Temporal Changes in the Retinal Pigment Epithelium-Bruch's Membrane Complex Thickness After Autologous Retinal Transplantation in Myopic Eyes.

Purpose: To investigate the association between the thickness of the retinal pigment epithelium (RPE)-Bruch's membrane (BM) complex and the development of retinal autograft edema as a postoperative complication following autologous retinal transplantation (ART). Methods: This retrospective study examined data from 28 eyes of 28 patients (14 males, 14 females; mean age, 61.5 ± 19.8 years) who underwent ART and were followed for 1 year. The RPE-BM complex thickness was measured 2000 µm from the fovea using Image J software. Additionally, the graft blood flow was also evaluated by optical coherence tomography angiography and fluorescein angiography. Results: Macular hole (MH) diameters ranged from 711.2 ± 251.9 µm to 1299.9 ± 333.0 µm, with MH closure achieved in all patients. RPE-BM complex thickness decreased by 4.17 µm at 6 months and 4.34 µm at 1 year, showing significant differences from preoperative measurements (29.88 ± 4.99 µm; 6 months: 95% confidence interval [CI], 1.62-6.71, P = 0.0018; 1 year: 95% CI, 2.03-6.65 µm, P = 0.00044). The decrease was significantly greater in the edema-positive group (95% CI, -8.33 to -0.82, P = 0.020). Furthermore, the rates of ellipsoid zone (EZ) recovery, alignment of neurosensory layers (ANL), and graft reperfusion were lower in the edema-positive group (EZ, P = 0.017; ANL, P = 0.0098; reperfusion, P = 0.039). Conclusions: After ART, RPE-BM complex thickness decreases, particularly in cases with postoperative edema, suggesting a potential relationship between RPE function and postoperative outcomes, highlighting the importance of monitoring RPE-BM complex thickness after surgery.

Clinical Outcomes and Targeted Genomic Analysis of Renal Cell Carcinoma Brain Metastases Treated with Stereotactic Radiosurgery.

BACKGROUND: Molecular profiles of renal cell carcinoma (RCC) brain metastases (BMs) are not well characterized. Effective management with locoregional therapies, including stereotactic radiosurgery (SRS), is critical as systemic therapy advancements have improved overall survival (OS). OBJECTIVE: To identify clinicogenomic features of RCC BMs treated with SRS in a large patient cohort. DESIGN, SETTING, AND PARTICIPANTS: A single-institution retrospective analysis was conducted of all RCC BM patients treated with SRS from January 1, 2010 to March 31, 2021. INTERVENTION: SRS for RCC BMs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Next-generation sequencing was performed to identify gene alterations more prevalent in BM patients. Clinical factors and genes altered in ≥10% of samples were assessed per patient using Cox proportional hazards models and per individual BM using clustered competing risks regression with competing risk of death. RESULTS AND LIMITATIONS: Ninety-one RCC BM patients underwent SRS to 212 BMs, with a median follow-up of 38.8 mo for patients who survived. The median intracranial progression-free survival and OS were 7.8 (interquartile range [IQR] 5.7-11) and 21 (IQR 16-32) mo, respectively. Durable local control of 83% was achieved at 12 mo after SRS, and 59% of lesions initially meeting the radiographic criteria for progression at 3-mo evaluation would be considered to represent pseudoprogression at 6-mo evaluation. A comparison of genomic alterations at both the gene and the pathway level for BM+ patients compared with BM- patients revealed phosphoinositide 3-kinase (PI3K) pathway alterations to be more prevalent in BM+ patients (43% vs 16%, p = 0.001, q = 0.01), with the majority being PTEN alterations (17% vs 2.7%, p = 0.003, q = 0.041). CONCLUSIONS: To our knowledge, this is the largest study investigating genomic profiles of RCC BMs and the only such study with annotated intracranial outcomes. SRS provides durable in-field local control of BMs. Recognizing post-SRS pseudoprogression is crucial to ensure appropriate management. The incidence of PI3K pathway alterations is more prevalent in BM+ patients than in BM- patients and warrants further investigation in a prospective setting. PATIENT SUMMARY: We examined the outcomes of radiotherapy for the treatment of brain metastases in kidney cancer patients at a single large referral center. We found that radiation provides good control of brain tumors, and certain genetic mutations may be found more commonly in patients with brain metastasis.

Relationships between depression, anxiety, and motivation in the real-world: Effects of physical activity and screentime.

Background: Mood and anxiety disorders are highly prevalent and comorbid worldwide, with variability in symptom severity that fluctuates over time. Digital phenotyping, a growing field that aims to characterize clinical, cognitive and behavioral features via personal digital devices, enables continuous quantification of symptom severity in the real world, and in real-time. Methods: In this study, N=114 individuals with a mood or anxiety disorder (MA) or healthy controls (HC) were enrolled and completed 30-days of ecological momentary assessments (EMA) of symptom severity. Novel real-world measures of anxiety, distress and depression were developed based on the established Mood and Anxiety Symptom Questionnaire (MASQ). The full MASQ was also completed in the laboratory (in-lab). Additional EMA measures related to extrinsic and intrinsic motivation, and passive activity data were also collected over the same 30-days. Mixed-effects models adjusting for time and individual tested the association between real-world symptom severity EMA and the corresponding full MASQ sub-scores. A graph theory neural network model (DEPNA) was applied to all data to estimate symptom interactions. Results: There was overall good adherence over 30-days (MA=69.5%, HC=71.2% completion), with no group difference (t(58)=0.874, p=0.386). Real-world measures of anxiety/distress/depression were associated with their corresponding MASQ measure within the MA group (t's > 2.33, p's < 0.024). Physical activity (steps) was negatively associated with real-world distress and depression (IRRs > 0.93, p's ≤ 0.05). Both intrinsic and extrinsic motivation were negatively associated with real-world distress/depression (IRR's > 0.82, p's < 0.001). DEPNA revealed that both extrinsic and intrinsic motivation significantly influenced other symptom severity measures to a greater extent in the MA group compared to the HC group (extrinsic/intrinsic motivation: t(46) = 2.62, p < 0.02, q FDR < 0.05, Cohen's d = 0.76; t(46) = 2.69, p < 0.01, q FDR < 0.05, Cohen's d = 0.78 respectively), and that intrinsic motivation significantly influenced steps (t(46) = 3.24, p < 0.003, q FDR < 0.05, Cohen's d = 0.94). Conclusions: Novel real-world measures of anxiety, distress and depression significantly related to their corresponding established in-lab measures of these symptom domains in individuals with mood and anxiety disorders. Novel, exploratory measures of extrinsic and intrinsic motivation also significantly related to real-world mood and anxiety symptoms and had the greatest influencing degree on patients' overall symptom profile. This suggests that measures of cognitive constructs related to drive and activity may be useful in characterizing phenotypes in the real-world.

Insurance Denials and Patient Treatment in a Large Academic Radiation Oncology Center.

Importance: Insurance barriers to cancer care can cause significant patient and clinician burden. Objective: To investigate the association of insurance denial with changes in technique, dose, and time to delivery of radiation oncology treatment. Design, Setting, and Participants: In this single-institution cohort analysis, data were collected from patients with payer-denied authorization for radiation therapy (RT) from November 1, 2021, to December 8, 2022. Data were analyzed from December 15, 2022, to December 31, 2023. Exposure: Insurance denial for RT. Main Outcomes and Measures: Association of these denials with changes in RT technique, dose, and time to treatment delivery was assessed using χ2 tests. Results: A total of 206 cases (118 women [57.3%]; median age, 58 [range, 26-91] years) were identified. Most insurers (199 [96.6%]) were commercial payers, while 7 (3.4%) were Medicare or Medicare Advantage. One hundred sixty-one patients (78.2%) were younger than 65 years. Of 206 cases, 127 (61.7%) were ultimately authorized without any change to the requested RT technique or prescription dose; 56 (27.2%) were authorized after modification to RT technique and/or prescription dose required by the payer. Of 21 cases with required prescription dose change, the median decrease in dose was 24.0 (range, 2.3-51.0) Gy. Of 202 cases (98.1%) with RT delivered, 72 (34.9%) were delayed for a mean (SD) of 7.8 (9.1) days and median of 5 (range, 1-49) days. Four cases (1.9%) ultimately did not receive any authorization, with 3 (1.5%) not undergoing RT, and 1 (0.5%) seeking treatment at another institution. Conclusions and Relevance: In this cohort study of patients with payer-denied cases, most insurance denials in radiation oncology were ultimately approved on appeal; however, RT technique and/or effectiveness may be compromised by payer-mandated changes. Further investigation and action to recognize the time and financial burdens on clinicians and clinical effects on patients caused by insurance denials of RT is needed.

Spatial confinement affects the heterogeneity and interactions between shoaling fish.

Living objects are able to consume chemical energy and process information independently from others. However, living objects can coordinate to form ordered groups such as schools of fish. This work considers these complex groups as living materials and presents imaging-based experiments of laboratory schools of fish to understand how activity, which is a non-equilibrium feature, affects the structure and dynamics of a group. We use spatial confinement to control the motion and structure of fish within quasi-2D shoals of fish and use image analysis techniques to make quantitative observations of the structures, their spatial heterogeneity, and their temporal fluctuations. Furthermore, we utilize Monte Carlo simulations to replicate the experimentally observed data which provides insight into the effective interactions between fish and confirms the presence of a confinement-based behavioral preference transition. In addition, unlike in short-range interacting systems, here structural heterogeneity and dynamic activities are positively correlated as a result of complex interplay between spatial arrangement and behavioral dynamics in fish collectives.

Clinical outcomes of stereotactic body radiation therapy for malignant pleural mesothelioma.

BACKGROUND: The objective of this study is to determine the outcomes and toxicities of patients with malignant pleural mesothelioma (MPM) treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Data were extracted from an institutional tumor registry for patients diagnosed with mesothelioma and treated with SBRT. Kaplan-Meier and Cox regression analyses were employed to determine local control (LC) and overall survival (OS). RESULTS: Forty-four patients with 59 total treated tumors from December 2006 to April 2022 were identified. Fifty-one (86.4 %) cases had oligoprogressive disease (five sites or less). The median prescription dose delivered was 3000 cGy in 5 fractions (range: 2700-6000 cGy in 3-8 fractions). Fifty-one (86.4 %) tumors were in the pleura, 4 (6.8 %) spine, 2 (3.4 %) bone, 1 (1.7 %) brain, and 1 (1.7 %) pancreas. The median follow-up from SBRT completion for those alive at last follow-up was 28 months (range: 14-52 months). The most common toxicities were fatigue (50.8 %), nausea (22.0 %), pain flare (15.3 %), esophagitis (6.8 %), dermatitis (6.8 %), and pneumonitis (5.1 %). There were no grade ≥ 3 acute or late toxicities. There were 2 (3.4 %) local failures, one of the pleura and another of the spine. One-year LC was 92.9 % (95 % CI: 74.6-98.2 %) for all lesions and 96.3 % (95 % CI: 76.5-99.5 %) for pleural tumors. One-year LC was 90.9 % (95 % CI: 68.1-97.6 %) for epithelioid tumors and 92.1 % (95 % CI: 72.1-98.0 %) for oligoprogressive tumors. One-year OS from time of SBRT completion was 36.4 % (95 % CI: 22.6-50.3 %). On multivariable analysis, KPS was the lone significant predictor for OS (p = 0.029). CONCLUSIONS: Our single-institutional experience on patients with MPM suggests that SBRT is safe with a low toxicity profile and potentially achieve good local control.

Film Coatings Based on Aqueous Shellac Ammonium Salt "Swanlac® ASL 10" and Inulin for Colon Targeting.

Over the past decades, increasing interests took place in the realm of drug delivery systems. Beyond treating intestinal diseases such as inflammatory bowel disease, colon targeting can provide possible applications for oral administration of proteins as well as vaccines due to the lower enzymatic activity in the distal part of GIT. To date, many strategies are employed to reach the colon. This article encompasses different biomaterials tested as film coatings and highlights appropriate formulations for colonic drug delivery. A comparison of different films was made to display the most interesting drug release profiles. These films contained ethylcellulose, as a thermoplastic polymer, blended with an aqueous shellac ammonium salt solution. Different blend ratios were selected as well for thin films as for coated mini-tablets, mainly varying as follows: (80:20); (75:25); (60:40). The impact of blend ratio and coating level was examined as well as the addition of natural polysaccharide "inulin" to target the colon. In vitro drug release was measured in 0.1 M HCl for 2 h followed by phosphate buffer saline pH 6.8 to simulate gastric and intestinal fluids, respectively. Coated mini-tablets were exposed to fresh fecal samples of humans in order to simulate roughly colonic content. Several formulations were able to fully protect theophylline as a model drug up to 8 h in the upper GIT, but allowing for prolonged release kinetics in the colon. These very interesting colonic release profiles were related to the amount of the natural polysaccharide added into the system.

Evaluation of a semi-automated approach for FDG PET image analysis for routine clinical application in patients with multiple myeloma.

BACKGROUND: FDG PET/CT is a tool for assessing response to therapy in various cancers, and may provide an earlier biomarker of clinical response. We developed a novel semi-automated approach for analyzing FDG PET/CT images in patients with multiple myeloma (MM) to standardize FDG PET application. METHODS: Patients (n = 8) with relapsed/refractory MM from the Phase 2 study (NCT02899052) of venetoclax plus carfilzomib and dexamethasone underwent FDG PET/CT at baseline and up to two timepoints during treatment. Images were processed using an established automated segmentation algorithm, with the modification that a red marrow region in an unaffected lumbar vertebra was used to define background standardized uptake value normalized to lean body mass (SUL) threshold above which uptake was considered disease-specific uptake. This approach was compared to lesion segmentation, and to International Myeloma Working Group (IMWG) response criteria, including minimal residual disease (MRD). RESULTS: The two FDG PET analysis techniques agreed on evaluation of patient-level SULpeak for 67% of scans. In the metabolic response assessment per PET Response Criteria in Solid Tumors (PERCIST), the two techniques agreed in 75% of patients. Differences between techniques occurred in low-uptake lesions due to greater reader sensitivity to lesions with uptake marginally above background. PERCIST outcomes were generally in agreement with IMWC and MRD. CONCLUSIONS: This semi-automated analysis was in high agreement with standard approaches for detecting response to MM therapy. This proof-of-concept study suggests that larger studies should be conducted to confirm how FDG PET analysis may aid early response detection in MM.

Lipoprotein-X: A Case of Falsely Elevated LDL Hypercholesterolemia.

Lipoprotein-X is an extremely rare cause of severe hyperlipidemia. We present a case of a 26-year-old man with primary sclerosing cholangitis who developed lipoprotein X-induced pseudohyponatremia with severe hyponatremia. In this case report, we also discuss the diagnostic approach and the treatment for lipoprotein X. (Level of Difficulty: Advanced.).

Clinical Outcomes and Complications of Primary Fingertip Reconstruction Using a Reverse Homodigital Island Flap: A Systematic Review.

BACKGROUND: Reverse homodigital island flaps (RHIFs) are increasingly used to reconstruct traumatic fingertip injuries, but there is limited evidence on the efficacy of this technique. We performed a systematic review of the literature to establish the safety and functional outcomes of RHIF for traumatic fingertip injuries. METHODS: Electronic searches were performed using 3 databases (PubMed, Ovid Medline, Cochrane CENTRAL) from their date of inception to April 2020. Relevant studies were required to report on complications and functional outcomes for patients undergoing RHIF for primary fingertip reconstruction. Data were extracted from included studies and analyzed. RESULTS: Sixteen studies were included, which produced a total cohort of 459 patients with 495 fingertip injuries. The index and middle fingers were involved most frequently (34.6% and 34.1%, respectively), followed by the ring finger (22%), the little finger (6.7%), and the thumb (2.6%). The mean postoperative static and moving 2-point discrimination was 7.2 and 6.7 mm, respectively. The mean time to return to work was 8.4 weeks. The mean survivorship was 98.4%, with the pooled complication rate being 28%. The pooled complication rate of complete flap necrosis was 3.6%, of partial flap necrosis was 10.3%, of venous congestion was 14.6%, of pain or hypersensitivity was 11.5%, of wound infection was 7.2%, of flexion contractures was 6.3%, and of cold intolerance was 17.7%. CONCLUSIONS: Reverse homodigital island flaps can be performed safely with excellent outcomes. To minimize complications, care is taken during dissection and insetting, with extensive rehabilitation adhered to postoperatively. Prospective studies assessing outcomes of RHIF compared with other reconstruction techniques would be beneficial.

Regional Pain Blocks and Perioperative Pain Control in Patients Undergoing Breast Implant Removal With Capsulectomy.

Background: Demand for breast implant removal is on the rise, with more than 36,000 explants performed in 2020, an increase of 7.5% from previous years. Postoperative (PO) analgesia is an important consideration in this patient group due to scar tissue surrounding the implant and the potential for extensive dissection during capsulectomy. Objectives: The authors sought to compare perioperative pain control between three different types of ultrasound (US)-guided regional anesthetic techniques in patients undergoing implant removal with capsulectomy. Methods: The authors reviewed all patients who received an US-guided block and underwent breast implant removal with capsulectomy at their outpatient surgical center over a 2-year period. They compared intraoperative (IO), PO opioid requirement, and patient-reported pain on the first postoperative day (POD1) between 3 different block techniques using chi-square analysis. A P-value of <.05 was considered statistically significant. Results: A total of 352 patients were included. Twenty-six patients (7.4%) underwent a serratus plane (SP) block, 13 (3.7%) underwent an erector spinae combined with pectointercostal fascial plane (ES + PIFP) block, and 313 (88.9%) underwent an erector spinae combined with pectoral nerve (ES + PECS1) block. ES + PECS1 was associated with less IO and PO opioid use compared with SP and ES + PIFP (1.9% vs 19.2% vs 61.5%, P < .001 for IO, 26.8% vs 34.6% vs 38.5% PO, P < .001). The ES + PECS1 block was associated with mild pain on POD1 compared with the other 2 regional block techniques (P = .001). Conclusions: Regional pain blocks, and specifically the ES block, offer effective pain control for patients undergoing breast implant removal with capsulectomy, demonstrating high patient satisfaction in the PO period with low opioid requirements.

A highly sensitive cell-based luciferase assay for high-throughput automated screening of SARS-CoV-2 nsp5/3CLpro inhibitors.

Effective drugs against SARS-CoV-2 are urgently needed to treat severe cases of infection and for prophylactic use. The main viral protease (nsp5 or 3CLpro) represents an attractive and possibly broad-spectrum target for drug development as it is essential to the virus life cycle and highly conserved among betacoronaviruses. Sensitive and efficient high-throughput screening methods are key for drug discovery. Here we report the development of a gain-of-signal, highly sensitive cell-based luciferase assay to monitor SARS-CoV-2 nsp5 activity and show that it is suitable for the screening of compounds in a 384-well format. A benefit of miniaturisation and automation is that screening can be performed in parallel on a wild-type and a catalytically inactive nsp5, which improves the selectivity of the assay. We performed molecular docking-based screening on a set of 14,468 compounds from an in-house chemical database, selected 359 candidate nsp5 inhibitors and tested them experimentally. We identified two molecules which show anti-nsp5 activity, both in our cell-based assay and in vitro on purified nsp5 protein, and inhibit SARS-CoV-2 replication in A549-ACE2 cells with EC50 values in the 4-8 µM range. The here described high-throughput-compatible assay will allow the screening of large-scale compound libraries for SARS-CoV-2 nsp5 inhibitors. Moreover, we provide evidence that this assay can be adapted to other coronaviruses and viruses which rely on a viral protease.

Clinical Outcomes of Dose-Escalated Hypofractionated External Beam Radiation Therapy (5 Gy × 5 Fractions) for Spine Metastasis.

Purpose: The objective of this study was to determine the toxicities and outcomes of patients with spinal metastasis treated with external beam radiation therapy (EBRT) to 25 Gy in 5 fractions. Methods and Materials: Data were extracted from an institutional tumor registry for patients with spinal metastasis who were treated with EBRT to 25 Gy in 5 fractions to their spinal lesion(s). Cox regression and Kaplan-Meier analyses to determine local control and overall survival (OS) were employed. Results: Seventy-five patients with 86 total treated spinal metastatic tumors were identified. The median follow-up was 7 months. The median age was 66 years. Fifty-six patients (75.7%) experienced partial or complete pain relief for a median duration of 6 months (range, 1-33). Fifty-one (59.3%) cases were planned using intensity modulated radiation therapy while 19 (22.1%) employed 3-dimensional conformal radiation therapy and 16 (18.6%) cases used nonconformal radiation technique. Greater than 90% of cases had a point dose maximum to the spinal cord/cauda equina <27.5 Gy. No patient experienced treatment-related myelopathy. The most common toxicities were fatigue (23.3%), pain flare (14.0%), and nausea (8.1%). There were no grade 3 toxicities. One-year local control was 80.6%, and 1-year OS was 38.4%. Higher Karnofsky performance status (P = .001) and radiosensitive tumor histology (P = .014) were significant predictors for better OS. Conclusions: Our single-institutional retrospective analysis of patients with spinal metastasis suggested that palliative EBRT to 25 Gy in 5 fractions is safe, with a low toxicity profile and minimal risk for myelopathy with an achievable dose maximum to the spinal cord and cauda equina ≤27 Gy (equivalent total dose in 2-Gy fractions ≤50 Gy), and it may provide durable palliation and local control in cases where stereotactic body radiation therapy may not be indicated.

Occupational Radiation Exposure Among General Surgery Residents: Should We Be Concerned?

BACKGROUND: Low-dose ionizing radiation exposure is associated with development of solid organ tumors as well as increased risk of cataract formation in a linear-dose response. While occupational radiation exposure has been studied across subspecialties with regular fluoroscopy exposure such as interventional radiology and urology, the contribution of increasing endovascular case volume to occupational radiation exposure among general surgery residents remains largely unreported. In this study, we sought to determine typical occupational radiation exposure among a pool of general surgery residents as part of a formal radiation safety curriculum. METHODS: A radiation safety program was introduced to a group of 28 general surgery residents who rotate on a vascular surgery service with a high endovascular volume in a hybrid room setting. All residents received training in proper use of a radiation dosimeter and minimizing exposure during fluoroscopy times in the operating room. Data was collected from radiation film dosimetry badges distributed to general surgery residents on a bimonthly basis throughout the year, and radiation exposure in mRem was compared between residents rotating on vascular and nonvascular surgical services during 4-week rotations. RESULTS: A total of 14 months of data were collected. Resident compliance was 84% with regular use and return of dosimeters at the end of each bimonthly cycle. The radiation exposure among residents rotating on vascular surgery was significantly higher compared to those on nonvascular rotations (mean = 71 mRem vs 3.13 mRem, p = 0.02). Exposure among senior residents was not statistically different than that of attending vascular surgeons (mean = 212 mRem vs 164 mRem, p = 0.20). All exposures were significantly lower than institutional ALARA dose limits for radiation exposure (5000 mRem/year). CONCLUSION: General surgery residents are routinely exposed to measurable occupational radiation levels, especially while participating in endovascular procedures during their training. However, data from our study suggests that these levels are below ALARA dose limits and senior surgical residents are not at greater risk than vascular surgery attending surgeons while on their vascular rotation. The results of this study will be used to help guide resident education on radiation safety and identify institution-specific practices which can minimize exposure and improve radiation safety adherence.

Fontan operation at less than 3 years of age is not a risk factor for long-term failure.

OBJECTIVES: The age at which the Fontan operation is performed varies globally. Over the last decade, the median age of patients having the Fontan in Australia and New Zealand has been 4.6 years, including 6% of patients younger than 3 years. Long-term outcomes of an early Fontan operation are unclear and are described in this study. METHODS: Patients from the Australian and New Zealand Fontan Registry were grouped by age at Fontan. A Fontan before 3 years (early Fontan) was compared to the combined second and third quartiles by age at surgery in the Registry (3.6-6.1 years; control). Outcomes included Fontan failure (death, transplant, New York Heart Association functional group III/IV heart failure, Fontan takedown or conversion, protein losing enteropathy and plastic bronchitis), arrhythmias, thromboembolism and reinterventions. RESULTS: A total of 191 patients who had early Fontan operations were compared to 781 controls. Profound or progressive cyanosis was noted more frequently in the early than in the control group (63% vs 23%; P < 0.001). The early group was followed up for a median 22.1 years. The incidence of long-term failure was similar between the 2 groups (early, 1.08 failures per 100 patient-years of follow-up vs control, 0.99; log-rank P = 0.79). Adjusted for risk factors, early age at Fontan was not a risk factor for long-term failure [hazard ratio (HR) 1.16, 95% confidence interval (CI) 0.77-1.76; P = 0.48], new-onset arrhythmia (HR 0.93, 95% CI 0.63-1.39; P = 0.73), thromboembolism (HR 0.50, 95% CI 0.28-0.91; P = 0.024) or reintervention (HR 1.08, 95% CI 0.80-1.45; P = 0.62). CONCLUSIONS: Having the Fontan operation at an early age was not a risk factor for short- or long-term adverse outcomes in our cohort.

Postoperative Complications Associated with the Choice of Reconstruction in Head and Neck Cancer: An Outcome Analysis of 4,712 Patients from the ACS-NSQIP Database.

BACKGROUND: Microsurgical free flaps have largely supplanted pedicled flaps as the gold standard for head and neck cancer reconstruction. However, incidence of postoperative complications after accounting for patient comorbidities based on choice of reconstruction has not been well-defined in the literature in recent years. METHODS: Patients undergoing head and neck reconstruction were identified in the 2011-2016 ACS-NSQIP (American College of Surgeons National Surgical Quality Improvement Program) database and stratified into groups by free flap, myocutaneous pedicled flap, and other reconstruction. Demographics were analyzed and covariates balanced using overlap propensity score-based weighting. Logistic regression was used for binary outcomes and Gamma generalized linear model was used for length of stay. RESULTS: A total of 4,712 patients met inclusion criteria out of which 1,297 patients (28%) underwent free flap, 208 patients (4%) pedicled flap, and 3,207 patients (68%) had other, or no reconstruction performed. After adjusting for patient and disease-specific factors, pedicled flap reconstruction was associated with a higher risk of deep vein thrombosis (odds ratio [OR] = 2.64, confidence interval [CI] 1.02-6.85, p = 0.045), sepsis (OR = 2.95, CI 1.52-5.71, p = 0.001), and infection (OR = 2.03, CI 1.39-2.96, p <0.001) compared with free flap reconstruction. Free flaps had the longest mean operative time compared with the other two groups (unadjusted 578 vs. 440 vs. 326, p <0.001). Pedicled flaps had a lower incidence of bleeding requiring transfusion (adjusted OR = 0.65, CI 0.50-0.85, p = 0.002), and lower incidence of prolonged mechanical ventilation (adjusted OR = 0.33, CI 0.12-0.92, p = 0.034) compared with free flaps. There was no difference in rates of reoperation, hospital readmission, or hospital length-of-stay between pedicled and free flaps. CONCLUSION: Myocutaneous pedicled flaps are associated with higher overall short-term postoperative complications compared with free flaps in head and neck reconstruction, which demonstrate a more favorable morbidity profile without significantly impacting hospital readmission, reoperation, or length-of-stay.

Metabolic Reprogramming of Nasal Airway Epithelial Cells Following Infant Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) is a seasonal mucosal pathogen that infects the ciliated respiratory epithelium and results in the most severe morbidity in the first six months of life. RSV is a common cause of acute respiratory infection during infancy and is an important early-life risk factor strongly associated with asthma development. While this association has been repeatedly demonstrated, limited progress has been made on the mechanistic understanding in humans of the contribution of infant RSV infection to airway epithelial dysfunction. An active infection of epithelial cells with RSV in vitro results in heightened central metabolism and overall hypermetabolic state; however, little is known about whether natural infection with RSV in vivo results in lasting metabolic reprogramming of the airway epithelium in infancy. To address this gap, we performed functional metabolomics, 13C glucose metabolic flux analysis, and RNA-seq gene expression analysis of nasal airway epithelial cells (NAECs) sampled from infants between 2-3 years of age, with RSV infection or not during the first year of life. We found that RSV infection in infancy was associated with lasting epithelial metabolic reprogramming, which was characterized by (1) significant increase in glucose uptake and differential utilization of glucose by epithelium; (2) altered preferences for metabolism of several carbon and energy sources; and (3) significant sexual dimorphism in metabolic parameters, with RSV-induced metabolic changes most pronounced in male epithelium. In summary, our study supports the proposed phenomenon of metabolic reprogramming of epithelial cells associated with RSV infection in infancy and opens exciting new venues for pursuing mechanisms of RSV-induced epithelial barrier dysfunction in early life.

Outcomes of Implant Removal and Capsulectomy for Breast Implant Illness in 248 Patients.

BACKGROUND: Breast implant illness (BII) is a term popularized by social media to describe systemic symptoms that patients ascribe to their breast implants. Though the concept of implants as an underlying cause for a systemic illness remains controversial, few studies have delineated the implant characteristics, capsular histology, and outcomes of patients who undergo explantation for BII. METHODS: We retrospectively reviewed the demographics, presenting symptoms, outcomes, capsular histology, and culture results of all women who presented to the senior author with symptoms attributed to BII and underwent breast implant removal with capsulectomy from August 2016 to February 2020. Chi-square and logistic regression analyses were performed to evaluate association between implant type, composition, and findings of inflammation on capsule pathology. RESULTS: Among 248 patients, 111 (23%) capsules demonstrated inflammatory changes on permanent pathology. Capsular inflammation was independently associated with silicone versus saline (right odds ratio [OR] = 2.18 [1.16-4.11], P = 0.016, left OR = 2.35 [1.08-5.12], P = 0.03) and textured versus smooth implants (right OR = 2.18 [1.16-4.11], P = 0.016, left OR = 2.25 [1.17-4.31], P = 0.01). Silicone material was present in the capsules of 12 patients (4.8%). Fourteen patients had positive cultures. There was one pneumothorax (0.4%), three hematomas requiring evacuation (1%), and two DVTs (0.8%). Of 228 patients, 206 (90.4%) reported high satisfaction with the outcome of the procedure. CONCLUSIONS: In a large cohort of BII patients, we found that capsular inflammation is significantly associated with silicone and textured implants. Implant removal with capsulectomy can be safely performed in patients with BII with a low complication rate and high patient satisfaction.