Slow oscillation-spindle cross-frequency coupling predicts overnight declarative memory consolidation in older adults.

Cross-frequency coupling (CFC) between brain oscillations during non-rapid-eye-movement (NREM) sleep (e.g. slow oscillations [SO] and spindles) may be a neural mechanism of overnight memory consolidation. Declines in CFC across the lifespan might accompany coinciding memory problems with ageing. However, there are few reports of CFC changes during sleep after learning in older adults, controlling for baseline effects. Our objective was to examine NREM CFC in healthy older adults, with an emphasis on spindle activity and SOs from frontal electroencephalogram (EEG), during a learning night after a declarative learning task, as compared to a baseline night without learning. Twenty-five older adults (M [SD] age = 69.12 [5.53] years; 64% female) completed a two-night study, with a pre- and post-sleep word-pair associates task completed on the second night. SO-spindle coupling strength and a measure of coupling phase distance from the SO up-state were both examined for between-night differences and associations with memory consolidation. Coupling strength and phase distance from the up-state peak were both stable between nights. Change in coupling strength between nights was not associated with memory consolidation, but a shift in coupling phase towards (vs. away from) the up-state peak after learning predicted better memory consolidation. Also, an exploratory interaction model suggested that associations between coupling phase closer to the up-state peak and memory consolidation may be moderated by higher (vs. lower) coupling strength. This study supports a role for NREM CFC in sleep-related memory consolidation in older adults.

Visions of TAVR Future: Development and Optimization of a Second Generation Novel Polymeric TAVR.

Tissue-based transcatheter aortic valve (AV) replacement (TAVR) devices have been a breakthrough approach for treating aortic valve stenosis. However, with the expansion of TAVR to younger and lower risk patients, issues of long-term durability and thrombosis persist. Recent advances in polymeric valve technology facilitate designing more durable valves with minimal in vivo adverse reactions. We introduce our second-generation polymeric transcatheter aortic valve (TAV) device, designed and optimized to address these issues. We present the optimization process of the device, wherein each aspect of device deployment and functionality was optimized for performance, including unique considerations of polymeric technologies for reducing the volume of the polymer material for lower crimped delivery profiles. The stent frame was optimized to generate larger radial forces with lower material volumes, securing robust deployment and anchoring. The leaflet shape, combined with varying leaflets thickness, was optimized for reducing the flexural cyclic stresses and the valve's hydrodynamics. Our first-generation polymeric device already demonstrated that its hydrodynamic performance meets and exceeds tissue devices for both ISO standard and patient-specific in vitro scenarios. The valve already reached 900 × 106 cycles of accelerated durability testing, equivalent to over 20 years in a patient. The optimization framework and technology led to the second generation of polymeric TAV design- currently undergoing in vitro hydrodynamic testing and following in vivo animal trials. As TAVR use is rapidly expanding, our rigorous bio-engineering optimization methodology and advanced polymer technology serve to establish polymeric TAV technology as a viable alternative to the challenges facing existing tissue-based TAV technology.

Robust immune responses to SARS-CoV-2 in a pediatric patient with B-Cell ALL receiving tisagenlecleucel.

Recipients of anti-CD19 targeted therapies such as chimeric antigen receptor (CAR)-T cell are considered at high risk for complicated Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection due to prolonged B cell aplasia and immunosuppression. These patients represent a unique cohort and so far, immune responses to SARS-CoV-2 have not been well characterized in this setting. We report a pediatric patient with B-cell acute lymphoblastic leukemia (B-ALL) who had asymptomatic SARS-CoV-2 infection while receiving blinatumomab, followed by lymphodepletion (LD) and tisagenlecleucel, a CD19 targeting CAR-T therapy. The patient had a complete response to tisagenlecleucel, did not develop cytokine release syndrome, or worsening of SARS-CoV-2 during therapy. The patient had evidence of ongoing persistence of IgG antibody responses to spike and nucleocapsid after LD followed by tisagenlecleucel despite the B-cell aplasia. Further we were able to detect SARS-CoV-2 specific T-cells recognizing multiple viral structural proteins for several months following CAR-T. The T-cell response was polyfunctional and predominantly CD4 restricted. This data has important implications for the understanding of SARS-CoV-2 immunity in patients with impaired immune systems and the potential application of SARS-CoV-2-specific T-cell therapeutics to treat patients with blood cancers who receive B cell depleting therapy.

Three-Dimensional Perioral Assessment Following Subnasal Lip Lift.

BACKGROUND: The subnasal lip lift is a surgical technique that elevates the "lip line" (interface between vertical maxillary incisor height and upper lip) to achieve a more youthful aesthetic. OBJECTIVES: The authors sought to offer the first ever definition, to their knowledge, of 3-dimensional (3D) changes to the upper lip due to subnasal lip lift. METHODS: A lip lift procedure was performed (on cadaveric samples) in a sequential manner from 2.5- to 5.0-mm intervals (n = 13). 3D photographs were taken with the VECTRA H1 system (Canfield Scientific, Fairfield, NJ), and 3D analysis was performed including vermillion height and width, philtral height, sagittal lip projection, vermillion surface area, and incisor show. A subset of samples (n = 9) underwent a modification of the technique by undermining the upper lip subcutaneous tissue off the underlying muscular fascia. RESULTS: Vermillion surface area (baseline range, 1.45-5.52 cm2) increased by an average of 20.5% and 43.1% with 2.5-mm and 5.0-mm lip lift, respectively. Anterior projection of the vermillion increased in all cases by an average of 2.13 and 4.07 mm at 2.5 and 5.0 mm, respectively. Philtral height decreased in all cases by an average of 3.37 and 7.23 mm at 2.5 and 5.0 mm, whereas incisal show increased on average of 1.9 and 4.09 mm, respectively. CONCLUSIONS: This study is the first to our knowledge to define the 3D morphometric changes to the upper lip following subnasal lip lift. Quantifying these changes aids the surgeon in preoperative planning and guiding patient expectations.

Patient-specific in vitro testing for evaluating TAVR clinical performance-A complementary approach to current ISO standard testing.

Following in vitro tests established for surgical prosthetic heart valves, transcatheter aortic valves (TAV) are similarly tested in idealized geometries-excluding effects that may hamper TAVR performance in situ. Testing in vitro in pulse duplicator systems that incorporated patient-specific replicas would enhance the testing veracity by bringing it closer to the clinical scenario. To that end we compare TAV hemodynamic performance tested in idealized geometries according to the ISO standard (baseline performance) to that obtained by testing the TAVs following deployment in patient-specific replicas. Balloon-expandable (n = 2) and self-expandable (n = 3) TAVs were tested in an idealized geometry in mock-circulation system (following ISO 5840-3 guidelines) and compared to the measurements in a dedicated mock-circulation system adapted for the five patient-specific replicas. Patient-specific deployments resulted in a decline in performance as compared to the baseline idealized testing, as well as a variation in performance that depended on the design features of each device that was further correlated with the radial expansion and eccentricity of the deployed TAV stent (obtained with CT-scans of the deployed valves). By excluding the deployment effects in irregular geometries, the current idealized ISO testing is limited to characterize the baseline device performance. Utilizing patient-specific anatomic contours provides performance indicators under more stringent conditions likely encountered in vivo. It has the potential to enhance testing and development complementary to the ISO standard, for improved TAV safety and effectiveness.

3D Printed Surgical Guides Applied in Rhinoplasty to Help Obtain Ideal Nasal Profile.

INTRODUCTION: As computer simulation for rhinoplasty continues to rise, the technology's utility extends beyond increasing patient conversion. Virtual simulation of the surgical result can assist with surgical planning and intraoperative decision-making. 3D printed anatomic models or surgical guides based on 3D images may help align surgeons with their original surgical plan. This study aims to evaluate the utility of 3D printed surgical guides as an intraoperative tool to help establish dorsal height and tip position. METHODS: Patients undergoing rhinoplasty had preoperative virtual 3D surgical simulations performed. Simulations were used to create a 3D printed nasal kits containing ceramic models of the preoperative nose and simulated nose, sagittal contour guide, and customized postoperative nasal splint. Nasal guides were sterilized for continual intraoperative assessment of profile contour (i.e., dorsal height and tip position). Postoperative 3D images (1-3 months post-op) were then compared to preoperative simulations. The difference between z coordinates and y coordinates determined the difference in projection and rotation, respectively. RESULTS: Fifteen patients met inclusion criteria for this study. With the use of 3D printed surgical guides, the final tip position was on average of 0.8±0.7mm from simulated projection and 0.3±0.2mm from simulated rotation. Similarly, projection for the cartilaginous and bony dorsum was within 1.0±0.8 and 0.8±0.7mm of the simulation, respectively. CONCLUSION: Virtual simulation is useful in defining aesthetic goals preoperatively, but the potential clinical value extends beyond this. 3D printed rhinoplasty guides extend the simulation's utility to decision-making intraoperatively. This technology offers a novel medium for anatomic reference, which may improve adherence to desired aesthetic goals. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266 .

Optimizing Reconstruction in Craniosynostosis: Review of Nonsyndromic Patients Treated With a Novel Technique.

PURPOSE: Open cranial vault remodeling (CVR) with autologous split calvarial bone grafts redistributes and recontours an abnormal calvarium to create an expanded cranial vault in patients with craniosynostosis. We report a 12-year retrospective review of 162 nonsyndromic patients who underwent operative repair using our previously-described technique which portends excellent surgical outcomes and can be applied to patients of any age group and with any variety of suture fusion. METHODS: Data was gathered on patients who underwent CVR from 2005 to 2016. Surgical records for each patient were analyzed and included operative time, estimated blood loss, and intraoperative transfusion volumes. Intraoperative and postoperative complications, the need for revision surgery, postoperative length of stay, and follow-up records were also reviewed. Syndromic patients were excluded, as well as patients with incomplete data sets. Patients who underwent either anterior or posterior vault remodeling were compared. RESULTS: A total of 162 patients were included in this case series. Patients undergoing anterior CVR were significantly older than those undergoing posterior CVR (13.3 versus 11.0 months, P < 0.015) and also had significantly greater intraoperative red blood transfusion volumes (20.3 versus 15.3cc/kg, P < 0.0207) and longer operative time than posterior CVR patients (274.9 versus 216.7 minutes, P < 0.0001). No patients required reoperation for resorption or recurrence or persistent contour irregularities. There were no visual or neurological complications. Calvarial bone was successfully split in 100% of cases. CONCLUSIONS: This surgical approach to CVR results in good surgical outcomes with a low recurrence rate, while also maximizing operative efficiency, and minimizing total blood loss and transfusion volume. This technique can be applied to any affected suture in a patient with craniosynostosis and in patients of any age group.

Analysis of Immediate versus Delayed Sternal Reconstruction with Pectoralis Major Advancement Versus Turnover Muscle Flaps.

BACKGROUND: The pectoralis major muscle flap is a versatile reconstructive option for deep sternal wound infections (DSWI). The timing and surgical technique of bilateral pectoralis major muscle advancement flaps versus unilateral pectoralis major muscle turnover and unilateral pectoralis major muscle advancement flap on patient outcomes remain to be elucidated. The purpose of this investigation was to compare timing, immediate versus delayed reconstruction, and the surgical technique in patients with deep sternal wounds infections on patient outcomes. METHODS: A retrospective review of patients who underwent sternal reconstruction with pectoralis major muscle was conducted. Patients diagnosed with DSWI after undergoing cardiac surgery were included for analysis. Patients were divided by flap timing and flap type for analyses. Bivariate tests were performed to compare patient clinical characteristics. Outcomes of interest were rates of postoperative complications, same admission mortality, reoperation, readmission, operating room time, and length of stay. RESULTS: A total of 88 patients were included for analyses (n = 57 bilateral advancement, n = 31 unilateral advancement with unilateral turnover; n = 62 immediate, and n = 26 delayed). Baseline characteristics did not differ between groups of flap type or timing. When postoperative complication rates were compared, the rate of tissue necrosis was significantly greater in patients with unilateral advancement with unilateral turnover flaps (n = 6 [19.4%]) compared with bilateral advancement flaps (n = 2 [3.5%]; p = 0.021). Mortality during admission did not differ with respect to flap type but differed significantly with respect to flap timing (immediate n = 7 [11.3%], delayed n = 9 [34.6%]; p = 0.015). Length of stay differed significantly by both type and timing (type: bilateral advancement = 26.9 ± 22.6 days, unilateral turnover = 38.0 ± 26.7 days, p = 0.042; timing: immediate = 26.8 ± 22.1 days, delayed = 40.2 ± 27.8, p = 0.019). CONCLUSION: Patients who underwent pectoralis major muscle advancement flaps had lower incidence of tissue necrosis. Furthermore, the timing of immediate sternal reconstruction was associated with a decreased hospital length of stay.

RELIABILITY OF THE CORTICOTROPIN RELEASING HORMONE STIMULATION TEST FOR DIFFERENTIATING BETWEEN ACTH DEPENDENT AND INDEPENDENT CUSHING SYNDROME.

CONTEXT: It is a challenge to determine the origin of Cushing syndrome (CS), especially in patients with low-normal adrenocorticotropic hormone (ACTH) concentrations. OBJECTIVE: To evaluate the reliability of the corticotropin-releasing hormone (CRH) stimulation test in patients with CS whose origin of disease was not clearly identified using ACTH values, the high-dose dexamethasone suppression test (HDDST), and imaging in a single tertiary referral center. DESIGN AND METHODS: Twenty-one patients with CS who were admitted to the endocrinology-metabolism clinic between 2004 and 2016 whose ACTH concentrations were 5-20 pg/mL and needed CRH stimulation test were retrospectively assessed. RESULTS: Nine out of 21 patients were diagnosed as having Cushing's disease (CD) and 12/21 had adrenal CS. The CRH stimulation test had a sensitivity and specificity of 100% and 8%, and positive and negative predictive values of 100% and 45% according to the current diagnostic criteria, respectively. An increase in ACTH ≥115% at 15 minutes and cortisol ≥86% at 60 minutes after CRH were associated with the highest likelihood ratio. The sensitivity and specificity of ACTH was 67% and 83% (AUC=0.75±0.12, 95% CI: [0.5-0.9]; p=0.03), and for cortisol it was 75% and 78% (AUC=0.71±0.15, 95% CI: [0.5-0.9]; p=0.03). Cortisol suppression of more than 64% from basal level in the HDDST suggested CD with the highest likelihood ratio. When these cut-off values were used together, both tests were negative in the patients with CD. CONCLUSION: The CRH stimulation test has low specificity to localize CS in patients with ACTH concentrations of 5-20 pg/mL according to the current diagnostic criteria. Different diagnostic criteria may be used in the CRH stimulation test and also in the HDDST in this group of patients.

Rank and Research: The Correlation Between Integrated Plastic Surgery Program Reputation and Academic Productivity.

BACKGROUND: Determinants of residency program reputation are multifactorial and include operative training, academic productivity, and geographic location. However, little is known about these relationships. This study aims to investigate the correlation between academic reputation of integrated plastic surgery programs and the research productivity of their respective full time faculty members. METHODS: Program rankings were identified from the 2016 Doximity standings and divided into 4 quartiles (Q1-Q4). Full-time faculty and program directors were identified through program websites. Publications by faculty members from 2000 to 2015 were identified through PubMed. Variables collected included affiliated institution, date of publication, authorship position, and journal. RESULTS: A total of 67 programs with 607 full-time faculty members were identified. Although not significantly different, program directors had a higher mean number of publications compared with faculty members for Q1, Q2, and Q4. Program departmental chairs had a significantly higher mean number of publications for Q1 and Q2. The Q1 faculty had a significantly higher mean number of publications as compared with Q2, Q3, and Q4. Although all quartiles had similar mean first author publications, Q1 and Q2 had more middle and last author publications. In addition, the higher-ranked programs were more likely to have faculty as middle authors of articles with more contributors. They were also more likely to publish in Plastic Reconstructive Surgery compared with other journals. CONCLUSIONS: Academic reputation of integrated plastic surgery residency programs is correlated with the scholarly activity of full-time faculty.

Association of sociodemographic profile, dyslipidemias, and obesity in smoker, former smoker, and nonsmoker patients with coronary artery disease.

INTRODUCTION: In patients with established coronary artery disease (CAD), there are different reports on gender, age, dyslipidemia, and obesity according to smoking behavior. Smoking, obesity, and dyslipidemia are targets in secondary prevention. In this study, we aimed to investigate the sociodemographic differences, lipid profiles, body mass index (BMI), and cigarette smoking status in patients diagnosed with CAD. METHODS: Patients with records of angiography, smoking behavior, sociodemographic information, lipid levels, and BMI present at the outpatient visits were included in the study. Patients were grouped as active smokers, nonsmokers, and former smokers. Statistical methods were used for comparison of variables and means. RESULTS: A total of 235 patients, 167 (71.1%) men and 68 (28.9%) women, were included in the study. Nonsmokers group (31.4%) consisted of mostly women while active (22.6%) and former smoker (46%) groups consisted mostly of men (P < 0.0001). The mean age was 60.65 ± 11.55. Age was associated with the smoking status of patients, and nonsmokers consisted of geriatric patients significantly (P = 0.001). Educational status was associated with smoking history. Cessation of smoking after CAD diagnosis was achieved in 46% of patients. Active smokers had highest mean triglyceride (TG) values while nonsmokers had highest mean high-density lipoprotein-cholesterol (HDL-C) values. Active smokers had the highest mean TG values while nonsmokers had the highest mean HDL-C values. BMI was higher in nonsmokers than active smokers. CONCLUSION: Gender, age, and educational status are determinants of smoking behavior in patients with CAD. BMI is associated with smoking history. In nonsmokers, values of HDL were highest while TG values were lowest. To prevent reoccurring cardiovascular events, young patients and men are two groups which health professionals need to concentrate in motivating to quit smoking.

A comprehensive comparative analysis of treatment modalities for sinonasal malignancies.

BACKGROUND: Sinonasal malignancies are a rare and heterogeneous group of tumors for which there is a paucity of robust data with which to guide management decisions. The authors used the National Cancer Data Base to better understand the presenting characteristics of these tumors and to compare outcomes by treatment modality. METHODS: The National Cancer Data Base was queried for sinonasal malignancies diagnosed between 2004 and 2012. Overall survival was assessed using multivariate analyses and propensity score matching. RESULTS: A total of 11,160 patients were identified for the initial analysis. The majority were male, aged 40 to 69 years, with tumors of the nasal cavity or maxillary sinus. Squamous cell histology was most common. The majority of patients presented with advanced tumor stage but without locoregional lymph node or distant metastases. Treatment modalities were compared for squamous cell carcinomas. In multivariate analysis, compared with surgery alone, patients who received adjuvant radiotherapy (hazard ratio [HR], 0.658 [P<.001]), adjuvant chemoradiotherapy (HR, 0.696 [P = .002]), or neoadjuvant therapy (HR, 0.656 [P = .007]) had improved overall survival. Patients who received radiotherapy alone (HR, 1.294 [P = .001]) or chemotherapy alone (HR, 1.834 [P<.001]) had worse outcomes. These findings were validated in propensity score matching. It is important to note that neoadjuvant chemoradiotherapy was associated with achieving a negative surgical margin (odds ratio, 2.641 [P = .045]). CONCLUSIONS: Surgery is the mainstay of therapy for patients with sinonasal malignancies, but multimodality therapy is associated with improved overall survival. Cancer 2017;123:3040-49. © 2017 American Cancer Society.

Test-Retest Reliability of Pediatric Heart Rate Variability: A Meta-Analysis.

Heart rate variability (HRV), an established index of autonomic cardiovascular modulation, is associated with health outcomes (e.g., obesity, diabetes) and mortality risk. Time- and frequency-domain HRV measures are commonly reported in longitudinal adult and pediatric studies of health. While test-retest reliability has been established among adults, less is known about the psychometric properties of HRV among infants, children, and adolescents. The objective was to conduct a meta-analysis of the test-retest reliability of time- and frequency-domain HRV measures from infancy to adolescence. Electronic searches (PubMed, PsycINFO; January 1970-December 2014) identified studies with nonclinical samples aged ≤ 18 years; ≥ 2 baseline HRV recordings separated by ≥ 1 day; and sufficient data for effect size computation. Forty-nine studies (N = 5,170) met inclusion criteria. Methodological variables coded included factors relevant to study protocol, sample characteristics, electrocardiogram (ECG) signal acquisition and preprocessing, and HRV analytical decisions. Fisher's Z was derived as the common effect size. Analyses were age-stratified (infant/toddler < 5 years, n = 3,329; child/adolescent 5-18 years, n = 1,841) due to marked methodological differences across the pediatric literature. Meta-analytic results revealed HRV demonstrated moderate reliability; child/adolescent studies (Z = 0.62, r = 0.55) had significantly higher reliability than infant/toddler studies (Z = 0.42, r = 0.40). Relative to other reported measures, HF exhibited the highest reliability among infant/toddler studies (Z = 0.42, r = 0.40), while rMSSD exhibited the highest reliability among child/adolescent studies (Z = 1.00, r = 0.76). Moderator analyses indicated greater reliability with shorter test-retest interval length, reported exclusion criteria based on medical illness/condition, lower proportion of males, prerecording acclimatization period, and longer recording duration; differences were noted across age groups. HRV is reliable among pediatric samples. Reliability is sensitive to pertinent methodological decisions that require careful consideration by the researcher. Limited methodological reporting precluded several a priori moderator analyses. Suggestions for future research, including standards specified by Task Force Guidelines, are discussed.

Spindle Oscillations in Sleep Disorders: A Systematic Review.

Measurement of sleep microarchitecture and neural oscillations is an increasingly popular technique for quantifying EEG sleep activity. Many studies have examined sleep spindle oscillations in sleep-disordered adults; however reviews of this literature are scarce. As such, our overarching aim was to critically review experimental studies examining sleep spindle activity between adults with and without different sleep disorders. Articles were obtained using a systematic methodology with a priori criteria. Thirty-seven studies meeting final inclusion criteria were reviewed, with studies grouped across three categories: insomnia, hypersomnias, and sleep-related movement disorders (including parasomnias). Studies of patients with insomnia and sleep-disordered breathing were more abundant relative to other diagnoses. All studies were cross-sectional. Studies were largely inconsistent regarding spindle activity differences between clinical and nonclinical groups, with some reporting greater or less activity, while many others reported no group differences. Stark inconsistencies in sample characteristics (e.g., age range and diagnostic criteria) and methods of analysis (e.g., spindle bandwidth selection, visual detection versus digital filtering, absolute versus relative spectral power, and NREM2 versus NREM3) suggest a need for greater use of event-based detection methods and increased research standardization. Hypotheses regarding the clinical and empirical implications of these findings, and suggestions for potential future studies, are also discussed.

Effect of teleradiology upon pattern of transfer of head injured patients from a rural general hospital to a neurosurgical referral centre: follow-up study.

INTRODUCTION: The optimal management strategy for patients with head injury admitted to a non-specialist hospital is uncertain. The aim of this study was to evaluate the outcomes of victims of head injury requiring hospitalisation but initially admitted to a rural level II trauma centre without a neurosurgical facility but with a system for neurosurgical consultation via teleradiology. METHODS: Patients admitted for head injury during 2006-2011 were included. Late transfer of patients initially hospitalised in the level II trauma centre was evaluated for treatment failure, defined as clinical or radiological deterioration. RESULTS: Five hundred and sixty-two patients were initially hospitalised in the level II trauma centre. Evaluation of late transfers showed that only 23 (4.1%) represented real treatment failures due to clinical or radiological deterioration. The clinical course was altered by primary intent to hospitalise patients in the level II trauma centre in only one patient. CONCLUSIONS: Selected patients with head trauma who have a pathological CT scan may be safely managed in level II trauma centres following neurosurgical consultation using teleradiology. Review of treatment failures is necessary to ensure proper ongoing management of a system in which neurosurgical patients are selectively transferred to trauma centres with neurosurgical capacity.

Putting our heads together: The future of craniopagus twin separation.

Computer-assisted design and computer-assisted modeling (CAD/CAM), virtual surgical planning (VSP) and augmented/virtual reality (AR/VR) aid our ability to plan and perform complex craniofacial procedures. This study seeks to define the role of the aforementioned techniques in the separation of craniopagus conjoined twins. Six teams were identified who had successfully performed craniopagus twin separation with the use of CAD/CAM, VSP and/or AR/VR. Surgeons involved in separating craniopagus twins have increasingly utilized tools such as CAD/CAM models, VSP and AR/VR to plan and execute successful separation, and these tools are associated with higher success rates than historical controls.