) were significantly decreased by ezetimibe. Overall, the gut microbiota and their SCFAs metabolites were relatively stable after treatment with the two drugs, with alteration of some low-abundant bacteria, i.e., significantly increased Proteobacteria and decreased Alloprevotella after orlistat, and increased Fusobacteria and Fusobacterium after ezetimibe therapy. These results indicated that intestinal malabsorption of dietary fat and cholesterol caused by orlistat and ezetimibe had a limited effect on the overall gut microbial community and their metabolites. Nevertheless, significant correlations between several core microbes that responded to the medications and biochemical data were found; in particular, Actinomyces and Bacteroides were positively correlated with FBG after orlistat intervention, while Clostridium XVIII and Lachnospiracea incertae sedis were negatively correlated with TC and LDL-C after ezetimibe intervention, thus indicating their roles in improving glucolipid metabolism in obesity by acting as potential microbial targets.

Objective. To explore the cancer stemness features and develop a novel cancer stemness-related prognostic signature for colon adenocarcinoma (COAD). Methods. We downloaded the mRNA expression data and clinical data of COAD from TCGA database and GEO database. Stemness index, mRNAsi, was utilized to investigate cancer stemness features. Weighted gene coexpression network analysis (WGCNA) was used to identify cancer stemness-related genes. Univariate and multivariate Cox regression analyses were applied to construct a prognostic risk cancer stemness-related signature. We then performed internal and external validation. The relationship between cancer stemness and COAD immune microenvironment was investigated. Results. COAD patients with higher mRNAsi score or EREG-mRNAsi score have significant longer overall survival (OS). We identified 483 differently expressed genes (DEGs) between the high and low mRNAsi score groups. We developed a cancer stemness-related signature using fifteen genes (including RAB31, COL6A3, COL5A2, CCDC80, ADAM12, VGLL3, ECM2, POSTN, DPYSL3, PCDH7, CRISPLD2, COLEC12, NRP2, ISLR, and CCDC8) for prognosis prediction of COAD. Low-risk score was associated with significantly preferable OS in comparison with high-risk score, and the area under the ROC curve (AUC) for OS prediction was 0.705. The prognostic signature was an independent predictor for OS of COAD. Macrophages, mast cells, and T helper cells were the vital infiltration immune cells, and APC costimulation and type II IFN response were the vital immune pathways in COAD. Conclusions. We developed and validated a novel cancer stemness-related prognostic signature for COAD, which would contribute to understanding of molecular mechanism in COAD.

LEOPARD was a single arm, phase II study of lenalidomide (LEN) and alternate day prednisolone maintenance in patients with newly diagnosed multiple myeloma (MM) following autologous stem cell transplantation (ASCT). Sixty patients were enrolled. Estimated median potential follow-up was 44 m, median PFS was 38.3 m, median OS was not reached (landmark 36 m OS: 71.4%). Correlative immunohistochemistry performed on pre-ASCT trephines demonstrated high MM tumor cereblon (total/cytoplasmic) was associated with superior OS (p = .045, p = .031, respectively), whereas high c-Myc was associated with inferior PFS (p = .04). Patients with high cereblon (total/nuclear) were more likely to improve depth of response, whereas patients with high c-Myc were less likely, suggesting alternative/more effective post-ASCT strategies for patients with high c-Myc need identification. Peripheral blood immune profiling (mass cytometry) informed a more sustained response to LEN maintenance, demonstrating enrichment of activated/cytotoxic NK cells and cytotoxic T cells in patients with durable responses, contrasting with enrichment of B-regs in early relapsers.

Background: Given the increased use and diversity of diagnostic procedures, it is important to understand genetic susceptibility to radiation-induced thyroid cancer. Methods: On the basis of self-declared diagnostic radiology examination records in addition to existing literature, we estimated the radiation dose delivered to the thyroid gland from diagnostic procedures during childhood and adulthood in two case–control studies conducted in France. A total of 1,071 differentiated thyroid cancer (DTC) cases and 1,188 controls from the combined studies were genotyped using a custom-made Illumina OncoArray DNA chip. We focused our analysis on variants in genes involved in DNA damage response and repair pathways, representing a total of 5,817 SNPs in 571 genes. We estimated the OR per milli-Gray (OR/mGy) of the radiation dose delivered to the thyroid gland using conditional logistic regression. We then used an unconditional logistic regression model to assess the association between DNA repair gene variants and DTC risk. We performed a meta-analysis of the two studies. Results: The OR/mGy was 1.02 (95% confidence interval, 1.00–1.03). We found significant associations between DTC and rs7164173 in CHD2 (P = 5.79 × 10−5), rs6067822 in NFATc2 (P = 9.26 × 10−5), rs1059394 and rs699517 both in ENOSF1/THYS, rs12702628 in RPA3, and an interaction between rs7068306 in MGMT and thyroid radiation doses (P = 3.40 × 10−4). Conclusions: Our results suggest a role for variants in CDH2, NFATc2, ENOSF1/THYS, RPA3, and MGMT in DTC risk. Impact: CDH2, NFATc2, ENOSF1/THYS, and RPA3 have not previously been shown to be associated with DTC risk.

Clinical question What are the benefits and harms of sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists when added to usual care (lifestyle interventions and/or other diabetes drugs) in adults with type 2 diabetes at different risk for cardiovascular and kidney outcomes? Current practice Clinical decisions about treatment of type 2 diabetes have been led by glycaemic control for decades. SGLT-2 inhibitors and GLP-1 receptor agonists are traditionally used in people with elevated glucose level after metformin treatment. This has changed through trials demonstrating atherosclerotic cardiovascular disease (CVD) and chronic kidney disease (CKD) benefits independent of medications’ glucose-lowering potential. Recommendations The guideline panel issued risk-stratified recommendations concerning the use of SGLT-2 inhibitors or GLP-1 receptor agonists in adults with type 2 diabetes • Three or fewer cardiovascular risk factors without established CVD or CKD: Weak recommendation against starting SGLT-2 inhibitors or GLP-1 receptor agonists. • More than three cardiovascular risk factors without established CVD or CKD: Weak recommendation for starting SGLT-2 inhibitors and weak against starting GLP-1 receptor agonists. • Established CVD or CKD: Weak recommendation for starting SGLT-2 inhibitors and GLP-1 receptor agonists. • Established CVD and CKD: Strong recommendation for starting SGLT-2 inhibitors and weak recommendation for starting GLP-1 receptor agonists. • For those committed to further reducing their risk for CVD and CKD outcomes: Weak recommendation for starting SGLT-2 inhibitors rather than GLP-1 receptor agonists. How this guideline was created An international panel including patients, clinicians, and methodologists created these recommendations following standards for trustworthy guidelines and using the GRADE approach. The panel applied an individual patient perspective. The evidence A linked systematic review and network meta-analysis (764 randomised trials included 421 346 participants) of benefits and harms found that SGLT-2 inhibitors and GLP-1 receptor agonists generally reduce overall death, and incidence of myocardial infarctions, and end-stage kidney disease or kidney failure (moderate to high certainty evidence). These medications exert different effects on stroke, hospitalisations for heart failure, and key adverse events in different subgroups. Absolute effects of benefit varied widely based on patients’ individual risk (for example, from five fewer deaths in the lowest risk to 48 fewer deaths in the highest risk, for 1000 patients treated over five years). A prognosis review identified 14 eligible risk prediction models, one of which (RECODe) informed most baseline risk estimates in evidence summaries to underpin the risk-stratified recommendations. Concerning patients’ values and preferences, the recommendations were supported by evidence from a systematic review of published literature, a patient focus group study, a practical issues summary, and a guideline panel survey. Understanding the recommendation We stratified the recommendations by the levels of risk for CVD and CKD and systematically considered the balance of benefits, harms, other considerations, and practical issues for each risk group. The strong recommendation for SGLT-2 inhibitors in patients with CVD and CKD reflects what the panel considered to be a clear benefit. For all other adults with type 2 diabetes, the weak recommendations reflect what the panel considered to be a finer balance between benefits, harms, and burdens of treatment options. Clinicians using the guideline can identify their patient’s individual risk for cardiovascular and kidney outcomes using credible risk calculators such as RECODe. Interactive evidence summaries and decision aids may support well informed treatment choices, including shared decision making.

Objective This study aimed to investigate the changes in inflammatory biomarkers between newly diagnosed type 2 diabetes (T2DM) patients under one-year acarbose treatments and those under metformin managements. Methods Seventy patients with newly diagnosed T2DM and 32 volunteers with normal glucose tolerance (normal controls, NCs) were enrolled. Seventy patients with T2DM were randomly assigned to two subgroups and treated with acarbose (n=34) or metformin (n=36) for 1 year. Blood glucose, insulin, glycosylated hemoglobin (A1C), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and inflammatory biomarker levels (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), and ferritin) were detected at 0, 6 and 12 months. Results After adjusting for sex, the waist-to-hip ratio (WHR) and body mass index (BMI), higher fasting plasma glucose (FPG), standard meal test 1/2 hr and 2 hr glucose, TG, TC, LDL-C, IL-6, TNF-α, IL-2 and ferritin levels were observed in T2DM group than in NCs (P

Objective The aim of this study was to investigate the satisfaction of age-related hearing loss (ARHL) or presbycusis patients with individual, accurate, and precise fitting progress, which is a priority for bilateral hearing aids, and to explore the related influencing factors and their role in predicting the efficiency of hearing aids. Methods A total of 73 cases of presbycusis patients aged 60-95 years old underwent pure tone audiometry and speech recognition ability examination to obtain the pure tone audiometry of the better ear (BPTA) and maximum speech recognition rate of the better ear (BSRR) in quiet environment before hearing aid fitting. Audiologists evaluated the efficiency and satisfaction of participants according to the International Outcome Inventory for Hearing Aids (IOI-HA) questionnaire scores by face-to-face or telephone investigations after using the hearing aids for at least 3 months. The data were analyzed related to possible influencing factors. Results Total satisfaction percentage according to IOI-HA scores was 86.3%. There was no significant correlation between age, first fitting age, unilateral or bilateral hearing aids, BPTA, and IOI-HA total score. BSRR was strongly correlated to total IOI-HA scores (r=0.768). According to the multiple linear regression analysis, BPTA and BSRR both had a statistically significant effect on the total IOI-HA scores after hearing aid intervention. Conclusion ARHL patients with accurate hearing aid fitting will have high satisfaction and bilateral hearing aids are better than unilateral ones. Age and first fitting age are not meaningful to satisfaction with hearing aids. A higher maximum speech recognition rate before hearing aids fitting could predict better efficiency and satisfaction with hearing aids. Therefore, completing speech recognition ability examination before fitting would make a great contribution to the efficiency of hearing aids, and help ARHL patients have realistic expectations.

BACKGROUND There is a need for an imaging-based tool for measuring vascular endothelial growth factor (VEGF) expression and overall survival (OS) in patients with glioma. PURPOSE To assess the correlation between cerebral blood flow (CBF), measured by 3D pseudo-continuous arterial spin-labeling (3D-ASL), and VEGF expression in gliomas on the basis of coregistered localized biopsy, and investigate whether CBF correlated with survival month (SM) in glioma patients. STUDY TYPE Prospective cohort. SUBJECTS Thirty-seven patients with gliomas from whom 63 biopsy specimens were obtained. SEQUENCE 3D-ASL acquired with a 3.0T MR unit. ASSESSMENT Biopsy specimens were grouped as high-grade (HGG) or low-grade glioma (LGG). CBF measurements were spatially matched with VEGF expression by coregistered localized biopsies, and the CBF value was correlated with quantitative VEGF expression for each specimen. Patients' survival information was derived and connected with CBF. STATISTICAL TESTS Patients' OS was analyzed by Kaplan-Meier and Cox-regression methods. VEGF expression and CBF were compared in both LGG and HGG. The Spearman rank correlation was calculated for CBF and VEGF expression, SM. Significance level, P < 0.05. RESULTS CBF-derived 3D-ASL positively correlated significantly with VEGF expression in both LGG (31 specimens) and HGG (32 specimens), r = 0.604 (P < 0.001) and r = 0.665 (P < 0.001), respectively. LGG and HGG together gave a correlation coefficient r = 0.728 (P < 0.001). Median survival for LGG and HGG patients was 34.19 and 17.17 months, respectively (P = 0.037); CBF value negatively correlated significantly with SM with r = -0.714 (P < 0.001) regardless of glioma grade. CBF was an independent risk factor for OS with HR = 1.027 (P = 0.044), 1.028 (P = 0.010) for univariate/multivariate regression analysis. DATA CONCLUSION CBF determined by 3D-ASL correlates with VEGF expression in glioma and is an independent risk factor for OS in these patients. LEVEL OF EVIDENCE 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:209-220.

Objectives To examine, through a cross-sectional survey, how well safety information was reported among drug systematic reviews predating PRISMA harms checklist and explore factors associated with better reporting. Study Design and Setting We searched PubMed to identify all systematic reviews published in the Cochrane Database of Systematic Review or the core clinical journals in 2015, one year before the PRISMA harms checklist was published. We randomly selected, in a 1:1 ratio, Cochrane and non-Cochrane systematic reviews assessing drug effects (including both efficacy and safety). We used the PRISMA harms checklist published in 2016 to assess the quality of reporting of drug safety information. Multivariable linear regression analyses were used to explore the association of six prespecified variables with more complete reporting of PRISMA harms items. Results We included 120 systematic reviews, including 60 Cochrane and 60 non-Cochrane reviews. Scores on the PRISMA harms checklist (23 items) were low (median 4, [first, third quartile: 2, 6]), with no difference between Cochrane and non-Cochrane reviews (4.5 [2, 7] vs. 4 [2.5, 5]; P = 0.29). Among all eligible reviews, only one item (i.e., state conclusions in coherence with the review findings) was reported adequately (proportion of adherence 81.6%); proportion of reporting for other items ranged from 1.7% to 68.3%. The four essential reporting items from PRISMA harms checklist were also poorly complied (proportion of adherence ranged from 1.7% to 9.2%). Multivariable linear regression analyses found no significant associations between any study characteristic and reporting on the PRISMA harms, likely because of limited variability in scores across studies. Conclusions The reporting of safety information was poor both for Cochrane and non-Cochrane drug systematic reviews predating PRISMA harms checklist. The findings suggested a strong need to use the PRISMA harms checklist for reporting safety among drug systematic reviews.

Exposure to nicotine during adolescence may cause neurophysiological changes and increase the risks of developing nicotine dependence; it can even lead to lifelong smoking. The intake of nicotine may also lead to abnormal patterns of oscillatory brain activity and inhibition control deficits. However, little is known about the specific relationship between oscillatory brain activity during the resting state and inhibition control capacity in young smokers. In the present study, we acquired resting-state electroencephalography (EEG) data from thirty-four young smokers and 39 age-matched non-smoking controls. Inhibition control performance was measured by a Go/NoGo task. Compared with non-smoking controls, we detected reduced low-frequency delta band activity in the frontal, central and posterior cortices of young smokers. Furthermore, young smokers committed more errors in response to infrequent NoGo trials. Notably, we demonstrated that delta absolute power in the frontal region was negatively correlated with NoGo errors and that alpha power in the central region was positively correlated with NoGo errors in non-smoking controls but not in young smokers. These findings may suggest that these inhibitory control processes were associated with alterations in oscillatory brain activity during the resting state. Our findings suggest that alterations of power spectra in delta bands may act as a useful biomarker of inhibitory control performance and provide a scientific basis for the diagnosis and treatment of nicotine addiction in adolescents.

ObjectivePrimary adrenal lymphoma (PAL) is easily misdiagnosed as other adrenal masses, such as adrenocortical carcinoma and pheochromocytoma, but patients with PAL benefit little from surgery. The diagnostic method for PAL thus far is limited to adrenal biopsy. In our study, we aimed to develop a quick and efficient diagnostic method for PAL.Methods and ResultsAt the same institution, 505 patients (between 2009 and 2019) and 171 patients (between 2019 and 2020) were separately included in the primary and validation studies. Univariate and multivariate analyses were conducted to evaluate clinical manifestations, laboratory findings, and radiological characteristics. Four determinants (age, bilateral masses, high-density lipoprotein cholesterol, and lactate dehydrogenase) were selected and further incorporated into a regression model to screen PAL. Accordingly, the nomogram was developed for clinical practice. In the primary study, the nomogram showed good discrimination, with an area under the receiver operating characteristic (ROC) curve (AUC) of 95.4% (95% CI, 90.6%–100.0%). Further validation study verified the efficacy of the nomogram, with an AUC of 99.0% (95% CI, 96.9%–100.00%) and 100.0% in all patients and patients with bilateral masses, respectively, and a sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV) of 66.67%/99.40%/66.67%/99.40%, 66.67%/100%/100%/92.86%, 50%/99.20%/50%/99.20%, and 100%/100%/100%/100%, in all patients, patients with bilateral adrenal masses, patients with nonfunctional adrenal masses, and patients with positive catecholamine results, respectively. The validation study also revealed a diagnostic specificity of 99.35% and 100% for patients with a unilateral adrenal mass and functional PCC, respectively.ConclusionsThe presented nomogram is the first user-friendly diagnostic model for PAL that simplifies the complex diagnostic process into personalized numeric estimates. We deem that patients who score below 50 are less likely to have PAL. We suggest that clinicians should arrange adrenal biopsy and surgery for patients with nonfunctional tumors and overt catecholamine-secreting tumors, respectively, who receive a score of 50 points or higher to confirm the diagnosis as soon as possible.

To investigate the association between glycated hemoglobin (HbA1c) and myocardial dysfunction and to determine whether its association is independent of myocardial perfusion.Sixty-four patients with type 2 diabetes mellitus (T2DM) were recruited. They were divided into groups according to their HbA1c level: the controlled T2DM group (HbA1c 7%) and uncontrolled T2DM groups (HbA1c ≥ 7%). Meanwhile, 30 age-matched healthy volunteers were included. All patients with T2DM and healthy controls underwent cardiovascular magnetic resonance imaging to evaluate the myocardial mechanics and perfusion parameters.The circumferential and longitudinal peak strain (PS) (p = 0.009 and 0.002 respectively) and global radial, circumferential, and longitudinal peak strain diastolic strain rates (PDSRs) (p = 0.002, 0.001, and 0.001 respectively) were lower in the uncontrolled T2DM group than in the controls without diabetes. In multivariable linear regression analysis, HbA1c was independently related to all directions of the PS and PDSR. The myocardial perfusion parameters were not independently associated with the PS or PDSR.Cardiac function is impaired in Chinese T2DM patients with poor glucose control (HbA1c ≥ 7%), with preserved left ventricular (LV) ejection fraction, and disease duration10 years. Poor blood glucose control is an independent predictor of LV myocardial dysfunction for patients with short-term T2DM.

INTRODUCTION This study developed a method for quantifying the JAK2V617F mutation load in patients with myeloproliferative neoplasm (MPN) using droplet digital PCR (ddPCR), which provides a new laboratory method for diagnosing polycythemia vera (PV), essential thrombocythemia (ET), and pre-primary myelofibrosis (pre-PMF). METHODS Patients with MPN who had JAK2V617F mutations from March 2013 to August 2019 were enrolled in this study. JAK2V617F mutation loads were quantified using ddPCR technology. RESULTS The study examined 225 patients, including 135 with ET, 58 with PV, and 32 with PMF. JAK2V617F mutation loads significantly differed (P

To further understand the fundamentals of photon-counting spectral CT and provide guidelines on its design and implementation, we propose a singular value decomposition (SVD) based approach to assess the conditioning of spectral channelization and its impact on the performance of spectral imaging under both ideal and realistic detector spectral response. The study runs over two- and three-material decomposition based spectral imaging (material specific imaging). A specially designed phantom that mimics the soft and bony tissues in the head is used to reveal the relationship between the conditioning of spectral channelization and the imaging performance (noise and contrast-to-noise ratio). The study also runs over the cases with up to 50% spectral overlapping and gapping. Under ideal detector spectral response, the condition number of spectral channelization reaches the minimum while no overlapping occurs in spectral channels, and increments with increasing spectral overlapping, and so does in the situation while gapping occurs. The distortion in detector’s spectral response due to charge-sharing and fluorescent escaping inevitably leads to spectral overlapping and thus degrades the conditioning of spectral channelization. With increasing condition number, the noise increases and contrast-to-noise ratio decreases, respectively. The proposed approach, especially its coverage on the situation wherein gapping occurs in spectral channelization, is novel and may provide information for insightful understanding of the fundamentals and guidelines on implementation of spectral imaging in photon-counting and energy-integration CT, and other x-ray imaging modalities such as radiography and tomosynthesis.

ObjectivesThe main cardiac features of primary aldosteronism (PA) are impaired left ventricular (LV) diastolic function, and some articles also reported more cardiac fibrosis in PA patients. However, the correlation between LV dysfunction and diffuse myocardial fibrosis in PA remains unknown.MethodsWe enrolled 84 PA patients and 28 essential hypertension (EH) patients in West China Hospital. Cardiac magnetic resonance imaging (CMR) contrast enhancement was arranged for all subjects. Postcontrast T1 time and left ventricular myocardial strains and strain rates were measured.Results76 PA patients and 27 essential hypertension (EH) patients were included in the final analysis. Blood pressure, LV mass indexes, and LV ejection fractions were comparable in both groups, while the global circumferential peak diastolic strain rate (PDSR) was lower (0.9 ± 0.3 vs. 1.1 ± 0.4, p ConclusionsThe global circumferential PDSR derived by CMR is decreased, and the diffuse myocardial fibrosis is increased in PA patients compared to those in blood pressure matched EH patients. The severity of cardiac diastolic dysfunction independently relates to the degree of diffuse myocardial fibrosis in PA patients, and the diffuse myocardial fibrosis may be caused by high PAC level.Clinical Trial Registrationhttp://www.chictr.org.cn/listbycreater.asp, identifier ChiCTR2000031792.

ObjectiveOur study aimed to systematically review the methodological characteristics of studies that identified prognostic factors or developed or validated models for predicting mortalities among patients with acute aortic dissection (AAD), which would inform future work.Design/settingA methodological review of published studies.MethodsWe searched PubMed and EMBASE from inception to June 2020 for studies about prognostic factors or prediction models on mortality among patients with AAD. Two reviewers independently collected the information about methodological characteristics. We also documented the information about the performance of the prognostic factors or prediction models.ResultsThirty-two studies were included, of which 18 evaluated the performance of prognostic factors, and 14 developed or validated prediction models. Of the 32 studies, 23 (72%) were single-centre studies, 22 (69%) used data from electronic medical records, 19 (59%) chose retrospective cohort study design, 26 (81%) did not report missing predictor data and 5 (16%) that reported missing predictor data used complete-case analysis. Among the 14 prediction model studies, only 3 (21%) had the event per variable over 20, and only 5 (36%) reported both discrimination and calibration statistics. Among model development studies, 3 (27%) did not report statistical methods, 3 (27%) exclusively used statistical significance threshold for selecting predictors and 7 (64%) did not report the methods for handling continuous predictors. Most prediction models were considered at high risk of bias. The performance of prognostic factors showed varying discrimination (AUC 0.58 to 0.95), and the performance of prediction models also varied substantially (AUC 0.49 to 0.91). Only six studies reported calibration statistic.ConclusionsThe methods used for prognostic studies on mortality among patients with AAD—including prediction models or prognostic factor studies—were suboptimal, and the model performance highly varied. Substantial efforts are warranted to improve the use of the methods in this population.

Introduction: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, a serious neurological autoimmune disorder caused by autoantibodies with diverse clinical manifestations, may simultaneously onset with antimyelin oligodendrocyte glycoprotein (MOG) demyelination after recurrent central nervous system (CNS) demyelination.Case Report: We present a case of anti-NMDAR encephalitis combining with anti-MOG CNS demyelination following recurrent CNS demyelination. A 38-year-old man admitted to hospital developed epileptic seizures following recurrent episodes of cross-sensory disturbance and dizziness. Magnetic resonance imaging (MRI) showed a demyelinating lesion in the right brainstem initially. Despite a good response to methylprednisolone pulse therapy at the beginning, the patient still had relapses and progression after corticosteroid reduction or withdrawal. Then brain MRI discovered new serpentine lesions involving extensive cerebral cortex on his second relapse. Repeat autoantibodies test indicated cerebrospinal fluid (CSF) NMDAR antibodies coexisted with MOG-Abs simultaneously, suggesting the diagnosis of anti-NMDAR encephalitis with anti-MOG CNS demyelination.Results: After a definite diagnosis, the patient was treated with mycophenolate mofetil (MMF) and corticosteroid. He was discharged after his symptoms ameliorated. No neurological sequels remained, and there were no effects on his activities of daily living after 6 months of immunoregulatory therapy of MMF and corticosteroid.Conclusion: For individuals with recurrent CNS demyelination, especially combining with cortical encephalitis, repeated detection of autoantibodies against AE, and demyelination in CSF/serum can be helpful to enable a definite early diagnosis. For patients who suffer from anti-NMDAR encephalitis combining with anti-MOG CNS demyelination, second-line immunotherapy is recommended when first-line treatment such as steroids, intravenous immunoglobulin G (IVIG) and plasma exchange has been proven ineffective to prevent the relapse of disease.