Alterations in Sphenoid Anatomy in Craniosynostosis: Implications for Fronto-Orbital Advancement.

OBJECTIVE: Fronto-orbital advancement involves removal of the fronto-orbital bandeau. Visualization of the saw blade is lost as it passes through the fronto-orbital-sphenoid junction (FOSJ), placing the temporal lobe at risk of injury. We aim to provide a 3D analysis of the space surrounding this osteotomy to differentiate various types of craniosynostoses. DESIGN: Retrospective cohort. SETTING: Institutional. PATIENTS: Thirty patients with isolated unicoronal synostosis, nonsyndromic bicoronal synostosis, metopic synostosis, Apert syndrome, Crouzon syndrome, and Muenke syndrome. INTERVENTIONS: CT scans conducted between 2 months to 2 years of age were 3D reconstructed to compare craniometrics against normal controls. MAIN OUTCOME MEASURE(S): Craniometrics. RESULTS: The mean bone thickness of the FOSJ at the level of the supraorbital rim was significantly small for the Apert, unicoronal and bicoronal groups. The mean vertical height of the middle cranial fossa from the lesser sphenoid wing was significantly greater in the unicoronal group. The mean vertical height of the tip of the temporal lobe from the lateral sphenoid ridge was greater in the unicoronal, isolated bicoronal, and Apert groups. The mean corneal protrusion beyond the lateral orbital rim was significantly greater in the Apert and unicoronal groups. The mean horizontal depth of the orbit was smallest in the Apert group. The mean vertical distance between the dacryon and the foramen cecum, and the mean volume of temporal lobe beneath the sphenoid shelf were the largest in the Apert group. CONCLUSIONS: Patients with Apert syndrome have the most unfavorable morphology of the anterior and middle cranial fossae.

Patient-specific Composite Anatomic Models: Improving the Foundation for Craniosynostosis Repair.

Preoperative surgical planning incorporating computer-aided design and manufacturing is increasingly being utilized today within the fields of craniomaxillofacial, orthopedic, and neurosurgery. Application of these techniques for craniosynostosis reconstruction can include patient-specific anatomic reference models, "normal" reference models or patient-specific cutting/marking guides based on the presurgical plan. The major challenge remains the lack of tangible means to transfer the preoperative plan to the operating table. We propose a simple solution to utilize a digitally designed, 3D-printed "composite model" as a structural template for cranial vault reconstruction. The composite model is generated by merging the abnormal patient cranial anatomy with the "dural surface topography" of an age-matched, sex-matched, and ethnicity-matched normative skull model. We illustrate the applicability of this approach in 2 divergent cases: 22-month-old African American male with sagittal synostosis and 5-month-old White male with metopic synostosis. The aim of this technical report is to describe our application of this computer-aided design and modeling workflow for the creation of practical 3D-printed skulls that can serve as intraoperative frameworks for the correction of craniosynostosis. With success in our first 2 cases, we believe this approach of a composite model is another step in reducing our reliance on subjective guesswork, and the fundamental aspect of the workflow has a wider application within the field of craniofacial surgery for both clinical patient care and education.

Long-term Outcomes After Pediatric Free Flap Reconstruction.

INTRODUCTION: Whereas free tissue transfer has evolved to minimize morbidity in adults, less is known about outcomes after free flaps in children. This study sought to assess short- and long-term outcomes after microvascular reconstruction in the pediatric population. METHODS: Short- and long-term outcomes of free tissue transfer were assessed using chart-review and quality-of-life surveys. The Pediatric Outcomes Data Collection Instrument was used to evaluate overall health, pain, and ability to participate in normal daily and more vigorous activities. Patient or parent responses were compared against normative data. RESULTS: Forty-two patients underwent 48 flap reconstructions at a mean age of 8 years. Median follow-up was 14.9 years. Indications included congenital nevi (n = 19, 42%), lymphatic/vascular malformations (n = 8, 19%), and trauma/burns (n = 6, 14%). There were 21 fasciocutaneous (44%), 19 muscle/myocutaneous (40%), 6 fascial/peritoneal (13%), and 2 osteocutaneous flaps (4%). Major flap complications were observed in 4 patients (9%), whereas major donor-site complications occurred in 2% (1 patient). Valid contact information was available for 25 patients; 16 of these completed surveys (64%). Pediatric Outcomes Data Collection Instrument scores for mobility (median, 52), sports/physical functioning (median, 56), happiness (median, 50), and pain/comfort (median, 56) were not significantly different from normative population score of 50. Similarly, median global functioning score was 99 (maximum, 100) and did not differ between flap types. DISCUSSION: Free tissue transfer in the pediatric population is reliable and well-tolerated over time. Surgeons should not hesitate to use free flaps when clinically indicated for pediatric patients.

Genetic polymorphisms in the prostaglandin pathway genes and risk of head and neck cancer.

OBJECTIVE: Previous studies examining the association between genetic variations in prostaglandin pathway and risk of head and neck cancer (HNC) have only included polymorphisms in the PTGS2 (COX2) gene. This study investigated the association between genetic polymorphisms of six prostaglandin pathway genes (PGDS, PTGDS, PTGES, PTGIS, PTGS1 and PTGS2), and risk of HNC. METHODS: Interviews regarding the consumption of alcohol, betel quid, and cigarette were conducted with 222 HNC cases and 214 controls. Genotyping was performed for 48 tag and functional single-nucleotide polymorphisms (SNPs). RESULTS: Two tag SNPs of PTGIS showed a significant association with HNC risk [rs522962: log-additive odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.01-1.99 and dominant OR = 1.58, 95% CI: 1.02-2.47; rs6125671: log-additive OR = 1.49, 95% CI: 1.08-2.05 and dominant OR = 1.96, 95% CI: 1.16-3.32]. In addition, a region in PTGIS tagged by rs927068 and rs6019902 was significantly associated with risk of HNC (global P = 0.007). Finally, several SNPs interacted with betel quid and cigarette to influence the risk of HNC. CONCLUSIONS: Genetic variations in prostaglandin pathway genes are associated with risk of HNC and may modify the relationship between use of betel quid or cigarette and development of HNC.

Exchange hybrid cranioplasty using particulate bone graft and demineralized bone matrix: the best of both worlds.

Reconstruction of craniofacial defects in children presents several challenges that are not encountered in the adult population. Autologous bone grafts have long been the criterion standard for repairing these defects. Recently, several new materials and techniques have expanded our arsenal of reconstructive options. In this clinical report, we describe the use of both particulate bone grafting and demineralized bone matrix together to repair craniofacial defects encountered in pediatric patients.

Normscan: open-source Python software to create average models from CT scans.

PURPOSE: Age-matched average 3D models facilitate both surgical planning and intraoperative guidance of cranial birth defects such as craniosynostosis. We aimed to develop an algorithm that accepts any number of CT scans as input and generates highly accurate, average models with minimal user input that are ready for 3D printing and clinical use. METHODS: Using a compiled database of 'normal' pediatric computed tomography (CT) scans, we report Normscan, an open-source platform built in Python that allows users to generate normative models of CT scans through user-defined landmarks. We use the basion, nasion, and left and right porions as anatomical landmarks for initial correspondence and then register the models using the iterative closest points algorithm before downstream averaging. RESULTS: Normscan is fast and easy to use via our user interface and also creates highly accurate average models of any number of input models. Additionally, it is highly repeatable, with coefficients of variance for the surface area and volume of the average model being less than 3% across ten independent trials. Average models can then be 3D printed and/or visualized in augmented reality. CONCLUSIONS: Normscan provides an end-to-end pipeline for the creation of average models of skulls. These models can be used for the generation of databases of specific demographic anatomical models as well as for intraoperative guidance and surgical planning. While Normscan was designed for craniosynostosis repair, due to the modular nature of the algorithm, Normscan has many applications in other areas of surgical planning and research.

Prompt engineering to increase GPT3.5's performance on the Plastic Surgery In-Service Exams.

This study assesses ChatGPT's (GPT-3.5) performance on the 2021 ASPS Plastic Surgery In-Service Examination using prompt modifications and Retrieval Augmented Generation (RAG). ChatGPT was instructed to act as a "resident," "attending," or "medical student," and RAG utilized a curated vector database for context. Results showed no significant improvement, with the "resident" prompt yielding the highest accuracy at 54%, and RAG failing to enhance performance, with accuracy remaining at 54.3%. Despite appropriate reasoning when correct, ChatGPT's overall performance fell in the 10th percentile, indicating the need for fine-tuning and more sophisticated approaches to improve AI's utility in complex medical tasks.

Primary Cleft Rhinoplasty: A Systematic Review of Results, Growth Restriction, and Avoiding Secondary Rhinoplasty.

BACKGROUND: Primary rhinoplasty during correction of unilateral cleft lip continues to be a topic of debate because of concerns that early nasal intervention may affect nasal and maxillary development over the long term. This study aims to determine the volume and quality of evidence for and against primary unilateral cleft rhinoplasty. METHODS: A systematic review was performed adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles were pulled from PubMed and EMBASE and screened by title and abstract. Studies with human participants undergoing rhinoplasty at the time of unilateral cleft lip repair and some evaluation of the nasal outcome were included. Studies with a large proportion of syndromic patients, case reports, editorials, letters, reviews, studies exclusive to bilateral clefts, and studies not available in English were excluded. Those that met criteria were then systematically reviewed. RESULTS: Twenty-five articles were included. Ten articles that assessed the results of primary rhinoplasty subjectively all supported cleft lip repair with primary rhinoplasty. Sixteen articles assessed the results of primary rhinoplasty objectively, with 15 supporting primary rhinoplasty during cleft lip repair. Eight of nine studies that evaluated nasal growth and development over time found no restriction in nasal development. Five studies with a follow-up period of at least 6 years found that the percentage of patients who avoided revision rhinoplasty ranged from 43% to 100%. There were significant risks of bias in the majority of studies. CONCLUSION: The majority of studies reviewed support that primary rhinoplasty during unilateral cleft lip repair results in good outcomes with limited or no effect on nasal growth.

Outcomes of perineal wound closure techniques after abdominoperineal resections in rectal cancer: an NSQIP propensity score matched study.

Perineal defects following abdominoperineal resections (APRs) for rectal cancer may require myocutaneous or omental flaps depending upon anatomic, clinical and oncologic variables. However, studies comparing their efficacy have shown contradictory results. We aim to compare postoperative complication rates of APR closure techniques in rectal cancer using propensity score-matching. The American College of Surgeons Proctectomy Targeted Data File was queried from 2016 to 2019. The study population was defined using CPT and ICD-10 codes for patients with rectal cancer undergoing APR, stratified by repair technique. Perioperative demographic and oncologic variables were controlled for by propensity-score matching. Multivariate logistic regression analysis was performed for wound and major complications (MCs). Of the 3291 patients included in the study, 85% underwent primary closure (PC), 8.3% rectus abdominis myocutaneous (RAM) flap, 4.9% pedicled omental flap with PC, and 1.9% lower extremity (LE) flap repair. Primary closure rates were significantly higher for patients with stage T1 and T2 tumors (p < 0.001). RAM and LE flaps were most used with multi-organ resections, 24% and 25%, respectively (p < 0.001). Similarly, cases with T4 tumors used these flaps more frequently, 30% and 40%, respectively (p < 0.001). After propensity score matching for comorbidities and oncologic variables, there was no significant difference in 30-day postoperative wound or MC rates between perineal closure techniques. The complication rates of the different closure techniques are comparable when tumor stage is considered. Therefore, tumor staging and concurrent procedures should guide clinical decision making regarding the appropriate use of each technique.

Comparison of Perineal Closure Techniques after Abdominoperineal Resections for Carcinoma of the Anus.

BACKGROUND: Perineal reconstruction following salvage APR's for squamous cell carcinoma of the anus (SCCA) are scant with conflicting results from large and single center studies. We analyzed these techniques taking into account sociodemographic and oncologic variables. METHODS: This is a retrospective cohort study from 2016-2019 using a targeted ACS/NSQIP database stratified into primary closure (PC), abdominal myocutaneous (AM), lower extremity (LE), and omental pedicled (OP) flaps. We analyzed major and wound complications through univariate and multivariate regression analysis. RESULTS: A total of 766 patients were analyzed, 512 (67%) had PC, 196 (25%) AM, 36 (5%) OP and 22 (3%) LE. Rates of chemotherapy and radiation within 90 days were similar between the groups. Having 2 or more additional organs resected was more common for the AM group (AM 4.1%, PC 1.6%, OP 3.3%, LE 0%). Overall, major complication rate was 41% (n = 324). Primary closure had 35.0%, OP 47.2%, AM 52.6%, and LE 45.5%. Wound complication rate was highest in AM with 11.7%, followed by OP 8.3%, PC 5.9%, and LE 0%. The multivariate regression analysis demonstrated none of the closure techniques to be associated with increasing or decreasing the probability of having a major or wound complication. Morbidity probability was the sole predictor of major complication (OR 1.07, 95% CI 1.04-1.1). CONCLUSIONS: Myocutaneous and omental flaps are associated with comparable wound and major complications when taking into account the baseline, oncologic and perioperative variables that drive the clinical decision making when selecting a perineal reconstruction.

A Southeast Asian collaborative Delphi consensus on surveying risk factors for head and neck cancer screening and prevention.

The objective of this study was to determine high value questions for early detection and prevention of head and neck cancer by querying content experts on patient risk factors relevant to local communities in Southeast Asia (i.e., Vietnam, Laos, China, and Singapore). The Delphi method was employed using three rounds of asynchronous surveying which included participants among five different collaborating medical centers. 60 total survey items were assessed for consensus defined by a priori measures on the relative level of value of these questions for use in head and neck cancer screening. 77% of items reached a consensus and no items were concluded to be of low value despite differences in conclusions regarding relative importance. Survey items focused on patient demographic information and physical examination were examined across variables such as expert department affiliation, academic designation, and years of experience and found to be without statistically significant differences. However, with consensus items related to social risk factors, it was determined that participants who had 15 or more years of experience or identified as otolaryngologists rated these items at a relatively lower value than their peers with less experience (p < 0.0001, p = 0.0017) or outside the field of otolaryngology (p = 0.0101). This study explicitly identifies patient variables to consider in head and neck cancer screening that have not previously been comprehensively or methodically assessed in current literature. Increasing awareness of these risk factors may benefit the design and implementation of future head and neck cancer early detection and prevention programs in Southeast Asia and beyond as well as positively impact head and neck cancer outcomes.

A Novel Method of Fibula Flap In Situ Distraction Osteogenesis Prior to Flap Transfer.

BACKGROUND: The fibula flap is the workhorse for mandibular reconstruction, but fibula bone width is not ideal to match mandibular height. In this study, in situ widening of the fibula with distraction osteogenesis before transfer is evaluated as a solution. The authors present a proof of concept of this technique with a patient series, including one patient who has undergone subsequent orthognathic surgery of the reconstructed mandible. METHODS: A retrospective review of patients undergoing the authors' technique was performed. A longitudinal fibula osteotomy was made in situ and distraction was performed in the leg to widen the fibula. After distraction and consolidation periods, flaps were osteotomized and transferred to the mandible. RESULTS: This technique was applied to three patients (ages 9, 11, and 13 years) with Pruzansky III mandibular hypoplasia at the authors' institution over 15 years. In all cases, bony union was achieved. Mean surgical follow-up was 5 years. No significant morbidity occurred at the donor sites. Partial flap resorption was observed a number of years postoperatively in one patient. Temporomandibular joint ankylosis developed in one patient after closed treatment of an unrelated mandible fracture. A sinus tract developed in one patient, requiring débridement of a partial flap necrosis. One patient had orthognathic surgery, including osteotomy of the fibula. CONCLUSIONS: In situ fibula distraction osteogenesis is a novel technique to prelaminate a fibula flap before transfer to the mandible. This method allows for the reconstruction of challenging mandibular defects without compromising bone height, pedicle length, or the ability to perform orthognathic surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Memory T cells are anergic to the superantigen staphylococcal enterotoxin B.

We have used staphylococcal enterotoxin B (SEB) to study the role of naive and memory T cells in the induction of peripheral tolerance. After administration of SEB to mice, the numbers of naive and memory T cells increase, as does the proportion of memory T cells, which are unresponsive to further stimulation with SEB in vitro. In addition, memory T cells generated in response to conventional antigen, which proliferate and provide help to B cells in the presence of the conventional antigen, fail to respond to superantigen. Hence, memory T cells, in general, are anergized by SEB. These results suggest that SEB-induced activation and anergy reflect the combined responses of naive and memory T cells. The differential activation vs. anergy of naive and memory T cells by superantigen may be related to cytokine production and may play an important role in the etiology of autoimmune diseases or immunodeficiency diseases such as acquired immune deficiency syndrome.

The murine lymphocyte receptor for IgE. II. Characterization of the multivalent nature of the B lymphocyte receptor for IgE.

The murine B lymphocyte Fc epsilon R is functionally multivalent. Radiolabeled rat IgE, when bound to the B cell Fc epsilon R will co-isolate with the Fc epsilon R on a rat IgE affinity column; examination of the affinity column eluate by SDS-PAGE reveals the component previously identified as the Fc epsilon R as well as E and L chains from IgE. At low levels of Fc epsilon R saturation, up to 30% of the Fc epsilon R bound IgE becomes bound to IgE-Affi-Gel. By using a biotin-avidin system, the coprecipitation of non-haptenated IgE with haptenated IgE was examined and the results suggest (but do not prove) a divalent receptor.

The role of per cent predicted 6-min walk distance in pulmonary arterial hypertension.

Absolute 6-min walk distance (6MWD) predicts mortality in pulmonary arterial hypertension (PAH), but varies greatly between normal individuals due to physiological factors such as age, sex, height and weight. The % predicted 6MWD adjusts for these factors and may predict mortality more reliably. The aim of the study was to compare the strength of mortality prediction by absolute and % predicted 6MWD in PAH at baseline and on treatment. % predicted 6MWD was calculated using four different reference equations in 137 PAH patients (idiopathic and connective tissue disease associated) diagnosed between November 2000 and November 2009. Cox proportional hazards and receiver-operating characteristic (ROC) analyses were used to compare the prognostic strength of absolute and % predicted 6MWD. % predicted 6MWD was predictive of all-cause mortality at baseline (hazard ratio 0.74-0.83 per 10% increase; p<0.05) and on treatment (0.67-0.75 per 10% increase; p<0.01), but each respective area under the ROC curve was not different from that of absolute 6MWD for predicting 2-yr mortality at baseline (absolute versus % predicted: 0.74 versus 0.71-0.75) or on treatment (0.77 versus 0.72-0.78). In conclusion, % predicted 6MWD may help clinicians interpret the 6-min walk test, but its prognostic value is not superior to that of absolute 6MWD.

Urinary dopamine in aromatic L-amino acid decarboxylase deficiency: the unsolved paradox.

INTRODUCTION: In aromatic L-amino acid decarboxylase (AADC) deficiency, a neurotransmitter biosynthesis defect, paradoxical normal or increased levels of urinary dopamine have been reported. Genotype/phenotype correlations or alternative metabolic pathways may explain this remarkable finding, but were never studied systematically. METHODS: We studied the mutational spectrum and urinary dopamine levels in 20 patients with AADC-deficiency. Experimental procedures were designed to test for alternative metabolic pathways of dopamine production, which included alternative substrates (tyramine and 3-methoxytyrosine) and alternative enzymes (tyrosinase and CYP2D6). RESULTS/DISCUSSION: In 85% of the patients the finding of normal or increased urinary levels of dopamine was confirmed, but a relation with AADC genotype could not be identified. Renal microsomes containing CYP2D were able to convert tyramine into dopamine (3.0 nmol/min/g protein) but because of low plasma levels of tyramine this is an unlikely explanation for urinary dopamine excretion in AADC-deficiency. No evidence was found for the production of dopamine from 3-methoxytyrosine. Tyrosinase was not expressed in human kidney. CONCLUSION: Normal or increased levels of urinary dopamine are found in the majority of AADC-deficient patients. This finding can neither be explained by genotype/phenotype correlations nor by alternative metabolic pathways, although small amounts of dopamine may be formed via tyramine hydroxylation by renal CYP2D6. CYP2D6-mediated conversion of tyramine into dopamine might be an interesting target for the development of new therapeutic strategies in AADC-deficiency.

Sentinel node biopsy in head and neck squamous cell cancer: 5-year follow-up of a European multicenter trial.

BACKGROUND: Sentinel node biopsy (SNB) may represent an alternative to elective neck dissection for the staging of patients with early head and neck squamous cell carcinoma (HNSCC). To date, the technique has been successfully described in a number of small single-institution studies. This report describes the long-term follow-up of a large European multicenter trial evaluating the accuracy of the technique. METHODS: A total of 227 SNB procedures were carried out across 6 centers, of which 134 were performed in clinically T1/2 N0 patients. All patients underwent SNB with preoperative lymphoscintigraphy, intraoperative blue dye, and handheld gamma probe. Sentinel nodes were evaluated with hematoxylin and eosin (H&E) staining, step-serial sectioning (SSS), and immunohistochemistry (IHC). There were 79 patients who underwent SNB as the sole staging tool, while 55 patients underwent SNB-assisted elective neck dissection. RESULTS: Sentinel nodes were successfully identified in 125 of 134 patients (93%), with a lower success rate observed for floor-of-mouth tumors (FoM; 88% vs. 96%, P = 0.138). Also, 42 patients were upstaged (34%); of these, 10 patients harbored only micrometastatic disease. At a minimum follow-up of 5 years, the overall sensitivity of SNB was 91%. The sensitivity and negative predictive values (NPV) were lower for patients with FoM tumors compared with other sites (80% vs. 97% and 88% vs. 98%, respectively, P = 0.034). CONCLUSIONS: Sentinel node biopsy is a reliable and reproducible means of staging the clinically N0 neck for patients with cT1/T2 HNSCC. It can be used as the sole staging tool for the majority of these patients, but cannot currently be recommended for patients with tumors in the floor of the mouth.

Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma.

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method of determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histological nodal staging and avoids over-treating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This article was designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. These guidelines were prepared by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial Committee.

Plasma calcitonin gene-related peptide in diagnosing and predicting paediatric migraine.

To investigate the role of plasma calcitonin gene-related peptide (CGRP) in paediatric migraine, we prospectively collected 134 blood samples during or between attacks from 66 migraine, 33 non-migraine headache (non-migraine) and 22 non-headache patients, aged 4-18 years. Plasma CGRP concentrations were measured by enzyme-linked immunosorbent assay and disability by Pediatric MIgraine Disability ASsessment (PedMIDAS) questionnaire. Migraineurs had higher plasma CGRP levels than non-migraine patients (P = 0.007). The attack level was higher than the non-attack level in migraine (P = 0.036), but not in non-migraine, patients. This was also revealed in paired comparison (n = 9, P = 0.015 vs. n = 4, P = 0.47). Using a threshold of 55.1 pg/ml, the sensitivity of the attack level in predicting migraine was 0.81, and specificity 0.75. The PedMIDAS score tended to be higher in the high CGRP (> 200 pg/ml, n = 7) group than in the low (< 200 pg/ml, n = 33) group (26.07 vs. 19.32, P = 0.16) using Mann-Whitney test. Plasma CGRP is useful for diagnosis in paediatric migraine.