Incomes to Outcomes: A Global Assessment of Disparities in Cleft and Craniofacial Treatment.

OBJECTIVE: Recent investigations focused on health equity have enumerated widespread disparities in cleft and craniofacial care. This review introduces a structured framework to aggregate findings and direct future research. DESIGN: Systematic review was performed to identify studies assessing health disparities based on race/ethnicity, payor type, income, geography, and education in cleft and craniofacial surgery in high-income countries (HICs) and low/middle-income countries (LMICs). Case reports and systematic reviews were excluded. Meta-analysis was conducted using fixed-effect models for disparities described in three or more studies. SETTING: N/A. PATIENTS: Patients with cleft lip/palate, craniosynostosis, craniofacial syndromes, and craniofacial trauma. INTERVENTIONS: N/A. RESULTS: One hundred forty-seven articles were included (80% cleft, 20% craniofacial; 48% HIC-based). Studies in HICs predominantly described disparities (77%,) and in LMICs focused on reducing disparities (42%). Level II-IV evidence replicated delays in cleft repair, alveolar bone grafting, and cranial vault remodeling for non-White and publicly insured patients in HICs (Grades A-B). Grade B-D evidence from LMICs suggested efficacy of community-based speech therapy and remote patient navigation programs. Meta-analysis demonstrated that Black patients underwent craniosynostosis surgery 2.8 months later than White patients (P < .001) and were less likely to undergo minimally-invasive surgery (OR 0.36, P = .002). CONCLUSIONS: Delays in cleft and craniofacial surgical treatment are consistently identified with high-level evidence among non-White and publicly-insured families in HICs. Multiple tactics to facilitate patient access and adapt multi-disciplinary case in austere settings are reported from LMICs. Future efforts including those sharing tactics among HICs and LMICs hold promise to help mitigate barriers to care.

A critical eye on metopic craniosynostosis: A retrospective study assessing orbital dysmorphology as a marker of disease.

This investigation sought to ascertain whether orbital morphology could predict genuine metopic craniosynostosis (MCS). The study retrospectively analyzed preoperative three-dimensional computed tomography (3D-CT) scans of patients who underwent surgical correction for MCS. MCS severity was evaluated using the interfrontal angle (IFA). Orbital dysmorphology was assessed based on multiple angles, including supraorbital notches and nasion (SNS), infraorbital foramina and nasion (INI), zygomaticofrontal suture-supraorbital notch-dacryon (ZSD), and orbital long axis (OLA). Results were juxtaposed against age/gender-matched controls and individuals with non-synostotic metopic ridge (MR). The study included 177 patients: 68 MCS, 35 MR, and 74 control subjects. All orbital measurements exhibited significant differences across groups. IFA demonstrated a strong association with all orbital measurements, particularly SNS (B = 0.79, p < 0.001). SNS showed the highest area under the curve among orbital measurements (0.89). Using a 95% sensitivity threshold, the optimal diagnostic angle for SNS was 129.23° (specificity 54%, sensitivity 96%). These findings suggest a correlation between orbital dysmorphology and trigonocephaly severity. The observed dysmorphology manifested in a superomedially accentuated rotational pattern. Importantly, SNS angle predicted MCS, with an angle greater than 130° indicating <5% likelihood of MCS diagnosis. The simplicity of measuring SNS angle on any 3D-CT scan highlights its practical use for assisting with MCS diagnosis.

Validating the Supraorbital Notch-Nasion-Supraorbital Notch Angle as a Marker for Metopic Craniosynostosis Severity.

OBJECTIVE: Metopic craniosynostosis (MCS) can be difficult to differentiate from metopic ridge (MR) or normal frontal morphology. This study assess whether the supraorbital notch-nasion-supraorbital notch (SNS) angle can help identify MCS. METHODS: Records of 212 patients with preoperative three-dimensional computed tomography scans were examined. The SNS angles, surgeon craniofacial dysmorphology rankings, and CranioRate metopic severity scores (MSSs) were compared with the Spearman rank correlation coefficient. Receiver operating characteristic (ROC) curves with Youden J-statistic and cross-validation of regression models assessed the ability of these measures to predict surgery. RESULTS: A total of 212 patients were included, consisting of 78 MCS, 37 MR, and 97 controls. Both the mean SNS angle (MCS: 111.7 ± 10.7 degrees, MR: 126.0 ± 8.2 degrees, controls: 130.7 ± 8.8 degrees P < 0.001) and MSS (MCS: 5.9 ± 2.0, MR: 1.4 ± 1.9, controls: 0.2 ± 1.9, P < 0.001) were different among the cohorts. The mean SNS angle (111.5 ± 10.7 versus 129.1 ± 8.8, P < 0.001) was lower in those who had surgery and CranioRate score (5.9 ± 2.1 versus 0.8 ± 2.2, P < 0.001) was higher in those who underwent surgery. SNS angles were positively correlated with surgeon craniofacial dysmorphology rankings ( r = 0.41, P < 0.05) and CranioRate MSS ( r = 0.54, P < 0.05). The ROC curve requiring high sensitivity revealed an SNS angle of 124.8 degrees predicted surgery with a sensitivity of 88.7% and a specificity of 71.3%. A ROC curve using the CranioRate MCC values ≥3.19 predicted surgery with 88.7% sensitivity and 94.7% specificity. CONCLUSION: Orbital dysmorphology in patients with MCS is well captured by the supraorbital-nasion angle. Both the SNS angle and CranioRate MSS scores accurately predict surgical intervention.

Orthognathic Considerations of Maxillary and Mandibular Asymmetry at Skeletal Maturity in Patients with Cleft Lip and Palate.

BACKGROUND: Improving occlusion and aesthetics is the primary objective of orthognathic surgery for patients with cleft lip and palate (CLP). However, these patients often suffer from horizontal, vertical, and rotational asymmetry in addition to maxillary retrusion. This study aims to describe maxillary and mandibular asymmetry in patients with CLP undergoing orthognathic surgery and analyze its anatomic basis. METHODS: Patients with isolated CLP undergoing CT imaging prior to orthognathic surgery were retrospectively reviewed. Maxillary and mandibular positioning and dimensional symmetry were evaluated. Incidence of clinically significant asymmetry, correlations between areas of asymmetry, and associations with clinical history were analyzed. RESULTS: Fifty-eight patients, with mean age 17 years were analyzed, including 32 patients with unilateral CLP and 26 with bilateral CLP. Twenty (34%) patients demonstrated chin deviation ≥4mm and 21 (36%) had a ≥5% discrepancy in mandibular ramus lengths. Horizontal occlusal plane cant of ≥2° was seen in 20 (34%) maxillae and 28 (48%) mandibles, with dental arch yaw ≥2° noted in 32 (55%) of both maxillae and mandibles. Chin deviation correlated with maxillary cant, discrepancy in ramus length, discrepancy in mandibular body length, and discrepancy in condylar volume (p<0.05). Bilateral and unilateral CLP did not show significantly different asymmetry on any measure (p>0.05). CONCLUSIONS: Both maxillary and mandibular asymmetry is common in skeletally mature patients with CLP and frequently results in notable chin deviation. Preoperative three-dimensional imaging and virtual surgical planning of orthognathic surgery aid in recognition of facial asymmetries and reveal opportunities to optimize results in this population.

Effects of light- vs. heavy-load squat training on velocity, strength, power, and total mechanical work in recreationally trained men and women.

The purpose of this study was to investigate the effects of light and heavy loads in the squat exercise on kinematics and mechanical variables in recreationally trained men and women. Twenty-two men and sixteen women were assigned to 4 groups: 40% and 80% one-repetition maximum (1RM) male (M40 and M80) and female (F40 and F80). Over 6 weeks, participants performed twice a week the full back-squat (SQ) exercise with initially equated relative volume load (Sets*Repetitions/Set*%1RM). All groups performed different amounts of work (p < 0.05), while relative work (work/1RM) only differed between load groups (p < 0.001). There was no significant Time*Sex*Load interaction. Based on the magnitude of effect sizes: M80 achieved small improvements in the SQ maximum isometric force (MIF; ES = 0.43, 95% CI [0.16, 0.81]); small gains in squat estimated 1RM strength were observed in the 80%-1RM groups (M80: 0.42 [0.18, 0.77]; F80: 0.44 [0.26, 0.76]) and the F40 group (0.42 [0.17, 0.81]); all groups made moderate to large gains in the average velocity attained against heavy loads (> 60%1RM; F40: 1.20 [0.52, 2.27]; F80: 2.20 [1.23, 3.93]; M40: 0.85 [0.29, 1.59]; M80: 1.03 [0.55, 1.77]), as well as small to moderate improvements in the average velocity against light loads (< 60%1RM; F40: 0.49[-0.24, 1.68]; F80: 1.10 [0.06, 3.16]; M40: 0.80 [0.41, 1.35]; M80: 0.93 [0.25, 1.84]). Lastly, only the F40 group showed small improvements in countermovement jump (CMJ) height (ES = 0.65 [0.14, 1.37]). In conclusion, light and heavy loads produced similar strength gains in men and women when initially equated by relative volume load, although the standardized mean differences suggest nuances depending on the sample and task.

Psychosocial Status and Self-Perception in Patients with Cleft Lip and/or Palate.

OBJECTIVE: To describe how the psychosocial status of patients with cleft lip and/or palate (CL/P) relates to patient-reported outcomes (PROs). DESIGN: Cross-sectional retrospective chart review. SETTING: Tertiary care pediatric hospital. PATIENTS/PARTICIPANTS: Patients aged 8 to 29 years attending cleft team evaluations during a 1-year period. MAIN OUTCOME MEASURES: CLEFT-Q. RESULTS: Patients (N = 158) with isolated or syndromic CL/P and mean age 13.4 ± 3.0 years were included. Fifteen (9%) patients had siblings who also had CL/P. Of 104 patients who met with the team psychologist, psychosocial concerns were identified in 49 (47%) patients, including 25 (24%) with Attention-Deficit/Hyperactivity Disorder or behavior concerns, 28 (27%) with anxiety, and 14 (13%) with depression or mood concerns. Younger age and having siblings with cleft were associated with better PROs, while psychosocial concerns were associated with worse PROs on Speech, Psychosocial, and Face Appearance scales. CONCLUSIONS: Patient perception of cleft outcomes is linked to psychosocial factors.

Sociodemographic Factors Predict Long-Term Attrition from Multidisciplinary Cleft Clinic.

OBJECTIVE: Identify and describe factors associated with retention and attrition of patients during longitudinal follow-up at multidisciplinary cleft clinic. DESIGN: Retrospective cohort study. SETTING: Single, tertiary care center. PATIENTS, PARTICIPANTS: Patients born between 1995 and 2007 with a diagnosis of cleft palate with or without cleft lip attending multidisciplinary cleft clinic. INTERVENTIONS: None tested, observational study. MAIN OUTCOME MEASURE(S): Age at last clinical appointment with a multidisciplinary cleft team provider. Attrition was defined as absence of an outpatient appointment following 15 years of age. RESULTS: Six hundred seventy-eight patients were included. The average age at last appointment across the entire cohort was 13.1 years (IQR 6.6-17.2). Patients who were Black (HR 1.60, 95% CI 1.10-2.32, p = 0.014) and other races (HR 1.90, 95% CI 1.22-2.98, p = 0.004) were more likely to be lost to follow-up compared to white patients. Publicly insured patients were more likely to experience attrition than those who were privately insured (HR 1.30, 95% CI 1.03-1.65, p = 0.030). Estimated income was not significantly associated with length of follow-up (p = 0.259). Those whose residence was in the fourth quartile of driving distance from our center experienced loss to follow-up significantly more than those who lived the closest (HR 2.04, 95% CI 1.50-2.78, p < 0.001). CONCLUSIONS: There is a high degree of follow-up attrition among patients with cleft lip and palate. Race, insurance status, and driving distance to our center were associated with attrition in a large, retrospective cohort of patients who have reached the age of cleft clinic graduation.

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

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

Long-Term Orbito-ocular Outcomes Following LeFort III and Monobloc Distraction Osteogenesis in Patients with Syndromic Craniosynostosis.

INTRODUCTION: Exorbitism in patients with syndromic craniosynostosis is often managed by LeFort III (LF3) or Monobloc (MB) distraction osteogenesis (DO). This study compared short- and long-term orbital craniometrics after LF3DO/MBDO and related these findings to symptom relief. METHODS: Patients undergoing LF3DO or MBDO from 2000-2021 with pre- and postoperative imaging were included. Postoperative CTs were categorized as early (<1 year) or late (>1 year), and age-matched control CTs were compared to late postoperative scans. Superior/inferior orbital rim position, relative globe position, and orbital volume were analyzed. Symptoms were assessed by a patient-reported outcome (PRO) analysis. RESULTS: Thirty-four patients (16 LF3DO, 18 MBDO) were matched by age at surgery, sex, syndrome, and age at imaging. Time to late CT was 6.2 years (LF3DO) and 7.5 years (MBDO). Between early and late postoperative time points, LF3DO patients experienced no change in inferior rim position. MBDO patients experienced a decrease in inferior orbital rim position of 4.7mm (p=0.005), but superior orbital rim distance remained stable. Comparison of late scans and age-matched controls revealed no difference in inferior or superior orbital rim position in LF3DO patients, but the superior orbital rim distance was longer in MBDO patients (p=0.015). PRO response rate was 76% with a median follow up of 13.7 years. Most (81%) symptomatic patients improved, 19% remained symptomatic, and no patients worsened. CONCLUSIONS: LF3DO and MBDO achieved stable orbital craniometric changes, with improved stability at the inferior orbital rim after LF3DO. Craniometric changes were associated with long-term exorbitism symptom relief.

Predisposing Factors for Postoperative Complications in the Year Following Fronto-Orbital Advancement and Remodeling: A Single Institution Study of 267 Patients.

BACKGROUND: Fronto-orbital advancement and remodeling (FOAR) is a common surgical approach used for craniosynostosis conferring functional and aesthetic benefit. There are few reports examining predisposing factors for postoperative complications within the first year after surgery. This study aimed to establish complication rates and identify risk factors for inferior outcomes in a large population of patients undergoing FOAR. METHODS: All patients who underwent fronto-orbital advancement and remodeling from 2013-2022 at our institution were retrospectively studied. Perioperative and postoperative data were collected to yield outcomes analyses. Multivariable logistic regression with backwards selection was performed to identify predictors of postoperative complications. RESULTS: 267 patients underwent FOAR. The overall complication rate was 14.2%, most commonly delayed wound healing (7.4%), postoperative blood transfusion (5.8%), and infection requiring readmission (1.9%). Tense closure independently predicted delayed wound healing (p<0.001) and infection requiring readmission (p=0.03). Syndromic patients were more likely than non-syndromic children to have undergone prior craniofacial surgery (45.3% vs 23.8%, p=0.003). Syndromic status and prior craniofacial surgery were associated with increased risk of developing infection requiring readmission (p=0.012 and p=0.004, respectively). A greater proportion of malnourished patients experienced postoperative complications compared to patients without malnourishment (24.4% vs 12.1%, p=0.031), though there were no significant differences in individual postoperative outcomes. CONCLUSIONS: Identified risk factors for complications included syndromic status, tense closure, and prior craniofacial surgery. Most complications were managed nonoperatively. These factors may be considered in preoperative planning and when counseling patient families.

ARGEN SHOCK: Mortality related to the use of Swan Ganz and to the hemodynamic pattern found in patients with AMICS.

The Swan Ganz Catheter (SGC) allows us to diagnose different types of cardiogenic shock (CS). OBJECTIVES: 1) Determine the frequency of use of SGC, 2) Analyze the clinical characteristics and mortality according to its use and 3) Analyze the prevalence, clinical characteristics and mortality according to the type of Shock. METHODS: The 114 patients (p) from the ARGEN SHOCK registry were analyzed. A "classic" pattern was defined as PCP > 15 mm Hg, CI < 2.2 L/min/ m2, SVR > 1,200 dynes × sec × cm-5. A "vasoplegic/mixed" pattern was defined when p did not meet the classic definition. CS due to right ventricle (RV) was excluded. RESULTS: SGC was used in 35 % (n:37). There were no differences in clinical characteristics according to SGC use, but those with SGC were more likely to receive dobutamine, levosimendan, and intra aortic balloon pump (IABP). Mortality was similar (59.4 % vs 61.3 %). The pattern was "classic" in 70.2 %. There were no differences in clinical characteristics according to the type of pattern or the drugs used. Mortality was 54 % in patients with the classic pattern and 73 % with the mixed/vasoplegic pattern, but the difference did not reach statistical significance (p:0.23). CONCLUSIONS: SGC is used in one third of patients with CS. Its use does not imply differences in the drugs used or in mortality. Most patients have a classic hemodynamic pattern. There are no differences in mortality or in the type of vasoactive agents used according to the CS pattern found.

Severity of Mandibular Dysmorphology in Treacher Collins Syndrome for Stratification of Perioperative Airway Risk.

BACKGROUND: Patients with Treacher Collins syndrome (TCS) and attendant airway dysmorphology may be predisposed to airway complications in the perioperative period. However, limited data correlates severity of mandibular hypoplasia and airway status. This study aims to improve risk stratification for perioperative airway insufficiency in TCS by using a previously proposed mandibular severity index. METHODS: Patient demographics, perioperative airway status, difficulty of intubation, and Cormack Lehane grade were collected and compared using a TCS mandibular hypoplasia severity grading scale in patients with TCS treated between 2000 and 2022. RESULTS: Twenty-six patients underwent 222 procedures with institutional mandibular severity gradings as follows: 23% Grade I, 31% Grade II, 39% Grade III, 8% Grade IV. Our severity index was associated with intubation difficulty ( P <0.001) and difficult airway status ( P <0.001), with 72% of difficult airways found in grade III and grade IV patients. Mandibular retrusion and ramal hypoplasia subscores were positively correlated with measures of airway severity ( P <0.001), whereas the gonial angle was negatively correlated ( P <0.001). Age was negatively correlated with difficult visualization for endotracheal intubation ( P =0.02) but had no association with difficult airway status ( P =0.2). CONCLUSIONS: This study found a positive correlation between severity of maxillomandibular dysmorphology and perioperative airway difficulty in TCS patients. Our findings suggest that severely affected patients require heightened vigilance throughout life, as difficult airways may not completely resolve with aging. Given the risk of morbidity and mortality associated with airway complications, proper identification and preparation for challenging airways is critical for TCS patients.

LeFort III Versus Monobloc Frontofacial Advancement: A Comparative Analysis of Soft Tissue Changes.

INTRODUCTION: The LeFort III and monobloc are commonly used midface advancement procedures for patients with syndromic craniosynostosis with well characterized postoperative skeletal changes. However, the differential effects of these procedures on facial soft tissues are less understood. The purpose of this study was to critically analyze and compare the effects of these 2 procedures on the overlying soft tissues of the face. METHODS: Frontal and lateral preoperative and postoperative photographs of patients undergoing monobloc or LeFort III were retrospectively analyzed using ImageJ to measure soft tissue landmarks. Measurements included height of facial thirds, nasal length and width, intercanthal distance, and palpebral fissure height and width. Facial convexity was quantified by calculating the angle between sellion (radix), subnasale, and pogonion on lateral photographs. RESULTS: Twenty-five patients with an average age of 6.7 years (range 4.8-14.5) undergoing monobloc (n=12) and LeFort III (n=13) were identified retrospectively and analyzed preoperatively and 6.4±3.6 months postoperatively. Patients undergoing LeFort III had a greater average postoperative increase in facial convexity angle acuity (28.2°) than patients undergoing monobloc (17.8°, P =0.021). Patients in both groups experience postoperative increases in nasal width ( P <0.001) and decreases in palpebral fissure height ( P <0.001). CONCLUSIONS: Both subcranial LeFort III advancements and monobloc frontofacial advancements resulted in significant changes in the soft tissues. Patients undergoing LeFort III procedures achieved greater acuity of the facial convexity angle, likely because the nasion is not advanced with the LeFort III segment.

Risk of ADHD, Autism Spectrum Disorder, and Executive Function Impairment in Metopic Craniosynostosis.

INTRODUCTION: Favorable behavioral interactions are critical for academic and interpersonal success. An association between metopic synostosis and behavioral impairments has not been fully elucidated. Behavioral dysfunction in school age children with surgically corrected metopic synostosis was evaluated using targeted testing to detect the most common behavioral abnormalities in this population. METHODS: Parents of children 6-18 years old with metopic synostosis completed the Conners Short 3 rd edition (Conners-3: ADHD), Social Responsiveness Scale 2 nd edition (SRS-2: autism spectrum disorder), Behavior Rating Inventory of Executive Function 2 nd edition (BRIEF-2: executive functioning), and Child's Behavioral Checklist (CBCL: behavioral/emotional functioning). Children also completed neurocognitive testing. Multivariable regression was used to determine predictors of clinically significant behavioral impairments. RESULTS: 60 children were enrolled. Average age at surgery was 9.2 ± 7.9 months, with an average age at assessment of 10.3 ± 3.5 years. Nearly half of patients demonstrated symptoms associated with ADHD, demonstrated by reaching or exceeding borderline clinical levels for inattention and hyperactivity subscales of the Conners-3. Greater age at surgery was associated with worse executive function, measured by reaching or exceeding clinically significant levels of the executive function subscale of the Conners-3 (p=0.04) and subscales of the BRIEF-2 (behavioral regulator index [p=0.05], cognitive regulatory index [p=0.03], and global executive composite [p=0.04]). CONCLUSIONS: Nearly half of patients with surgically corrected metopic synostosis reached borderline clinical scores for inattention and hyperactivity. Greater age at surgery was associated with worse executive function. Prompt surgical correction of metopic synostosis may portend improved long-term emotional and behavioral function.

Shock cardiogénico en el contexto de los síndromes coronarios agudos en Argentina: resultados del Registro ARGEN SHOCK 2 / Cardiogenic Shock in the Setting of Acute Coronary Syndromes in Argentina: Results from the ARGEN SHOCK 2 Registry

RESUMEN El shock cardiogénico (SC) es una complicación grave del infarto agudo de miocardio (IAM) y constituye una de sus principales causas de muerte. Objetivos: Conocer las características clínicas, estrategias de tratamiento, evolución intrahospitalaria y mortalidad a 30 días del SC en Argentina. Material y métodos: Se trata de un registro prospectivo, multicéntrico, de pacientes internados con SC en el contexto de los IAM con y sin elevación del segmento ST durante 14 meses (1 de agosto 2021 al 30 de septiembre 2022) en 23 centros de Argentina. Resultados: Se incluyeron 114 pacientes, edad 64 (58-73) años, 72% hombres. El 76,3% de los casos corresponden a IAM con elevación del segmento ST, 12,3% a IAM sin elevación del segmento ST, el 7% a infarto de ventrículo derecho y el 4,4% a complicaciones mecánicas. El SC estuvo presente desde el ingreso en el 66,6% de los casos. Revascularización: 91,1%, uso de inotrópicos: 98,2%, asistencia respiratoria mecánica: 59,6%, SwanGanz: 33,3%, balón de contrapulsación intraaórtico: 30,1%. La mortalidad intrahospitalaria global fue 60,5%, sin diferencias entre los IAM con o sin elevación del segmento ST, y a 30 días del 62,6%. Conclusiones: La morbimortalidad del SC es muy elevada a pesar de la alta tasa de reperfusión empleada.

ABSTRACT Background: Cardiogenic shock (CS) is a life-threatening complication of acute myocardial infarction (AMI) and constitutes one of the leading causes of death. Objective: The aim of this study was to investigate the clinical characteristics, treatment strategies, hospital outcome and 30-day mortality of CS in Argentina. Methods: We conducted a prospective, and multicenter registry of patients with acute myocardial infarction (AMI) with and without ST-segment elevation complicated with CS that were hospitalized in 23 centers in Argentina for 14 months (between August 1, 2021, and September 30, 2022). Results: The cohort was made up of 114 patients; median age was 64 years (58-73) and 72% were women; 76.3% corresponded to ST-segment elevation AMI, 12.3% to non-ST-segment elevation AMI, 7% had right ventricular infarction and 4.4% had mechanical complications. In 66.6% of cases CS was present on admission. Revascularization: 91.1%, use of inotropic agents: 98.2%, mechanical ventilation: 59.6%, Swan-Ganz catheter: 33.3%, intra-aortic balloon pump: 30.1%. Overall in-hospital mortality was 60.5%, with no differences between AMI with or without ST-segment elevation, and was 62.6% at 30 days. Conclusion: Morbidity and mortality of CS are high despite the high rate of reperfusion therapy used.

(Epi)genotype and Timing of Tongue Reduction Predict Safety and Long-Term Outcomes in Beckwith-Wiedemann Syndrome.

INTRODUCTION: Macroglossia is a cardinal feature of Beckwith-Wiedemann syndrome (BWS) with a clinical spectrum where the indication and timing for surgery remain to be validated. This study leverages a cohort of molecularly characterized patients with BWS to correlate epigenetic diagnosis with phenotype and treatment outcome. METHODS: Patients with BWS seen in consultation for macroglossia from 2009-2022 were reviewed for phenotype, molecular diagnosis, tongue reduction status, timing of surgery (early = under 12 months), and perioperative complications. RESULTS: Two hundred thirty-seven patients were included. Imprinting control region 2 loss of methylation (IC2 LOM) was the most common epigenotype (61%). Paternal uniparental isodisomy for chromosome 11 (pUPD11) comprised a larger proportion of patients undergoing tongue reduction (18%) than those not undergoing surgery (8%, p = 0.024) and was associated with need for repeat surgery (OR 4.49, 95% CI 1.06-18.98, p = 0.041). Complications including wound dehiscence, ventilator associated pneumonia, and unplanned extubation were more common in patients undergoing early surgery (20%) than late surgery (4%, OR 5.70, 95% CI 1.14-28.55, p = 0.034). CONCLUSIONS: This study presents one of the largest cohorts correlating molecular diagnosis with clinical course of macroglossia treatment in BWS. Macroglossia in patients with pUPD11 is associated with higher rates of reoperation. Relief of obstructive sleep apnea with early tongue reduction must be weighed against risk of perioperative complications, most of which are non-surgical. This study highlights how molecular diagnosis advances clinical care by risk stratifying clinical outcomes in a center providing integrated multidisciplinary care for the BWS population.

Task Shifting and Task Sharing to Strengthen the Surgical Workforce in Sub-Saharan Africa: A Systematic Review of the Existing Literature.

BACKGROUND: A major constraint to surgical care delivery in low-resource settings is inadequate workforce availability. Surgical task shifting (TShifting) and task sharing (TSharing), in which non-surgeon clinicians (NSCs) are trained to perform select surgical procedures, have been proposed as one solution. However, patterns of safety and efficacy of surgical TShifting/TSharing are not well-established. This study aims to summarize the current literature and assess clinical outcomes and impact of surgical TShifting/TSharing in sub-Saharan Africa. METHODS: A two-tiered systematic, PRISMA-adherent literature review of surgical TShifting/TSharing in sub-Saharan Africa was conducted. Collected data included healthcare settings; types of surgeries performed; attitudes toward NSCs; and categories, training, capacity, clinical outcomes, safety, retention, cost-effectiveness, and supervision of NSCs. A random effects meta-analysis of morbidity and mortality rates between NSCs and surgeons was conducted. RESULTS: Among the 659 abstracts screened, 31 studies met inclusion criteria and were integrated in the final analysis. Eighteen studies (58%) report on the capacity and aptitude of NSCs, 16 (52%) on clinical outcomes and safety, and seven (23%) on attitudes. NSCs performed 1999 (61%) of 3304 total surgical cases studied. The most common operations reported were hernia repair (n = 12, 57%), acute abdominal (n = 12, 57%), and orthopedic procedures (n = 6, 29%). No differences were found between NSC and surgeon case morbidity [315 (16%) vs. 224 (17%); p > 0.05] and mortality [44 (2.2%) vs. 33 (2.5%); p > 0.05] rates. CONCLUSION: NSCs are increasingly performing surgical tasks in regions of sub-Saharan Africa deficient in trained surgeons and appear to have non-inferior safety outcomes in select programs.

Extracellular Acetylated Histone 3.3 Induces Inflammation and Lung Tissue Damage.

Extracellular histones, part of the protein group known as damage-associated molecular patterns (DAMPs), are released from damaged or dying cells and can instigate cellular toxicity. Within the context of chronic obstructive pulmonary disease (COPD), there is an observed abundance of extracellular histone H3.3, indicating potential pathogenic implications. Notably, histone H3.3 is often found hyperacetylated (AcH3.3) in the lungs of COPD patients. Despite these observations, the specific role of these acetylated histones in inducing pulmonary tissue damage in COPD remains unclear. To investigate AcH3.3's impact on lung tissue, we administered recombinant histones (rH2A, rH3.3, and rAcH3.3) or vehicle solution to mice via intratracheal instillation. After 48 h, we evaluated the lung toxicity damage and found that the rAcH3.3 treated animals exhibited more severe lung tissue damage compared to those treated with non-acetylated H3.3 and controls. The rAcH3.3 instillation resulted in significant histological changes, including alveolar wall rupture, epithelial cell damage, and immune cell infiltration. Micro-CT analysis confirmed macroscopic structural changes. The rAcH3.3 instillation also increased apoptotic activity (cleavage of caspase 3 and 9) and triggered acute systemic inflammatory marker activation (TNF-α, IL-6, MCP-3, or CXCL-1) in plasma, accompanied by leukocytosis and lymphocytosis. Confocal imaging analysis confirmed lymphocytic and monocytic/macrophage lung infiltration in response to H3.3 and AcH3.3 administration. Taken together, our findings implicate extracellular AcH3.3 in inducing cytotoxicity and acute inflammatory responses, suggesting its potential role in promoting COPD-related lung damage progression.

Secreted folate receptor γ drives fibrogenesis in metabolic dysfunction-associated steatohepatitis by amplifying TGFß signaling in hepatic stellate cells.

Hepatic fibrosis is the primary determinant of mortality in patients with metabolic dysfunction-associated steatohepatitis (MASH). Transforming growth factor-ß (TGFß), a master profibrogenic cytokine, is a promising therapeutic target that has not yet been translated into an effective therapy in part because of liabilities associated with systemic TGFß antagonism. We have identified that soluble folate receptor γ (FOLR3), which is expressed in humans but not in rodents, is a secreted protein that is elevated in the livers of patients with MASH but not in those with metabolic dysfunction-associated steatotic liver disease, those with type II diabetes, or healthy individuals. Global proteomics showed that FOLR3 was the most highly significant MASH-specific protein and was positively correlated with increasing fibrosis stage, consistent with stimulation of activated hepatic stellate cells (HSCs), which are the key fibrogenic cells in the liver. Exposure of HSCs to exogenous FOLR3 led to elevated extracellular matrix (ECM) protein production, an effect synergistically potentiated by TGFß1. We found that FOLR3 interacts with the serine protease HTRA1, a known regulator of TGFBR, and activates TGFß signaling. Administration of human FOLR3 to mice induced severe bridging fibrosis and an ECM pattern resembling human MASH. Our study thus uncovers a role of FOLR3 in enhancing fibrosis.

Speech Outcomes and Rates of Secondary Speech Surgery from Childhood to Skeletal Maturity Following Modified-Furlow Palatoplasty.

BACKGROUND: This study updates our institutional experience with modified Furlow palatoplasty, evaluating speech outcomes and incidence of secondary speech surgery throughout development and at skeletal maturity. METHODS: Nonsyndromic patients undergoing primary modified Furlow palatoplasty between 1985 and 2005 with post-operative speech evaluations were retrospectively reviewed. Secondary speech surgery and Pittsburgh Weighted Speech Scale (PWSS) scores prior to secondary speech or orthognathic surgeries were assessed in the 5-7, 8-11, 12-14, and 15+ age groups and analyzed by Veau cleft type. RESULTS: Five hundred fifty-one patients with 895 total speech assessments were analyzed. Of 364 patients followed to age 15 or older, 19.8% underwent secondary speech surgery. Speech assessment of patients aged 15 or older without prior secondary speech surgery showed competent velopharyngeal mechanisms in 77% of patients. PWSS nasal emission scores were worse in the 5-7 age range (p=0.02), while resonance scores remained stable throughout development (p=0.2). Patients with Veau type I or II clefts had worse overall PWSS classifications in the age 5-7 and 8-11 age groups (p=0.01, p=0.03), with greater odds of secondary speech surgery relative to those with Veau type III (OR 2.9, p<0.001) or IV clefts (OR 3.6, p=0.001). CONCLUSIONS: Most patients undergoing primary modified Furlow palatoplasty do not require secondary speech surgery and achieve socially acceptable speech at skeletal maturity. However, Veau type I and II clefts are associated with increased risk for early velopharyngeal dysfunction and secondary speech surgery. Incidence of secondary speech surgery was 19.8%, an increase from our previously reported rate of 8%.