Retinal Layer Segmentation in OCT Images With Boundary Regression and Feature Polarization.

The geometry of retinal layers is an important imaging feature for the diagnosis of some ophthalmic diseases. In recent years, retinal layer segmentation methods for optical coherence tomography (OCT) images have emerged one after another, and huge progress has been achieved. However, challenges due to interference factors such as noise, blurring, fundus effusion, and tissue artifacts remain in existing methods, primarily manifesting as intra-layer false positives and inter-layer boundary deviation. To solve these problems, we propose a method called Tightly combined Cross-Convolution and Transformer with Boundary regression and feature Polarization (TCCT-BP). This method uses a hybrid architecture of CNN and lightweight Transformer to improve the perception of retinal layers. In addition, a feature grouping and sampling method and the corresponding polarization loss function are designed to maximize the differentiation of the feature vectors of different retinal layers, and a boundary regression loss function is devised to constrain the retinal boundary distribution for a better fit to the ground truth. Extensive experiments on four benchmark datasets demonstrate that the proposed method achieves state-of-the-art performance in dealing with problems of false positives and boundary distortion. The proposed method ranked first in the OCT Layer Segmentation task of GOALS challenge held by MICCAI 2022. The source code is available at https://www.github.com/tyb311/TCCT.

The potential of high-order features of routine blood test in predicting the prognosis of non-small cell lung cancer.

BACKGROUND: Numerous studies have demonstrated that the high-order features (HOFs) of blood test data can be used to predict the prognosis of patients with different types of cancer. Although the majority of blood HOFs can be divided into inflammatory or nutritional markers, there are still numerous that have not been classified correctly, with the same feature being named differently. It is an urgent need to reclassify the blood HOFs and comprehensively assess their potential for cancer prognosis. METHODS: Initially, a review of existing literature was conducted to identify the high-order features (HOFs) and classify them based on their calculation method. Subsequently, a cohort of patients diagnosed with non-small cell lung cancer (NSCLC) was established, and their clinical information prior to treatment was collected, including low-order features (LOFs) obtained from routine blood tests. The HOFs were then computed and their associations with clinical features were examined. Using the LOF and HOF data sets, a deep learning algorithm called DeepSurv was utilized to predict the prognostic risk values. The effectiveness of each data set's prediction was evaluated using the decision curve analysis (DCA). Finally, a prognostic model in the form of a nomogram was developed, and its accuracy was assessed using the calibration curve. RESULTS: From 1210 documents, over 160 blood HOFs were obtained, arranged into 110, and divided into three distinct categories: 76 proportional features, 6 composition features, and 28 scoring features. Correlation analysis did not reveal a strong association between blood features and clinical features; however, the risk value predicted by the DeepSurv LOF- and HOF-models is significantly linked to the stage. Results from DCA showed that the HOF model was superior to the LOF model in terms of prediction, and that the risk value predicted by the blood data model could be employed as a complementary factor to enhance the prognosis of patients. A nomograph was created with a C-index value of 0.74, which is capable of providing a reasonably accurate prediction of 1-year and 3-year overall survival for patients. CONCLUSIONS: This research initially explored the categorization and nomenclature of blood HOF, and proved its potential in lung cancer prognosis.

A lightweight network guided with differential matched filtering for retinal vessel segmentation.

The geometric morphology of retinal vessels reflects the state of cardiovascular health, and fundus images are important reference materials for ophthalmologists. Great progress has been made in automated vessel segmentation, but few studies have focused on thin vessel breakage and false-positives in areas with lesions or low contrast. In this work, we propose a new network, differential matched filtering guided attention UNet (DMF-AU), to address these issues, incorporating a differential matched filtering layer, feature anisotropic attention, and a multiscale consistency constrained backbone to perform thin vessel segmentation. The differential matched filtering is used for the early identification of locally linear vessels, and the resulting rough vessel map guides the backbone to learn vascular details. Feature anisotropic attention reinforces the vessel features of spatial linearity at each stage of the model. Multiscale constraints reduce the loss of vessel information while pooling within large receptive fields. In tests on multiple classical datasets, the proposed model performed well compared with other algorithms on several specially designed criteria for vessel segmentation. DMF-AU is a high-performance, lightweight vessel segmentation model. The source code is at https://github.com/tyb311/DMF-AU.

The role of aldosterone and ideal cardiovascular health in incident cardiovascular disease: The Jackson heart study.

Background: Higher levels of ideal cardiovascular health (ICH) are associated with lower levels of aldosterone and incidence of cardiovascular disease (CVD). However, the degree to which aldosterone mediates the association between ICH and CVD incidence has not been explored. Thus, we investigated the mediational role of aldosterone in the association of 5 components of ICH (cholesterol, body mass index (BMI), physical activity, diet and smoking) with incident CVD and the mediational role of blood pressure (BP) and glucose in the association of aldosterone with incident CVD in a cohort of African Americans (AA). Methods: The Jackson Heart Study is a prospective cohort of AAs adults with data on CVD outcomes. Aldosterone, ICH metrics and baseline characteristics were collected at exam 1 (2000-2004). ICH score was developed by summing 5 ICH metrics (smoking, dietary intake, physical activity, BMI, and total cholesterol) and grouped into two categories (0-2 and ≥3 metrics). Incident CVD was defined as stroke, coronary heart disease, or heart failure. Cox proportional hazard regression models were used to model the association of categorical ICH score with incident CVD. The R Package Mediation was utilized to examine: 1) The mediational role of aldosterone in the association of ICH with incident CVD and 2) The mediational role of blood pressure and glucose in the association of aldosterone with incident CVD. Results: Among 3,274 individuals (mean age: 54±12.4 years, 65% female), there were 368 cases of incident CVD over a median of 12.7 years. The risk of incident CVD was 46% lower (HR: 0.54; 95%CI 0.36, 0.80) in those with ≥3 ICH metrics at baseline compared to 0-2. Aldosterone mediated 5.4% (p = 0.006) of the effect of ICH on incident CVD. A 1-unit increase in log-aldosterone was associated with a 38% higher risk of incident CVD (HR 1.38, 95%CI: 1.19, 1.61) with BP and glucose mediating 25.6% (p<0.001) and 4.8% (p = 0.048), respectively. Conclusion: Aldosterone partially mediates the association of ICH with incident CVD and both blood pressure and glucose partially mediate the association of aldosterone with incident CVD, emphasizing the potential importance of aldosterone and ICH in risk of CVD among AAs.

The role of aldosterone and ideal cardiovascular health in incident diabetes: The Jackson Heart Study.

Background: Greater attainment of ideal cardiovascular health (ICH) and lower serum aldosterone are associated with lower diabetes risk. Higher levels of ICH are associated with lower aldosterone. The mediational role of aldosterone in the association of ICH with incident diabetes remains unexplored. Thus, we examined the mediational role of aldosterone in the association of 5 ICH components (smoking, diet, physical activity, body mass index [BMI], and cholesterol) with incident diabetes. Additionally, we investigated the mediational role of glucose and blood pressure (BP) in the association of aldosterone with incident diabetes in an African American (AA) cohort. Methods: We conducted a prospective cohort analysis among AA adults, aged 21-94 years, in the Jackson Heart Study. Data on ICH, aldosterone, and cardiometabolic risk factors were collected at exam 1 (2000-2004). Diabetes (fasting glucose ≥ 126 mg/dL, physician diagnosis, use of diabetes drugs, or glycated hemoglobin ≥ 6.5%) was assessed at exams 1 through 3 (2009-2012). ICH metrics were defined by American Heart Association 2020 goals for smoking, dietary intake, physical activity, BMI, total cholesterol, BP and glucose. The number of ICH metrics attained at exam 1, excluding BP and fasting glucose, were summed (0-2, vs. 3+). R Package Mediation was used to examine: 1) The mediational role of aldosterone in the association of ICH with incident diabetes; and 2) the mediational role of BP and glucose in the association of aldosterone with incident diabetes. Results: Among 2,791 participants (mean age: 53±12, 65% female) over a median of 7.5 years, there were 497 incident diabetes cases. Risk of incident diabetes was 37% (HR: 0.63, 95%CI: 0.47, 0.84) lower in 3+ ICH category compared to 0-2 ICH category. Aldosterone mediated 6.98% (95% CI: 1.8%, 18.0%) of the direct effect of ICH on incident diabetes. A 1-unit increase in log-aldosterone was associated with a 44% higher risk of diabetes (HR 1.44, 95%CI 1.25-1.64). BP and glucose mediated 16.3% (95% CI: 7.0%, 31.0%) and 19.7% (95% CI: 6.5%, 34.0%) of the association of aldosterone with incident diabetes, respectively. Conclusion: Aldosterone is a mediator of the association of ICH with incident diabetes, whereas BP and glucose are mediators of the association of aldosterone with incident diabetes, emphasizing the importance of the renin-angiotensin-aldosterone system and ICH in lowering risk of diabetes in AA populations.

For Which Children with ADHD is TBR Neurofeedback Effective? Comorbidity as a Moderator.

We examined psychiatric comorbidities moderation of a 2-site double-blind randomized clinical trial of theta/beta-ratio (TBR) neurofeedback (NF) for attention deficit hyperactivity disorder (ADHD). Seven-to-ten-year-olds with ADHD received either NF (n = 84) or Control (n = 58) for 38 treatments. Outcome was change in parent-/teacher-rated inattention from baseline to end-of-treatment (acute effect), and 13-month-follow-up. Seventy percent had at least one comorbidity: oppositional defiant disorder (ODD) (50%), specific phobias (27%), generalized anxiety (23%), separation anxiety (16%). Comorbidities were grouped into anxiety alone (20%), ODD alone (23%), neither (30%), or both (27%). Comorbidity (p = 0.043) moderated acute effect; those with anxiety-alone responded better to Control than to TBR NF (d = - 0.79, CI - 1.55- - 0.04), and the other groups showed a slightly better response to TBR NF than to Control (d = 0.22 ~ 0.31, CI - 0.3-0.98). At 13-months, ODD-alone group responded better to NF than Control (d = 0.74, CI 0.05-1.43). TBR NF is not indicated for ADHD with comorbid anxiety but may benefit ADHD with ODD.Clinical Trials Identifier: NCT02251743, date of registration: 09/17/2014.

[Safety and efficacy of different doses of tranexamic acid in posterior cervical laminectomy with lateral mass screw fixation and bone graft fusion].

Objective: To investigate the safety and efficacy of different doses of tranexamic acid (TXA) in posterior cervical laminectomy with lateral mass screw fixation and bone graft fusion by a prospective clinical study. Methods: The middle-aged and elderly patients with cervical spondylotic myelopathy, who were admitted between January 2020 and January 2022 and scheduled to undergo posterior cervical laminectomy with lateral mass screw fixation and bone graft fusion, were studied as the research subjects. Among them, 165 patients met the selection criteria and were included in the study. The patients were allocated into 3 groups ( n=55) by random double-blind lottery. Groups A and B were given intravenous infusion of TXA at 30 minutes before operation according to the standards of 15 and 30 mg/kg, respectively; and group C was given normal saline in the same way. There was no significant difference in gender, age, body mass index, and preoperative D-dimer, hemoglobin (Hb), and hematocrit (HCT) between groups ( P>0.05). The intraoperative bleeding, intraoperative blood transfusion, postoperative drainage volume, drainage days, and postoperative hospital stay were recorded. The Hb, HCT, and D-dimer were compared before operation and at 3 days after operation. Venous ultrasonography of the lower extremities was taken after operation to assess thrombosis; and the postoperative hematoma and epilepsy were also observed. Results: All operations were successfully completed, and the incisions healed by first intention. The differences in intraoperative bleeding volume, postoperative drainage volume, drainage days, and postoperative hospital stay between groups were significant ( P<0.05). The above indexes were significantly less in group B than in groups A and C. During operation, 14 patients in group A and 23 patients in group C were transfused, and no patient in group B had blood transfusions. Compared with groups A and C, the blood transfusion volume in group B significantly decreased ( P<0.05), and the difference between groups A and C was not significant ( P>0.05). There was no significant difference in the differences of D-dimer, Hb, and HCT before and after operation between groups ( P>0.05). At 5 days after operation, the venous ultrasonography of the lower extremities showed that the 2 cases of intermuscular venous thrombosis occurred in groups A, B, and C, respectively. No hematoma or epilepsy occurred after operation. Conclusion: The application of 15 and 30 mg/kg TXA in posterior cervical laminectomy with lateral mass screw fixation and bone graft fusion can reduce intraoperative bleeding and postoperative drainage volume, postoperative drainage days, and postoperative hospital stay. And application of 30 mg/kg TXA can reduce intraoperative blood transfusion, without increasing the risk of lower extremity venous thrombosis, hematoma, and epilepsy.

PentaRay® Multielectrode Mapping Catheter for Atrial Tachyarrhythmia in Adults With Congenital Heart Disease.

BACKGROUND: Ablation of atrial tachyarrhythmia in adults with congenital heart disease (ACHD) is challenging because of complex anatomy and high scar burden. We proposed that the addition of high-density mapping with the PentaRay® (Biosense Webster, Inc) mapping catheter (EAM+P) to 3-dimensional electroanatomic mapping (EAM) allows for rapid acquisition of high-resolution maps and shorter procedure times. METHODS: In this single-center, retrospective cohort study of patients with ACHD who underwent atrial arrhythmia ablation, patients were divided those who underwent ablation with EAM and those who underwent ablation with EAM+P. RESULTS: Fifteen ablations were performed in 13 patients using standard EAM, and 11 ablations were performed in 10 patients using EAM+P. There was no difference in mean age or complexity of congenital heart disease. The procedure duration was 1.5 times longer in the EAM than in the EAM+P group (P = .015). The dose area product was 12 times higher in the EAM than in the EAM+P group (P = .001). A higher number of venous access sites were used for EAM cases than for EAM+P cases (P = .008). Acute success rates of ablation and recurrence rates at 1 year were similar in the 2 groups. There were no procedure-related complications in either group. CONCLUSION: This is the first study to evaluate the use of the PentaRay® high-density mapping catheter for ablation of atrial tachyarrhythmia in patients with ACHD. The use of the PentaRay® high-density mapping catheter results in shorter procedure time, decreased radiation exposure, and fewer venous access sites.

Phase I study of trametinib in combination with whole brain radiation therapy for brain metastases.

INTRODUCTION: Trametinib is a MEK inhibitor with intracranial activity indicated for BRAF-mutant metastatic malignancies. Yet, the safety of trametinib concurrent with whole brain radiation therapy (WBRT) is unknown. We performed a single-institution, prospective, 3 + 3, phase I clinical trial to determine the maximum tolerated dose (MTD) of trametinib with WBRT. METHODS AND MATERIALS: Patients with brain metastases (BM) received daily trametinib for 28 days, starting 7 days prior to and continuing through WBRT (37.5 Gy/15 fractions). Dose levels (DL)1-3 were 1.0, 1.5, and 2.0 mg. The MTD of trametinib plus WBRT, the max dose where ≤1 of 6 patients experienced a dose limiting toxicity (DLT), was the primary endpoint. RESULTS: 10 patients were enrolled (median age-59 [47-64], BM-5 [1-10], 50% melanoma). Three and 7 patients were assigned to DL1 and 2. One DL2 patient withdrew. 89% of remaining patients completed therapy per protocol, but 1 DL2 patient with systemic progression discontinued therapy at 30 Gy. Thirteen grade (G)3-4 toxicities were observed, of which 12 occurred at DL2 (4/6 of patients). DLT was reached at DL2 (G4 thrombocytopenia and G3 diarrhea, 1 each). There were no G5 toxicities. Median overall survival was 2.2 months. During the study period, changing practice patterns favored utilization of stereotactic radiosurgery (SRS). Thus, the trial closed early prior to completion. CONCLUSIONS: In a patient population representative of modern candidates for WBRT, trametinib plus WBRT is highly toxic with a MTD <1.5 mg. The safety of trametinib with SRS remains an important question for future study.

Retinal Vessel Segmentation With Skeletal Prior and Contrastive Loss.

The morphology of retinal vessels is closely associated with many kinds of ophthalmic diseases. Although huge progress in retinal vessel segmentation has been achieved with the advancement of deep learning, some challenging issues remain. For example, vessels can be disturbed or covered by other components presented in the retina (such as optic disc or lesions). Moreover, some thin vessels are also easily missed by current methods. In addition, existing fundus image datasets are generally tiny, due to the difficulty of vessel labeling. In this work, a new network called SkelCon is proposed to deal with these problems by introducing skeletal prior and contrastive loss. A skeleton fitting module is developed to preserve the morphology of the vessels and improve the completeness and continuity of thin vessels. A contrastive loss is employed to enhance the discrimination between vessels and background. In addition, a new data augmentation method is proposed to enrich the training samples and improve the robustness of the proposed model. Extensive validations were performed on several popular datasets (DRIVE, STARE, CHASE, and HRF), recently developed datasets (UoA-DR, IOSTAR, and RC-SLO), and some challenging clinical images (from RFMiD and JSIEC39 datasets). In addition, some specially designed metrics for vessel segmentation, including connectivity, overlapping area, consistency of vessel length, revised sensitivity, specificity, and accuracy were used for quantitative evaluation. The experimental results show that, the proposed model achieves state-of-the-art performance and significantly outperforms compared methods when extracting thin vessels in the regions of lesions or optic disc. Source code is available at https://www.github.com/tyb311/SkelCon.

Workforce demographics and unit structure in paediatric cardiac critical care in the United States.

OBJECTIVE: To assess current demographics and duties of physicians as well as the structure of paediatric cardiac critical care in the United States. DESIGN: REDCap surveys were sent by email from May till August 2019 to medical directors ("directors") of critical care units at the 120 United States centres submitting data to the Society of Thoracic Surgeons Congenital Heart Surgery Database and to associated faculty from centres that provided email lists. Faculty and directors were asked about personal attributes and clinical duties. Directors were additionally asked about unit structure. MEASUREMENTS AND MAIN RESULTS: Responses were received from 66% (79/120) of directors and 62% (294/477) of contacted faculty. Seventy-six percent of directors and 54% of faculty were male, however, faculty <40 years old were predominantly women. The majority of both groups were white. Median bed count (n = 20) was similar in ICUs and multi-disciplinary paediatric ICUs. The median service expectation for one clinical full-time equivalent was 14 weeks of clinical service (interquartile range 12, 16), with the majority of programmes (86%) providing in-house attending night coverage. Work hours were high during service and non-service weeks with both directors (37%) and faculty (45%). CONCLUSIONS: Racial and ethnic diversity is markedly deficient in the paediatric cardiac critical care workforce. Although the majority of faculty are male, females make up the majority of the workforce younger than 40 years old. Work hours across all age groups and unit types are high both on- and off-service, with most units providing attending in-house night coverage.

Immediate effects of treadmill walking in individuals with Lewy body dementia and Huntington's disease.

BACKGROUND: Treadmill training may improve gait disorders associated with neurodegenerative diseases. In Parkinson's disease (PD), treadmill training alters gait patterns after one session, and long-term training improves gait parameters, fall risk, and quality of life. RESEARCH QUESTION: What is the feasibility and safety of using this intervention for people with Lewy body dementia (LBD) or Huntington's disease (HD)? METHODS: In this observational study, 10 individuals with HD, 8 individuals with LBD, and 10 control individuals walked for 20 min on a treadmill using a speed dependent protocol starting at a slow comfortable speed and increasing incrementally toward their normal overground speed. Feasibility was determined by compliance to protocol and safety by no incidents of abnormal vital signs or expressions of distress. Changes in gait measures, Timed Up and Go (TUG) scores and quantitative motor function measures (Q-Motor; precision grasp force variability, finger and foot tapping frequency) before and after treadmill walking were analyzed using linear models. RESULTS: Treadmill training is feasible and safe in LBD and HD; although, participants could not initiate treadmill walking at their comfortable overground speeds, and only 3 participants with HD were able to achieve their overground walking speed within the 20-minute session. No changes in gait measures, TUG times, and Q-Motor measures were found among LBD and HD participants after treadmill walking, although control participants demonstrated significant increases in several gait measures, and foot tap frequency (estimated difference = 0.290; p = 0.026). SIGNIFICANCE: Longer and more frequent treadmill sessions may be needed to see gait and motor function effects in LBD and HD. Motor and cognitive impairments associated with these diseases may make them less amenable to the effects of treadmill training.

Tricuspid Valve and Right Ventricular Function Throughout the Hybrid Palliation Strategy for Hypoplastic Left Heart Syndrome and Variants.

BACKGROUND: Tricuspid valve (TV) and right ventricular (RV) function are major determinants of morbidity and mortality in patients with hypoplastic left heart syndrome (HLHS). We sought to retrospectively evaluate these parameters throughout the hybrid palliation strategy. METHODS: From 2002 to 2018, 203 patients with HLHS and variants presented for hybrid stage I (HS1). Echocardiographic evaluation of tricuspid regurgitation (TR) and RV function was assessed at multiple time points. Clinical outcomes including tricuspid valvuloplasty, transplantation, and death were reviewed. RESULTS: The most prevalent HLHS subtype was aortic atresia/mitral atresia. The presence of significant TR and/or RV dysfunction was 14.78% and 9.36%, respectively, at the time of initial HS1. There were 185 survivors following HS1 (91.13%, n = 185/203), while 147 patients underwent comprehensive stage II or bidirectional Glenn shunt (72.41%, n = 147/203). Tricuspid valvuloplasty was undertaken in nine patients (4.86%, n = 9/185). Ultimately, 100 patients underwent the Fontan procedure. The odds of development of significant TR and/or RV dysfunction were not statistically different throughout the stages of palliation (TR: odds ratio [OR] = 0.14-0.25, P = .5260; RV dysfunction: OR = 0.02-0.13, P = .3992). However, the risk of death and/or transplant was 2.5- to 3.8-fold when either were present alone or in combination (TR: OR = 2.58, P = .0356; RV dysfunction: OR = 3.84, P = .0262). Transplant-free survival at 15 years was 44.8%. CONCLUSION: Following hybrid palliation for HLHS, the majority of survivors have normal RV and TV functions. Tricuspid valvuloplasty was required in few patients. Once significant TR and/or RV dysfunction ensues, there is a two- to three-fold risk of death and/or transplant.

Incidence and impact of acute kidney injury in patients with hypoplastic left heart syndrome following the hybrid stage 1 palliation.

OBJECTIVE: Acute kidney injury leads to worse outcomes following paediatric cardiac surgery. There is a lack of literature focusing on acute kidney injury after the Hybrid stage 1 palliation for single ventricle physiology. Patients undergoing the Hybrid Stage 1, as a primary option, may have a lower incidence of kidney injury than previously reported. When present, kidney injury may increase the risk of post-operative morbidity and mortality. METHODS: A retrospective, single centre review was conducted in patients with hypoplastic left heart syndrome who underwent Hybrid Stage 1 from 2008 to 2018. Acute kidney injury was defined as a dichotomous yes (meeting any injury criteria) or no (no injury) utilising two different criteria utilised in paediatrics. The impact of kidney injury on perioperative characteristics and 30-day mortality was analysed. RESULTS: The incidence of acute kidney injury is 13.4-20.7%, with a severe injury rate of 2.4%. Patients without a prenatal diagnosis of hypoplastic left heart syndrome have a higher incidence of kidney injury than those prenatally diagnosed, (40% versus 14.5%, p = 0.024). Patients with acute kidney injury have a significantly higher incidence of 30-day mortality, 27.3%, compared to without, 5.6% (p = 0.047). DISCUSSION: The incidence of severe acute kidney injury after the Hybrid Stage 1 palliation is low. A prenatal diagnosis may be associated with a lower incidence of kidney injury following the Hybrid Stage 1. Though uncommon, severe acute kidney injury following Hybrid Stage 1 may be associated with higher 30-day mortality.

A Pilot Trial Evaluating Stereotactic Body Radiation Therapy to Induce Hyperemia in Combination With Transarterial Chemoembolization for Hepatocellular Carcinoma.

PURPOSE: Despite the survival benefit of transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC), a majority of tumors recur, attributed to hypovascularity and treatment resistance. Preclinical studies show that moderate radiation doses induce changes in tumor permeability and perfusion, suggesting an opportunity for TACE sensitization by radiation. In this prospective phase 1 trial, we evaluated the feasibility, safety, tolerability, response, and functional magnetic resonance imaging (MRI) changes associated with single-fraction stereotactic body radiation therapy (SBRT) followed by TACE within 24 hours. METHODS AND MATERIALS: Patients with HCC, 1 to 3 lesions, Childs-Pugh A/B liver function, and no major vascular invasion were enrolled. The primary objective was to establish the feasibility of single-dose SBRT (7.5 or 10 Gy) followed by TACE within 24 hours. Secondary endpoints included safety, tolerability, perfusional changes via functional MRI, overall response rate (ORR), clinical benefit rate (CBR), freedom from local progression, progression-free survival, and overall survival. RESULTS: Sixteen patients were enrolled, and 13 received SBRT and TACE. Median follow-up was 15.3 months. Best overall ORR and CBR were 76.9% and 92.3%, respectively. The 1- and 3-month ORR was 76.9% and 69.2%, respectively, and 1- and 3-month CBR was 92.3% and 69.2%, respectively. Median overall survival, progression-free survival, and freedom from local progression were 14.0, 5.2, and 5.9 months, respectively. Crude rates of grade 1+ and grade 2+ toxicity were 85% and 38%, respectively. No grade 3 to 4 toxicities were recorded. One grade 5 toxicity occurred due to hemorrhage 4 days after TACE. On dynamic contrast-enhanced MRI, the transfer rate constant from blood plasma to extracellular extravascular space (kpe) increased within 6 hours post-SBRT but decreased by 24 hours. CONCLUSIONS: We hypothesized a strategy of SBRT preceding TACE for the purpose of enhancing TACE delivery and efficacy and tested this strategy in a small pilot study. We found that single-dose SBRT followed by TACE within 24 hours is feasible and tolerable. Dynamic contrast-enhanced MRI revealed acute changes in tumor permeability/perfusion after SBRT. Additional studies are needed to establish the safety and efficacy of this combination and the effects of SBRT on the HCC microenvironment.

Activity of PD1 inhibitor therapy in advanced sarcoma: a single-center retrospective analysis.

BACKGROUND: Sarcomas constitute a heterogeneous group of tumors with different clinical behaviors and variable responses to systemic therapies. Recent immunotherapy studies with PD1 inhibitors (PD1i) show promising results with use in certain soft-tissue sarcomas; however, the clinical and molecular features that best predict response to PD1i remain unclear. METHODS: Demographic, imaging, histologic, and genetic sequencing data was collected for sarcoma patients who received nivolumab or pembrolizumab (PD1i) treatment at our institution between January 1st 2015 and April 23rd 2018. The primary objective was to determine progression-free survival (PFS) in patients with advanced sarcomas receiving PD1i. Secondary objectives included determining overall survival (OS) and assessment of characteristics associated with response to PD1i. Fifty-six patients who were treated with PD1i therapy met inclusion criteria for this study. RESULTS: Partial response towards PD1i treatment was seen in 3 in 26 evaluable patients, but no complete responses were observed (overall response rate 11.5%). Within this group of patients, the 90 day PFS was found to be 48.8%. In patients in whom PD1 expression was known, there was a statistically significant positive correlation between expression of PD1 and longer PFS and OS rates. Patients that were treated with more than four cycles of PD1i therapy were also more likely to have a greater OS. CONCLUSIONS: This study suggests activity of PD1i in a pretreated cohort of advanced sarcoma patients, particularly for the subset of patients with PD1 positive tumors. Our results highlight the importance of further research to better target the optimal patient population and markers of response.

Compliance With Standard Therapies and Remission Rates After Implementation of an Infantile Spasms Management Guideline.

BACKGROUND: We implemented an infantile spasms management guideline recommending standard therapies and, early start of next treatment. After six years, we determined (1) our compliance with standard therapies, (2) time to next treatment, and (3) rate of initial and three-month electroclinical remission with first, second, and third treatments. METHODS: This is a retrospective record review of newly diagnosed spasms from September 2012 to September 2018, with the onset age of two months to two years. RESULTS: Standard therapies (hormone or vigabatrin) were the first treatments in 114 of 115 consecutive patients. The second and third treatments were started within 14 days of failed treatment in only 21% and 24%, respectively. Remission with the first and second treatments was similar (41% and 40%). Remission was lower for the third treatment (15%), although higher if standard therapy was used (36%). Initial and three-month remission by the first treatment was significantly higher for adrenocorticotropic hormone (ACTH, 66% and 79%, respectively) and prednisolone (53% and 83%, respectively) than for vigabatrin (19% and 40%, respectively). There were no significant differences in patient characteristics or rates of remission between ACTH and prednisolone. CONCLUSIONS: Although we achieved excellent compliance with standard therapies as initial treatment, a next treatment often started after two weeks. Given the superiority of hormone therapies over vigabatrin and standard therapies over nonstandard therapies, as well as the potentially negative impact of delays in effective treatment, future interventions need to focus on increasing the use of hormone over vigabatrin (for patients without tuberous sclerosis complex), use of standard therapies as second and third treatments, and reducing delays to next treatment.

Function-switchable metal/semiconductor junction enables efficient photocatalytic overall water splitting with selective water oxidation products.

A novel metal/semiconductor photocatalyst, Cu nanoparticles (NPs) modified TiO2 hollow spheres (Cu/TiO2), was designed for efficient photocatalytic overall water splitting (POWS) under both ultraviolet (UV) and visible (Vis) light. This Cu/TiO2 photocatalyst possesses excellent POWS performance under Vis light at the highest level among the reported TiO2-based photocatalysts. Interestingly, the metal/semiconductor junction formed between Cu and TiO2 enables controlled water-oxidation product selectivity (H2O2 or O2) via different reaction pathways regulated by irradiation wavelengths. Under UV light, the electrons excited in TiO2 are captured by Cu NPs through the Cu/TiO2 Schottky interface for H2 production, with the photoholes in TiO2 producing H2O2 through a two-electron process; whilst under Vis light, Cu NPs act as plasmon to inject hot electrons to TiO2 for H2 production, while O2 is produced by hot holes on Cu NPs via a four-electron process. This rational design of function-switchable metal/semiconductor junction may be helpful to understand the mechanisms for POWS with desired gas/liquid water-oxidation products.

Mode of anesthesia and major perioperative outcomes associated with vaginal surgery.

INTRODUCTION AND HYPOTHESIS: The primary aim was to compare the incidence of major perioperative complications in women undergoing vaginal reconstructive surgery with general, regional, and monitored anesthesia care using a national database. The secondary aim was to compare length of hospital stay, 30-day readmission rates, urinary tract infections, and reoperation rates between anesthesia types. MATERIALS AND METHODS: The National Surgical Quality Improvement Program database was used to study women undergoing vaginal surgery for pelvic floor disorders from 2006 to 2015 via Current Procedural Terminology codes. Demographic and clinical variables were abstracted. The incidence of major perioperative complications was defined as the occurrence of any of the following within 30 days of surgery: death, surgical-site infection, pneumonia, venous thromboembolism, intensive care unit admission, stroke, transfusion, sepsis, and myocardial infarction. Regression analysis was used to estimate the relative risks (RR) associated with anesthesia type for each outcome. RESULTS: From the database, we gathered data on 37,426 women who underwent vaginal reconstructive surgery between 2006 and 2015; 87.2% (n = 32,623) underwent general, 6.9% (n = 2565) regional, and 5.9% (n = 2238) monitored anesthesia care. Major perioperative complications occurred in 560 women (1.5%). Relative to general anesthesia, the adjusted risk of major perioperative complications was not significantly different in those receiving monitored or regional anesthesia [monitored vs. general, adjusted RR 0.74, 95% confidence interval (CI) 0.45-1.20; regional vs. general, adjusted RR 1.23, 95% CI 0.92-1.65]. DISCUSSION: Major perioperative complications in vaginal reconstructive surgery were uncommon, and no differences were observed between monitored, regional, and general anesthesia outcomes.