Comparison of emotional and behavioral regulation between metopic and sagittal synostosis.

PURPOSE: Children with surgically corrected nonsyndromic craniosynostosis have been previously found to have neurocognitive and behavioral difficulties. Children with metopic synostosis have been described to have more difficulties than children with sagittal synostosis. This study aims to characterize the behavioral differences between children with metopic and sagittal synostosis. METHODS: Children with metopic and sagittal synostosis were recruited at school age. Parents completed four separated behavioral assessments: Conners-3 (evaluation of ADHD), Social Responsiveness Scale-2 (SRS-2: evaluation of autism), Behavior Rating Inventory of Executive Function-2 (BRIEF-2: evaluation of executive function), and Child Behavior Checklist (CBCL: evaluation of overall behavioral problems). Children underwent intelligence quotient (IQ) testing using the Wechsler Abbreviated Scale of Intelligence (WASI-II). RESULTS: There were 91 children (45 with metopic and 46 with sagittal synostosis). More children with metopic synostosis reported requiring supportive services (57.7% vs 34.7%, p = 0.02) and more reached or exceeded borderline clinical levels of two executive function subscales of the BRIEF-2 (emotion regulation index: 33.3% vs 17.4%, p = 0.05; global executive composite: 33.3% vs 17.4%, p = 0.05). Children with sagittal synostosis had higher scores on the rule-breaking and externalizing problem subscales of the CBCL. Increasing age at surgery was associated with worse executive function scores. CONCLUSIONS: A relationship between suture subtype and behavioral outcomes exists at school age. More children with metopic synostosis required social services indicating more overall difficulties. Children with metopic synostosis have more specific problems with executive function, while children with sagittal synostosis had more difficulties with externalizing behaviors.

Sports participation after craniosynostosis repair: the critical role of post-operative guidance in parental decision-making.

PURPOSE: Despite previous research supporting patient safety in sports after craniosynostosis surgery, parental anxiety remains high. This study sought to evaluate the role of healthcare providers in guiding patients and families through the decision-making process. METHODS: Parents of children with repaired craniosynostosis were asked to assess sports involvement and parental decision-making in children ages 6 and older. Questions were framed primarily on 5-point Likert scales. Sport categorizations were made in accordance with the American Academy of Pediatrics. Chi-squared, linear regression, and Pearson correlation tests were used to analyze associations between the questions. RESULTS: Forty-three complete parental responses were recorded. Mean ages at surgery and time of sports entry were 7.93 ± 4.73 months and 4.76 ± 2.14 years, respectively. Eighty-two percent of patients participated in a contact sport. Discussions with the primary surgeon were more impactful on parental decisions about sports participation than those with other healthcare providers (4.04 ± 1.20 vs. 2.69 ± 1.32). Furthermore, children whose parents consulted with the primary surgeon began participating in sports at a younger age (4.0 ± 1.0 vs. 5.8 ± 2.7 years, p = 0.034). The mean comfort level with contact sports (2.8 ± 1.4) was lower than that with limited-contact (3.8 ± 1.1, p = 0.0001) or non-contact (4.4 ± 1.3, p < 0.0001) sports. CONCLUSION: This study underscores the critical role that healthcare professionals, primarily surgeons, have in guiding families through the decision-making process regarding their children's participation in contact sports.

Radiographic severity is associated with worse executive function in metopic craniosynostosis.

BACKGROUND: Children with metopic synostosis have been found to have more neurocognitive and behavioral difficulties. The variables that may affect future neurodevelopmental outcomes, including presenting morphologic severity, have not been fully studied. In the largest study to date, we aimed to assess what portends worse neurocognitive and behavioral outcomes at school age. METHODS: Children 6-18 years old with surgically corrected metopic nonsyndromic craniosynostosis underwent neurocognitive testing. Parents completed behavior rating surveys about their child: Conners-3 (ADHD), Social Responsiveness Scale-2 (autism spectrum disorder), Behavior Rating Inventory of Executive Function-2 (BRIEF-2: executive function), and Child's Behavior Checklist (overall behavior). The endocranial bifrontal angle (EBA), adjusted EBA (aEBA), frontal angle (FA), and AI-derived metopic severity score (MSS) were determined on pre-operative CT images. Multivariate linear regressions were used to evaluate the association of age at surgery and severity. RESULTS: There were 87 children who underwent neurocognitive testing (average age 10.9 ± 3.3 years) of whom 67 also completed behavioral assessments. Greater phenotypical severity of metopic synostosis (lower FA, aEBA, and EBA) was associated with worse scores on the subscales of the BRIEF-2 (executive function) and executive subscale of the Conners-3. Increasing age at surgery was associated with worse executive function subscale scores of the Conners-3 when controlling for each severity measurement and sociodemographic risk. CONCLUSION: Children with greater phenotypic severity of metopic synostosis have worse executive function at school age. The majority of children with metopic synostosis have signs of ADHD. Later surgeries (greater than 12 months) may impact executive functioning, regardless of the degree of severity. Future research should aim at identifying the direct structural changes to the brain.

A diffusion tensor imaging comparison of white matter development in nonsyndromic craniosynostosis to neurotypical infants.

PURPOSE: Nonsyndromic craniosynostosis (NSC) is associated with neurocognitive deficits, and intervention at infancy is standard of care to limit the negative effects of NSC on brain development. In this study, diffusion tensor imaging (DTI) was implemented to investigate white matter microstructure in infants with NSC undergoing cranial vault remodeling, and a comparison was made with white matter development in neurotypical controls. METHODS: Infants presenting with NSC (n = 12) underwent DTI scans before and after cranial vault remodeling. Neurotypical infants (n = 5), age matched to NSC patients at preoperative scans, were compared to preoperative DTI scans. Pre- and postoperative NSC scans were compared in aggregate, and the sagittal synostosis (n = 8) patients were evaluated separately. Finally, neurotypical infants from the University of North Carolina/University of New Mexico Baby Connectome Project (BCP), who underwent DTI scans at timepoints matching the NSC pre- and postoperative DTI scans, were analyzed (n = 9). Trends over the same time period were compared between NSC and BCP scans. RESULTS: No significant differences were found between preoperative NSC scans and controls. White matter development was more limited in NSC patients than in BCP patients, with microstructural parameters of the corpus body and genu and inferior and superior longitudinal fasciculi consistently lagging behind developmental changes observed in healthy patients. CONCLUSION: Infant white matter development appears more limited in NSC patients undergoing cranial vault remodeling relative to that in neurotypical controls. Further investigation is needed to explore these differences and the specific effects of early surgical intervention.

Quantification of Cephalometric Changes in Gonial Angle Morphology Following Facial Feminization Surgery.

Facial feminization surgery (FFS) is a type of gender-affirming surgery aimed at bringing masculine facial features more in line with typically feminine characteristics. Specifically, mandibular contouring can create a softer jawline and help create a more round, feminine face. As the popularity of FFS continues to increase, improving surgical techniques and patient satisfaction is imperative. However, no quantitative measurement system currently exists to measure these changes. In this study, the authors describe the use of a novel segmentation technique using computerized tomography imaging to quantify the bony changes that occur during gonial angle reduction. Further, authors utilize this technique to describe changes in a cohort of 13 patients, and how these changes correlate with patient satisfaction. The authors found that gonial angle volume and surface area significantly decreased, as well as the intergonial:interzygomatic ratio, with a smaller ratio associated with more feminine features. In addition, patient satisfaction significantly increased post-operatively both specifically regarding jawline appearance (P = 0.0014) and regarding overall social and psychological function (P = 0.0021 and P = 0.0032, respectively), as captured by the FACE-Q and World Health Organization Quality of Life (WHOQOL) surveys. Patients with greater changes in surface area reported greater improvements in WHOQOL psychological scores (P = 0.0086), and patients with greater changes in the intergonial:interzygomatic ratio reported greater improvements in WHOQOL social scores (P = 0.0299). Overall, our novel technique captures significant changes in gonial angle shape and can be applied to a wide range of future studies to improve the quality and accessibility of FFS.

Perceived Age and Gender Perception Using Facial Recognition Software Following Facial Feminization Surgery.

Measures of success for facial feminization surgery (FFS) have previously included improved rates of external gender perception as female and patient-reported outcome measures. In this study, we used artificial intelligence facial recognition software to objectively evaluate the effects of FFS on both perceived gender and age among male-to-female transgender patients, as well as their relationship with patient facial satisfaction. Standardized frontal preoperative and postoperative images of 27 transgender women undergoing FFS were analyzed by Amazon's AI facial recognition software to determine gender, femininity confidence score, and perceived age. Female gender-typing, improvement in gender-typing (preoperatively to postoperatively), and femininity confidence scores were analyzed. To assess patient satisfaction, FACE-Q modules were completed postoperatively. Preoperatively, FFS images were perceived as female 48.1% of the time, and postoperatively, this improved to 74.1% ( P =0.05). Femininity confidence scores improved from a mean score of 0.04 preoperatively to 0.39 postoperatively ( P =0.003). FFS was associated with a decrease in perceived age relative to the patient's true age (-2.4 y, P <0.001), with older patients experiencing greater reductions. Pearson correlation matrix found no significant relationship between improved female gender typing and patient facial satisfaction. Undergoing surgery at a younger age was associated with higher overall facial satisfaction ( r =-0.6, P =0.01). Transfeminine patients experienced improvements in satisfaction with facial appearance, perceived gender, and decreases in perceived age following FFS. Notably, patient satisfaction was not directly associated with improved AI-gender typing, suggesting that other factors may influence patient satisfaction.

Evolution of Virtual Surgical Planning Use Among Craniofacial Surgeons.

Virtual surgical planning (VSP) has benefits in craniofacial surgery with growing popularity. However, while specific use cases are highlighted in the literature, no studies exist providing an overview of VSP use among craniofacial surgeons, and little is known about the extent of exposure to VSP during plastic surgery training. This study surveyed members of The American Society of Maxillofacial Surgeons (ASMS) to better characterize both the landscape of VSP use among practicing craniofacial surgeons and the extent of exposure to VSP throughout surgical training. An electronic survey was administered in the fall of 2023. Response data included surgeon demographics, VSP usage, including the use in residency/fellowship, procedures for which VSP is used, and assessment of VSP's impact on the surgeon's practice. Demographics and VSP use were analyzed using descriptive statistics, while categorical and continuous variables were analyzed using χ2 tests and t-tests, respectively. Of the 44 respondents, 40 (90.9%) completed a craniofacial surgery fellowship, and 18 (40.9%) utilized VSP in either residency or fellowship. In respondents' current practice, VSP is utilized most commonly for orthognathic surgery (n=32, 91.4%), postablative reconstruction (n=23, 82.1%), and facial feminization (n=11, 73.3%). Shorter operative time and improved esthetic outcomes were frequently reported as benefits derived from VSP use. Finally, surgeons in practice for less than 10 years were significantly more likely to have used VSP in both residency (OR=20.3, P<0.01) and in fellowship (OR=40.6, P<0.01) than those practicing for more than 10 years. These findings suggest that craniofacial surgeons apply VSP more commonly for certain procedure types. Our results additionally suggest that incorporation of VSP into residency and fellowship training has become significantly more common over time, with a pivot towards integration in the last decade.

Safety and activity of anti-CD14 antibody IC14 (atibuclimab) in ALS: Experience with expanded access protocol.

INTRODUCTION/AIMS: IC14 (atibuclimab) is a monoclonal anti-CD14 antibody. A previous phase 1 trial of 10 participants with amyotrophic lateral sclerosis (ALS) demonstrated initial safety of IC14 in an acute treatment setting. We provided long-term treatment with IC14 to individuals with ALS via an expanded access protocol (EAP) and documented target engagement, biomarker, safety, and disease endpoints. METHODS: Participants received intravenous IC14 every 2 weeks. Consistent with United States Food and Drug Administration guidelines, participants were not eligible for clinical trials and the EAP was inclusive of a broad population. Whole blood and serum were collected to determine monocyte CD14 receptor occupancy (RO), IC14 levels, and antidrug antibodies. Ex vivo T-regulatory functional assays were performed in a subset of participants. RESULTS: Seventeen participants received IC14 for up to 103 weeks (average, 30.1 weeks; range, 1 to 103 weeks). Treatment-emergent adverse events (TEAEs) were uncommon, mild, and self-limiting. There were 18 serious adverse events (SAEs), which were related to disease progression and unrelated or likely unrelated to IC14. Three participants died due to disease progression. Monocyte CD14 RO increased for all participants after IC14 infusion. One individual required more frequent dosing (every 10 days) to achieve over 80% RO. Antidrug antibodies were detected in only one participant and were transient, low titer, and non-neutralizing. DISCUSSION: Administration of IC14 in ALS was safe and well-tolerated in this intermediate-size EAP. Measuring RO guided dosing frequency. Additional placebo-controlled trials are required to determine the efficacy of IC14 in ALS.

Expanded access protocol (EAP) program for access to investigational products for amyotrophic lateral sclerosis (ALS).

INTRODUCTION/AIMS: Expanded access protocols (EAPs) are a Food and Drug Administration (FDA)-regulated pathway for granting access to investigational products (IPs) to individuals with serious diseases who are ineligible for clinical trials. There is limited information about the use of EAPs in amyotrophic lateral sclerosis (ALS); the aim of this report is to share the design, operational features, and costs of an EAP program for ALS. METHODS: The program was launched in 2018 at a single center. In alignment with FDA guidance, protocols were designed as individual (single participant) or intermediate size. Inclusion criteria were broad (e.g., no restrictions due to long disease duration or low vital capacity). Safety information was collected in all EAPs. Selected biomarkers were collected in nine of the EAPs. RESULTS: From July 2018 through February 2022, 17 EAPs were submitted for FDA and institutional review board (IRB) approval. The mean time from submission to approval from the FDA and IRB were 24 days and 37 days, respectively. A total of 164 participants were enrolled and, of these, 77 participants were still receiving IP as of February 2022. The mean duration of participation in an EAP was 12.6 mo. No drug-related serious adverse events were reported from any of the EAPs. Average site cost was $613.47 per participant per month, not including IP costs. CONCLUSION: EAPs provide a framework through which access to IP can be safely provided to people with ALS who do not qualify for clinical trials. Site resources are needed to launch and maintain these programs.

Virtual Surgical Planning in Craniosynostosis Reduces Operative Time and Length of Stay for Cranial Vault Remodeling.

Cranial vault remodeling (CVR) with and without frontal orbital advancement remodels the skull in craniosynostosis. Virtual surgical planning (VSP) for preoperative planning has been previously shown to be effective in CVR. In this study, the authors aimed to evaluate the impact of VSP on operative and perioperative efficiency for craniosynostosis surgery. A retrospective chart review was conducted of patients with craniosynostosis who underwent CVR. Patient demographics, perioperative variables, use of VSP, and complications were obtained. Perioperative variables collected include operative time and length of stay. An independent t test was used to compare variables from patients who had surgery with VSP and patients who did not. Records were available for 126 patients with craniosynostosis who underwent CVR of whom 79 (62.7%) utilized VSP. There was no difference in average age at surgery (9.3±5.7 mo versus 13.2±31.1 mo, P =0.39). Surgeries planned using VSP demonstrated a decreased operative time of 1.3 hours (3.7±1.1 versus 5.0±1.1 h, P <0.001) and a shorter length of stay (3.9±1.3 versus 4.6±1.7 d, P =0.01). There were no differences in complication rates of dehiscence, infection, returns to the operating room, or 30-day readmission. These trends were similar among patients who underwent fronto-orbital advancement in addition to CVR. Virtual surgical planning was associated with decreased operative time and length of stay for patients with craniosynostosis and comparable complication rates. Virtual surgical planning is an effective tool for reducing anesthetic exposure time.

An update on long-term mental health in eight face transplant recipients - A single center experience.

OBJECTIVE: Face transplantation is a groundbreaking and complex surgical intervention offering profound physical and psychological benefits to patients with severe facial disfigurements. This report provides an update on the long-term psychosocial outcome of eight face transplant recipients. METHOD: All transplant recipients were initially transplanted at Brigham and Women´s Hospital (Boston, USA) between 2011 and 2020 and are seen as outpatient patients at Yale New Haven Hospital (New Haven, USA). A mixed-methods approach was used to assess the psychological well-being of these patients. The Short-Form 12, Brief-COPE, EQ-VAS and CES-D were administered between October 2022 and October 2023. RESULTS: Older age of face transplant recipients was significantly and positively associated with better mental health and increased use of both emotional and instrumental support (Brief-COPE). The initial enhancement in patients' self-reported quality of life, as assessed by the EQVAS, declined on the EQ-VAS score at the last follow-up period. Similarly, an increase in depression score was observed (CES-D score) up through the last follow-up assessment. Both of the latter results, however, did not reach statistical significance. CONCLUSIONS: These results underscore the importance of ongoing psychological support throughout the long-term journey of recovery for face transplant recipients. They emphasized the need for a comprehensive, patient-centered approach that also addresses the complex psychological dimensions and contributes to our understanding of the mental health dynamics involved in face transplantation, underscoring the need for guidelines and continued research in this evolving field.

Ear Molding Therapy of Congenital Ear Anomalies: Long-Term Aesthetic Outcomes and Caretaker Satisfaction.

INTRODUCTION: Ear molding is a safe, non-surgical approach to treat newborns with congenital ear anomalies. In this study, we aimed to investigate long-term aesthetic outcomes and caretaker satisfaction from ear molding therapy. METHODS: A retrospective chart review from 2018 to 2020 was conducted for infants who underwent ear molding treatment at our institution. Patient demographics and treatment related variables were collected. Caretakers were surveyed regarding their experience, expectations, and aesthetic outcome at 1 year (short-term) and 3 years (long-term) from treatment. Independent physicians evaluated treatment efficacy. Responses were converted to a Likert scale (1-5), with 5 representing most desirable. RESULTS: Overall, 38 of 42 patients participated in our long-term study (90%) for a total of 62 ears. Average follow-up was 3.31 ± 0.50 years after completion of treatment. Mean age at treatment was 23.2 ± 19.7 days with a mean treatment duration of 21.7 ± 7.7 days. Caretakers' satisfaction regarding auricular appearance remained high (short-term: 4.18 vs. long-term: 4.17, p = 0.54) and anticipated social distress decreased over time. Physician aesthetic evaluations were favorable between "somewhat effective" and "very effective" and remained consistent over time (short term: 3.46 vs. long-term: 3.31, p = 0.31). Furthermore, physician evaluations were higher for deformations than malformations (p = 0.04) and in children who began treatment by 30 days old (p = 0.04). CONCLUSION: Caretaker satisfaction from ear molding therapy remained high after long-term follow up, and social distress from the perception of their child's ears decreased with time. Physician aesthetic ratings confirmed efficacy, with better outcomes seen in deformations than in malformations. LEVEL OF EVIDENCE IV: 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 the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

An expanded access protocol of RT001 in amyotrophic lateral sclerosis-Initial experience with a lipid peroxidation inhibitor.

INTRODUCTION/AIMS: Lipid peroxidation is thought to play a biologically important role in motor neuron death in amyotrophic lateral sclerosis (ALS). 11,11 Di-deuterated linoleic ethyl ester (RT001) prevents lipid peroxidation in cellular and mitochondrial membranes. Herein we report on the use of RT001 under expanded access (EA). METHODS: We provided RT001 to patients with ALS via EA at a single site. The starting dose was 2.88 g/day, which was increased to to 8.64 g/day as tolerated. Participants were not eligible for alternative clinical trials. Participants were followed for adverse events and pharmacokinetic (PK) parameters were measured approximately 3 months after RT001 initiation. RESULTS: Sixteen participants received RT001 (5.6 ± 1.6 g/day; dose range, 1.92 to 8.64 g/day) for a mean period of 10.8 ± 7.1 months. After 3 months of treatment, PK studies showed that RT001 was absorbed, metabolized, and incorporated into red blood cell membranes at concentrations expected to be therapeutic based on in vitro models. The most common adverse events were gastrointestinal, including diarrhea, which occurred in 25% of the participants, and were considered possibly related to RT001. One participant (6%) discontinued due to an adverse event. Ten serious adverse events occurred: these events were recognized complications of ALS and none were attributed to treatment with RT001. DISCUSSION: RT001 was administered safely to a small group of people living with ALS in the context of an EA protocol. Currently, there is an ongoing randomized, double-blind, controlled study of RT001 in ALS.

Thirty-day unplanned readmission in hospitalised asthma patients in the USA.

INTRODUCTION: Hospital quality improvement and hospital performance are commonly evaluated using parameters such as average length of stay (LOS), patient safety measures and rates of hospital readmission. Thirty-day readmission (30-DR) rates are widely used as a quality indicator and a quantifiable metric for hospitals since patients are often readmitted for the exacerbation of conditions from index admission. The quality of patient education and postdischarge care can influence readmission rates. We report the 30-DR rates of patients with asthma using a national dataset for the year 2013. OBJECTIVES: The aim of our study was to assess the 30- day readmission (30-DR) rate as well as, the causes and predictors of readmissions. STUDY DESIGNS/METHODS: Using the Nationwide Readmission Database (NRD) (2013), we identified primary discharge diagnoses of asthma by using International Classification of Diseases, Ninth Revision, Clinical Modification code '493'. Categorical and continuous variables were assessed by a χ2 test and a Student's t-test, respectively. The independent predictors of unplanned 30-DR were detected by multivariate analysis. We used sampling weights, which are provided in the NRD, to generate the national estimates. RESULTS: There were 130 490 (weighted N=311 173) inpatient asthma admissions during 2013. The overall 30-DR for asthma was 11.9%. The associated factors for 30-DR were age 45-84 years (40.32% vs 29.05%; p<0.001), enrolment in Medicare (49.33% vs 30.61% p<0.001), extended LOS (mean, 4.40±0.06 vs 3.25±0.04 days; p<0.001), higher mean cost (US$8593.91 vs US$6741.31; p<0.001) and higher disposition against medical advice (DAMA) (4.14% vs 1.51%; p<0.001). The factors that increased the chance of 30-DR were advanced age (≥45-64 vs ≤17 years; OR 4.61, 95% CI 4.04 to 5.27, p<0.0001), male sex (OR 1.19, 95% CI 1.13 to 1.26, p<0.0001), a higher Charlson Comorbidity Index (CCI) (OR 1.16, 95% CI 1.14 to 1.18, p<0.0001), DAMA (OR 2.32, 95% CI 2.08 to 2.59, p<0.0001), non-compliance with medication (OR 1.34, 95% CI 1.24 to 1.46, p<0.0001), post-traumatic stress disorder (OR 1.48, 95% CI 1.22 to 1.79, p<0.0001), alcohol use (OR 1.45, 95% CI 1.27 to 1.65, p<0.0001), gastro-oesophageal reflux disease (OR 1.20, 95% CI 1.14 to 1.27, p<0.0001), obstructive sleep apnoea (OR 1.11, 95% CI 1.03 to 1.18, p<0.0042) and hypertension (OR 1.11, 95% CI 1.06 to 1.17, p<0.0001). CONCLUSIONS: We found that the overall 30-DR rate for asthma was 11.9% all-cause readmission. Major causes of 30-DR were asthma exacerbation (36.74%), chronic obstructive pulmonary disease (11.47%), respiratory failure (6.46%), non-specific pneumonia (6.19%), septicaemia (3.61%) and congestive heart failure (3.32%). One-fourth of the revisits occurred in the first week, while half of the revisits took place in the first 2 weeks. Education regarding illness and the importance of medicine compliance could play a significant role in preventing asthma-related readmission.

Software-based Detection of Acute Rejection Changes in Face Transplant.

BACKGROUND: An objective, non-invasive method for redness detection during acute allograft rejection in face transplantation (FT) is lacking. METHODS: A retrospective cohort study was performed with 688 images of 7 patients with face transplant (range, 1 to 108 months post-transplant). Healthy controls were matched to donor age, sex, and had no prior facial procedures. Rejection state was confirmed via tissue biopsy. An image-analysis software developed alongside VicarVision (Amsterdam, Netherlands) was used to produce R, a measure of differences between detectable color and absolute red. R is inversely proportional to redness, where lower R values correspond to increased redness. Linear mixed models were used to study fixed effect of rejection state on R values. Estimated marginal means of fitted models were calculated for pairwise comparisons. RESULTS: Of 688 images, 175, 170, 202, and 141 images were attributable to Banff Grade 0,1,2, and 3, respectively. Estimated change in R value of facial allografts decreased with increasing Banff Grade (p = 0.0001). The mean R value of clinical rejection (Banff Grade ⅔) (16.67, 95% Confidence Interval [CI] 14.79-18.58) was lower (p = 0.005) than non-rejection (Banff Grade 0/1) (19.38, 95%CI 17.43-21.33). Both clinical and non-rejection mean R values were lower (p = 0.0001) than healthy controls (24.12, 95%CI 20.96-27.28). CONCLUSION: This proof-of-concept study demonstrates that software-based analysis can detect and monitor acute rejection changes in FT. Future studies should expand on this tool's potential application in telehealth and as a screening tool for allograft rejection.

Asthma in the older adult.

Objective: The older adult population is increasing worldwide, and a significant percentage has asthma. This review will discuss the challenges to diagnosis and management of asthma in older adults. Data Sources: PubMed was searched for multiple terms in various combinations, including asthma, older adult, elderly, comorbid conditions, asthma diagnosis, asthma treatment, biologics and medication side effects, and adverse events. From the search, the data sources that were utilized included peer reviewed scholarly review articles, peer reviewed scientific research articles, and peer reviewed book chapters. Study Selections: Study selections that were utilized included peer reviewed scholarly review articles, peer reviewed scientific research articles, and peer reviewed book chapters. Results: Asthma in older adults is frequently underdiagnosed and has higher morbidity and mortality rates compared to their younger counterparts. A detailed history and physical examination as well as judicious testing are essential to establish the asthma diagnosis and exclude alternative ones. Medical comorbidities, such as cardiovascular disease, cognitive impairment, depression, arthritis, gastroesophageal reflux disease (GERD), rhinitis, and sinusitis are common in this population and should also be assessed and treated. Non-pharmacologic management, including asthma education on inhaler technique and self-monitoring, is vital. Pharmacologic management includes standard asthma therapies such as inhaled corticosteroids (ICS), inhaled corticosteroid-long acting ß-agonist combinations (ICS-LABA), leukotriene antagonists, long acting muscarinic antagonists (LAMA), and short acting bronchodilators (SABA). Newly approved biologic agents may also be utilized. Older adults are more vulnerable to polypharmacy and medication adverse events, and this should be taken into account when selecting the appropriate asthma treatment. Conclusions: The diagnosis and management of asthma in older adults has certain challenges, but if the clinician is aware of them, the morbidity and mortality of this condition can be improved in this growing population.

Systemic and tumor-directed therapy for oligometastatic prostate cancer: study protocol for a phase II trial for veterans with de novo oligometastatic disease.

BACKGROUND: The treatment paradigm for metastatic hormone-sensitive prostate cancer (mHSPC) patients is evolving. PET/CT now offers improved sensitivity and accuracy in staging. Recent randomized trial data supports escalated hormone therapy, local primary tumor therapy, and metastasis-directed therapy. The impact of combining such therapies into a multimodal approach is unknown. This Phase II single-arm clinical trial sponsored and funded by Veterans Affairs combines local, metastasis-directed, and systemic therapies to durably render patients free of detectable disease off active therapy. METHODS: Patients with newly-diagnosed M1a/b prostate cancer (PSMA PET/CT staging is permitted) and 1-5 radiographically visible metastases (excluding pelvic lymph nodes) are undergoing local treatment with radical prostatectomy, limited duration systemic therapy for a total of six months (leuprolide, abiraterone acetate with prednisone, and apalutamide), metastasis-directed stereotactic body radiotherapy (SBRT), and post-operative fractionated radiotherapy if pT ≥ 3a, N1, or positive margins are present. The primary endpoint is the percent of patients achieving a serum PSA of < 0.05 ng/mL six months after recovery of serum testosterone ≥150 ng/dL. Secondary endpoints include time to biochemical progression, time to radiographic progression, time to initiation of alternative antineoplastic therapy, prostate cancer specific survival, health related quality-of-life, safety and tolerability. DISCUSSION: To our knowledge, this is the first trial that tests a comprehensive systemic and tumor directed therapeutic strategy for patients with newly diagnosed oligometastatic prostate cancer. This trial, and others like it, represent the critical first step towards curative intent therapy for a patient population where palliation has been the norm. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03298087 (registration date: September 29, 2017).

Recent advances in gynecologic radiation oncology.

PURPOSE OF REVIEW: Radiation has long been a primary treatment modality in locally advanced gynecologic carcinomas and a tool for palliation of metastatic disease. Here we review advances in imaging and radiation technologies and the corresponding clinical evolution of the role for radiation oncology in the treatment of gynecologic malignancies. RECENT FINDINGS: Advances in MRI are impacting diagnosis, radiation target delineation, planning, treatment delivery, and response assessment. The combination of MRI and PET-computed tomography (PET-CT) has the potential to significantly change treatment recommendations as compared with a single imaging modality. Advances in radiation delivery including intensity modulated radiation therapy (IMRT) and stereotactic ablative radiotherapy (SABR) have expanded the role for radiation in the definitive treatment of high risk and oligometastatic ovarian cancer. Finally, global disparities in oncology resources has led to the development of resource stratified treatment guidelines for gynecologic malignancies. The use of ultrasound for brachytherapy planning may help improve access to this critical treatment modality. SUMMARY: As imaging and radiation technologies advance, the indications for radiation in the treatment of gynecologic malignancies continues to evolve. Here we review the changing landscape of radiation oncology in the multidisciplinary management of gynecologic cancers.

Role of Galectin-3 in the pathophysiology underlying allergic lung inflammation in a tissue inhibitor of metalloproteinases 1 knockout model of murine asthma.

Asthma is a chronic inflammatory respiratory disease characterized by airway inflammation, airway hyperresponsiveness and reversible airway obstruction. Understanding the mechanisms that underlie the various endotypes of asthma could lead to novel and more personalized therapies for individuals with asthma. Using a tissue inhibitor of metalloproteinases 1 (TIMP-1) knockout murine allergic asthma model, we previously showed that TIMP-1 deficiency results in an asthma phenotype, exhibiting airway hyperreactivity, enhanced eosinophilic inflammation and T helper type 2 cytokine gene and protein expression following sensitization with ovalbumin. In the current study, we compared the expression of Galectins and other key cytokines in a murine allergic asthma model using wild-type and TIMP-1 knockout mice. We also examined the effects of Galectin-3 (Gal-3) inhibition on a non-T helper type 2 cytokine interleukin-17 (IL-17) to evaluate the relationship between Gal-3 and the IL-17 axis in allergic asthma. Our results showed a significant increase in Gal-3, IL-17 and transforming growth factor-ß1 gene expression in lung tissue isolated from an allergic asthma murine model using TIMP-1 knockout. Gal-3 gene and protein expression levels were also significantly higher in lung tissue from an allergic asthma murine model using TIMP-1 knockout. Our data show that Gal-3 may regulate the IL-17 axis and play a pivotal role in the modulation of inflammation during experimental allergic asthma.

United States National Trends in Mortality, Length of Stay (LOS) and Associated Costs of Cognitive Impairment in HIV Population from 2005 to 2014.

We evaluated national trends of in-hospital discharge rates, mortality outcomes, health care costs, length of stay in HIV patients with cognitive disorders. Neurological involvement in HIV is commonly associated with cognitive impairment termed as HIV-associated neurocognitive disorder (HAND) which includes a spectrum of neurocognitive dysfunction associated with HIV infection. Although severe and progressive neurocognitive impairment has become rare in HIV patients in the era of potent antiretroviral therapy, a majority of HIV patients have mild to moderate degree of neurocognitive impairment. Study population for this analysis was derived from the Nationwide Inpatient Sample from 2005 to 2014. Patients with ICD-9 code of HIV (042) with discharge diagnosis (Dx) listed top 1 through 5 were included in the analysis. Within this population, we identified patients with cognitive impairment using ICD-9 codes of 294 (persistent mental disorders; organic psychotic brain syndromes (chronic), 323.9 (encephalitis, myelitis, and encephalomyelitis), 331.83 (mild cognitive impairment) with Dx listed from 1 to 25. Patient variables obtained included: age, race, gender, length of stay, in-hospital mortality and insurance status. Hospital level variables included teaching status, location and region of country. SAS 9.4 software was used for data analysis. Comparisons of variables between hospitalized HIV patients with and without HAND showed significant increase in cost per hospital admissions, longer hospital stay and higher risk of mortality in patients with HAND.