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Patients with continuous flow destination therapy (DT) left ventricular assist devices (LVAD) comprise a heterogeneous population. We hypothesized that phenotypic clustering of individuals with DT LVADs by their implantation characteristics will be associated with different long-term risk profiles. We analyzed 5,999 patients with continuous flow DT LVADs in Interagency Registry for Mechanically Assisted Circulatory Support using 18 continuous variable baseline characteristics. We Z-transformed the variables and applied a Gaussian finite mixture model to perform unsupervised clustering resulting in identification of 4 phenogroups. Survival analyses considered the competing risk for cumulative incidence of transplant or the composite end point of death or heart transplant where appropriate. Phenogroup 1 (n = 1,163, 19%) was older (71 years) and primarily white (81%). Phenogroups 2 (n = 648, 11%) and 3 (n = 3,671, 61%) were of intermediate age (70 and 62 years), weight (85 and 87 kg), and ventricular size. Phenogroup 4 (n = 517, 9%) was younger (40 years), heavier (108 kg), and more racially diverse. The cumulative incidence of death, heart transplant, bleeding, LVAD malfunction, and LVAD thrombosis differed among phenogroups. The highest incidence of death and the lowest rate of heart transplant was seen in phenogroup 1 (p0.001). For adverse outcomes, phenogroup 4 had the lowest incidence of bleeding, whereas LVAD device thrombosis and malfunction were lowest in phenogroup 1 (p0.001 for all). Finally, the incidence of stroke, infection, and renal dysfunction were not statistically different. In conclusion, the present unsupervised machine learning analysis identified 4 phenogroups with different rates of adverse outcomes and these findings underscore the influence of phenotypic heterogeneity on post-LVAD implantation outcomes.

This prospective non-randomized, multicenter clinical trial was performed to investigate efficacy and safety of 131I-labeled metuximab in adjuvant treatment of unresectable hepatocellular carcinoma. Methods: Patients were assigned to treatment with transcatheter arterial chemoembolization (TACE) combined with 131I-metuximab or TACE alone. The primary outcome was overall tumor recurrence. The secondary outcomes were safety and overall survival. Results: The median time to tumor recurrence was 6 months in the TACE+131I-metuximab group (n = 160) and 3 months in the TACE group (n = 160) (hazard ratio, 0.55; 95% confidence interval, 0.43 to 0.70; P < 0.001). The median overall survival was 28 months in the TACE+131I-metuximab group and 19 months in the TACE group (hazard ratio, 0.62; 95% confidence interval, 0.47 to 0.82; P = 0.001). Conclusion: TACE+131I-metuximab showed a greater anti-recurrence benefit, significantly improved the 5-year survival of patients with advanced hepatocellular carcinoma, and was well tolerated by patients.

Background This study aims to investigate the current use of pediatric flexible bronchoscopy (PFB) in western China. Methods A cross-sectional survey was conducted in western China between January 1, 2018 to December 30, 2018. Fifty-four centers were invited to answer a questionnaire for seeking information about performance of PFB. The data collected were analyzed to investigate the current status of western China, and hierarchical cluster analysis was conducted to identify developmental level of PFB of cities. Results Forty-seven centers were included in analysis. A total of 22,585 flexible bronchoscopies were carried out in the participating centers from January 1, 2018 to December 30, 2018. Eight centers (17.0%) performed more than 1,000 pediatric flexible bronchoscopies for children, but 20 centers (42.6%) performed less than 100. The median proportion of systematic and professional trained physicians in a single team was 50%, and the pooled rate was 59% (95% CI, 47-70%). Only 10, 8 and 11 centers performed balloon dilatation, thermal ablation and cryoablation, respectively. Obvious cough was the most frequent complication after the PFB procedure, the pooled rate is 24% (95% CI, 18-29%). No one died during and after the PFB procedure. Hierarchical cluster analysis showed that the development of PBF in western China varies, and Chongqing might be the most developed area in PFB use in western China. Conclusions Flexible bronchoscopy in children is now a mature and safe procedure, while the development of PFB varies in western China, especially for the advanced bronchoscopic intervention.

Aims Patients with obesity and ischaemic heart failure may counter‐intuitively have better outcomes compared with patients with normal body weight due to an ‘obesity paradox’. This study sought to determine if body mass index (BMI) impacts the treatment effects or safety outcomes of the treatment of ischaemic heart failure with coronary artery bypass grafting (CABG). Methods and results We obtained and reviewed the Surgical Treatment of Ischaemic Heart Failure (STICHES) data for 1212 patients. We categorized obesity by the World Health Organization (WHO) classes to define baseline characteristics and test for treatment interactions for the primary and secondary STICHES outcomes by treatment groups. While CABG decreased the risk of death, there was no evidence of treatment interaction by BMI per 5 kg/m2 (P = 0.83) or WHO obesity class. For the overall cohort, there was no interaction by WHO obesity class for the cumulative incidence of death in either the medical therapy or CABG plus medical therapy (P‐interaction = 0.90). There was a non‐significant trend for higher BMI and a lower risk of death [hazard ratio 0.92, 95% confidence interval (CI) 0.85–1.00, P = 0.051]. Increasing body size (per 5 kg/m2) was associated with return to the operating room (odds ratio 2.48, 95% CI 1.45–4.26, P

BACKGROUND Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have shown promising local benefits for advanced hepatocellular carcinoma (HCC). S-1, a composite preparation of a 5-fluorouracil prodrug, has proven to be a convenient oral chemotherapeutic agent with definite efficacy against advanced HCC. AIM To evaluate the efficacy and safety of TACE followed by HAIC with or without oral S-1 for treating advanced HCC. METHODS In this single-center, open-label, prospective, randomized controlled trial, 117 participants with advanced HCC were randomized to receive TACE followed by oxaliplatin-based HAIC either with (TACE/HAIC + S-1, n = 56) or without (TACE/HAIC, n = 61) oral S-1 between December 2013 and September 2017. Two participants were excluded from final analysis for withdrawing consent. The primary endpoint was progression-free survival (PFS) and secondary endpoints included overall survival (OS), objective response rate, disease control rate and safety. RESULTS In total, 115 participants (100 males and 15 females; mean age, 57.7 years ± 11.9) were analyzed. The median PFS and OS were 5.0 mo (0.4–58.6 mo) (95% confidence interval (CI): 3.82 to 6.18) vs 4.4 mo (1.1–54.4 mo) (95%CI: 2.54 to 6.26; P = 0.585) and 8.4 mo (0.4–58.6 mo) (95%CI: 6.88 to 9.92) vs 8.3 mo (1.4–54.4 m) (95%CI: 5.71 to 10.96; P = 0.985) in the TACE/HAIC + S-1 and TACE/HAIC groups, respectively. The objective response rate and disease control rate were 30.9% vs 18.4% and 72.7% vs 56.7% in the TACE/HAIC + S-1 and TACE/HAIC groups, respectively. Grade 3/4 adverse events had a similar frequency in both treatment groups. CONCLUSION No improvements in tumor response rates, PFS or OS were observed with the addition of S-1 to TACE/HAIC in advanced HCC. Both treatment regimens had a similar safety profile.

This study investigates the psychometric properties of patient-reported outcome instruments for assessing outcomes in postsurgical traumatic digit amputation patients. The authors hypothesize that the Michigan Hand Outcomes Questionnaire (MHQ) and Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire are the most valid and reliable instruments.The authors studied traumatic digit amputation patients as part of the Finger Replantation and Amputation Challenges in Assessing Impairment, Satisfaction, and Effectiveness (FRANCHISE) study initiated by The Plastic Surgery Foundation. The MHQ, DASH questionnaire, Patient-Reported Outcomes Measurement Information System (PROMIS), and 36-Item Short-Form Health Survey were used to assess patients at least 1 year postoperatively. Internal consistency was measured by Cronbach's alpha and criterion validity with Pearson correlation coefficient (r). Construct validity was tested with four predefined hypotheses. Discriminant validity was analyzed by receiver operating characteristic curves.One hundred sixty-eight replantation and 74 revision amputation patients met the inclusion criteria. All instruments demonstrated fair to good internal consistency in both cohorts (0.7α0.9). The MHQ and DASH questionnaire scores correlated strongly (r0.60) in both cohorts. The 36-Item Short-Form Health Survey had moderate to weak correlation with the remaining instruments, and its mental component had poor discriminant validity (area under the curve, 0.64 to 0.67). The MHQ, DASH questionnaire, and PROMIS demonstrated good construct validity confirming 75 to 100 percent of predefined hypotheses, whereas the 36-Item Short-Form Health Survey confirmed only 25 percent.The authors recommend using the Michigan Hand Outcomes Questionnaire or the Disabilities of the Arm, Shoulder and Hand questionnaire when assessing patient-reported outcomes in digit amputation patients based on good internal consistency and validity. The Patient-Reported Outcomes Measurement Information System has fair validity and reliability but should be an adjunct instrument. The 36-Item Short-Form Health Survey should not be used as a primary assessment tool, but as an adjunct to assess overall quality of life.

Objective: To investigate the optimal age for the baseline serum prostate-specific antigen (PSA) test and for repeat screening and its economic burden in a single center in China. Materials and Methods: 35,533 men with PSA screening were retrospectively enrolled in this study. Follow-ups were conducted in 1,586 men with PSA >4 ng/mL, and receiver-operating characteristic (ROC) curves were employed to investigate the optimal cutoffs. Results: ROC analysis indicated that the optimal age for initial PSA screening was 57.5 years (AUC = 0.84), 62.5 years (AUC = 0.902), 60.5 years (AUC = 0.909), and 61.5 years (AUC = 0.890) for individuals with PSA >4 and >10 ng/mL, a diagnosis of prostate cancer (PCa), and clinically significant PCa defined as the focus events, respectively. For Chinese men aged 50–59, 60–69, and >70 years, the initial PSA levels of 1.305 ng/mL (AUC = 0.699), 1.975 ng/mL (AUC = 0.711), and 2.740 ng/mL (AUC = 0.720) might have a PSA velocity >0.75 ng/mL per year during the follow-up. In addition, the total cost amounts to CNY 13,609,260 in these cases, but only 60 of the 35,533 (0.17%) men gained benefit from PSA screening. Conclusion: In our opinion, the optimal starting age for initial PSA testing was 57.5 years. The necessity for repeat screening should be based on the first PSA level depending on age. A cost-­benefit analysis should be included in population-based screening.

What is known and objective Clinical use of fluconazole against fungal infections in renal transplant patients is complicated by the potentially marked and unpredictable drug-drug interactions (DDIs). We report a case of tacrolimus-fluconazole DDI in a stable renal transplant recipient and describe the mechanism, magnitude and duration of this DDI through a literature review. Case summary A 38-year-old woman experienced a 9.1-fold increase in dose-normalized tacrolimus trough level (trough concentration/weight-normalized daily dose) and an 87% decrease in weight-normalized daily dose (daily dose/body weight) in the treatment of documented Candida albicans oesophagitis by fluconazole. After discontinuation of fluconazole for 161 day, a 26% reduction in weight-normalized daily dose was required to maintain therapeutic exposure. What is new and conclusion Oral fluconazole has a more significant impact on its drug interactions with tacrolimus than intravenous fluconazole. Gene screening for CYP3A5 6986 A>G and ABCB1 3435 C>T in organ transplant recipients may help in preventing DDI and facilitating tacrolimus dose adjustment.

Flap reconstruction is recommended for select patients undergoing abdominoperineal resection to mitigate complications. However, the clinical effectiveness and financial implications of flap reconstruction remain unknown. The authors aim to compare the costs and complications for patients undergoing abdominoperineal resection with and without flap reconstruction.The Truven MarketScan Databases (2009 to 2016) were used to perform retrospective population-based analysis of colorectal carcinoma patients who underwent abdominoperineal resection with and without flap reconstruction. Univariate and multivariable logistic regressions were used to study effective cost (cumulative cost/number of healthy days) and complications.Of 2557 total abdominoperineal resection patients, 194 patients underwent flap reconstruction. Patients undergoing flap reconstruction had a higher Elixhauser Comorbidity Index (p = 0.004) and were more likely to have local invasion (p0.001). At 6 months postoperatively, there were no differences in complications between the two groups (p = 0.116). Flap reconstruction was protective against intraabdominal infections (OR, 0.4; 95 percent CI, 0.2 to 0.9; p = 0.033) but conferred an increased risk of wound complications (OR, 1.5; 95 percent CI, 1.0 to 2.3; p = 0.039). Total median cost of care was similar (abdominoperineal resection alone, $40,050; abdominoperineal resection with flap, $41,380; p = 0.456). Effective cost was greater for abdominoperineal resection alone ($259/healthy day) than abdominoperineal resection with flap ($186/healthy day) but was not statistically significant (p = 0.17).Patients with flap reconstruction displayed a higher comorbidity score and more extensive disease, but these unfavorable factors did not result in a higher complication rate, total cost, or effective cost. Therefore, flap reconstruction for complex perineal defects confers a benefit in select patients and is a judicious use of health care resources.Therapeutic, III.

BACKGROUND Tumor recurrence after orthotopic liver transplantation (OLT) remains a serious threat for long-term survival of the recipients with hepatocellular carcinoma (HCC), since very few factors or measures have shown impact on overcoming HCC recurrence after OLT. Postoperative infection suppresses tumor recurrence and improves patient survival in lung cancer and malignant glioma probably via stimulating the immune system. Post-transplant infection (PTI), a common complication, is deemed to be harmful for the liver transplant recipients from a short-term perspective. Nevertheless, whether PTI inhibits HCC recurrence after OLT and prolongs the long-term survival of HCC patients needs to be clarified. AIM To investigate the potential influence of PTI on the survival and tumor recurrence of patients with HCC after OLT. METHODS A total of 238 patients with HCC who underwent OLT between August 2002 and July 2016 at our center were retrospectively included and accordingly subdivided into a PTI group (53 patients) and a non-PTI group (185 patients). Univariate analyses, including the differences of overall survival (OS), recurrence-free survival (RFS), and post-recurrence survival (PRS), between the PTI and non-PTI subgroups as well as survival curve analysis were performed by the Kaplan-Meier method, and the differences were compared using the log rank test. The variables with a P-value < 0.1 in univariate analyses were included in the multivariate survival analysis by using a Cox proportional-hazards model. RESULTS The 1-, 3-, and 5-year OS and RFS rates of the whole cohort were 86.6%, 69.0%, and 63.6%, and 75.7%, 60.0%, and 57.3%, respectively. The 1-, 3-, and 5-year OS rates for the PTI patient group (96.0%, 89.3%, and 74.0%) were significantly higher than those for the non-PTI group (84.0%, 63.4%, and 60.2%) (P = 0.033). The absence of PTI was an independent risk factor for dismal OS (relative risk [RR] = 2.584, 95%CI: 1.226-5.449) and unfavorable RFS (RR = 2.683, 95%CI: 1.335-5.390). Subgroup analyses revealed that PTI remarkably improved OS (P = 0.003) and RFS (P = 0.003) rates of HCC patients with vascular invasion (IV), but did not impact on OS (P = 0.404) and RFS (P = 0.304) of patients without VI. Among the patients who suffered post-transplant tumor recurrence, patients with PTI showed significantly better OS (P = 0.026) and PRS (P = 0.042) rates than those without PTI. CONCLUSION PTI improves OS and RFS of the transplant HCC patients at a high risk for post-transplant death and tumor recurrence, which is attributed to suppressive effect of PTI on HCC recurrence.

BACKGROUND Health care reforms aimed at bundling payments attempt to contain costs. Uncovering variation in spending provides one strategy for decreasing expenditure. This study aims to investigate interhospital cost variation for thumb replantation. METHODS A retrospective cross-sectional analysis of patients undergoing thumb replantation using data from the Healthcare Cost and Utilization Project National Inpatient Sample database from 2001 to 2011 was performed. Univariate and multivariable logistic regression models were used to investigate associations between patient-level and hospital-level characteristics and cost. RESULTS A total of 778 patients were included in the study, with a mean cost for thumb replantation of $20,965. Thumb replantations performed at high-volume hospitals were significantly more expensive than those performed at low-volume hospitals (median cost, $20,395 versus $13,463; p < 0.001), with longer lengths of stay (5 days versus 4 days), despite having similar surgical complication rates (p = 0.07). Thumb replantations performed in the West were significantly more expensive than those performed in the South (median cost, $22,579 in the West versus $14,823 in the South; p < 0.001), with longer lengths of stay (5 days versus 4 days; p = 0.005) and similar surgical complications (p = 0.239). In multivariable logistic regression, hospital volume (p < 0.001), hospital region (p < 0.001), and increased length of stay (p < 0.001) were predictive of higher cost. CONCLUSIONS High-volume hospitals and hospitals in the West are more expensive, with longer lengths of stay, despite having similar complications. Expedited discharge may be one avenue for decreasing expenditure without compromising care.

Background Nonalcoholic fatty liver disease (NAFLD) and heart failure (HF) are increasing in prevalence. The independent association between NAFLD and downstream risk of HF and HF subtypes (HF with preserved ejection fraction and HF with reduced ejection fraction) is not well established. Methods and Results This was a retrospective, cohort study among Medicare beneficiaries. We selected Medicare beneficiaries without known prior diagnosis of HF. NAFLD was defined using presence of 1 inpatient or 2 outpatient claims using International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD‐9‐CM ), claims codes. Incident HF was defined using at least 1 inpatient or at least 2 outpatient HF claims during the follow‐up period (October 2015–December 2016). Among 870 535 Medicare patients, 3.2% (N=27 919) had a clinical diagnosis of NAFLD. Patients with NAFLD were more commonly women, were less commonly Black patients, and had a higher burden of comorbidities, such as diabetes, obesity, and kidney disease. Over a mean 14.3 months of follow‐up, patients with (versus without) baseline NAFLD had a significantly higher risk of new‐onset HF in unadjusted (6.4% versus 5.0%; P Conclusions Patients with NAFLD are at an increased risk of incident HF, with a higher risk of developing HF with preserved ejection fraction versus HF with reduced ejection fraction. The persistence of an increased risk after adjustment for clinical and demographic factors suggests an epidemiological link between NAFLD and HF beyond the basis of shared risk factors that requires further investigation.

Background: Patients with comitant exotropia (CE) are accompanied by abnormal eye movements and stereovision. However, the neurophysiological mechanism of impaired eye movements and stereovision in patient with CE is still unclear.Purpose: The purpose of this study is to investigate spontaneous neural activity changes in patients with CE using the amplitude of low-frequency fluctuation (ALFF) method and the machine learning method.Materials and Methods: A total of 21 patients with CE and 21 healthy controls (HCs) underwent resting-state magnetic resonance imaging scans. The ALFF and fractional amplitude of low-frequency fluctuation (fALFF) values were chosen as classification features using a machine learning method.Results: Compared with the HC group, patients with CE had significantly decreased ALFF values in the right angular (ANG)/middle occipital gyrus (MOG)/middle temporal gyrus (MTG) and bilateral supplementary motor area (SMA)/precentral gyrus (PreCG). Meanwhile, patients with CE showed significantly increased fALFF values in the left putamen (PUT) and decreased fALFF values in the right ANG/MOG. Moreover, patients with CE showed a decreased functional connectivity (FC) between the right ANG/MOG/MTG and the bilateral calcarine (CAL)/lingual (LING) and increased FC between the left PUT and the bilateral cerebellum 8/9 (CER 8/9). The support vector machine (SVM) classification reaches a total accuracy of 93 and 90% and the area under the curve (AUC) of 0.93 and 0.90 based on ALFF and fALFF values, respectively.Conclusion: Our result highlights that patients with CE had abnormal brain neural activities including MOG and supplementary motor area/PreCG, which might reflect the neural mechanism of eye movements and stereovision dysfunction in patients with CE. Moreover, ALFF and fALFF could be sensitive biomarkers for distinguishing patients with CE from HCs.

Background Patient‐reported outcomes may be discordant to severity of illness as assessed by objective parameters. The frequency of this discordance and its influence on clinical outcomes in patients with heart failure is unknown. Methods and Results In HF‐ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), participants (N=2062) had baseline assessment of health‐related quality of life via the Kansas City Cardiomyopathy Clinical Summary score (KCCQ‐CS) and objective severity by cardiopulmonary stress testing (minute ventilation [V E ]/carbon dioxide production [VCO 2 ] slope). We defined 4 groups by median values: 2 concordant (lower severity: high KCCQ‐CS and low V E /VCO 2 slope; higher severity: low KCCQ‐CS and high V E /VCO 2 slope) and 2 discordant (symptom minimizer: high KCCQ‐CS and high V E /VCO 2 slope; symptom magnifier: low KCCQ‐CS and low V E /VCO 2 slope). The association of group assignment with mortality was assessed in adjusted Cox models. Symptom magnification (23%) and symptom minimization (23%) were common. Despite comparable KCCQ‐CS scores, the risk of all‐cause mortality in symptom minimizers versus concordant–lower severity participants was increased significantly (hazard ratio [HR], 1.79; 95% CI, 1.27–2.50; P P =0.18, respectively). Conclusions Severity of illness by patient report versus cardiopulmonary exercise testing was frequently discordant. Mortality tracked more closely with the objective data, highlighting the importance of relying not only on patient report, but also objective data when risk stratifying patients with heart failure.

Background Complement component(C7) gene has been shown to influence the prognosis in Hepatocellular carcinoma (HCC) patients. The association between C7 and HCC recurrence after orthotopic liver transplantation (OLT), however, is still unknown. The purpose of this study was to evaluate whether the donor and recipient C7 gene polymorphisms are related to HCC recurrence after OLT in the Han Chinese population. Methods A total of 73 consecutive patients with HCC who had undergone OLT, both donors and recipients, were involved in this research. A single nucleotide polymorphism of C7, rs9292795, was genotyped using Sequenom MassARRAY in the cohort. The expression of C7 and the association between C7 gene polymorphisms and HCC recurrence following OLT were analyzed by bioinformatics and statistical analysis, respectively. Results As shown in database, the expression of C7 was higher in HCC tissues than that in normal tissues, and represented a worse prognosis. We also found that recipient C7 rs9292795 polymorphism, rather than the donor, was significantly associated with HCC recurrence after OLT. Multivariate logistic regression analysis confirmed that TNM stage (P = 0.001), Milan criteria (P = 0.000) and recipient rs9292795 genotype (TT vs AA/AT, P = 0.008) were independent risk factors for HCC recurrence. Furthermore, the recipient carrying AA/AT showed higher recurrence-free survival (RFS) and overall survival (OS) than that carrying TT (P P Conclusions Recipient C7 rs9292795 gene polymorphism is related to the recurrence of HCC after OLT, which may be a helpful prognostic marker for HCC patients who receive OLT.

Brain-derived neurotrophic factor (BDNF) is a pleiotropic neuronal growth and survival factor that is indispensable in the brain, as well as in multiple other tissues and organs, including the cardiovascular system. In approximately 30% of the general population, BDNF harbors a nonsynonymous single nucleotide polymorphism that may be associated with cardiometabolic disorders, coronary artery disease, and Duchenne muscular dystrophy cardiomyopathy. We recently showed that transgenic mice with the human BDNF rs6265 polymorphism (Val66Met) exhibit altered cardiac function, and that cardiomyocytes isolated from these mice are also less contractile. To identify the underlying mechanisms involved, we compared cardiac function by echocardiography and performed deep sequencing of RNA extracted from whole hearts of all three genotypes (Val/Val, Val/Met, and Met/Met) of both male and female Val66Met mice. We found female-specific cardiac alterations in both heterozygous and homozygous carriers, including increased systolic (26.8%, p = 0.047) and diastolic diameters (14.9%, p = 0.022), increased systolic (57.9%, p = 0.039) and diastolic volumes (32.7%, p = 0.026), and increased stroke volume (25.9%, p = 0.033), with preserved ejection fraction and fractional shortening. Both males and females exhibited lower heart rates, but this change was more pronounced in female mice than in males. Consistent with phenotypic observations, the gene encoding SERCA2 (Atp2a2) was reduced in homozygous Met/Met mice but more profoundly in females compared to males. Enriched functions in females with the Met allele included cardiac hypertrophy in response to stress, with down-regulation of the gene encoding titin (Tcap) and upregulation of BNP (Nppb), in line with altered cardiac functional parameters. Homozygous male mice on the other hand exhibited an inflammatory profile characterized by interferon-γ (IFN-γ)-mediated Th1 immune responses. These results provide evidence for sex-based differences in how the BDNF polymorphism modifies cardiac physiology, including female-specific alterations of cardiac-specific transcripts and male-specific activation of inflammatory targets.

Aims: This study sought to describe originating from the spontaneous scarring of left atrial anterior wall (LAAW) left atrial macroreentry tachycardia (LAMRT) clinical and electrophysiological characteristics, mechanisms, the formation of substrates.Methods and Results: 9 of 123 patients (89% female, age 79.78±5.59 years) had LAMRT originating from the LAAW and no cardiac surgery or prior left atrial (LA) ablation. The mean tachycardia cycle length (TCL) was 241.67±38.00 milliseconds. Spontaneous scars areas and low voltage areas (LVAs) in the LAAW were found in all patients. Successful ablation of the critical isthmus caused terminated of the LAMRT and was not inducible in all patients. Arrhythmogenic substrates of LAMRT were the spontaneous scars of LAAW, which matched with the aorta or/and pulmonary artery contact area. The area under the curve (AUC) of age and combination of gender and age for predicting the LAMRT originating from the LAAW were 0.918 and 0.951, respectively, with a cutoff value of ≥73.5 years of age and gender (female) predicting LAMRT with 88.9% sensitivity and 89% specificity.Conclusion: Combination of gender and age provides a simple and useful criterion to distinguish LAMRT from cavo-tricuspid isthmus (CTI) -dependent atrial tachycardia in macroreentry atrial tachycardia (MRAT) in patients without a history of surgery or ablation. Aorta or/and pulmonary artery contacting LA may be related to spontaneous scars. Ablation the isthmus eliminated LAMRT in all patients.

Paraganglioma is a rare neuroendocrine tumor arising from undifferentiated cells of the primitive neural crest. We report a case of renal paraganglioma in a 67-year-old patient. Computed tomography demonstrated a solid mass in the middle and lower pole of the right kidney. Sonography revealed an enlarged right kidney with an irregular shape but distinct border. Renal cell carcinoma was diagnosed provisionally; the tumor was completely resected and submitted for pathological examination. Unexpectedly, histopathology and immunohistochemistry confirmed paraganglioma arising from the renal parenchyma. In this study, we report the exceptional occurrence of Paired box gene 8 (PAX-8) expression in a renal paraganglioma. In addition, we demonstrated diffuse cytokeratin positivity in this renal paraganglioma. Although our report of a paraganglioma originating from the kidney is not unique, our finding expands the known immunophenotypic spectrum of this tumor. The awareness of the possible occurrence of cytokeratin diffuse positivity in paraganglioma is relevant to avoiding misdiagnosis of paraganglioma.

Background Previous neuroimaging studies demonstrated that primary angle closure glaucoma patients were associated with abnormal intrinsic brain activity in primary visual cortex (V1). Purpose The purpose of this study was to investigate the effective connectivity patterns of V1 in patients with primary angle closure glaucoma. Material and Methods Thirty-seven patients with primary angle closure glaucoma (20 men, 17 women) and 36 healthy controls (20 men, 16 women) closely matched for age, sex, and education, underwent resting-state MRI scans. A voxel-wise Granger causality analysis method was performed to explore different effective connectivity pattern of V1 between the two groups. Results Compared with healthy controls, patients with primary angle closure glaucoma showed decreased effective connectivity from the left V1 to left cuneus and increased effective connectivity from the left V1 to left precentral gyrus and right supplementary motor area. Meanwhile, patients with primary angle closure glaucoma showed decreased effective connectivity from left precentral gyrus to left V1 and right frontal middle gyrus to left V1. In addition, patients with primary angle closure glaucoma showed a decreased effective connectivity from the right V1 to left cuneus/calcarine and increased effective connectivity from the right V1 to left inferior frontal gyrus and right caudate. Meanwhile, patients with primary angle closure glaucoma showed decreased effective connectivity from right middle frontal gyrus/precentral gyrus to right V1 and left precentral gyrus to right V1. Conclusion Our results highlighted that patients with primary angle closure glaucoma had abnormal effective connectivity between V1 and higher visual area, motor cortices, somatosensory cortices, and frontal lobe, which indicated that they might present with abnormal top-down modulations, visual imagery, vision-motor function, and vision-related higher cognition function.

Tian Gao,1,* Xiao-xin Huang,1,* Wu-yun Wang,1,2Miao-fang Wu,1 Zhong-qiu Lin,1 Jing Li11Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, People’s Republic of China; 2Department of Gynecology, Hangzhou Women’s Hospital, Hangzhou 310008, People’s Republic of China*These authors contributed equally to this workObjectives: For patients with advanced ovarian cancer, neoadjuvant chemotherapy (NACT) can significantly increase the rate of optimal cytoreduction. However, this does not translate into a survival benefit. The aim of this study was to investigate the feasibility and effect of neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (NLHIPEC).Methods: Between March 2016 and February 2018, 14 patients with advanced ovarian cancer who were not candidates for optimal cytoreduction via primary debulking surgery (PDS) received NLHIPEC. Their clinical data were retrospectively analyzed.Results: No patients experienced intraoperative complications during NLHIPEC. Grade 3 adverse events (AEs) were noted in two (14.3%) patients, and all patients received planned NACT without dose delay or dose reduction. Following NACT, CA125 levels

Objective: To investigate the safety, efficacy, and prognostic factors of hepatic arterial infusion chemotherapy (HAIC) with raltitrexed and oxaliplatin post-transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (uHCC). Methods: Thirty-seven patients with uHCC who received HAIC with raltitrexed and oxaliplatin post-TACE between June 2014 and December 2016 at our hospital were recruited. The primary endpoint was overall survival (OS), and secondary endpoint was progression-free survival (PFS). The overall response rate (ORR) was evaluated using the modified Response Evaluation Criteria in Solid Tumors. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (v4.0). The OS and prognostic factors were analyzed using the Kaplan–Meier method, log-rank test, and Cox regression models. Results: Three (8.1%) patients achieved complete response, 17 (46.0%) patients achieved partial response, and the ORR was54.0%.The median OS and median PFS were 19.0 months and 12.0 months, respectively. The common toxicities included grade 3–4 increased aspartate aminotransferase levels (8/37,21.6%), grade 1–2 hyperbilirubinemia (75.7%, 28/37), nonspecific abdominal pain and fever, and grade 2–3 thrombocytopenia (18.9%, 7/37); no patients developed grade 3–4 neutropenia. Univariate analysis showed that the tumor diameter (≤50 mm, p = 0.028), Barcelona Clinic Liver Cancer (BCLC) stage (p = 0.012), hepatitis B virus DNA level (p = 0.033), and derived neutrophil-to-lymphocyte ratio (dNLR; derived neutrophils/leukocytes minus neutrophils) (p = 0.003) were predictive factors for prognosis. Multivariate analysis showed that patients with BCLC stage B disease (p = 0.029) and dNLR≤2 before therapy (p = 0.004) had better prognosis. Conclusions: HAIC with raltitrexed and oxaliplatin post-TACE is a safe and efficacious therapy for patients with uHCC; in particular, those with BCLC stage B and dNLR≤2 have better prognosis. Keywords: Hepatocellular carcinoma, Transcatheter arterial chemoembolization (TACE), Hepatic arterial infusion chemotherapy (HAIC), Oxaliplatin, Raltitrexed

Background Liver transplantation (LT) is considered the standard treatment for end-stage liver disease, but ideal donors remain in limited supply, resulting in an unavoidable increase in the need to use grafts from marginal donors. The attenuation of ischemia-reperfusion injury (IRI) in such marginal donors is therefore crucial for reducing the possibility of the primary non-function of grafts and graft loss. Some reports have found that molecular-hydrogen showed antioxidant and anti-inflammatory effects in preventing IRI in some non-hepatic transplant models. Therefore, we investigated whether or not molecular-hydrogen could attenuate IRI in LT model rats. Methods We used a hydrogen-rich water bath to dissolve hydrogen into solution and graft tissues and performed isogenic and orthotopic LT in Lewis rats with University of Wisconsin (UW) solution. Blood and tissue samples were collected 6 h after the reperfusion. Hepatic enzymes in serum were measured. Pathological findings including the expressions of cytokines and heme oxygenase (HO)-1 in liver tissues were evaluated. Results The concentration of hydrogen inside the graft tissues increased depending on the storage time, plateauing after 1 h. Serum liver enzyme levels were significantly lower and the histology score of liver damage markedly attenuated in the group given grafts preserved in hydrogen-rich UW solution than in the control group. The hydrogen-rich UW solution group also showed less oxidative damage and hepatocyte apoptosis than the control group, and the expression of proinflammatory cytokines tended to be lower while the protein levels of HO-1 were significantly increased (n = 3–12 per group, P

AIM To analyze the survival data between patients diagnosed with right-sided primary (RSP) tumors and patients diagnosed with left-sided primary (LSP) tumors after hepatic arterial infusion chemotherapy (HAIC) at our center. METHODS A retrospective analysis of pretreated metastatic colorectal cancer patients who received HAIC from May 2006 to August 2015 was conducted. A Cox proportional hazard regression analysis was used to assess the long-term survival outcomes. The mean and median age of patients was 61 years (range 27-85 years). There were 115 males and 53 females in our study. RESULTS One hundred sixty-eight patients were enrolled in this study. The overall response rate was 28.9% in LSP patients and 27.3% in RSP patients. The disease control rate was 76.3% in LSP patients and 69.7% in RSP patients. The median overall survival in response to HAIC was 16.3 mo in the LSP arm and 9.3 mo in the RSP arm (P = 0.164). The median progression-free survival was 5.7 mo in the LSP arm and 4.2 mo in the RSP arm (P = 0.851). CONCLUSION There was no significant difference in survival between LSP patients and RSP patients after HAIC. Further prospective studies are needed to confirm these findings.

BACKGROUND Although national efforts to minimize gender biases exist, gender differences in surgery persist. This study aims to investigate gender differences in preoperative resource use of patients undergoing wrist arthroscopy for nontraumatic wrist pain. METHODS Patients who underwent a wrist arthroscopy for nontraumatic pain from 2009 to 2015 were selected from the Truven MarketScan databases. Demographic and preoperative resource use data were recorded. Multivariable regression models were performed to examine the relationship between gender and preoperative resource use and to investigate the cost of these services. RESULTS A total of 8792 patients, 3805 men and 4987 women, met our inclusion criteria. Women were less likely to use imaging modalities preoperatively (OR, 0.08; 95 percent CI, 0.07 to 1.00; p = 0.02). However, women used more occupational therapy (OR, 1.2; 95 percent CI, 1.1 to 1.3; p = 0.002), nonnarcotic analgesia (OR, 1.2; 95 percent CI, 1.1 to 1.3; p = 0.001), and narcotic analgesia (OR, 1.6; 95 percent CI, 1.5 to 1.8; p < 0.001). Preoperative costs during the 12 months before surgery were similar between genders ($1308 versus $1367, respectively; p = 0.07). However, women accrued more costs from occupational therapy ($130 versus $93; p = 0.003), and nonnarcotic ($65 versus $46; p < 0.001) and narcotic medications ($568 versus $197; p < 0.001). CONCLUSIONS Significant gender differences exist in the preoperative care for patients undergoing wrist arthroscopy. Men use more imaging, implying more intense preoperative investigation for wrist pain, whereas women use more conservative measures, highlighting possible implicit provider biases in preoperative management and potential gender differences in disease presentation.

Hypertension is a common comorbidity in patients receiving antiangiogenic therapy. Prior studies have reported worsening or new-onset hypertension as an adverse event of antiangiogenetic therapy, which can be managed by dose reduction or discontinuation of the culprit medication. By contrast, other studies have found that the occurrence of hypertension is a potential biomarker associated with greater efficacy of antiangiogenic therapy and predicts improved survival. At present, there is no consensus on the effects of hypertension in patients treated with antiangiogenic drugs. The present study reviewed the relationship between antiangiogenic drugs and hypertension in different types of cancer. It was demonstrated that the use of antiangiogenic drugs was associated with an increased risk of hypertension in most types of solid cancers. There was no significant difference in the incidence of hypertension between monoclonal antibody and small-molecule tyrosine kinase inhibitor treatments. Hypertension was more likely to occur in patients younger than 75 years old, female, and those with no history of bevacizumab use. Discontinuation or death caused by hypertension was rare, although previous studies have reported that hypertension was a risk factor for acute and chronic cardiovascular diseases and ischemic stroke. Of note, the early development of hypertension may serve as a potential biomarker associated with greater efficacy of antiangiogenic therapy.

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.

Summary Background Pepsinogen A (PGA)/pepsin A is often used as a diagnostic marker of extra-gastroesophageal reflux. We aimed to explore whether its positivity in upper aerodigestive tract (UADT) was specific enough to diagnose reflux. Methods PGA/pepsin A protein levels were examined in 10 types of tissues and 10 types of body fluid by immunological staining, western blot or Elisa, using three different commercially available brands simultaneously. Liquid chromatography-tandem mass spectrometry parallel reaction monitoring (LC-MS/MS PRM) served as a gold reference for the detection of PGA/pepsin A proteins. PGA gene expression was analyzed by reverse transcriptase sequencing methods for tissue samples. Specifically, 24 hour pH monitoring technique was conducted for patients who donated saliva samples. Results Eight out of ten types of human tissue samples (stomach, esophagus, lung, kidney, colon, parotid gland, nasal turbinate and nasal polyps) were confirmed positive for PGA/pepsin A gene and protein by genetic and PRM technique, respectively. Two out of ten types of body fluid samples (gastric fluid, urine) were confirmed positive for PGA/pepsin A protein by PRM technique. The consistence rates of PGA/pepsin A positivity among three commercial antibody brands and Elisa kit were poor, and Elisa results of salivary did not match with 24-hour pH monitoring. Conclusions Multiple tissues and body fluid could be detected baseline expression levels of PGA/pepsin A gene and protein. However, those commercially available PGA/pepsin A antibodies achieved poor sensitivity and specificity, therefore, relying on the detection of PGA/pepsin A in UADT by single antibodies to diagnose extra-gastroesophageal reflux without a specific positive cut-off value is unreliable.

Background As a novel ultrasonic technique, superb microvascular imaging (SMI) can quickly, simply and noninvasively observe the microvascular distribution in a tumor and evaluate the microvascular perfusion. Previous studies have shown that SMI can detect the blood flow signals of neovascularization in tumors and increase the sensitivity for detecting thyroid cancer. However, the results of these studies have been contradictory, and the sample sizes were too small. Therefore, the present meta-analysis will aim at evaluating the value of a thyroid imaging report and data system (TI-RADS) combined with SMI in distinguishing between benign and malignant thyroid nodules. Methods We will search PubMed, Web of Science, Cochrane Library, Google Scholar, and Chinese biomedical databases from their inceptions to the June 31, 2020. Two authors will independently carry out searching literature records; scanning titles, abstracts, and full texts; collecting data; and assessing risk of bias. Review Manager 5.2 and Stata14.0 software will be used for data analysis. Results This systematic review will evaluate the value of TI-RADS combined with SMI in distinguishing between benign and malignant thyroid nodules. Systematic review registration INPLASY202070113.

Background. Survival of patients with portal vein tumor thrombosis (PVTT) is extremely poor; transarterial chemoembolization (TACE) is a treatment for patients with HCC and PVTT. Some studies showed that hepatic arterial infusion chemotherapy (HAIC) might improve the survival of HCC with PVTT. There were few researches of combining TACE with HAIC for patients with HCC and PVTT. Aim. This study was aimed at comparing overall survival (OS) and progression-free survival (PFS) following treatment with conventional transarterial chemoembolization plus hepatic arterial infusion chemotherapy (cTACE-HAIC) or conventional transarterial chemoembolization (cTACE) alone in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT). Methods. From January 2011 to December 2016, 155 patients with HCC and PVTT who received cTACE-HAIC (cTACE-HAIC group) ( n = 86 ) or cTACE alone (cTACE group) ( n = 69 ) were retrospectively evaluated. Propensity score matching (PSM) reduced the confounding bias and yielded 60 matched patient pairs. The tumors’ responses were evaluated using the modified response evaluation criteria in solid tumors (mRECIST). OS and PFS of groups were compared using the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression models. Results. The median follow-up duration was 93 months (range: 1–93 months). The cTACE-HAIC group’s OS (9.0 months) and PFS (6.0 months) were significantly longer than the cTACE group’s OS (5.0 months) and PFS (2.0 months) ( p = 0.018 and p = 0.045 , respectively) in the matched cohort. Multivariate analyses showed that cTACE-HAIC was independently associated with OS (hazard ratio (HR) 0.602, p = 0.010 ) and PFS (HR 0.66, p = 0.038 ). The matched groups did not differ regarding grade 3 or 4 adverse events. Conclusion. cTACE-HAIC was superior to cTACE alone regarding OS and PFS in patients with HCC and PVTT. Treatment-associated toxicities were generally well tolerated.

Several studies revealed that non–small cell lung cancers (NSCLCs) frequently express ER, PR, HER2 and carry BRCA mutation. However, these markers in histological subtypes of lung adenocarcinoma have not been thoroughly investigated. We retrospectively evaluated a total of 640 lung adenocarcinoma samples for ERα, ERβ, PR and HER2 expression by immunohistochemistry and western-blotting, for EGFR and BRCA mutation by real-time PCR and sequencing. Furthermore, HER2 amplification and mutation were explored in samples harboring immunopositivity HER2 using fluorescence in situ hybridization and real-time PCR, respectively. The micropapillary and invasive mucinous predominant adenocarcinoma were frequently detected the higher level of cytoplasmic ERβ (64.9% and 56.6%), HER2 (68.1% and 60.1%) protein expression. But, amplification of HER2 was detected in only three cases (3/110, 2.7%) and 26 HER2 mutations in 110 cases were identified (23.6%) in the HER2 immunopositivity patients. Logistic regression analysis showed that cytoplasmic ERβ (P = 0.032) and HER2 (P = 0.015) expression were independently associated with EGFR mutation. 8 patients (8/640, 1.25%) harbored pathogenic BRCA mutations, 6 with germline BRCA mutations and 2 with somatic BRCA1 mutations were detected with lacking ERβ, PR and HER2 expression. Acinar predominant adenocarcinoma had the higher percentage of BRCA mutations than other subtypes. A systematic examination of ERβ, HER2 and BRCA biomarkers could potentially be useful to diagnosis and identify patients with the histological subtypes of lung adenocarcinoma, who might benefit from the further individualized treatment of anti-hormone, anti-HER2 and/or PARP inhibitors therapeutics.

Introduction: Amyloid cardiomyopathy (ACM) is recognized increasingly as a cause of advanced heart failure. There are limited data describing clinical outcomes for ACM patients who receive durable mechanical circulatory support (MCS). Methods: This analysis included adult patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) with a primary diagnosis of dilated cardiomyopathy (DCM, N=19,921), non-amyloid restrictive cardiomyopathy (RCM, N=248), or ACM (N=48) who received durable MCS of any type or strategy from 2005-2017. We compared baseline characteristics and adverse events for the 3 groups. The primary endpoint was death with heart transplantation as a competing risk with follow-up censored at device explantation. Results: Patients with ACM (N=48) were older (61 y [IQR 55-69] versus 58 y [IQR 49-66] for DCM and 55 y [IQR 46-62] for non-amyloid RCM, P Conclusion: Compared to DCM or non-amyloid RCM patients, those with durable MCS for ACM have the highest risk of early adverse events and lowest survival. These data highlight concerns with durable MCS for ACM.

Introduction: Although patient-reported outcomes are increasingly emphasized, symptoms may be discordant to objective parameters of heart failure severity. The frequency of such discordance, associated characteristics, and its influence on clinical outcomes is unknown. Methods: This is a post-hoc analysis of the HF-ACTION trial (N=2062). Participants were divided by median baseline values for Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ, subjective measure) and V E /VCO 2 slope (objective measure) into 4 groups: “concordant-lower severity” (high KCCQ, low V E /VCO 2 slope), “concordant-higher severity” (low KCCQ, high V E /VCO 2 slope), “symptom magnifier” (low KCCQ, V E /VCO 2 slope), and “symptom minimizer” (high KCCQ, V E /VCO 2 slope). Baseline characteristics were compared, and the relationship between group and clinical outcomes over a median follow-up of 442 days was assessed in adjusted Cox models. Results: Discordance of patient-reported and objective illness severity was common (46%). Depression was more prevalent among symptom magnifiers (N=480) versus concordant-lower severity (N=566) and symptom minimizer (N=465) groups (30%, 18%, 14%, respectively; P Conclusion: A high rate of discordance was observed between patient-reported and objective heart failure severity. Depression was associated with symptom magnification. Hospitalization was influenced by patient-reported severity but mortality tracked more closely with objective data, highlighting potential limitations of static patient-reported outcomes for risk stratification.

Background: Many patients with amyloid cardiomyopathy (ACM) develop advanced heart failure, and durable mechanical circulatory support (MCS) may be a consideration. However, data describing clinical outcomes after MCS in this population are limited. Methods: Adult patients in the Interagency Registry for Mechanically Assisted Circulatory Support with dilated cardiomyopathy (DCM, n=19 921), nonamyloid restrictive cardiomyopathy (RCM, n=248), or ACM (n=46) between 2005 and 2017 were included. Patient and device characteristics were compared between cardiomyopathy groups. The primary end point was the cumulative incidence of death with heart transplantation as a competing risk. Results: Patients with ACM (n=46) were older (61 years [interquartile range, 55–69 years] versus 58 years [interquartile range, 49–66 years] for DCM and 55 years [interquartile range, 46–62 years] for nonamyloid RCM, P P =0.04) at device implantation. Use of biventricular support (biventricular assist device or total artificial heart) was the highest for patients with ACM (41.3% versus 6.7% and 19.4% for patients with DCM and nonamyloid RCM, respectively, P =0.014). The cumulative incidence of death was highest for patients with ACM relative to those with DCM or nonamyloid RCM ( P Conclusions: Compared with patients with DCM or nonamyloid RCM who received durable MCS, those with ACM experienced the highest use of biventricular support and the worst survival. These data highlight concerns with the use of durable MCS for patients with ACM.

This national cohort study evaluates trends in heart failure incidence across risk factor strata, including hypertension, diabetes, obesity, acute myocardial infarction, and atrial fibrillation among Medicare beneficiaries., Key Points Question What are the trends in heart failure (HF) incidence across strata of risk factor burden? Findings In this national cohort study of 1 799 027 Medicare beneficiaries at risk for HF, the incidence of HF declined despite a concomitant increase in the prevalence of associated risk factors. This decline reflects a decrease in HF incidence among those with primary HF risk factors (hypertension, diabetes, and obesity). Meaning Individuals with risk factors, including hypertension, diabetes, and obesity, had a temporal decline in HF incidence; however, the incidence of HF increased among those with prevalent predisposing cardiovascular conditions, highlighting a potential target population for further HF prevention., Importance Heart failure (HF) incidence is declining among Medicare beneficiaries. However, the epidemiological mechanisms underlying this decline are not well understood. Objective To evaluate trends in HF incidence across risk factor strata. Design, Setting, and Participants Retrospective, national cohort study of 5% of all fee-for-service Medicare beneficiaries with no prior HF followed up from 2011 to 2016. The study examined annual trends in HF incidence among groups with and without primary HF risk factors (hypertension, diabetes, and obesity) and predisposing cardiovascular conditions (acute myocardial infarction [MI] and atrial fibrillation [AF]). Exposures The presence of comorbid HF risk factors including hypertension, diabetes, obesity, acute MI, and AF identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes. Main Outcomes and Measures Incident HF, defined using at least 1 inpatient HF claim or at least 2 outpatient HF claims among those without a previous diagnosis of HF. Results Of 1 799 027 unique Medicare beneficiaries at risk for HF (median age, 73 years [interquartile range, 68-79 years]; 56% female [805 060-796 253 participants during the study period]), 249 832 had a new diagnosis of HF. The prevalence of all 5 risk factors increased over time (0.8% mean increase in hypertension per year, 1.9% increase in diabetes, 2.9% increase in obesity, 0.2% increase in acute MI, and 0.4% increase in AF). Heart failure incidence declined from 35.7 cases per 1000 beneficiaries in 2011 to 26.5 cases per 1000 beneficiaries in 2016, consistent across subgroups based on sex and race/ethnicity. A greater decline in HF incidence was observed among patients with prevalent hypertension (relative excess decline, 12%), diabetes (relative excess decline, 3%), and obesity (relative excess decline, 16%) compared with those without corresponding risk factors. In contrast, there was a relative increase in HF incidence among individuals with acute MI (26% vs no acute MI) and AF (22% vs no AF). Conclusions and Relevance Findings of this study suggest that the temporal decline in HF incidence among Medicare beneficiaries reflects a decrease in HF incidence among those with primary HF risk factors. The increase in HF incidence among those with acute MI and those with AF highlights potential targets for future HF prevention strategies.

Brain-derived neurotrophic factor (BDNF) is a neuronal growth and survival factor that harbors cardioprotective qualities that may attenuate dilated cardiomyopathy. In ~30% of the population, BDNF has a common, nonsynonymous single nucleotide polymorphism rs6265 (Val66Met), which might be correlated with increased risk of cardiovascular events. We previously showed that BDNF correlates with better cardiac function in Duchenne muscular dystrophy (DMD) patients. However, the effect of the Val66Met polymorphism on cardiac function has not been determined. The goal of the current study was to determine the effects of rs6265 on BDNF biomarker suitability and DMD cardiac functions more generally. We assessed cardiovascular and skeletal muscle function in human DMD patients segregated by polymorphic allele. We also compared echocardiographic, electrophysiologic, and cardiomyocyte contractility in C57/BL-6 wild-type mice with rs6265 polymorphism and in mdx/mTR (mDMD) mouse model of DMD. In human DMD patients, plasma BDNF levels had a positive correlation with left ventricular function, opposite to that seen in rs6265 carriers. There was also a substantial decrease in skeletal muscle function in carriers compared to the Val homozygotes. Surprisingly, the opposite was true when cardiac function of DMD carriers and non-carriers were compared. On the other hand, Val66Met wild-type mice had only subtle functional differences at baseline but significantly decreased cardiomyocyte contractility. Our results indicate that the Val66Met polymorphism alters myocyte contractility, conferring worse skeletal muscle function but better cardiac function in DMD patients. Moreover, these results suggest a mechanism for the relative preservation of cardiac tissues compared to skeletal muscle in DMD patients and underscores the complexity of BDNF signaling in response to mechanical workload.

Background Left ventricular assist devices (LVADs) improve outcomes in patients with end‐stage heart failure and are increasingly implanted for destination therapy. We describe dynamic estimates of event‐free survival with conditional survival probabilities in a destination therapy LVAD population. Methods and Results We studied 8245 adult patients in INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) implanted with a continuous‐flow destination therapy LVAD. The composite primary end point was death, device exchange or removal, or heart transplantation. Conditional survival probabilities were calculated and stratified by implantation characteristics and nonfatal adverse events experienced within the first year after implant. Probabilities of surviving an additional 1 to 3 years were numerically higher after longer prior event‐free survival. INTERMACS profile 1, extracorporeal membrane oxygenation support, prior or concomitant surgery, and dialysis within 48 hours of implantation were associated with significantly lower event‐free survival in the first year but did not impact event‐free survival beyond then. For patients who experienced a nonfatal adverse event within the first year, subsequent 1‐year conditional survival was lower than in the absence of that event for stroke (65% [95% CI, 57%–73%] versus 75% [95% CI, 73%–77%]; P P P Conclusions Conditional survival in patients with destination therapy LVADs improves over time, even for patients with unfavorable implantation characteristics. However, LVAD‐related complications including stroke, device‐related infection, and pump thrombosis or malfunction have an enduring negative influence on dynamic estimates of long‐term prognosis.

Background No-reflow occurs in 3–4% of all percutaneous coronary interventions (PCIs) and has a strong negative impact on clinical outcomes of acute coronary syndrome. (ACS). Therefore, the discovery of a biomarker that can early predict the occurrence of no-reflow has great clinical significance. Multiple factors including platelet activation are relevant to no-reflow. Calprotectin is found to be a biomarker of plaque instability and is identified to be a novel diagnostic and prognostic biomarker of cardiovascular diseases. But theThe association of plasma calprotectin with platelet activation and no-reflow phenomenon in acute coronary syndromeACS is not clear. Methods In this prospective study performed at Yantai Yuhuangding Hospital from 2017 to 2018, a total of 176 Chinese patients with acute coronary syndromeACS who had undergone percutaneous coronary interventionsPCIs were recruited consecutively, aged from 30 to 88 years. The coronary angiography and percutaneous coronary intervention procedures were performed and angiographicAngiographic no-reflow was defined as a thrombolysis in myocardial infarction scores grade less than 3. Blood samples were collected immediately at admission for the detection of plasma calprotectin and platelet–monocyte aggregates formation. Statistical analysis was performed for the variable’s comparisons between groups and for the prediction value of plasma calprotectin for no-reflow.Results In this study, we have demonstrated that acute coronary syndromeThe mean age of the 176 included ACS patients were 64(±11) years and acute ST-segment elevation myocardial infarction (STEMI) was present in 41.5 percent of patients. 22 patients had no-reflow during the PCI procedures and the prevalence was 12.5%. Patients with higher plasma calprotectin had an elevateda higher level of platelet activation–monocyte aggregates (PMA) and a higher incidenceprevalence of no-reflow. Plasma (p

Key Points Question Is implementation of a novel high-sensitivity cardiac troponin T protocol in patients with chest pain associated with less resource use and within acceptable safety parameters? Findings This cohort study of 31 543 emergency department encounters found that implementation of the protocol was associated with a shorter length of stay in the emergency department and a higher proportion of patients discharged. There was no difference in the rate of 30-day hospitalization for myocardial infarction or death. Meaning This or similar protocols that rapidly rule out myocardial infarction have the potential to reduce emergency department overcrowding and improve health care quality., This cohort study of patients at a large US safety net hospital examines the safety of and resource use associated with a new protocol for excluding myocardial infarction from diagnosis of patients with chest pains through the use of high-sensitivity troponin., Importance High-sensitivity cardiac troponin T (hs-cTnT) protocols for the evaluation of chest pain in the emergency department (ED) may reduce unnecessary resource use and overcrowding. Objective To determine whether the implementation of a novel hs-cTnT protocol, which incorporated troponin values drawn at 0, 1, and 3 hours after ED presentation and the modified HEART score (history, electrocardiogram, age, risk factors), was associated with improvements in resource use while maintaining safety. Design, Setting, and Participants This retrospective cohort study from Parkland Health and Hospital System, a large safety net hospital in Dallas, Texas, included data on 31 543 unique ED encounters in which patients underwent electrocardiographic and troponin testing from January 1, 2017, to October 16, 2018. The hs-cTnT protocol was implemented in December 2017. Main Outcomes and Measures Resource use outcomes included trends in ED dwell time, troponin to disposition decision time (the difference between the first troponin draw time and the time an order was placed for inpatient admission, admission to observation, or discharge), and final patient disposition. Safety outcomes included readmission for myocardial infarction and death. Results In 31 543 encounters, mean (SD) patient age was 54 (14.4) years and 14 675 patients (48%) were female. Department dwell time decreased by a mean of −1.09 (95% CI, −2.81 to 0.64) minutes per month in the preintervention period. The decline was steeper after the intervention (−4.69 [95% CI, −9.05 to −0.33] minutes per month) (P for interaction = .007). The troponin to disposition time was increasing in the preintervention period by 1.72 (95% CI, 1.08 to 2.36) minutes per month; postintervention, the mean difference increased more slowly (0.37 [95% CI, −1.25 to 1.99 minutes per month; P value for interaction = .007]). The proportion of patients discharged from the ED increased after the intervention (48% vs 54%, P

Background Exercise is widely known to lower intraocular pressure and increase ocular blood flow, which may be beneficial for glaucoma management. However, there are few studies that have reported on the relationship between exercise and glaucoma progression. The aim of our study was to investigate the exercise habits of those with primary open angle glaucoma (POAG) and its association with the progression of visual field (VF) loss. Methods Daily physical activity (PA) was monitored by an accelerometer (ActiGraph wGT3x-BT) which patients wore for more than 10 h of being awake on their right wrists for 1 week. Results Seventy-one non-progressive and 27 progressive patients were enrolled in the study. 24-h moderate to vigorous physical activity (MVPA) exercise showed that POAG patients had similar variation trends consisting of 3 wave peaks and 2 wave hollows. Minutes spent in MVPA was 19.89 ± 15.81 and 21.62 ± 15.10 during 07:00–09:00 h (p = 0.204), 15.40 ± 14.49 and 15.67 ± 12.43 during 15:00–17:00 h (p = 0.822) and 17.26 ± 21.11 and 11.42 ± 11.58 during 18:00–20:00 h (p = 0.001) in the non-progressive and progressive group, respectively. Univariate analysis indicated that 10 min of MVPA (18:00–20:00 h) [odds ratio, OR (95% CI) = 0.82 (0.73, 0.92)], average mean arterial pressure [OR (95% CI) = 0.96 (0.94, 0.98)], age [OR (95% CI) = 1.06 (1.03, 1.08)], male [OR (95% CI) = 0.67 (0.48, 0.96)], spherical equivalent [OR (95% CI) = 1.14 (1.07, 1.22)] and IOP-lowering medications [OR (95% CI) = 1.54 (1.16, 2.05)] were significantly correlated with having progressive VF damage. Multivariable analysis showed that 10 min of MVPA (18:00–20:00 h) [OR (95% CI) = 0.85 (0.75, 0.97)] was associated with progressive VF loss even after adjusting for other risk factors. Conclusions Evening exercise may lower the odds of VF progression, suggesting that exercise habits possibly play an important role in glaucoma progression.

Background: To identify neoplastic and reactive neoformation bone by quantitative CT radiomics analysis, and to further validate the performance of the model by the diagnosis of osteosarcoma (OS) and chondrosarcoma (CS). Methods: A total of 478 bone tumor patients were retrospectively enrolled from 5 hospitals. Crucial radiomics features were selected and employed to construct radiomics signature by Least absolute shrinkage and selection operator (LASSO) regression. Then radiomics signature and clinical characteristics were combined to construct the model identifying neoplastic and reactive neoformation bone (ModelRN) in the training set (n = 300), and then validated in the validation set (n = 178). Furthermore, a new model (ModelOC) incorporating the clinical characteristics and the comprehensive scores produced by ModelRN was constructed to differentiate OS and CS (training set: n = 103; validation set: n = 41). The performance of the model was evaluated with respect to discrimination, calibration, and clinical usefulness. Findings: ModelRN incorporating radiomics signature, tumor position and course of disease achieved promising results with high identification accuracy (AUC: 0.9319 in the training set and 0.9350 in the validation set). ModelOC was built incorporating alkaline phosphatase with the comprehensive score produced by ModelRN. ModelOC also showed satisfying performance in the training (AUC: 0.8752) and validation (AUC: 0.9032) sets. Decision curve analysis showed the clinical usefulness of the model. Interpretation: This study suggested that CT-based radiomics can help radiologists to identify neoplastic and reactive neoformation bone, thereby more effectively distinguishing osteosarcoma from chondrosarcoma than current clinical images diagnosis. Funding Statement: This paper is supported by the National Natural Science Foundation of China (Grant Nos. 81871510, 81871511), Ministry of Science and Technology of China under Grant (No.2017YFA0205200, 2017YFA0700401, 2016YFA0100902, 2016YFC0103803, 2016YFA0201401, 2016YFC0103702). Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: Ethical approval was obtained from the institutional review board (IRB) of the Third Affiliated Hospital of Southern Medical University, and the need for informed consent from the patients was waived.

Background:Most lesions of the upper extremity are common and benign, and many have questioned the need for routine pathologic evaluation of these specimens. The authors aim to examine the national use of routine pathologic examination of nonmalignant hand lesions to help guide health care policy an

Background:Contralateral prophylactic mastectomy may be unnecessary from an oncologic perspective; therefore, the debate persists about the value of contralateral prophylactic mastectomy in women with early-stage unilateral breast cancer. Given finite health care resources, this study aims to evalua

BACKGROUND Rising contralateral prophylactic mastectomy rates are a subject of national concern. This study assessed (1) factors critical to patients when deciding on contralateral prophylactic mastectomy and (2) patients' quality of life related to concerns about recurrence after unilateral or bilateral breast reconstruction. METHODS Patients with stage 0 to III breast cancer who underwent unilateral mastectomy or contralateral prophylactic mastectomy and breast reconstruction at a single institution between 2000 and 2012 were identified. Demographic and clinical data were extracted by chart review. Women's fears about breast cancer recurrence were assessed using the Concerns About Recurrence Scale, and motivational factors for contralateral prophylactic mastectomy were identified using the Decisions for Contralateral Prophylactic Mastectomy Survey. RESULTS Survey responses were received from 157 patients (59%) who underwent unilateral reconstruction and 109 (41%) who underwent bilateral reconstruction. The top 3 reasons for choosing contralateral prophylactic mastectomy were (1) decreasing the risk of contralateral breast disease (97%), (2) peace of mind (96%), and (3) improved survival (93%). Women who chose contralateral prophylactic mastectomy reported significantly greater overall fear and worry compared with the unilateral group, specifically, greater fears of dying and worries about adequately fulfilling roles of daily life (P < 0.05). CONCLUSIONS Despite no proven survival benefit, women chose contralateral prophylactic mastectomy primarily to optimize oncologic outcomes. Among breast reconstruction patients, women who underwent contralateral prophylactic mastectomy had greater anxiety and overall fear of breast cancer recurrence compared with those who chose unilateral mastectomy. These findings are important to consider when counseling women contemplating contralateral prophylactic mastectomy.

Objectives To develop and evaluate the efficacy and feasibility of Intracapsular Rotary-cut Procedure (IRCP) in laparoscopic myomectomy (LM). Study design It is a retrospective study conducted in Peking University Shenzhen Hospital (PUSH) in Shenzhen, China. A total of 96 patients who were treated with LM because of big and moderate size of myomas in PUSH from January 2013 and December 2015 were enrolled in this study. Among them 35 were managed with IRCP −integrated LM as the study group, while the other 61 were treated with normal LM as the control group. The core steps of IRCP include minimized uterine incision, rotary cuttings in the fibroid inside the pseudocapsule, and preserving the fibers and vessels of the fibroid pseudocapsule. The operation data and outcome variables of each patient in the two groups were collected and compared to evaluate the efficacy and feasibility of this new improved surgery procedure. Results The ages, body mass indexes, main indication for myomectomy, and the diameters, numbers and types of the fibroids of patients in the two groups were similar. There is no significant difference in enucleation time and days of postoperative in-hospital staying between the two groups. In comparison with normal LM, application of IRCP significantly reduced the length of uterine incisions (P = 0.000), the overall time of operations (P = 0.001), and the time for uterine cavity suturing (P = 0.000), and application of IRCP was also associated with less operation bleeding (P = 0.003) and postoperative hemoglobin dropping (P = 0.001). Five cases (8.2%) in the control group were referred to laparotomy, while no case was done so in the study group. No patient in the study group needed blood transfusion but six patients (9.8%) in the control group did. Follow-up to all the patients showed no uterine malignant tumor. Conclusions Our study provided strong supportive evidences showing that Intracapsular Rotary-cut Procedures is safe and practicable. The less uterine incision length, less surgery time, and less bleeding than the normal LM procedures all suggests that IRCP should be adopted in LM for facilitation to the operation procedures, minimization of operative invasiveness, and protection to patients’ infertility.

The follicular variant of peripheral T-cell lymphoma, not otherwise specified, is very rare. Primary epiglottic follicular variant of peripheral T-cell lymphoma is extremely rare in clinical practice. Here, we report the first case of a follicular variant of peripheral T-cell lymphoma not otherwise specified in a 44-year-old Chinese man, who presented with a tumor in the middle of the epiglottis tongue surface. Microscopically, the tumor had a vague nodular growth pattern and the morphology of the nodules was different from each other at low power. Atypical lymphoid cells were medium to large in size and had round nuclei, with an irregular nuclear membrane, distinct nucleoli, and rapid mitotic activity. Plasma cells were found surrounding the nodules. The tumor cells were positive for follicular helper T-cell markers (CD10, PD-1, CXCL13, and BCL-6). The EBER was negative by in situ hybridization. Polymerase chain reaction-based analysis showed monoclonal rearrangements of TCRβ, TCRγ, and polyclonal rearrangements of IgH, IgK, and IgL. The clinical and imaging features and the prognostic factors of FV PTCL-NOS remain poorly understood. Thus, investigation of more cases and longer follow-up is necessary to understand the disease and to identify the best treatment to improve prognosis.

Purpose: The purpose of this study was to retrospectively evaluate the association between Interleukin-18 (IL-18) gene polymorphisms of the donor and recipient in liver transplant patients with bacterial infections. Methods: Five single nucleotide polymorphisms (SNPs) (rs7106524, rs5744247, rs1946518, rs549908 and rs187238) of the IL-18 gene from the donors were genotyped and their association with post-operative bacterial infections was evaluated in liver transplant patients (N=113). A second independent group of liver transplant patients from a different organ transplant centre was also recruited for validation purposes (N=44). Results: IL-18 mRNA mean expression levels and protein levels were significantly lower in liver transplant patients with bacterial infections. For the donor SNP rs1946518, more recipients carried the A allele in the bacterial-infected group than the uninfected group (61.4% vs 39.7%; P ≤0.002). The mean IL-18 mRNA expression and protein levels were significantly lower in the transplanted livers of recipients carrying the rs1946518 AA genotype compared with those from recipients with CC genotype (3.64, 3.33 vs. 2.75, P≤0.048). The A allele of rs1946518 also resulted in lower luciferase activity than the C allele in a reporter assay. The area under ROC curve indicated that the rs1946518 SNP genotype in the donor liver predicted an increased risk of bacterial infection after liver transplantation (AUROC>0.82). Conclusions: These findings indicate that the IL-18 rs1946518 SNP in the donor liver is a risk factor for developing bacterial infection after liver transplantation.