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Hereditary aceruloplasminemia (ACP) is a rare adult-onset autosomal recessive disease characterized by a ceruloplasmin (CP) gene mutation and defective or absent CP function. In the present study, we report a case of ACP in a 34-year-old Chinese woman with diabetes, fatigue, anxiety, and progressive membrane loss with low hemoglobin associated with microcytosis. The fasting glucose level was 5.6-7.96 mmol/L. Postprandial blood glucose ranged from 6.8 to 9.6 mmol/L. The Stumvoll first-phase and second-phase insulin secretion disposition indices were very low, and the serum iron content was low, even though transferrin levels were normal. Moreover, the transferrin saturation was low (5%), and the ferritin level was extremely high, above 2,000 μg/L in the patient. Furthermore, her serum CP level was extremely low ( A) in the CP gene and was diagnosed with ACP. To date, less than 60 family cases of ACP have been reported worldwide, and only two cases of ACP have been reported in China. Here, we report a case of ACP accompanied by diabetes with a novel mutation of the CP gene, which suggests that increased awareness should be highlighted in this disorder as diabetes is an important typical symptom.

Background Brugada syndrome is a major cause of sudden cardiac death in young people with a distinctive electrocardiogram (ECG) feature. We aimed to develop a deep learning-enabled ECG model for automatic screening Brugada syndrome to identify these patients at an early time, thus allowing for life-saving therapy. Methods A total of 276 ECGs with a type 1 Brugada ECG pattern (276 type 1 Brugada ECGs and another randomly retrieved 276 non-Brugada type ECGs for one to one allocation) were extracted from the hospital-based ECG database for a two-stage analysis with a deep learning model. After trained network for identifying right bundle branch block pattern, we transferred the first-stage learning to the second task to diagnose the type 1 Brugada ECG pattern. The diagnostic performance of the deep learning model was compared to that of board-certified practicing cardiologists. The model was further validated in the independent ECG dataset, collected from the hospitals in Taiwan and Japan. Results The diagnoses by the deep learning model (AUC: 0.96, sensitivity: 88.4%, specificity: 89.1%) were highly consistent with the standard diagnoses (Kappa coefficient: 0.78). However, the diagnoses by the cardiologists were significantly different from the standard diagnoses, with only moderate consistency (Kappa coefficient: 0.63). In the independent ECG cohort, the deep learning model still reached a satisfactory diagnostic performance (AUC 0.89, sensitivity: 86.0%, specificity: 90.0%). Conclusions We presented the first deep learning-enabled ECG model for diagnosing Brugada syndrome, which appears to be a robust screening tool with a diagnostic potential rivaling trained physicians.

Objective Transcutaneous auricular vagus nerve stimulation (taVNS) can relieve the symptoms of functional dyspepsia (FD) and improve the quality of life of patients, however, the mechanism underlying this effect remains unclear. Therefore, this study aimed to investigate the effects of taVNS on the expression of intestinal mucosal ligandins. Methods This study was conducted on 24 specific Spathogen-free Sprague–Dawley rats (12 males and 12 females). The rat model of FD was established by tail-clip stimulation. After FD was established successfully, all rats were randomized to either the normal group (n = 6), model group (n = 6), taVNS group (n = 6), or sham-taVNS group (n = 6). After two weeks of the respective intervention, the score of their general conditions, 3 h food intake, gastric emptying rate, and the histology of gastric antrum tissues were observed to evaluate modeling success, and then the effect of taVNS was evaluated. Western blotting was used to assess the expression of the tight junction ligandins —ZO-1 and occludin—and the adhesion ligandin—β-catenin—in the duodenum. The effect of taVNs on the expression of intestinal mucosal barrier ligandins—ZO-1, occludin, and β-catenin—in FD rats was preliminarily investigated. Results When the model-induced period was finished, the manifestations of FD in the model group rats were mental exhaustion, reduced activities, decreased score of the general conditions, and decreased 3 h food intake, compared to the normal group rats. In addition, minimal eosinophil infiltration, without any mucosal erosion or ulcer, was observed in the gastric antrum mucosa. At the end of the study, the mental state of the FD rats improved, and their activities and gastric emptying rate increased in the taVNS group rats. Compared to the normal rats, the duodenal mucosa had less expression of the tight junction ligandins ZO-1 and occludin, but β-catenin expression remained unchangedin the model rats. The expression of the tight junction ligandins ZO-1 and occludin were increased in the duodenal mucosa of model rats after the taVNS intervention. Conclusion TaVNS can improve the gastric motility and mental state of rats with FD. It may play a therapeutic role by improving the expression of the tight junction ligandin ZO-1 and occludin in the duodenal mucosa, while also repairing the duodenal mucosal barrier.

Objective The role of ideal cardiovascular health (CVH) metrics in developing hearing loss remains uncertain. Thus, our objective was to analyze the connection between hearing loss and ideal CVH metrics in a 10-year retrospective cohort. Study design Retrospective cohort study. Setting A health management center in Taiwan. Participants Participants who underwent the first annual health check-up between 2000 and 2006 and with a follow-up check-up more than ten years later. Main outcome measures Hearing thresholds were measured at 500 Hz, 1000 Hz, 2000 Hz, and 4000 Hz. Individuals with a best ear pure-tone audiometry four-frequency average of >25 dB HL were defined as having hearing loss. The ideal CVH metrics were classified into 7 categories based on the American Heart Association's definition. The associations of hearing loss with the sum of the ideal CVH metrics and each ideal CVH metric were examined by multiple logistic regression analysis. Results The present study consisted of 6,974 participants. The 10-year follow-up showed that the odds ratio (OR) of hearing loss was 0.74 for participants with 5-7 ideal CVH metrics (95% CI, 0.59-0.93, p=0.01) compared to those with 0-2 ideal CVH metrics. Among the CVH metrics, participants with an ideal smoking status might have reduced odds of developing hearing loss; the OR was 0.72 (95% CI, 0.58-0.89, p=0.003). Conclusions Participants with an increased number of ideal CVH metrics and better performance on the smoking metric had a significantly protective effect regarding hearing loss development.

In spite of the preliminary evidence suggesting a link between gestational use of antidepressant and neurodevelopmental disorders in their offspring, the association between maternal use of antidepressants during pregnancy and the risk of neurologically-related adverse outcomes such as neonatal seizure is still unclear. This study summarises the available evidence on the association between gestational exposure to any antidepressants and the risk of seizure in neonates and children. We found that gestational antidepressant exposure is associated with a 2.3-fold higher incidence of seizure in offspring. Although a causal relationship cannot be confirmed in view of other potential confounders, our findings warrant future research on related clinical aspects, and possibly more careful monitoring of foetal neurodevelopment in pregnant women taking antidepressants during pregnancy. However, this does not suggest the abrupt withdrawal of antidepressants during pregnancy for all cases at risk of seizure in offspring as this must be balanced with the risk of negative consequences caused by untreated maternal depression, and decision-making should be individualised for each patient.

Background Although open reduction and internal fixation (ORIF) is recommended for lateral condylar humerus fractures (LCHFs) displaced by > 4 mm, several studies have reported the use of closed reduction and percutaneous pinning (CRPP) to treat LCHFs with significant displacement. However, little is known about the clinical differences between these two surgical techniques. This study aimed to compare the therapeutic effects of CRPP and ORIF in treating LCHFs displaced by > 4 mm. Methods We retrospectively reviewed pediatric LCHFs displaced by > 4 mm treated with either CRPP or ORIF at our center from June 2019 to October 2020. Song and Milch fracture classifications were used. Variables such as age at injury, sex, side injured, fracture displacement, fracture type, operating time, postoperative treatment, and complications were compared between the two techniques. Results One hundred twenty LCHFs met inclusion criteria. There were 36 Milch type I and 84 type II LCHFs, and 69 Song stage 4 and 51 stage 5 LCHFs. CRPP was performed in 45 cases and ORIF in 75 cases. No differences were found in age, sex, side injured, preoperative displacement, postoperative displacement, and length of immobilization between the CRPP and ORIF groups. There was a difference between operation time and pin duration. The CRPP group had shorter operation times and pin duration, and required no additional operations to remove internal pins. The average follow-up duration was 13.9 months. All patients achieved fracture union, and no complications such as infection, nonunion, delayed union, osteonecrosis, fishtail deformity, cubitus varus or valgus, or pain were recorded during follow-up. Bone spurs, lateral prominences, and decreased carrying angle were common complications in all groups. No obvious cubitus varus was observed. Unaesthetic scars were only observed in the ORIF groups. No differences in range of motion or elbow function was found among the different therapies. Conclusions Both CRPP and ORIF can achieve satisfactory clinical outcomes in treating LCHFs displaced by > 4 mm. No differences were found in complications or prognoses between the two groups. However, CRPP shows some advantages over ORIF, like less invasive surgery, no obvious scarring, and no need for secondary surgery with anesthesia for pin removal.

BACKGROUND Postconcussion symptoms (PCSs) are common complaints reported by patients after a mild traumatic brain injury (TBI), and these symptoms may lower quality of life. Previous investigations have primarily focused on PCSs in children, adults, and athletes. The frequency, and risk factors, and effects of PCSs for older adults with mild TBIs are unclear. PURPOSE To investigate the frequency and risk factors of PCSs, and investigate their effects on quality of life over time after mild TBI in older adults. METHODS A prospective longitudinal study was performed. All participants were enrolled from the emergency department or neurosurgical outpatient clinics of a medical center. The measurement tools were the Rivermead Post-Concussion Symptoms Questionnaire and the Quality of Life after Traumatic Brain Injury. Measurements were performed on the seventh day, at the first month, and at the sixth month after the head injury. A generalized estimating equation model was used for data analyses. RESULTS One hundred and one older adults (mean age of 76.0 years) with mild TBIs with negative neuroimaging findings were included. Overall, 32.7%, 4%, and 15.8% of the sample reported PCS after 7 days, 1 month, and 6 months of head injury, respectively, revealing a U-shaped trend. We observed that comorbidity measured using the modified Charlson Comorbidity Index was associated with differences in PCSs (P < .05). PCSs were an independent predictor of changes in postinjury quality of life (P < .001). CONCLUSIONS The results indicate that PCS after a mild TBI in older adults is prevalent, even in the chronic phase after a TBI, and PCSs significantly affected the quality of life of our cohort. Therefore, to improve patient quality of life, healthcare providers should employ effective interventions to manage PCSs at different phases after a TBI.

Background The mechanisms underlying angiotensin receptor-neprilysin inhibitor (ARNi) suppression of ventricular arrhythmia (VA) are unclear. This study aimed to investigate the mechanism of ARNi-related suppression of VA in a heart failure (HF) model. Methods New Zealand white rabbits (n = 6 per group) were assigned to normal, HF [4 weeks of left ascending artery (LAD) ligation], angiotensin receptor blocker (ARB, valsartan at 27 mg/kg/day for 3 weeks after 1 week of LAD ligation), and ARNi (sacubitril at 34 mg/kg/day and valsartan at 27 mg/kg/day for 3 weeks after 1 week of LAD ligation) groups. Experiments involving echocardiogram, optical mapping, histological of trichrome stain and immunostain, and flow cytometry were performed. Results HF group had larger left ventricular (LV) internal dimensions in diastole and systole, and lower LV ejection fraction and fractional shortening than normal, ARB, and ARNi groups. HF group had a prolonged action potential duration (APD) and decreased conduction velocity (CV), which was mitigated in ARB and ARNi groups. HF group had a prolonged QRS duration, QT and QTc intervals, which was reversed in ARB and ARNi groups. HF group had a steeper maximum slope of APD restitutions, which was attenuated in normal, ARB, and ARNi groups. HF group had increased number of phase singularities (PSs) and VA inducibility than normal, ARB, and ARNi groups. A higher content of fibrosis was found in HF group than that in normal, ARB, and ARNi groups. Compared to ARB group, ARNi had a lower context of fibrosis. HF group had more peripheral blood CD4+ and CD8+ cells count than normal, ARB, and ARNi group. Conclusions In a rabbit model of ischemic HF, ventricular arrhythmogenesis could be suppressed by ARNi treatment. This appears to be mediated by reversing changes in the APD, CV, maximum slope of the APDR, PSs, fibrosis, and inflammation.

Importance : The risk of birth and neurodevelopmental complications with prenatal exposure to antipsychotics is unclear.\ud \ud Objective : To evaluate the association between prenatal antipsychotics exposure and the risk of birth and neurodevelopmental problems.\ud \ud Design, Setting, and Participants : This population-based cohort study included children born between January 2001 and January 2015 with follow-up to December 2019 who were identified by the Hong Kong Clinical Data Analysis and Reporting System. Pregnancies with maternal antidepressant/lithium exposure were removed. Primary analyses compared gestationally exposed and gestationally nonexposed individuals with propensity score fine stratification. Additional analyses included gestationally exposed individuals vs those with past exposure and a sibling-matched analysis to evaluate the effect of confounding by indication.\ud \ud Exposures : Prenatal antipsychotic exposure.\ud \ud Main Outcomes and Measures : Preterm birth (

Background Fluid overload is associated with poor outcomes. Clinicians might be reluctant to initiate diuretic therapy for patients with recent vasopressor use. We estimated the effect on 30-day mortality of withholding or delaying diuretics after vasopressor use in patients with probable fluid overload. Methods This was a retrospective cohort study of adults admitted to ICUs of an academic medical centre between 2008 and 2012. Using a database of time-stamped patient records, we followed individuals from the time they first required vasopressor support and had >5 L cumulative positive fluid balance (plus additional inclusion/exclusion criteria). We compared mortality under usual care (the mix of care actually delivered in the cohort) and treatment strategies restricting diuretic initiation during and for various durations after vasopressor use. We adjusted for baseline and time-varying confounding via inverse probability weighting. Results The study included 1501 patients, and the observed 30-day mortality rate was 11%. After adjusting for observed confounders, withholding diuretics for at least 24 h after stopping most recent vasopressor use was estimated to increase 30-day mortality rate by 2.2% (95% confidence interval [CI], 0.9–3.6%) compared with usual care. Data were consistent with moderate harm or slight benefit from withholding diuretic initiation only during concomitant vasopressor use; the estimated mortality rate increased by 0.5% (95% CI, –0.2% to 1.1%). Conclusions Withholding diuretic initiation after vasopressor use in patients with high cumulative positive balance (>5 L) was estimated to increase 30-day mortality. These findings are hypothesis generating and should be tested in a clinical trial.

Po-En Chiu,1,2,&ast; Zhonghua Fu,3,&ast; Guan-Wei Jian,4,5 Ching-Hsuan Huang,2,6 Te-Mao Li,2 Li-Wei Chou7– 9 1Department of Chinese Medicine, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan; 2School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 3Institute of Fu’s Subcutaneous Needling, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan; 5Department of Chinese Medicine, Sinying Hospital, Ministry of Health and Welfare, Tainan, Taiwan; 6Department of Chinese Traumatology Medicine, China Medical University Hospital, Taichung, Taiwan; 7Department of Physical Medicine and Rehabilitation, China Medical University Hospital, Taichung, Taiwan; 8Department of Physical Therapy and Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan; 9Department of Physical Medicine and Rehabilitation, Asia University Hospital, Asia University, Taichung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Li-Wei ChouDepartment of Physical Medicine and Rehabilitation, China Medical University Hospital, No. 2 Yuh-Der Road, Taichung, 40447, TaiwanTel +886-4-22052121-2381Fax +886-4-22026041Email chouliwe@gmail.comBackground: Knee osteoarthritis (OA) is a common clinical disease. Knee pain is the major symptom of knee OA and the primary reason why patients seek treatment. Fu’s subcutaneous needling (FSN) has been used to treat knee OA for more than 20 years. However, the establishment of treatment methods and rigorous evaluation of FSN’s efficacy are still lacking. A randomized single-blind clinical trial will be conducted to evaluate whether FSN treatment can immediately alleviate pain due to knee OA surrounding the patella and the curative effective of 1-week and 2-week treatments. In addition, the feasibility and initial effect of FSN treatment for patients with knee OA will be discussed.Materials and Methods: Patients with confirmed knee OA, as diagnosed by doctors using X-ray films or from clinical symptoms, who are over 50 years old will be participants recruited. They will be randomly assigned either FSN treatment or transcutaneous electrical nerve stimulation treatment. In addition, their pressure pain threshold, muscle tone of lower leg muscle, and physical ability will be measured. Participants will be asked to complete the questionnaires of Western Ontario and McMaster Universities Osteoarthritis Index and Lequesne’ index as the measurements for quality of life.Results: The findings of this study will reveal whether FSN or transcutaneous electrical nerve stimulation is clinically efficacious for treating pain due to knee OA, with respect to muscle stiffness, gait, dynamic balance, the pressure pain threshold, and quality of life before and after treatment.Study Registration: This study is approved by the Research Ethics Committee of China Medical University & Hospital, Taichung, Taiwan (CMUH107-REC3-027) and registered at the ClinicalTrials.gov Protocol Registration and Results System (registration number NCT04356651).Keywords: dry needling, Fu’s subcutaneous needling, knee osteoarthritis, myofascial trigger point, tightened muscle

Breast cancer is one of the most common malignancies. Pathological image processing of breast has become an important means for early diagnosis of breast cancer. Using medical image processing to assist doctors to detect potential breast cancer as early as possible has always been a hot topic in the field of medical image diagnosis. In this paper, a breast cancer recognition method based on image processing is systematically expounded from four aspects: breast cancer detection, image segmentation, image registration, and image fusion. The achievements and application scope of supervised learning, unsupervised learning, deep learning, CNN, and so on in breast cancer examination are expounded. The prospect of unsupervised learning and transfer learning for breast cancer diagnosis is prospected. Finally, the privacy protection of breast cancer patients is put forward.

The relationship between height and incident atrial fibrillation (AF) has recently been demonstrated. We aimed to evaluate the impact of height on outcomes of ablation in patients with drug-refractory symptomatic paroxysmal AF (PAF). A total of 689 patients (470 males; age, 53.0 ± 11.7 years) with symptomatic paroxysmal AF receiving index catheter ablation (CA) between 2003 and 2013 were enrolled in this study. The baseline characteristics, ablation, and follow-up results were evaluated. The patients were categorized according to the quartiles of height for each sex. Patients in the lower quartiles of height had a lower incidence of AF recurrence (log-rank p = 0.022). Height in female patients was strongly associated with AF recurrence (p = 0.027) after an index ablation in the 6.33 ± 4.32 years of follow-up. Female patients > 159 cm in height had a higher likelihood of AF recurrence after index CA (HR = 2.01, 95% CI: 1.24–3.25, p = 0.005) than that in those below this height. In computed tomography (CT) scan, the superoinferior diameter of the left atrium (LA) correlated with body height in females, but not in male patients. Height is associated with AF recurrence after the index CA of PAF in female patients. In Asian populations, women above height 159 cm are twice as likely to have AF recurrence post-ablation as shorter women.

The electrophysiological (EP) effects and safety of renal artery denervation (RDN) in chronic kidney disease (CKD) are unclear.The purpose of this study was to investigate the arrhythmogenicity of RDN in a rabbit model of CKD.Eighteen New Zealand white rabbits were randomized to control (n = 6), CKD (n = 6), and CKD-RDN (n = 6) groups. A 5/6 nephrectomy was selected for the CKD model. RDN was applied in the CKD-RDN group. All rabbits underwent cardiac EP studies for evaluation. Immunohistochemistry, myocardial fibrosis, and renal catecholamine levels were evaluated.The CKD group (34.8% ± 9.2%) had a significantly higher ventricular arrhythmia (VA) inducibility than the control (8.6% ± 3.8%; P.01) and CKD-RDN (19.5% ± 6.3%; P = .01) groups. In the CKD-RDN group, ventricular fibrosis was significantly decreased compared to the CKD group (7.4% ± 2.0 % vs 10.4% ± 3.7%; P = .02). Sympathetic innervation in the CKD group was significantly increased compared to the control and CKD-RDN groups [left ventricle: 4.1 ± 1.8 vs 0.8 ± 0.5 (10Neuromodulation by RDN demonstrated protective effects with less structural and electrical remodeling, leading to attenuated VAs. In a rabbit model of CKD, RDN plays a therapeutic role by lowering the risk of VA caused by autonomic dysfunction.

Context In 2020, the terminology of metabolic dysfunction–associated fatty liver disease (MAFLD) was proposed to replace nonalcoholic fatty liver disease (NAFLD). Objectives This work aimed to investigate the prevalence and incidence of MAFLD and evaluate its effects on incident extrahepatic diseases. Methods A total of 6873 individuals, with a 4.6-year follow-up, were included in this study. Associations of MAFLD and NAFLD with diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD) were examined using logistic regression and Cox proportional hazards models. Results The prevalence of NAFLD and MAFLD was 40.3% (95% CI, 39.2%-41.5%) and 46.7% (95% CI, 45.6%-47.9%), respectively. Additionally, 321 (4.7%) and 156 (2.3%) participants had MAFLD with excessive alcohol consumption and hepatitis B virus (HBV) infection. During the follow-up period, the incidence of NAFLD and MAFLD was 22.7% (95% CI, 21.3%-24.0%) and 27.0% (95% CI, 25.5%-28.4%). MAFLD was associated with higher risks of incident diabetes (risk ratio [RR] 2.08; 95% CI, 1.72-2.52), CKD (RR 1.64; 95% CI, 1.39-1.94), and CVD (hazard ratio 1.44; 95% CI, 1.15-1.81). Similar associations for NAFLD were observed. Furthermore, the MAFLD subgroups with excessive alcohol consumption (RR 2.49; 95% CI, 1.64-3.78) and HBV infection (RR 1.98; 95% CI, 1.11-3.52) were associated with higher risks of incident diabetes. Conclusion The change from NAFLD to MAFLD did not greatly affect the associations with diabetes, CKD, and CVD. MAFLD further identified those patients of metabolically fatty liver combined with excessive alcohol consumption and HBV infection, who had increased risks of incident diabetes compared with those of non–fatty liver.

Background The impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective study, we compared the outcomes of patients infected with B.1.1.7, B.1.351, and B.1.617.2 with wild-type strains from early 2020. Methods National surveillance data from January to May 2021 were obtained and outcomes in relation to VOCs were explored. Detailed patient-level data from all patients with VOC infection admitted to our center between December 2020 and May 2021 were analyzed. Clinical outcomes were compared with a cohort of 846 patients admitted from January to April 2020. Results A total of 829 patients in Singapore in the study period were infected with these 3 VOCs. After adjusting for age and sex, B.1.617.2 was associated with higher odds of oxygen requirement, intensive care unit admission, or death (adjusted odds ratio [aOR], 4.90; 95% confidence interval [CI]: 1.43-30.78). Of these patients, 157 were admitted to our center. After adjusting for age, sex, comorbidities, and vaccination, the aOR for pneumonia with B.1.617.2 was 1.88 (95% CI: .95-3.76) compared with wild-type. These differences were not seen with B.1.1.7 and B.1.351. Vaccination status was associated with decreased severity. B.1.617.2 was associated with significantly lower polymerase chain reaction cycle threshold (Ct) values and longer duration of Ct value ≤30 (median duration 18 days for B.1.617.2, 13 days for wild-type). Conclusions B.1.617.2 was associated with increased severity of illness, and with lower Ct values and longer viral shedding. These findings provide impetus for the rapid implementation of vaccination programs.

Associations between hepatitis C virus (HCV) and chronic kidney disease (CKD) have been reported; however, differences of renal progression between general and CKD population remain to be elucidated in prospective studies. A total of 1179 participants, who have tested for anti-HCV antibody, were enrolled and prospectively followed for 3 years. The risks associated with HCV infection, in terms of incidence of CKD, annual estimated glomerular filtration rate (eGFR) changes and 50% decline of eGFR at 3-year from baseline, were compared between normal renal function subjects and CKD patients. Overall, 111 of 233 (47.6%) CKD patients and 167 of 946 (17.7%) non-CKD subjects had HCV infection. The crude incidence rates of CKD were 226.9 per 1000 person-years and 14.8 per 1000 person-years in in HCV and non-HCV infected patients, respectively. The adjusted hazard ratio of HCV infection for incident CKD was 7.9 (95% CI 5–12.7). The HCV-infected normal renal function subjects were independently associated with increased risks of eGFR decline in the 1-year, 2-year and 3-year, respectively. The risk associations remained significant in 50% decline of eGFR at 3 years models and in different subgroup analyses. The increases of risks of eGFR decline were also notorious among overall HCV-infected CKD patients. However, the risk associations were less prominent in subgroup analyses (elderly, women and diabetic patients). The findings highlighted the importance of viral diagnosis with not only prognostic but also public health implications for preserving kidney function.

Aims To study the role and characteristics of activated microglia in poststroke depression (PSD) . Methods Twenty-four male Wistar rats were randomly divided into three groups: the poststroke (PS) group, PSD group, and Sham group. Neurobehavioral testing was performed 24 h postoperation. The body weights of the rats were regularly recorded, and behavioral testing was regularly performed at 1, 2 and 3 weeks postmodeling. Immunofluorescent staining was used to detect the microglial marker OX42. Real-time PCR was used to analyze the relative gene expression of microglial activation markers (TNF-a, IL-10, IL-1, TGF-β, CD86, iNOS, CD206, IL-1β, and Arg1) . Results The relative gene expression of proinflammatory markers (IL-1, TNF-a, iNOS, and IL1β) and anti-inflammatory markers (CD206 and Arg1) significantly increased in the hippocampal region compared with that in the right cerebral and left cerebral hemispheres in the PSD group. The relative gene expression of proinflammatory markers (TNF-a, IL-1, iNOS, and CD86) in the hippocampal region was significantly increased in the PSD group compared with that in the Sham and PS groups. The anti-inflammatory markers (TGF-β and CD206) in the hippocampal region were significantly increased in the PSD group compared with that in the Sham group, and the M2 marker Arg1 was significantly increased in the PSD group compared with that in the PS group. Correlation analysis showed that IL-1 was strongly negatively correlated with PSD . Conclusions Most microglia in the hippocampal region of PSD had a proinflammatory status and an anti-inflammatory status. IL-1 showed a strong negative correlation with PSD.

BACKGROUND Anterior cruciate ligament (ACL) injury experiences about 200,000 isolated cases annually, and ACL reconstruction has become the gold standard for the restoration of stability and functionality. In view of that incorrect graft placement is a common cause of ACL reconstruction failure, it is critically important to ensure that the tibial and femoral tunnels are properly placed during the operation. Therefore, we intend to conduct a network meta-analysis to comparatively evaluate the clinical outcomes among the different surgical techniques in ACL reconstruction. METHODS Embase, PubMed, and Cochrane Library will be searched through to retrieve the relevant literature up to April 2020. The outcomes include the International Knee Documentation Committee subjective/objective score, Lachman test, Lysholm score, laxity of knee joint, pivot-shift test, Tegner activity scale, and the number of adverse events. A Bayesian hierarchical framework will be used to evaluate the comparative efficacy among different fixation devices. Cochrane Q test and I statistics will be applied to evaluate the heterogeneity, and the Cochrane risk of bias assessment tool will be employed to evaluate the study quality and the risk of bias. RESULTS The comparative risk-benefit profiles of different femoral drilling techniques will be evaluated based on the existing evidence, in order to summarize a prioritization regimen. CONCLUSION Findings from this network meta-analysis will provide useful reference to patients, surgeons, and guideline makers in the related fields. REGISTRATION Open Science Framework (OSF) Preregistration. April 20, 2020. osf.io/uzahs.

Objective Diagnostic errors are major contributors to preventable patient harm. We validated the use of an electronic health record (EHR)-based trigger (e-trigger) to measure missed opportunities in stroke diagnosis in emergency departments (EDs). Methods Using two frameworks, the Safer Dx Trigger Tools Framework and the Symptom-disease Pair Analysis of Diagnostic Error Framework, we applied a symptom–disease pair-based e-trigger to identify patients hospitalized for stroke who, in the preceding 30 days, were discharged from the ED with benign headache or dizziness diagnoses. The algorithm was applied to Veteran Affairs National Corporate Data Warehouse on patients seen between 1/1/2016 and 12/31/2017. Trained reviewers evaluated medical records for presence/absence of missed opportunities in stroke diagnosis and stroke-related red-flags, risk factors, neurological examination, and clinical interventions. Reviewers also estimated quality of clinical documentation at the index ED visit. Results We applied the e-trigger to 7,752,326 unique patients and identified 46,931 stroke-related admissions, of which 398 records were flagged as trigger-positive and reviewed. Of these, 124 had missed opportunities (positive predictive value for “missed” = 31.2%), 93 (23.4%) had no missed opportunity (non-missed), 162 (40.7%) were miscoded, and 19 (4.7%) were inconclusive. Reviewer agreement was high (87.3%, Cohen’s kappa = 0.81). Compared to the non-missed group, the missed group had more stroke risk factors (mean 3.2 vs 2.6), red flags (mean 0.5 vs 0.2), and a higher rate of inadequate documentation (66.9% vs 28.0%). Conclusion In a large national EHR repository, a symptom–disease pair-based e-trigger identified missed diagnoses of stroke with a modest positive predictive value, underscoring the need for chart review validation procedures to identify diagnostic errors in large data sets.

BACKGROUND: Oral squamous cell carcinoma (OSCC) usually originates from oral potentially malignant disorders (OPMD), such as oral leukoplakia (OLK) and oral lichen planus (OLP). Identifying biomarkers for the early diagnosis and evaluation of malignant transformation in OPMD could improve the survival rate of OSCC patients. OBJECTIVE: The present study aimed to screen for potential salivary biomarkers for evaluating the malignant transformation of OPMD. METHODS: Salivary proteases from OLK and OSCC patients or healthy donors and proteases in cultural medium from DOK and Cal-27 cells were detected with a human protease array kit. The concentrations of the salivary Kallikrein 5 (KLK5) and urokinase-type plasminogen activator (uPA) proteases were measured by ELISA. Receiver operating characteristics (ROC) to determine the potential value of these proteases in clinical diagnosis were calculated using SPSS software. Immunohistochemistry was used to detect the KLK5 and uPA expression in the oral organizations. RESULTS: The salivary protease spectrum was different among patients with OLK and OSCC and healthy donors. KLK5 and uPA levels in saliva tended to increase as the disease progressed (healthy < OPMD [OLK and OLP] < OSCC). ROC curves showed the optimum diagnostic cutoffs for KLK5 as a biomarker for OLK, OLP, and OSCC were 5.97, 6.03, and 9.45 pg/mL, respectively, while the cutoffs for uPA were 17.19, 17.26, and 20.96 pg/mL. Their combined analysis showed a higher sensitivity for the differential diagnosis of disease. Furthermore, higher levels of KLK5 and uPA were observed in OSCC tissues than in OLK and OLP. CONCLUSIONS: Salivary KLK5 and uPA are potential biomarkers for evaluating OLK and OLP malignant transformation and early diagnosis of OSCC.

Medical literature emphasizes, “Every medicine has its side effects”. Therefore, we have to pay more attention in advocating preventive medicine today. Above all, Huangdi neijing emphasizes the pri...

We explored the feasibility of cardiac computed tomography (CCT) to evaluate postoperative ventricular function in children with congenital heart disease (CHD) and evaluated the accuracy and reproducibility of CCT using cardiac magnetic resonance (CMR) as a reference.Thirty-two postoperative children with CHD (20 boys and 12 girls) who underwent CMR and CCT were enrolled. Left and right ventricular ejection fraction, end-diastolic volume, end-systolic volume, stroke volume, and cardiac index were measured using cardiac function analysis software. Cardiac function data were compared between CMR and CCT. The agreement between the 2 modalities was assessed using a Bland-Altman analysis. Intraclass correlation coefficients were used to assess intraobserver and interobserver reproducibility in CCT functional measurements.All functional parameters showed no significant difference (P0.05) and were well-correlated (r0.5, P0.05) between CMR and CCT. The mean values of all ventricular function parameters in CCT were higher compared with CMR. As indicated by 95% limits of agreement, left ventricular function parameters showed a better level of agreement compared with right ventricular function parameters between the 2 modalities. Intraobserver and interobserver reproducibility were excellent in CCT measurements for all functional parameters (intraclass correlation coefficient0.9).Compared with the criterion standard of CMR, CCT is feasible for assessing postoperative ventricular function with sufficient diagnostic accuracy and reproducibility in children with CHD. In addition to its important role regarding anatomical characterization, CCT is a suitable alternative and convenient follow-up tool that can be used to functional evaluation in children who are intolerant with CMR or have contraindications to CMR.

Background The epidemiology of hepatitis C virus (HCV) infection in people living with HIV has been evolving, with increasing evidence of permucosal (sexual) transmission identified predominantly in HIV-positive men who have sex with men (MSM). The aim of this study was to estimate the incidence rate and elucidate epidemiological factors associated with HCV infection among HIV-infected men in Singapore from 2006 to 2018. Methods: A retrospective cohort study was conducted using a clinical database maintained by the Clinical HIV Program at the National Centre for Infectious Diseases, Singapore. Factors associated with incident HCV infections were identified using Cox proportional hazards regression analyses. Results: Among 1348 HIV-infected male patients who were HCV seronegative at baseline, 64 (4.7%) subsequently tested positive for HCV, giving an incidence of 0.88 per 100 person-years of follow-up (PYFU) (95% confidence interval (CI) 0.69–1.13). The incidence rate of HCV seroconversion increased from 0.33 (95% CI 0.12–0.71) per 100 PYFU in 2010–2012 to 1.93 (95% CI 1.36–2.67) in 2016–2018. Independent factors associated with incident HCV infection were younger age groups at HIV diagnosis versus ≥45 years, HIV acquisition via MSM or via both sexual contact and intravenous drug use versus heterosexual transmission, HIV diagnosis in later periods versus 2006–2009, and recent syphilis acquisition. Conclusions: An increasing trend of incident HCV infection was seen in HIV-infected men, particularly for MSM. Preventive and behavioural interventions should be targeted at HIV-infected individuals engaged in high-risk sexual behaviour.

BACKGROUND Colorectal mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease, and only a few cases have been reported to date. It has no specific clinical presentations and shows various endoscopic appearances. There is no uniform consensus on its treatment. With the advancement of endoscopic technology, endoscopic treatment has achieved better results in individual case reports of early-stage patients. CASE SUMMARY We report a case of rectal MALT in a 57-year-old Chinese man with no symptoms who received endoscopy as part of a routine physical examination, which incidentally found a 25 mm × 20 mm, laterally spreading tumor (LST)-like elevated lesion in the rectum. Therefore, he was referred to our hospital for further endoscopic treatment. Complete and curable removal of the tumor was performed by endoscopic submucosal dissection. We observed enlarged and dilated branch-like vessels similar to those of gastric MALT lymphoma on magnifying endoscopy with narrow-band imaging. And immunopathological staining showed hyperplastic capillaries in the mucosa. Histopathological findings revealed diffusely hyperplastic lymphoid tissue in the lamina propria, with a visible lymphoid follicle structure surrounded by a large number of diffusely infiltrated lymphoid cells that had a relatively simple morphology and clear cytoplasm. In addition, immunohistochemical analysis suggested strongly positive expression for CD20 and Bcl-2. Gene rearrangement results showed positivity for IGH-A, IGH-C, IGK-B, and IGL. Taking all the above findings together, we arrived at a diagnosis of extranodal marginal zone B-cell lymphoma of MALT lymphoma. Positron emission tomography-computed tomography examination showed no other lesions involved. The patient will be followed by periodic endoscopic observation. CONCLUSION In conclusion, we report a case of rectal MALT with an LST-like appearance treated by endoscopic submucosal dissection. Further studies will be needed to explore the clinical behavior, endoscopic appearance, and treatment of rectal MALT.

Qiao Tang, Li Wei, Xiaoqing Liu, Peng Hu Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Peng HuDepartment of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong District, Chongqing, 400000, People’s Republic of ChinaTel +86 13608338064Email hp_cq@163.comBackground: Previous studies have shown that sofosbuvir-based regimens yield high sustained virological response rates in patients with hepatitis C virus (HCV) infection except for genotype 3b complicated with cirrhosis. This real-world study aims to explore the efficacy and safety of sofosbuvir-based regimens in Chinese patients with genotypes 3 and 6 infections, especially the impact of ribavirin coadministration on sustained virological response in cirrhotic patients with genotype 3b infection.Methods: This is a retrospective cohort study that included 101 patients initiated on sofosbuvir-based regimens. The main endpoint of treatment was sustained virological response at posttreatment week 12 (SVR12).Results: Overall, the SVR12 rates were 95.0% (96/101); specifically, the rates were 100% in sofosbuvir, 88.2% in sofosbuvir+ribavirin, 100% in sofosbuvir+daclatasvir, 100% in sofosbuvir+daclatasvir+ribavirin, 95.0% in sofosbuvir/velpatasvir, and 97.1% in sofosbuvir/velpatasvir+ribavirin (p=0.534). The SVR12 rates were comparable in patients infected with genotypes 3 and 6 (93.2% versus 97.6%, p=0.339). The SVR12 rate was 93.9% in cirrhotic patients (31/33). Among those infected with genotype 3, the SVR12 rate was 91.7% (22/24); the rate was 95.0% in those with ribavirin coadministration regimens, which was numerically higher than the 75.0% in those without ribavirin. However, no statistical difference was found (p=0.312). In total, five patients failed to achieve SVR12, including 3 patients with genotype 3b infection treated with ribavirin coadministration regimens (one of them was cirrhotic), 1 cirrhotic patient with genotype 3k infection, and 1 noncirrhotic patient with genotype 6a infection. No severe adverse event occurred.Conclusion: Real-world data show that sofosbuvir-based regimens are highly effective and safe for patients with HCV genotypes 3 and 6 infections.Keywords: daclatasvir, hepatitis C virus, ribavirin, sofosbuvir, velpatasvir

Summary Background Inappropriate antibiotic use greatly accelerates antimicrobial resistance. The appropriateness of antibiotic prescriptions is well evaluated, using big observational data, in some high-income countries, whereas the evidence of this appropriateness is scarce in China. We aimed to assess the appropriateness of antibiotic prescriptions in ambulatory care settings in China to inform future antimicrobial stewardship. Methods We used data from the Beijing Data Center for Rational Use of Drugs, which was a national database designed for monitoring rationality of drug use. 139 hospitals that uploaded diagnosis and prescription information were included from 28 provincial-level regions of mainland China. Outpatient prescriptions were classified as appropriate, potentially appropriate, inappropriate, or not linked to any diagnosis for antibiotic use by following a published classification scheme. Antibiotic prescription rates for various diagnosis categories and proportions of inappropriate antibiotic prescriptions for different subgroups were estimated. Antibiotic prescribing patterns and proportions of individual antibiotics prescribed for different diagnosis categories were analysed and reported. Findings Between Oct 1, 2014, and April 30, 2018, 18 848 864 (10·9%) of 172 704 117 outpatient visits ended with antibiotic prescriptions. For conditions for which antibiotic use was appropriate, potentially appropriate, and inappropriate, 42·2%, 30·6%, and 7·6% of visits were associated with antibiotic prescriptions, respectively. Of all 18 848 864 antibiotic prescriptions, 9 689 937 (51·4%) were inappropriate, 5 354 224 (28·4%) were potentially appropriate, 2 893 102 (15·3%) were appropriate, and 911 601 (4·8%) could not be linked to any diagnosis. A total of 23 266 494 individual antibiotics were prescribed, of which 18 620 086 (80·0%) were broad-spectrum and the top four most prescribed antibiotics were third-generation cephalosporins (5 056 058 [21·7%]), second-generation cephalosporins (3 823 410 [16·4%]), macrolides (3 554 348 [15·3%]), and fluoroquinolones (3 285 765 [14·1%]). Interpretation Inappropriate antibiotic prescribing was highly prevalent nationwide in China. Over half of the antibiotic prescriptions were inappropriate in secondary-level and tertiary-level hospitals, suggesting an urgent need for outpatient antibiotic stewardship aimed at optimising antibiotic prescribing to achieve the goals set in China's 2016 national action plan to contain antimicrobial resistance. Funding The National Natural Science Foundation of China.

Introduction The efficacy of stereotactic body radiation therapy (SBRT) as an alternative treatment for recurrent ventricular tachycardia (VT) is still unclear. This study aimed to report the outcome of SBRT in VT patients with nonischemic cardiomyopathy (NICM). Methods The determination of the target substrate for radiation was based on the combination of CMR results and electroanatomical mapping merged with the real-time CT scan image. Radiation therapy was performed by Flattening-filter-free (Truebeam™) system, and afterward, patients were followed-up for 13.5±2.8 months. We analyzed the outcome of death, incidence of recurrent VT, ICD shocks, anti-tachycardia pacing (ATP) sequences, and possible irradiation side-effects. Results A total of 3 cases of NICM patients with anteroseptal scar detected by CMR. SBRT was successfully performed in all patients. During the follow-up, we found that VT recurrences occurred in all patients. In one patient, it happened during a 6-week blanking period, while the others happened afterward. Re-hospitalization due to VT only appeared in one patient. Through ICD interrogation, we found that all patients have reduced VT burden and ATP therapies. All of the patients died during the follow-up period. Radiotherapy-related adverse events did not occur in all patients. Conclusions SBRT therapy reduces the number of VT burden and ATP sequence therapy in NICM patients with VT, which had a failed previous catheter ablation. However, the efficacy and safety aspects, especially in NICM cases, remained unclear. This article is protected by copyright. All rights reserved.

Objectives This study aimed to assess the comparative efficacy of 4 ablation strategies on the incidence rates of freedom from atrial fibrillation (AF) or atrial tachycardia (AT) through a 3-year follow-up in patients with persistent AF. Background The optimal substrate modification strategies using catheter ablation for patients with persistent AF remain unclear. Methods Patients with persistent AF were enrolled consecutively to undergo each of 4 ablation strategies: (a) Group 1 (Gp 1, n=69), pulmonary vein isolation (PVI) plus rotor ablation assisted by similarity index and phase mapping; (b) Gp 2 (n=75), PVI plus linear ablations at the left atrium; (c) Gp 3 (n=42), PVI plus elimination of complex fractionated atrial electrograms; (d) Gp 4 (n=67), PVI only. Potential confounders were adjusted via a multivariate survival parametric model. Results Baseline characteristics were similar across the 4 groups. At a follow-up period of 34.9±38.6 months, patients in Gp 1 showed the highest rate of freedom from AF compared with the other 3 groups (p=0.002), while patients in Gp 3 and 4 showed lower rates of freedom from AT than those of the other two groups (p=0.006). Independent predictors of recurrence of AF were the ablation strategy (p=0.002) and left atrial diameter (LAD) (p=0.01). Conclusion In patients with persistent AF, a substrate modification strategy using rotor ablation assisted by similarity index and phase mapping provided a benefit for maintaining sinus rhythm compared to the other strategies. Both ablation strategy and baseline LAD predicted the 3-year outcomes of freedom from AT/AF This article is protected by copyright. All rights reserved.

Deeply involved with dyslipidemia, cardiovascular disease has becoming the leading cause of mortality since the early twentieth century in the modern world. Whose correlation with metabolic syndrome (MetS), hypertension and type 2 diabetes mellitus (T2DM) has been well established. We conducted a 9-year longitudinal study to identify the association between easily measured lipid parameters, future MetS, hypertension and T2DM by gender and age distribution. Divided into three groups by age (young age

Xin-Tian Cai,1 Li-Wei Ji,2 Sha-Sha Liu,1 Meng-Ru Wang,1 Mulalibieke Heizhati,1 Nan-Fang Li1 1Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Urumqi, People’s Republic of China; 2Laboratory of Mitochondrial and Metabolism, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Nan-Fang LiHypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Urumqi, Xinjiang, People’s Republic of ChinaTel +86 991 8564818Email lnanfang2016@sina.comPurpose: The aim of this study was to derivate and validate a nomogram based on independent predictors to better evaluate the 5-year risk of T2D in non-obese adults.Patients and Methods: This is a historical cohort study from a collection of databases that included 12,940 non-obese participants without diabetes at baseline. All participants were randomised to a derivation cohort (n = 9651) and a validation cohort (n = 3289). In the derivation cohort, the least absolute shrinkage and selection operator (LASSO) regression model was used to determine the optimal risk factors for T2D. Multivariate Cox regression analysis was used to establish the nomogram of T2D prediction. The receiver operating characteristic (ROC) curve, C-index, calibration curve, and decision curve analysis were performed by 1000 bootstrap resamplings to evaluate the discrimination ability, calibration, and clinical practicability of the nomogram.Results: After LASSO regression analysis of the derivation cohort, it was found that age, fatty liver, γ-glutamyltranspeptidase, triglycerides, glycosylated hemoglobin A1c and fasting plasma glucose were risk predictors, which were integrated into the nomogram. The C-index of derivation cohort and validation cohort were 0.906 [95% confidence interval (CI), 0.878– 0.934] and 0.837 (95% CI, 0.760– 0.914), respectively. The AUC of 5-year T2D risk in the derivation cohort and validation cohort was 0.916 (95% CI, 0.889– 0.943) and 0.829 (95% CI, 0.753– 0.905), respectively. The calibration curve indicated that the predicted probability of nomogram is in good agreement with the actual probability. The decision curve analysis demonstrated that the predicted nomogram was clinically useful.Conclusion: Our nomogram can be used as a reasonable, affordable, simple, and widely implemented tool to predict the 5-year risk of T2D in non-obese adults. With this model, early identification of high-risk individuals is helpful to timely intervene and reduce the risk of T2D in non-obese adults.Keywords: type 2 diabetes, prediction model, nomogram, risk factor

Objective: We describe the case of lower limb unilateral swelling due to a cystic mass (Adventitial Cystic Disease, ACD) compressing on the common femoral vein. This was misdiagnosed as a deep vein thrombosis on both CT venography and Doppler ultrasound. Method: We describe the diagnostic pathways and surgical excision of this venous adventitial cyst of the femoral vein. Conclusion: Venous adventitial cysts are a rare occurrence and diagnosis remains difficult. It often presents clinically as a DVT. Suspicions should be raised should symptoms persist despite appropriate DVT management. Surgical management include endovascular, minimally invasive procedures and complete evacuation of the mucoid cyst with excision of the cystic wall.

Objective The purpose of the present paper was to evaluate the safety and clinical efficacy of mini‐open retroperitoneal oblique lumbar interbody fusion (OLIF) for the treatment of lumbar spinal tuberculosis. Methods A total of 115 patients who suffered from lumbar spinal tuberculosis from June 2014 to December 2017 were included in this research. A total of 59 patients underwent OLIF and percutaneous pedicle screw fixation (OLIF group) and 56 patients underwent the anterior‐only approach (anterior‐only group). All patients were followed up for at least 24 months. Operation time, blood loss, and rate of complications were used to assess the safety of these two techniques. The visual analog scale (VAS) and the Oswestry disability index (ODI) were used to evaluate the relief of neurological and functional symptoms. The erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP) were measured to investigate the activity and recurrence of spinal tuberculosis. The Cobb angle, the sagittal vertical axis of the spine (SVA), the pelvic tilt (PT), the sacral slope (SS), the pelvic incidence (PI), and postoperative Frankel classification were also used to assess the efficiency of the spine deformity correction and the recovery of long‐term neurological function. Results Most patients were successfully treated with OLIF and the anterior‐only technique and attained satisfactory clinical efficiency during the 24‐month follow‐up period. In the perioperative period, the mean operative time (154.68 ± 23.64 min, P, Oblique lumbar interbody fusion is a new surgical technique for treating lumbar tuberculosis. Compared to the anterior‐only technique, it is more minimally invasive, is associated with a lower rate of complications, and has more effective deformity correction and pathological bone and soft tissues clearance.

Objective The aims of this study were to analyze the characteristics of the 100 top-cited articles on scrub typhus (ST), and to assess the present research landscape and future research directions using bibliometric analysis. Methods Web of Science was used to conduct a bibliometric analysis of the 100 top-cited articles on ST. The articles were analyzed by publication year, number of citations, document type, journals, keywords, institutions, country of origin, and authorship. Results The top 100 articles on ST were published between 1945 to 2017. The number of citations ranges from 39 to 227 and the interquartile range was 35.5. The United States published the highest number (n=21) of articles. Mahidol University was the most prolific institution in terms of articles (n=14). The American Journal of Tropical Medicine and Hygiene was the journal with the most articles (n=14), and Paris DH was the most productive author in terms of the Hirsh-index, which was 10 for that author. The study revealed a significant correlation between the total number of citations and the number of authors (r=0.668, p < 0.001), number of institutions (r=0.692, p < 0.001), number of years since publication (r=0.869, p < 0.001), and number of countries involved (r=0.963, p < 0.001). Conclusion The findings of this study provide landmarks in the publication and citation frequency of the most influential articles on ST. In addition, this study provides useful information for readers and health policy-makers in evaluating the literature on ST.

Left atrial appendage (LAA) closure decreases atrial natriuretic peptide (ANP) levels, which indirectly increases the risk of arrhythmogenicity. We aimed to determine the effect of a combined angiotensin receptor-neprilysin inhibitor (ARNi) on arrhythmogenicity following LAA closure in an animal model. Twenty-four rabbits were randomized into four groups: (1) control, (2) LAA closure (LAAC), (3) heart failure (HF)-LAAC, and (4) HF-LAAC with sacubitril/valsartan (+ARNi). HF models were developed in the HF-LAAC and HF-LAAC+ARNi groups. Epicardial LAA exclusion was performed in the LAAC, HF-LAAC, and HF-LAAC+ARNi groups. ANP levels were measured. An electrophysiological study was performed. The myocardium was harvested for histopathological analysis. The ANP level decreased in the LAAC group (785 ± 103 pg/mL, p = 0.03), failed to increase in the HF-LAAC group (917 ± 172 pg/mL, p = 0.3), and increased in the HF-LAAC+ARNi group (1524 ± 126 pg/mL, p

Accurate survival prediction of persons with plasma cell myeloma (PCM) is challenging. We interrogated clinical and laboratory co-variates and RNA matrices of 1040 subjects with PCM from public datasets in the Gene Expression Omnibus database in training (N = 1) and validation (N = 2) datasets. Genes regulating plasma cell metabolism correlated with survival were identified and seven used to build a metabolic risk score using Lasso Cox regression analyses. The score had robust predictive performance with 5-year survival area under the curve (AUCs): 0.71 (95% confidence interval, 0.65, 0.76), 0.88 (0.67, 1.00) and 0.64 (0.57, 0.70). Subjects in the high‐risk training cohort (score > median) had worse 5-year survival compared with those in the low‐risk cohort (62% [55, 68%] vs. 85% [80, 90%]; p

PURPOSEAs yet, no checkpoint inhibitor has been approved to treat nasopharyngeal carcinoma (NPC). This study was aimed to evaluate the antitumor activity, safety, and biomarkers of toripalimab, a new programmed death-1 (PD-1) inhibitor for recurrent or metastatic NPC (RM-NPC) refractory to standard chemotherapy.PATIENTS AND METHODSIn this single-arm, multicenter phase II study, patients with RM-NPC received 3 mg/kg toripalimab once every 2 weeks via intravenous infusion until confirmed disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). The secondary end points included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS).RESULTSAmong all 190 patients, the ORR was 20.5% with median DOR 12.8 months, median PFS 1.9 months, and median OS 17.4 months. Among 92 patients who failed at least two lines of systemic chemotherapy, the ORR was 23.9%. The ORRs were 27.1% and 19.4% in PD-L1+ and PD-L1− patients, respectively ( P = .31). Patients with ≥ 50% decrease of plasma Epstein-Barr virus (EBV) DNA copy number on day 28 had significantly better ORR than those with < 50% decrease, 48.3% versus 5.7% ( P = .0001). Tumor mutational burden had a median value of 0.95 muts/mega-base in the cohort and had no predictive value for response. Whole-exome sequencing results from 174 patients revealed that the patients with genomic amplification in 11q13 region or ETV6 genomic alterations had poor responses to toripalimab.CONCLUSIONThe POLARIS-02 study demonstrated a manageable safety profile and durable clinical response of toripalimab in patients with chemorefractory metastatic NPC. An early decrease in plasma EBV DNA copy number correlated with favorable response.

The application of compression sleeve (CS) has rapidly developed in the medicine and rehabilitation fields and is commonly used for improving sensorimotor function. Despite a considerable amount of sensorimotor-related evidence and clinical outcomes analysis being available, little is known about the effects of CS-induced sensory afferent input on corticomuscular functional connectivity (corticomuscular coherence, CMC) and reaction time (RT). Therefore, the purpose of this study was to investigate the effect of wearing CS on CMC and sensorimotor performance. Fourteen healthy volunteers were enrolled in this study and randomly performed visual tracking motor task, RT test and joint position sense (JPS) test with and without CS (CS and non-CS conditions). Electroencephalography and electromyography of the wrist extensor during the visual tracking motor task were used to calculate CMC. Joint angle steadiness, joint position error, pre-motor time (PMT), electromechanical delay (EMD) time and RT were calculated to compare sensorimotor performance with and without CS. When wearing CS decreased CMC, shortened both PMT and RT compared to the non-CS condition (p

Background Air pollution, especially fine particulate matter (PM), can cause brain damage, cognitive decline, and an increased risk of neurodegenerative disease, especially alzheimer’s disease (AD). Typical pathological findings of amyloid and tau protein accumulation have been detected in the brain after exposure in animal studies. However, these observations were based on high levels of PM exposure, which were far from the WHO guidelines and those present in our environment. In addition, white matter involvement by air pollution has been less reported. Thus, this experiment was designed to simulate the true human world and to discuss the possible white matter pathology caused by air pollution. Results 6 month-old female 3xTg-AD mice were divided into exposure and control groups and housed in the Taipei Air Pollutant Exposure System (TAPES) for 5 months. The mice were subjected to the Morris water maze test after exposure and were then sacrificed with brain dissection for further analyses. The mean mass concentration of PM2.5 during the exposure period was 13.85 μg/m3. After exposure, there was no difference in spatial learning function between the two groups, but there was significant decay of memory in the exposure group. Significantly decreased total brain volume and more neuronal death in the cerebral and entorhinal cortex and demyelination of the corpus callosum were noted by histopathological staining after exposure. However, there was no difference in the accumulation of amyloid or tau on immunohistochemistry staining. For the protein analysis, amyloid was detected at significantly higher levels in the cerebral cortex, with lower expression of myelin basic protein in the white matter. A diffuse tensor image study also revealed insults in multiple white matter tracts, including the optic tract. Conclusions In conclusion, this pilot study showed that even chronic exposure to low PM2.5 concentrations still caused brain damage, such as gross brain atrophy, cortical neuron damage, and multiple white matter tract damage. Typical amyloid cascade pathology did not appear prominently in the vulnerable brain region after exposure. These findings imply that multiple pathogenic pathways induce brain injury by air pollution, and the optic nerve may be another direct invasion route in addition to olfactory nerve.

BackgroundCeftriaxone is the preferred treatment for bacteraemia caused by non-MDR (antibiotic-susceptible) Klebsiella pneumoniae. Excessive and widespread ceftriaxone use creates selection pressure for ESBLs. Cefazolin is an alternative, although there are theoretical concerns that SHV-1 β-lactamase in K. pneumoniae may inactivate cefazolin in an inoculum-dependent manner.ObjectivesIn this retrospective study, we investigated the outcomes in K. pneumoniae bacteraemia patients treated with IV cefazolin versus IV ceftriaxone as definitive therapy.MethodsA total of 917 patients infected with K. pneumoniae from 1 January to 31 December 2016 in three public acute care hospitals in Singapore were screened for study eligibility. Consecutive unique episodes of monomicrobial bacteraemia caused by cefazolin- and/or ceftriaxone-susceptible K. pneumoniae were analysed (n = 284).ResultsThere were 143 patients (50.4%) in the cefazolin group and 141 patients (49.6%) in the ceftriaxone group. Demographics, baseline illness severity and risk factors for healthcare-associated bacteraemia were comparable in the two treatment groups. The primary outcome of 28 day all-cause mortality was not significantly different between the cefazolin and ceftriaxone groups (10.5% versus 7.1%, P = 0.403). Both in the crude analysis and using a multivariable logistic regression model with inverse probability weighting based on propensity score, cefazolin treatment was not associated with increased risk of 28 day mortality (OR 1.51 with ceftriaxone as the reference group, 95% CI 0.67–3.53; adjusted OR 1.55, 95% CI 0.33–7.40).ConclusionsCefazolin may be a ceftriaxone-sparing alternative treatment for antibiotic-susceptible K. pneumoniae bacteraemia. This observation may provide sufficient clinical equipoise for a randomized controlled trial.

Background: To investigate the correlation between hypertriglyceridemic waist circumference (HTWC) phenotype and gestational diabetes mellitus (GDM).Methods: A total of 1083 patients with gestational age ≤8 weeks were divided into four groups: normal triglyceride and waist circumference group (group A, n=575), simple abdominal obesity group (group B, n=317), simple high triglyceride group (group C, n=125), and HTWC group (group D, n=66). General information and serum biochemical indicators were measured and recorded. Analysis of variance (ANOVA) and logistic regression analysis were used to evaluate the relationship between HTWC with GDM.Results: The prevalence of GDM in the HTWC group was significantly greater than in the other three groups. After adjustment by multivariate logistic regression analysis, the proportion of GDM in the HTWC group was 1.753 times higher than in group A.Conclusion: These findings suggest that there is a significant correlation between HTWC phenotype and GDM, indicating that the HTWC phenotype could be applied as a simple marker for identifying GDM risk factors.

Introduction A drug provocation test (DPT) is important for the diagnosis of Brugada syndrome (BrS). The link, however, between dynamic changes of ECG features after DPT and unstable ventricular arrhythmia (VA) in BrS remains unknown. Methods Between 2014 and 2019, we assessed 27 patients with BrS (median age: 37.0 [interquartile range, IQR: 22.0-51.0] years; 25 men], including 9 (33.3%) with a history of unstable VA and 18 (66.7%) without. All patients in the study presented with Brugada-like ECG features before DPT. The ECG parameters and dynamic changes (∆) in 12-lead ECGs recorded from the 2nd , 3rd , and 4th intercostal spaces (ICS) before and at 1, 6, 12, 18, 24 hours after DPT (oral flecainide 400 mg) were analyzed. Results The total amplitude of V1 at the 3rd ICS 18 and 24 hours after DPT was significantly lower in patients with history of unstable VA than in those without. Patients with BrS and unstable VAs had a significantly larger ∆ amplitude of V1 at the 2nd ICS 12 hours after DPT than in those without unstable VAs (0.28[0.18-0.41] mV vs. 0.08[0.01-0.15] mV, p=0.01). A multivariate analysis revealed that the amplitude of V1 at the 3rd ICS 18 and 24 hours after DPT and the ∆ amplitude of V1 at the 2nd ICS 12 hours after DPT were associated with history of unstable VA. Conclusion Nonuniform changes and spatiotemporal differences in precordial ECG features after DPT were observed in patients with BrS and these may be surrogate markers for risk stratification. This article is protected by copyright. All rights reserved.

Purpose Robot-assisted gait rehabilitation has been proposed as a plausible supplementary rehabilitation strategy in stroke rehabilitation in the last decade. However, its exact benefit over traditional rehabilitation remain sparse and unclear. It is therefore the purpose of the current study to comparatively investigate the clinical benefits of the additional robot-assisted training in acute stroke patients compared to standard hospital rehabilitation alone. Methods Ninety acute stroke patients ( Results Both groups demonstrated significant improvement pre- and post-treatment for the BBS (robotic group p = 0.023; control group p = 0.033) but no significant difference (p > 0.1) between the groups were found. However, the robotic training group had more participants demonstrating larger BBS points of improvement as well as greater Brunnstrom stage of improvement, when compared to the control group. No significant within and between group statistical differences (p > 0.3) were found for Pittsburgh Sleep Quality Index and Taiwanese Depression Questionnaire. Conclusion The addition of robotic gait training on top of standard hospital neurorehabilitation for acute stroke patients appear to produce a slightly greater improvement in clinical functional outcomes, which is not transferred to psychological status.

Near-pure lung adenocarcinoma (ADC) subtypes demonstrate strong stratification of radiomic values, providing basic information for pathological subtyping. We sought to predict the presence of high-grade (micropapillary and solid) components in lung ADCs using quantitative image analysis with near-pure radiomic values. Overall, 103 patients with lung ADCs of various histological subtypes were enrolled for 10-repetition, 3-fold cross-validation (cohort 1); 55 were enrolled for testing (cohort 2). Histogram and textural features on computed tomography (CT) images were assessed based on the “near-pure” pathological subtype data. Patch-wise high-grade likelihood prediction was performed for each voxel within the tumour region. The presence of high-grade components was then determined based on a volume percentage threshold of the high-grade likelihood area. To compare with quantitative approaches, consolidation/tumour (C/T) ratio was evaluated on CT images; we applied radiological invasiveness (C/T ratio > 0.5) for the prediction. In cohort 1, patch-wise prediction, combined model (C/T ratio and patch-wise prediction), whole-lesion-based prediction (using only the “near-pure”-based prediction model), and radiological invasiveness achieved a sensitivity and specificity of 88.00 ± 2.33% and 75.75 ± 2.82%, 90.00 ± 0.00%, and 77.12 ± 2.67%, 66.67% and 90.41%, and 90.00% and 45.21%, respectively. The sensitivity and specificity, respectively, for cohort 2 were 100.0% and 95.35% using patch-wise prediction, 100.0% and 95.35% using combined model, 75.00% and 95.35% using whole-lesion-based prediction, and 100.0% and 69.77% using radiological invasiveness. Using near-pure radiomic features and patch-wise image analysis demonstrated high levels of sensitivity and moderate levels of specificity for high-grade ADC subtype-detecting. • The radiomic values extracted from lung adenocarcinoma with “near-pure” histological subtypes provide useful information for high-grade (micropapillary and solid) components detection. • Using near-pure radiomic features and patch-wise image analysis, high-grade components of lung adenocarcinoma can be predicted with high sensitivity and moderate specificity. • Using near-pure radiomic features and patch-wise image analysis has potential role in facilitating the prediction of the presence of high-grade components in lung adenocarcinoma prior to surgical resection.

Orthopedic device related infections (ODRI's) represent a difficult to treat situation owing to their biofilm based nature. Biofilm infections once established are difficult to eradicate even with an aggressive treatment regimen due to their recalcitrance towards antibiotics and immune attack. The involvement of antibiotic resistant pathogens as the etiological agent further worsens the overall clinical picture, pressing on the need to look into alternative treatment strategies. The present review highlightes the microbiological challenges associated with treatment of ODRI's due to biofilm formation on the implant surface. Further, it details the newer anti-infective modalities that work either by preventing biofilm formation and/or through effective disruption of the mature biofilms formed on the medical implant. The study, therefore aims to provide a comprehensive insight into the newer anti-biofilm interventions (non-antibiotic approaches) and a better understanding of their mechanism of action essential for improved management of orthopedic implant infections.

Objective To review systematically the therapeutic effect and safety of acupuncture or electroacupuncture (EA) on functional dyspepsia (FD). Methods Using computer, the randomized controlled trials (RCTs) of FD treated with acupuncture or EA were retrieved from the databases, i.e. Cochrane Library, PubMed, EMbase and Web of science, from the date of database establishment to June 1, 2020. Using the assessment tool of risk of bias in Cochrane Handbook for systematic reviews of interventions, 5.1.0, the quality of the included RCTs were evaluated in methodology. Meta-analysis was performed by RevMan 5.3 software. Results A total of 10 articles were included, with 1202 cases involved. In this study, the effectiveness of EA or acupuncture on FD was analyzed in comparison with the treatment with sham-acupuncture, sham-EA or western medication. The results indicated that compared with sham-acupuncture or sham-EA, acupuncture or EA greatly relieved the clinical symptoms of FD (SMD = −3.03, 95% CI [−3.56, −2.50], P 0.05). Compared with gastric prokinetics, acupuncture or EA more effectively reduced the symptom score (MD = −3.03, 95%CI [−3.56, −2.50], P = 0.02), but the differences were not significant in the aspects of the improvement of clinical effective rate (OR = 1.33, 95% CI [0.70, 2.52], P = 0.39), the promotion of gastric half-emptying (MD = 0.23, 95% CI [−1.94, 2.40], I2=0%, P = 0.83), the promotion of motilin secretion (SMD = −0.06, 95% CI [−0.23, 0.11], I2 = 0%, P = 0.50) and the increase of gastric electrical activity (MD = −0.01, 95% CI [−0.03, 0.01], I2 = 0%, P = 0.41). The three RCT studies with adverse events reported indicated that the difference in the incidence of the adverse events was not significant statistically in comparison of acupuncture with sham-acupuncture or gastric prokinetic agent (P Conclusion Regarding the improvement in the symptoms of FD, the effect of EA or acupuncture is superior to the sham-acupuncture group or the western medication group. Simultaneously, the clinical response rate in the treatment with EA or acupuncture is higher than the sham-acupuncture group. During the treatment with EA, some adverse reactions happened in treatment of FD with acupuncture or western medication. Even though there are the limitations in quality and quantity of the included trials, EA and acupuncture still deserve to be promoted in treatment of FD. However, more studies of RCTs with large-scale sample, high quality and multiple centers are required for a further verification of the therapeutic effect.

Background The optimal treatment for pediatric supracondylar humeral fractures accompanied with a pink pulseless hand is controversial. Some clinicians recommend close observation after closed reduction and percutaneous pinning of the fractures, while some recommend surgical exploration if the radial pulse is unpalpable. The present study aimed to analyze the benefits and outcomes of close observation for treating pediatric supracondylar humeral fractures with a pink pulseless hand. Methods Thirteen consecutive children presenting with a pink pulseless hand following supracondylar humeral fracture were enrolled in this study. Preoperative and postoperative color-flow Duplex ultrasound detection was used to assess brachial artery compromise in most cases. Urgent closed reduction and percutaneous pinning of the fractures were attempted first. Close observation was carried out when the hand was pink and pulseless with an absent radial pulse. Results Preoperative color-flow Duplex ultrasound showed no disruption of the brachial artery in cases detected. Compression of the artery by the proximal fragment was observed in most cases, with one case of entrapment of the artery between fragments, and thrombus considered in two cases. All cases underwent urgent surgery, after which nine experienced immediate return of the radial pulse. The remaining four without a palpable pulse were managed with close observation and no deterioration of the vascular status was observed; therefore, no surgical exploration was performed. Postoperative color-flow Duplex ultrasound revealed continuity of the artery and rich collateral circulation. Patients completed an average of 4.5 years of follow-up, during which no major complications occurred. All patients achieved excellent limb function. Conclusions Our study demonstrates that close observation after urgent closed reduction and percutaneous pinning is a sufficient approach for the treatment of pediatric supracondylar humeral fractures accompanied with a pink pulseless hand. Surgical exploration is not necessary as long as the hand is warm and well perfused. Color-flow Duplex ultrasound is beneficial for assessing vascular compromise and determining treatment strategies.

With the evolution of endoscopic instruments and techniques, full-endoscopic spine surgery has attracted more attention worldwide in recent years. At the initial stage, surgeons conducted endoscopic lumbar discectomy using the transforaminal approach. Next, interlaminar endoscopic lumbar discectomy was developed to treat a herniation disc at the L5-S1 level. The progression in interlaminar endoscopic techniques has further broadened the indications for full-endoscopic spine surgery. However, the steep learning curve of endoscopic procedures has remained challenging. The use of interlaminar endoscopic lumbar discectomy entails many essential skills to manage the different anatomical structures of the spine. From the perspective of successful and safe interlaminar endoscopic lumbar discectomy, we have discussed the technical considerations for endoscopic procedures.

Purpose The present study retrospectively evaluated the effectiveness and safety of iodine-125 interstitial brachytherapy for treatment of primary locally advanced adenoid cystic carcinoma (ACC) of the base of tongue (BOT). Material and methods This study was a retrospective analysis of data of 19 patients with ACC, who were treated with iodine-125 interstitial brachytherapy between March 2008 and April 2018. Overall survival (OS), disease-free survival (DFS), local control (LC), and radiation-related toxicities were determined. Factors affecting the outcomes were evaluated. Results Six males and 13 females were included in our study, with a median follow-up time of 35 months. 3- and 5-year OS rates were 71.5% and 47.6%, respectively. 3- and 5-year LC rates were 88.5% and 34.5%, respectively. 3- and 5-year DFS rates were 54.7% and 21.9%, respectively. A significant difference was observed in patients with or without brain metastases for OS rate. No severe acute toxicity was observed, while severe late toxicity was observed in one patient. Conclusions The results suggest that iodine-125 interstitial brachytherapy is an effective and safe option for the treatment of primary locally advanced ACC of the base of the tongue, with reasonably satisfactory LC and OS.