Multidisciplinary Velopharyngeal Dysfunction Evaluation Helps Detect Non-classic Cases of 22q11.2 Deletion.

OBJECTIVE: To explore the role of multidisciplinary velopharyngeal dysfunction (VPD) assessment in diagnosing 22q11.2 deletion syndrome (22q) in children. DESIGN: Retrospective cohort study. SETTING: Multidisciplinary VPD clinic at a tertiary pediatric hospital. PATIENTS, PARTICIPANTS: Seventy-five children with genetically confirmed 22q evaluated at the VPD clinic between February 2007 and February 2023, including both previously diagnosed patients and those newly diagnosed as a result of VPD evaluation. INTERVENTIONS: Comprehensive review of medical records, utilizing ICD-10 codes and an institutional tool for keyword searches, to identify patients and collect data on clinical variables and outcomes. MAIN OUTCOME MEASURES: Characteristics of children with 22q, pathways to diagnosis, and clinical presentations that led to genetic testing for 22q. RESULTS: Of the 75 children, 9 were newly diagnosed with 22q following VPD evaluation. Non-cleft VPI was a significant indicator for 22q in children not previously diagnosed, occurring in 100% of newly diagnosed cases compared to 52% of cases with existing 22q diagnosis (P = .008). Additional clinical findings leading to diagnosis included congenital heart disease, craniofacial abnormalities, and developmental delays. CONCLUSIONS: VPD evaluations, particularly the presence of non-cleft VPI, play a crucial role in identifying undiagnosed cases of 22q. This underscores the need for clinicians, including plastic surgeons, otolaryngologists, and speech-language pathologists, to maintain a high degree of suspicion for 22q in children presenting with VPI without a clear etiology. Multidisciplinary approaches are essential for early diagnosis and management of this complex condition.

Patient-Reported Outcomes After Reduction Mammoplasty Using BREAST-Q: A Systematic Review and Meta-Analysis.

BACKGROUND: The BREAST-Q questionnaire reduction module is an established tool for outcomes after reduction mammoplasty. OBJECTIVES: This systematic review and meta-analysis assess key parameters affecting pre- and postoperative scores, with specific foci on patient characteristics and tissue resection weights. METHODS: This study was conducted per PRISMA guidelines. PUBMED (National Institutes of Health; Bethesda, MD), Google Scholar (Google; Mountain View, CA), and Web of Science (Clarivate Analytics; Philadelphia, PA) were searched. All studies published before August 1, 2021, were assessed for eligibility by 2 independent reviewers. Inclusion criteria were prospective or retrospective studies in 6 languages that reported quality of life after reduction mammoplasty employing the BREAST-Q questionnaire reduction module. Quality of included studies was assessed employing the Newcastle-Ottawa-Scale. Analysis was performed per Cochrane Collaboration and the Quality of Reporting of Meta-analyses guidelines. RESULTS: A total of 28 papers were included in the systematic review, 13 for preoperative meta-analysis, and 17 for postoperative meta-analysis. Postoperative scores in all 3 quality of life domains (psychosocial, physical, and sexual well-being) and satisfaction with breasts increased significantly after reduction mammoplasty compared with preoperative scores. Satisfaction with breasts showed the greatest improvement, from 22.9 to 73.0. Preoperative scores were lower than normative data, with improvement to comparable scores as the healthy population postoperatively. Improvements in BREAST-Q scores did not correlate with patient comorbidities, complication rates, or amount of breast tissue resected. CONCLUSIONS: Reduction mammoplasty provides marked improvement in BREAST-Q patient-reported quality of life as well established in literature. However, these improvements do not correlate with tissue resection weights, warranting further inquiry of insurance-defined resection requirements.

Advances in Translational Regenerative Therapies.

Regenerative medicine aims to replace damaged cells and tissues following injury [...].

Normothermic Ex Situ Machine Perfusion of Vascularized Composite Allografts with Oxygen Microcarriers for 12 Hours Using Real-Time Mitochondrial Redox Quantification.

BACKGROUND: Normothermic ex situ perfusion of vascularized composite allografts (VCAs) necessitates high oxygen demand and, thus, increased metabolic activity, which, in turn, requires the use of blood-based perfusion solutions. However, blood-derived perfusates, in turn, constitute an antigenic load. To circumvent this immunogenic problem, we used a perfusate enriched with acellular dextrane oxygen microcarriers to perfuse rat hindlimbs. METHODS: Rat hindlimbs (n = 11) were perfused with either (non-), oxygenated dextrane-enriched Phoxilium, or Phoxilium enriched with dextrane oxygen microcarriers (MO2) for 12 h at 37 °C or stored on ice. Oxygenation of the skeletal muscle was assessed with Raman spectroscopy, tissue pO2-probes, and analysis of the perfusate. Transmission electronic microscopy was utilized to assess the ultrastructure of mitochondria of the skeletal muscle. RESULTS: For all evaluated conditions, ischemia time until perfusion was comparable (22.91 ± 1.64 min; p = 0.1559). After 12 h, limb weight increased significantly by at least 81%, up to 124% in the perfusion groups, and by 27% in the static cold storage (SCS) group. Raman spectroscopy signals of skeletal muscle did not differ substantially among the groups during either perfusion or static cold storage across the duration of the experiment. While the total number of skeletal muscle mitochondria decreased significantly compared to baseline, mitochondrial diameter increased in the perfusion groups and the static cold storage group. CONCLUSION: The use of oxygen microcarriers in ex situ perfusion of VCA with acellular perfusates under normothermic conditions for 12 h facilitates the maintenance of mitochondrial structure, as well as a subsequent recovery of mitochondrial redox status over time, while markers of muscle injury were lower compared to conventional oxygenated acellular perfusates.

Facial Expression after Face Transplant: An International Face Transplant Cohort Comparison.

BACKGROUND: Assessment of motor function restoration following face transplant (FT) is difficult, as standardized, bilateral tests are lacking. This study aims to bolster support for software-based analysis through international collaboration. METHODS: FaceReader (Noldus, Wageningen, The Netherlands), a facial expression analysis software, was used to analyze posttransplant videos of eight FT patients from Boston, Massachusetts (range, 1 to 9 years after transplant), two FT patients from Helsinki, Finland (range, 3 to 4 years after transplant), and three FT patients from Antalya, Turkey (range, 6.5 to 8.5 years after transplant). Age-matched healthy controls from respective countries had no history of prior facial procedures. Videos contained patients and controls performing facial expressions evaluated by software analysis using the Facial Action Coding System. Facial movements were assigned intensity score values between 0 (absent) and 1 (fully present). Maximum values were compared with respective healthy controls to calculate percentage restoration. RESULTS: Of 13 FT patients, eight patients were full FT, five patients were partial FT, and two patients were female patients. Compared with healthy controls, the median restoration of motor function was 36.9% (interquartile range, 28.8% to 52.9%) for all patients with FT ( P = 0.151). The median restoration of smile was 37.2% (interquartile range, 31.5% to 52.7%) for all patients with FT ( P = 0.065). When facial nerve coaptation was performed at the distal branch level, average motor function restoration was 42.7% ± 3.61% compared with 27.9% ± 6.71% at the proximal trunk coaptation level ( P = 0.032). Use of interpositional nerve grafts had no influence on motor outcomes. CONCLUSIONS: Software-based analysis is suitable to assess motor function after FT. International collaboration strengthens outcome data for FT. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Comparative Study of Pharyngeal Flap Outcomes between Children With 22q11.2 Deletion Syndrome and Non-Syndromic Cleft Lip and Palate.

BACKGROUND: Management of velopharyngeal insufficiency (VPI) in 22q11.2 deletion syndrome (22q) is challenging. This study compares pharyngeal flap outcomes in children with 22q to those with non-syndromic cleft lip and palate (CLP) to assess risk of poor speech outcomes and negative sequelae. METHODS: Children with 22q or CLP treated with pharyngeal flap through a multidisciplinary VPI clinic between 2009 and 2020 were retrospectively reviewed. Pre- and postoperative speech assessments, perioperative characteristics, and complications were identified. RESULTS: 36 children with ​22q and 40 with CLP were included. Age at surgery (p=0.121), pre-operative velopharyngeal competence score (VPC) (p=0.702), and pre-operative resonance (p=0.999) were similar between groups. Pharyngeal flaps were wider (p=0.038*) and length of stay longer in the 22q group (p=0.031*). On short term follow 4 months after surgery, similar speech outcomes were seen between groups. At long term follow up >12 months after surgery, 86.7% 22q v. 100% CLP (p=0.122) had improvement in velopharyngeal function, however fewer children with 22q (60.0%) achieved a completely "competent" VPC score compared to those with CLP (92.6%) (p=0.016*). Nasal regurgitation improved for both groups, with a greater improvement in those with 22q (p=0.026*). Revision rate (p=0.609) and new onset OSA (0.999) were similar between groups. CONCLUSION: Children with 22q have improved speech after pharyngeal flap, but may be less likely to reach normal velopharyngeal function over the long term than those with CLP; however, negative sequelae do not differ. Improvement in nasal regurgitation is a uniquely positive outcome in this population.

Visual Preoperative Risk Depiction Tools for Shared Decision-making: A Pilot Study from the Surgeon's Perspective.

Shared decision-making (SDM) and effective risk communication improve patient satisfaction, adherence to treatment, and understanding of perioperative care pathways. Available risk calculators are less relevant for low-risk operations. The aim of this pilot study was to develop graphical risk visualization tools to enhance surgical SDM discussions preoperatively. Methods: Complications for reduction mammoplasty and skin grafting in a burns setting were sourced from the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator, the American Society of Plastic Surgeons website, peer-reviewed literature, and available clinical data. Pre- and postoperative patient satisfaction data were collected from the published literature on Breast-Q patient-reported outcomes for reduction mammoplasty. Everyday risk comparisons were collected from a general online database search. Three distinct risk depiction tools (spiral, tile, and scatter plot) were developed in the Microsoft Office Suite. Anonymous REDCap surveys were sent to healthcare practitioners for feedback. Results: Twenty-six survey results were collected. Twenty-four respondents (92%) agreed these graphics would be useful for SDM discussions. Nineteen respondents (73%) either agreed or strongly agreed that these graphics depicted risk in a meaningful way. Fifteen respondents (58%) indicated they would use these graphics in daily practice. The majority of respondents preferred the spiral design (58%). Areas for improvement included design simplification and written explanations to accompany graphics. Feedback from the survey was incorporated into the spiral design. Conclusions: Risk visualization tools meaningfully depict surgical risks to improve communication in SDM. This study proposes a tool that can be adapted for many surgical procedures.

Racial disparities in short-term outcomes after breast reduction surgery-A National Surgical Quality Improvement Project Analysis with 23,268 patients using Propensity Score Matching.

BACKGROUND: Evidence of widespread disparities in healthcare for racial and ethnic minorities is well documented. This study aims to evaluate differences in surgical outcomes after breast reduction surgery (BRS) according to patients' ethnicities. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database (2005-2018) was utilized to analyze two propensity score matched patient cohorts-White and non-White-that underwent BRS. Preoperative variables assessed included demographic data and comorbidities such as diabetes mellitus, hypertension, and obesity. Postoperative outcomes assessed were medical complications, minor and major surgical complications, as well as mortality. RESULTS: In total, 23268 patients underwent BRS and met the inclusion criteria. After propensity score matching, the two cohorts were matched with respect to these preoperative variables, and 7187 patients were included in each cohort of White and non-White patients (total 14374). After matching, overall 30-day major complications were not significantly different between White and non-White cohort (2.25% vs 2.14%, p=0.65). After accounting for differences in confounding variables at the patient and socioeconomic level, racial and ethnic minorities who underwent breast reduction were found to experience fewer minor surgical complications. The analysis of temporal trends identified an overall rise in the number of patients seeking BRS, with a higher increase noted in the non-White population. CONCLUSION: Overall, our findings are reassuring exemptions to prevalent racial and ethnic health inequalities and can serve as a positive example for adequate and fair provision of surgical care.

Long-term sequelae of critical illness in sepsis, trauma and burns: A systematic review and meta-analysis.

BACKGROUND: Sepsis, major trauma, and severe burn injury are life-threatening critical illnesses that remain significant contributors to worldwide morbidity and mortality. The three underlying etiologies share pathophysiological similarities: hyperinflammation, hypermetabolism, and acute immunomodulation. The aims of this study were to assess the current state of long-term outcome research and to identify key outcome parameters between the three forms of critical illness. METHODS: This systematic review and meta-analysis (MA) were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed was searched from January 1, 1975, to December 31, 2019. Studies were assessed for eligibility by independent reviewers. Inclusion criteria were studies reporting at least a 6-month follow-up of health-related quality of life and organ-specific sequelae within the three etiologies: severe burn injury, sepsis, and major trauma. RESULTS: In total, 125 articles could be included in the systematic review and 74 in the MA. The mean follow-up time was significantly longer in burn studies, compared with sepsis and trauma studies. The majority of patients were from the sepsis group, followed by burns, and major trauma studies. In the overall health-related quality of life, as assessed by Short Form 36 and European Quality-of-Life Index, the three different etiologies were comparable with one another. CONCLUSION: The effects of critical illness on survivors persist for years after hospitalization. Well-reported and reliable data on the long-term outcomes are imperative, as they can be used to determine the treatment choice of physicians and to guide the expectations of patients, improving the overall quality of care of three significant patient cohorts. LEVEL OF EVIDENCE: Systematic review and MA, level III.

Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy.

Transplantation of patient-derived Schwann cells is a promising regenerative medicine therapy for spinal cord injuries; however, therapeutic efficacy is compromised by inefficient cell delivery. We present a materials-based strategy that addresses three common causes of transplanted cell death: (i) membrane damage during injection, (ii) cell leakage from the injection site, and (iii) apoptosis due to loss of endogenous matrix. Using protein engineering and peptide-based assembly, we designed injectable hydrogels with modular cell-adhesive and mechanical properties. In a cervical contusion model, our hydrogel matrix resulted in a greater than 700% improvement in successful Schwann cell transplantation. The combination therapy of cells and gel significantly improved the spatial distribution of transplanted cells within the endogenous tissue. A reduction in cystic cavitation and neuronal loss were also observed with substantial increases in forelimb strength and coordination. Using an injectable hydrogel matrix, therefore, can markedly improve the outcomes of cellular transplantation therapies.

Pterocellin A isolated from marine bryozoan Pterocella vesiculosa is cytotoxic to human HeLa cells via mitochondrial apoptotic processes.

Pterocellin A is a novel bioactive alkaloid isolated from the New Zealand marine bryozoan Pterocella vesiculosa. It exhibits potent antitumour activity towards the P388 (murine leukaemia) cell line in vitro and is selectively sensitive towards certain non-small cell lung, melanoma, and breast cancer cell lines, however, the biological mode of action of pterocellin A is unknown. Using the human cervical cancer cell line HeLa, we show that pterocellin A exhibited cytotoxicity against HeLa cells with an IC50 of 886 ng/mL. Time-course MTT and LDH assays were carried out and the results showed only a low level of cytosolic LDH was detected in the supernatant after all the cells have died from pterocellin A treatment at 2000 ng/mL. This indicated the cells maintained membrane integrity upon cell death which suggested apoptotic cell death. Additionally, morphological changes were observed under the microscope after 6 h of treatment. Cell shrinkage and nucleus condensation were observed, as well as apparent membrane blebbing, a key feature of apoptosis. The MTT data was also indicative of mitochondria impairment which could suggest that pterocellin A targets the mitochondria. This idea was supported by the observed changes in the morphology and location of the mitochondria after exposure to pterocellin A. Furthermore, the level of activated caspase-3 in HeLa cells increased after treatment with pterocellin A; activated caspase-3 can only be detected after a series of signalling events following the induction of apoptosis. These data support the notion that pterocellin A is an inducer of apoptosis in HeLa cells possibly via mitochondria related processes.