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Kristen Russomanno,1 Sara Abdel Azim,2 Vishal A Patel3 1Department of Dermatology, Medstar Georgetown University Hospital/Medstar Medical Group, Washington, DC, USA; 2School of Medicine, Georgetown University, Washington, DC, USA; 3Department of Dermatology, George Washington University, Washington, DC, USACorrespondence: Vishal A Patel, Department of Dermatology, George Washington University, 2150 Pennsylvania Avenue NW, 2nd Floor, Washington, DC, 20037, USA, Tel +1 202 741 2600, Email vapatel@mfa.gwu.eduAbstract: Non-melanoma skin cancers (NMSCs) are the most common cancers worldwide and may be associated with significant morbidity and mortality, especially in immunosuppressed populations. Successful management of NMSC must take primary, secondary and tertiary prevention strategies into consideration. In response to an improved understanding of the pathophysiology of NMSC and associated risk factors, multiple systemic and topical immunomodulatory drugs have been developed and integrated into clinical practice. Many of these drugs are efficacious in the prevention and treatment of precursor lesions (actinic keratoses; AKs), low-risk NMSC, and advanced disease. The identification of patients at high risk for the development of NMSC is critical in reducing disease morbidity. Understanding the various treatment options available and their comparative effectiveness is paramount for developing a personalized treatment regimen for such patients. This review article provides an updated overview of the various topical and systemic immunomodulatory drugs available for the prevention and treatment of NMSC, and the published data supporting their use in clinical practice.Keywords: non-melanoma skin cancer, squamous cell carcinoma, basal cell carcinoma, keratinocyte carcinoma

Securing data and the systems that manage or store it is known as cyber security. Cyber security violations are the most frequent crime performed by online attackers using one or more systems on one or more networks or systems. These cyberthreats can rapidly steal or lose data, as well as partially or totally shut down network systems. Because cyber-attacks are always developing, manually detecting them can be time-consuming and expensive. Consequently, they may be found and classified using machine learning approaches. This study focuses on a survey of the current algorithms for machine learning research in cyber security.

The article introduces a novel strategy for efficiently mitigating COVID-19 distribution at the local level due to contact with any surfaces. Our project aims to be a critical safety shield for the general people in the fight against the epidemic. An ultrasonic sensor is integrated with the automated doorbell system to ring the doorbell with a hand motion. A temperature sensor Mlx90614 is also included in the system, which records the temperature of the person standing in front of the door. The device also includes a camera module that captures the image of the person standing at the front entrance. The captured image is processed through an ML model which runs at over 30 fps to detect whether or not the person is wearing a mask. The image and the temperature of the person standing outside are sent to the owner through the configured iOS application. If the person outside is wearing a mask, one can open the door through the app itself and permit the entry of the person standing outside thereby integrating the edge device with an app for a better user experience. The system helps in reducing physical contact, and the results obtained are at par with the already existing solutions and provide a few advantages over them.

The electrocardiogram (ECG) signal carries vital information related to cardiac activities. While measuring ECG using electrodes, the signal is contaminated with powerline interference (PLI) from harmonics, baseline wandering (BW), motion artefacts (MA) and high frequency (HF) noise. The extraction of the ECG signal, without the loss of useful information from the noisy environment, is required. Therefore, the selection and implementation of an efficient filter design is proposed. The Finite Impulse Response (FIR)-based multiband needs separate digital filters, such as Lowpass, Highpass, and Bandstop Filter in cascade. The coefficients of the FIR multiband filter are optimised using a least squares optimisation method and realised in a direct form symmetrical structure. The capability of the proposed filter is evaluated on a Physionet ECG ID database, having records of inherent noisy ECG signals. The performance is also verified by measuring the power spectrum of the noisy and filtered ECG waveform. Also, the feasibility of the proposed multiband filter is investigated on Xilinx ISE and the design is implemented on a field programmable gate array (FPGA) platform. A low order simple multiband filter structure is designed and implemented on the reconfigurable FPGA device.

Study Design: Systematic, scoping literature review and case presentation., Objective: The goal of this study is to review current literature on management trends and outcomes of pediatric intranasal lobular capillary hemangioma (ILCH)., Case Presentation: A 14-year-old male patient presented with a 15-month history of unilateral epistaxis, nasal congestion, and mouth breathing. Further workup revealed a pale nasal mass obstructing the right nasal cavity. The patient was successfully treated using a minimally invasive endoscopic endonasal approach for mass resection and nasal floor free mucosal graft for septal reconstruction., Methods: Independent queries of the PubMed Central, MEDLINE, and Bookshelf databases were performed; articles from 1990 to 2023 were abstracted. All studies that described pediatric ILCH using the Boolean method and relevant search term combinations, including "Intranasal," "Lobular capillary hemangioma," "Pyogenic granuloma," "Pediatric," "Outcome," and "Management," were collected for subsequent analysis., Results: A total of 407 relevant unique articles were identified for analysis. Of these, 19 articles were deemed appropriate for inclusion in this literature review. Twenty-two pediatric ILCH cases were identified with a mean age at diagnosis of 10.5 years. The majority of cases occurred in males and presented with recurrent epistaxis and nasal obstruction. Most lesions originated from the anterior nasal septum and were resected using an endoscopic endonasal approach with no recurrence at last follow-up., Conclusions: Pediatric ILCH, a benign vascular neoplasm, often presents with unilateral nasal obstruction and severe, refractory epistaxis. This comprehensive review aims to highlight the importance of including this lesion in the differential diagnosis for unilateral nasal obstruction and epistaxis in young children., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Immunotherapies have revolutionized the management of advanced cutaneous malignancies. However, some patients fail to respond to these therapies, others are ineligible because of comorbidities, and a minority of patients experience treatment-limiting systemic immune-related adverse events. To address these issues and expand treatment options for patients with early-stage disease, a variety of immunotherapies are being developed for direct intratumoral administration. Agents including oncolytic viruses, monoclonal antibodies, cytokines, peptides, and pattern-recognition receptor agonists have been engineered to evoke a local immune response while minimizing systemic toxicity and have shown favorable results in preclinical and early clinical testing. This review covers the current landscape of intratumoral immunotherapies for the treatment of cutaneous melanoma, squamous cell carcinoma, and basal cell carcinoma, highlighting the diverse array of agents being explored and their potential benefits and challenges., Competing Interests: Conflicts of interest Dr Migden serves on the advisory boards of Regeneron and Replimune and is a scientific advisor for Stamford Pharmaceuticals and a consultant for Feldan Therapeutics. He has received honoraria for scientific advisory consultation from Regeneron, Replimune, Feldan Therapeutics, and Stamford Pharmaceuticals. Dr Patel serves on the advisory boards of Regeneron, Avstera, Almirall, Sun Pharma, and Biofrontera. He has received honoraria from PhD Biosciences, Jounce Therapeutics, Sun Pharma, and Regeron. He serves on the speaker’s bureau for Regeron. The remaining authors have no disclosures., (Copyright © 2024. Published by Elsevier Inc.)

The COVID-19 pandemic has underscored the critical importance of effective vaccines, yet their development is a challenging and demanding process. It requires identifying antigens that elicit protective immunity, selecting adjuvants that enhance immunogenicity, and designing delivery systems that ensure optimal efficacy. Artificial intelligence (AI) can facilitate this process by using machine learning methods to analyze large and diverse datasets, suggest novel vaccine candidates, and refine their design and predict their performance. This review explores how AI can be applied to various aspects of vaccine development, such as predicting immune response from protein sequences, discovering adjuvants, optimizing vaccine doses, modeling vaccine supply chains, and predicting protein structures. We also address the challenges and ethical issues that emerge from the use of AI in vaccine development, such as data privacy, algorithmic bias, and health data sensitivity. We contend that AI has immense potential to accelerate vaccine development and respond to future pandemics, but it also requires careful attention to the quality and validity of the data and methods used., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The work illustrates a step-by-step surgical approach to demonstrate technical feasibility of a single-stage endoscopic repair for bilateral choanal atresia with adjuvant bioabsorbable steroid-eluting stent placement to safely mitigate unique perioperative challenges in the pediatric population. Laryngoscope, 134:4414-4417, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Auditory Brainstem Implants (ABI) are used to restore hearing in patients lacking appropriate cochlear anatomy and/or cochlear nerve. The objective of this study was to examine the Manufacture and User Facility Device Experience (MAUDE) database to analyze adverse events., Study Design: This is a study of a multi-institutional database maintained by the US FDA., Setting: A database analysis was performed via collaboration of multiple clinicians at tertiary referral centers., Methods: The MAUDE database was queried for Medical Device Reports (MDRs) relating to ABIs. MDRs were identified using the advanced search term "Implant, Auditory Brainstem" and reviewing all reports with the basic search term "Brainstem Implant". All collected reports were individually reviewed., Results: A total of 265 individual patient reports were reviewed, of which 55 reports met inclusion criteria. Reports regarding audiologic outcome included failure to provide hearing benefit (n = 27), implant failure/device malfunction (n = 10), and device non-use (n = 6). Postoperative complications included local skin infection (n = 3), CSF leak (n = 3), elevated ICP (n = 1), surgical site dehiscence (n = 1), swelling (n = 1), seroma formation requiring drainage (n = 1), and meningitis (n = 2). Two patients had dislodged magnets during 1.5 Tesla MRI acquisition. There were 35 instances of full explantation of the device and 1 partial removal; 13 patients had a new device implanted following explantation., Conclusions: Poor hearing results, device failure, and non-use were commonly reported causes for explanation in this analysis. This information can aid physicians in counseling patients and family members and managing device expectations., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Importance: Cutaneous squamous cell carcinoma (CSCC) is the second most common malignant disease in the US. Although it typically carries a good prognosis, a subset of CSCCs are highly aggressive, carrying regional and distant metastatic potential. Due to its high incidence, this aggressive subset is responsible for considerable mortality, with an overall annual mortality estimated to equal or even surpass melanoma. Despite this morbidity, CSCC is excluded from national cancer registries, making it difficult to study its epidemiology and outcomes. Therefore, the bulk of the CSCC literature is composed of single-center and multi-institutional retrospective cohort analyses. Given variations in reporting measures and analyses in these studies, interpretability between studies and the ability to pool results are limited., Objective: To define standardized reporting measures for retrospective CSCC studies., Findings: An expert panel was convened to determine standardized guidelines for recording and analyzing retrospective CSCC data. A total of 13 dermatologists and dermatologic surgeons with more than 5 years of posttraining experience and considerable experience with performing CSCC outcomes research were recruited to the panel. Consensus recommendations were achieved for CSCC retrospective study reporting measures, definitions, and analyses., Conclusions and Relevance: The recommendations in this report present the potential to standardize future CSCC retrospective studies. With such standardization, future work may have greater interstudy interpretability and allow for pooled analyses.

Hypertrophic cardiomyopathy (HCM), a common genetic heart condition, is characterized by thickening of the left ventricle, which can result in a range of health issues, such as arrhythmias, heart failure, and sudden death. Despite traditional cautions against exercise in HCM patients due to potential exacerbation of symptoms and risk of sudden death, recent evidence suggests a paradigm shift toward the benefits of structured exercise rehabilitation. The pathogenesis of HCM, the physical and psychological effects of the illness on patients, and changing views on exercise as a therapeutic intervention are all covered in this review. Recent research shows that modest physical activity can considerably enhance functional ability, psychological health, and overall quality of life in individuals with heart failure without increasing the risk of unfavorable cardiac events, challenging earlier recommendations. Moreover, exercise rehabilitation has been shown to induce favorable myocardial remodeling and enhance cardiovascular fitness, suggesting a revaluation of exercise prescriptions tailored to individual patient profiles. Despite the promising role of exercise in managing HCM, this review also acknowledges the complexities of implementing rehabilitation programs, including the need for comprehensive patient assessment, personalized exercise regimens, and monitoring for potential complications. Future research should focus on optimizing exercise recommendations, understanding long-term outcomes, and integrating exercise rehabilitation into standard care protocols for HCM to foster a more holistic approach to patient management. Underscoring the necessity of a multidisciplinary strategy that balances the benefits of physical activity with the unique risks associated with HCM with the aim of improving patient outcomes through evidence-based, patient-centered care., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cutaneous squamous cell carcinoma (cSCC) is the most common keratinocyte carcinoma in dark-skinned ethnic groups. Available studies are primarily focused on white populations, with fewer data available for black Africans, including Ethiopians. Therefore, less priority may be given to treatment and prevention in this population., Objective: To determine the prevalence and risk factors of cSCC among patients presenting to All Africa Leprosy, Tuberculosis, and Rehabilitation Training Center , Addis Ababa, Ethiopia., Methods: A literature review was performed to determine existing knowledge. A retrospective descriptive cross-sectional study was then conducted based on stored data of confirmed cases of cSCC from 2011 to 2021 at ALERT. Demographics, other parameters related to cSCC (size, anatomic location, degree of differentiation, metastasis, and recurrence), and potential risk factors including scars, burns, HIV status, xeroderma pigmentosum, and leprosy were collected and entered on a prepared data extraction sheet and analyzed using SPSS version 25 manufactured by IBM., Results: Among 15,075 total pathologic samples reviewed, 3.8% ( n  = 570) were reported histopathologically as invasive cSCC ( n  = 437), keratoacanthoma, or (squamous cell carcinoma in-situ (Bowen disease). 50.3% ( n  = 287) occurred in female, and the mean age of affected patients was 50.1 years (SD 17.2). Nearly 70% were reported after >1 year of symptoms, including morphologic change, ulceration, and nonhealing wound. HIV status was not universally screened but was positive in 9.8% (46/437). Cases were commonly found to occur on the lower extremities (X 2  = 2.7196, Pr = 0.099) and >4 cm in size (46.3%). Among 274 cases with adequate histologic description, 82.5% ( n  = 226) were well-differentiated. Loco-regional metastases comprised 6.0% ( n  = 34) and 46.7% ( n  = 266) had ulceration., Conclusion: The biologic significance of ulceration in this population is unclear. Ulceration may indicate chronic wounds or Marjolin's ulcers. High rates of metastasis call for a better understanding of risk factors, preventive measures, and early diagnosis. This model of research may serve as a foundation for future nationwide investigations through the Federal Ministry of Health of Ethiopia's Disease Prevention and Control Directorate., Competing Interests: None disclosed., (© 2024 Published by Elsevier Inc. on behalf of the American Academy of Dermatology, Inc.)

Intra-abdominal arterial reconstructions in the setting of reoperative, contaminated, or frankly infected fields can be a challenging undertaking for even the most experienced vascular surgeons. Open surgical arterial transpositions have been less commonly performed than other methods of reconstruction in the current era of vascular surgery despite many historical reports of successful outcomes. Autologous artery transpositions represent a viable option in the case of an infected or a contaminated operative field. We have described the cases of three patients treated at our institution who had required intra-abdominal revascularization in a contaminated or frankly infected surgical field. All three patients were successfully treated using open native visceral artery transposition procedures. These cases presented multiple challenges secondary to the ongoing infections, infected operative field, and, sometimes, a history of multiple vascular bypasses involving the aorta and visceral arteries. In such circumstances, we have demonstrated the effectiveness of native visceral arterial transposition as a feasible technique., (© 2024 Published by Elsevier Inc. on behalf of Society for Vascular Surgery.)

The leading cause of gastroenteritis in children under the age of five is rotavirus infection, accounting for 37% of diarrhoeal deaths in infants and young children globally. Oral rotavirus vaccines have been widely incorporated into national immunisation programs, but whilst these vaccines have excellent efficacy in high-income countries, they protect less than 50% of vaccinated individuals in low- and middle-income countries. In order to facilitate the development of improved vaccine strategies, a greater understanding of the immune response to existing vaccines is urgently needed. However, the use of mouse models to study immune responses to human rotavirus strains is currently limited as rotaviruses are highly species-specific and replication of human rotaviruses is minimal in mice. To enable characterisation of immune responses to human rotavirus in mice, we have generated chimeric viruses that combat the issue of rotavirus host range restriction. Using reverse genetics, the rotavirus outer capsid proteins (VP4 and VP7) from either human or murine rotavirus strains were encoded in a murine rotavirus backbone. Neonatal mice were infected with chimeric viruses and monitored daily for development of diarrhoea. Stool samples were collected to quantify viral shedding, and antibody responses were comprehensively evaluated. We demonstrated that chimeric rotaviruses were able to efficiently replicate in mice. Moreover, the chimeric rotavirus containing human rotavirus outer capsid proteins elicited a robust antibody response to human rotavirus antigens, whilst the control chimeric murine rotavirus did not. This chimeric human rotavirus therefore provides a new strategy for studying human-rotavirus-specific immunity to the outer capsid, and could be used to investigate factors causing variability in rotavirus vaccine efficacy. This small animal platform therefore has the potential to test the efficacy of new vaccines and antibody-based therapeutics.

Occupational immunization is an integral part of institutional occupational safety and health (OSH) programs. Laboratory animal workers (LAWs) are personnel working with various small and large vertebrate animals. LAWs are at the risk of contracting a myriad of zoonotic infections as they are occupationally exposed to animals and their biological products. Immunizing employees against such zoonotic pathogens is the best way to prevent disease transmission. This review provides information on various zoonotic diseases, vaccines available to protect against such infections, and vaccination schedules. Certain sections of institutional occupational immunization programs such as risk evaluation, immunizing special categories of personnel and exemption from immunization among others are also described. Additionally, the authors have discussed various probable modes of impact through which occupational immunization of laboratory animal workers fulfills different United Nations Sustainable Development Goals.

Objective: Provide clinicians with current evidence for biologic therapy in children with chronic rhinosinusitis with nasal polyposis (CRSwNP)., Data Sources: PubMed, MEDLINE, Cochrane, and clinical trial registries., Review Methods: Key search terms related to biologic therapy in pediatric CRSwNP were identified via a structured query of current medical literature and clinical trial databases., Conclusions: There is a dearth of active clinical trials and research studies for biologics targeting pediatric CRSwNP. There is an ongoing compassionate-use clinical trial involving Dupilumab for children with nasal polyps as well as only 1 published work specifically focused on Dupilumab for pediatric CRSwNP in the setting of aspirin-exacerbated respiratory disease., Implications for Practice: For children with atopic dermatitis, asthma, and chronic idiopathic urticaria, biologic therapies such as Omalizumab, Dupilumab, and Mepolizumab have gained Food and Drug Administration approval. The role of biologic therapy in pediatric CRSwNP demonstrates significant promise in the comprehensive management of the unified airway. Additional Phase III trials are necessary to broaden clinical indications for children with comorbid conditions and complex sinonasal disease., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

The β-hemolytic factor streptolysin S (SLS) is an important linear azol(in)e-containing peptide (LAP) that contributes significantly to the virulence of Streptococcus pyogenes. Despite its discovery 85 years ago, SLS has evaded structural characterizing owing to its notoriously problematic physicochemical properties. Here, we report the discovery and characterization of a structurally analogous hemolytic peptide from Enterococcus caccae, termed enterolysin S (ELS). Through heterologous expression, site-directed mutagenesis, chemoselective modification, and high-resolution mass spectrometry, we found that ELS contains an intriguing contiguous octathiazole moiety. The discovery of ELS expands our knowledge of hemolytic LAPs by adding a new member to this virulence-promoting family of modified peptides., (© 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

In this study, through the utilization of the sol-gel combustion tactic, gadolinium (Gd)-doped cerium oxide (CeO 2 ), Ce 1- x Gd x O 2 ( x = 0.00, 0.10, 0.20 and 0.30 (GDC)) ceramics were attained. The synthesized GDC ceramics were investigated using X-ray diffraction (XRD) to scrutinize their crystal structures and phase clarities. The obtained GDC ceramics have a single-phase cubic structure and belong to the crystallographic space group fm 3̄ m (225). The measurement of the diffraction angle of each reflection and the subsequent smearing of the renowned Bragg's relation provided coarse d -interplanar spacings. The stacking fault (SF) values of pure and Gd-doped CeO 2 ceramics were assessed. To muse the degree of preferred orientation ( σ ) of crystallites along a crystal plane ( h k l ), the texture coefficient ( C i ) of each XRD peak of GDC ceramics is gauged. By determining the interplanar distance ( d h k l ), the Bravais theory sheds light on the material's development. By exploiting Miller indices for the prime (1 1 1) plane, the lattice constants of GDC ceramics and cell volumes were obtained. Multiple techniques were employed to ascertain the microstructural parameters of GDC ceramics. A pyrometer substantiated the density of GDC ceramics. The room temperature (RT) Fourier transform infrared (FTIR) spectra of both un-doped and Gd-doped CeO 2 were obtained. The UV-vis-NIR spectrometer recorded the GDC ceramics' reflectance ( R ) spectra at RT. For both undoped and Gd-doped CeO 2 , the absorption coefficient ( α ) spectra showed two distinct peaks. The R -dependent refractive index ( η ) and the α -dependent extinction coefficient ( k ) were determined for all GDC samples. The optical band gap ( E g ) was obtained by integrating the Tauc and Kubelka-Munk approaches for GDC ceramics. For each GDC sample, the imaginary ( ε i ) and real ( ε r ) dielectric constants, as well as the dissipation factor (tan  δ ), were determined local to the characteristic wavelength ( λ c ). Calculations were made for the Urbach energy ( E U ) and Urbach absorption coefficient ( α 0 ) for GDC ceramics. The minimum and maximum values of optical ( σ o ) and electrical ( σ e ) conductivity for GDC ceramics were determined. The volume (VELF) and surface (SELF) energy loss functions, which depend on the constants ε i and ε r , were used to measure electrons' energy loss rates as they travel across the surface. Raman spectroscopy revealed various vibrational modes in GDC ceramics. Finally, the implications are discussed herein., Competing Interests: “The authors have no related financial or non-financial interests to disclose.”, (This journal is © The Royal Society of Chemistry.)

Background: The Patient-Reported Outcomes in Actinic Keratosis (PROAK) study evaluated patient- and clinician-reported outcomes (PRO; ClinRO) during 24 weeks of follow-up among adult patients with actinic keratosis (AK) on the face or scalp who were administered tirbanibulin 1% ointment in real-world community practices in the United States.  Methods: Quality of life (QoL) was assessed by Skindex-16 at week (W) 8. Additionally, effectiveness (Investigator Global Assessment [IGA]), PRO and ClinRO (Treatment Satisfaction Questionnaire for Medication and Expert Panel Questionnaire), safety, and tolerability were assessed at W8 and W24., Results: The safety population included 300 patients; the full analysis set included 290 patients (278 patients at W24). At W8, a statistically significant difference (P<0.03) was observed for Skindex-16 domains in all assessed subgroups. Clinicians and patients reported high global satisfaction (mean [SD] scores of 74.9 [23.9] and 72.0 [24.6], respectively) at W24. Overall skin appearance improved from baseline to W24 (83.6% clinicians; 78.5% patients). IGA success (IGA score of 0-1) was achieved by 71.9% of patients at W24 with a similar % at W8 (73.8%) suggesting a stable effectiveness over time. About 5% of patients reported at least one adverse event, 4% reported at least one serious adverse event and no patients reported serious adverse drug reactions. At W8, the most frequently reported local skin reactions were mild/moderate erythema (47.6%) and flaking/scaling (49.6%)., Conclusions: Treatment with tirbanibulin demonstrated effectiveness in the management of AK lesions and a favorable safety and tolerability profile. Furthermore, QoL was improved as early as W8, and both patients and clinicians reported high levels of treatment satisfaction, independently of patients' characteristics. J Drugs Dermatol. 2024;23(5):338-346. doi:10.36849/JDD.8264.

Objective: The authors of this study aimed to investigate independent prognostic factors of survival with a particular focus on comparing the safety and efficacy of endoscopic endonasal versus open approaches in the surgical management of skull base chordoma., Methods: A retrospective National Cancer Database review of skull base chordoma patients was performed to capture resection cases from 2010 to 2020, evaluating overall survival (OS), early postoperative mortality, readmission rates, and hospital length of stay (LOS) between surgical approaches and the independent prognostication of death utilizing Cox multivariate regression analysis., Results: Among the 736 patients included in the cohort, 456 patients (62.0%) and 280 patients (38.0%) underwent endoscopic endonasal and open resection, respectively. These values represent a rate of change over the study period of +4.1 versus -0.14 cases per year, respectively. Gross-total resection was achieved in 32.5% of cases. A positive margin status was found in 51.8% of cases. There was no association between extent of resection and surgical approach (p = 0.257). There was no difference in OS (p = 0.562), 30- and 90-day mortality (p = 0.209 and 0.126, respectively), and 30-day readmission (p = 0.438) between the two surgical groups. The mean LOS was reduced by 2.1 days in the endoscopic cohort (p = 0.013) compared with the open approach cohort. Finally, multivariate analysis revealed a tumor size ≥ 4 cm (HR 4.03, p = 0.005) and public insurance (HR 2.76, p = 0.004) as negative predictors of survival and treatment at an academic center (HR 0.36, p = 0.043) as a positive prognosticator of survival., Conclusions: The endoscopic endonasal approach has been increasingly utilized over time and touts noninferiority with respect to safety and efficacy with a marked improvement in LOS, which carries substantial implications for both healthcare costs and enhanced patient recovery. Future prospective studies are necessary to further delineate trends and surgical outcomes for skull base chordoma.

Background and Importance: Basal encephaloceles are the result of a concomitant cranial and dural defect that allows for inferior displacement of cerebral tissue, meninges, and cerebrospinal fluid into the paranasal sinuses and outside the cranial vault. This work illustrates a step-by-step surgical approach of a successful single-stage, endoscopic repair of a congenital basal encephalocele in a 10-year-old child, using a free mucosal middle turbinate graft that provided effective results without utilization of traditional open reconstructive techniques or vascularized flaps., Clinical Presentation: A previously healthy 10-year-old male with a history of unilateral clear rhinorrhea was admitted as an inpatient because of an acute episode of nausea, vomiting, and confusion, accompanied by fever, diplopia, and bilateral abducens nerve palsies. Preoperative imaging revealed a 2-cm right-sided intranasal mass accompanied by a subcentimeter skull base defect spanning the lateral lamella. After completing a course of intravenous antibiotic therapy for 1 week after a negative lumbar puncture to ensure clearance of intracranial infection, the decision was made to proceed with definitive endoscopic skull base repair to obviate recurrent bacterial meningitis episodes and potential neurological complications., Conclusion: This study demonstrates technical feasibility of a single-stage endoscopic endonasal approach for pediatric basal encephalocele resection and repair which minimizes craniofacial morbidity associated with traditional open approaches and sinonasal morbidity associated with local pedicle-based flaps for small cranial base defects in this unique patient population., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Originally pioneered in adults, endoscopic endonasal approaches for skull base pathology are being increasingly applied as a minimally invasive alternative for young children. Intrinsic anatomic differences between these patient populations have sparked discussions on the feasibility, safety, and efficacy of these techniques in pediatric patients. This work aims to serve as a primer for clinicians engaged in the rapidly evolving field of pediatric endoscopic skull base surgery. A succinct overview of relevant embryology, sinonasal anatomy, and diagnostic workup is presented to emphasize key differences and unique technical considerations. Additional discussions regarding select skull base lesions, reconstructive paradigms, potential surgical complications, and postoperative care are also highlighted in the setting of multidisciplinary teams., Competing Interests: The authors declare no conflict of interest.

Electrocardiographic evaluation is performed in rhesus monkeys to establish the cardiovascular safety of candidate molecules before progressing to clinical trials. These animals are usually immobilized chemically by ketamine (KTM) and tiletamine-zolazepam (TZ) to obtain a steady-state heart rate and to ensure adequate human safety. The present study aimed to evaluate the effect of these anesthetic regimens on different electrocardiographic parameters. Statistically significant lower HR and higher P-wave duration, RR, QRS, and QT intervals were observed in the KTM-anesthetized group in comparison to TZ-anesthetized animals. No significant changes were noticed in the PR interval and p-wave amplitude. Sex-based significance amongst these parameters was observed in male and female animals of TZ- and KTM-anesthetized groups. Regression analysis of four QTc formulas in TZ-anesthetized rhesus monkeys revealed that QTcNAK (Nakayama) better corrected the QT interval than QTcHAS (Hassimoto), QTcBZT (Bazett), and QTcFRD (Fridericia) formulas. QTcNAK exhibited the least correlation with the RR interval (slope closest to zero and r = .01) and displayed no statistical significance between male and female animals. These data will prove useful in the selection of anesthetic regimens for chemical restraint of rhesus monkeys in nonclinical safety evaluation studies., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

RVU valuations need to be revisited regularly as procedure complexity and patient care pathways continue to evolve. The NSQIP-P database was queried for craniofacial procedures performed in North America between 2012 and 2019. Multivariate regression was performed to determine correlation coefficients of perioperative variables deemed to reflect procedure severity, including procedure duration, blood transfusion, length of stay, serious adverse events, related readmission, and related reoperation. CPT 21159 Le Fort III with forehead advancement remains the craniofacial procedure with the highest RVUs using our model at 33.93 units. The most underestimated procedure is CPT 42235 Repair of anterior palate, including vomer flap, with a suggested change of +8.27 units, which is a 194% increase from current compensation. Adjusted RVUs based on quantitative and nationally representative perioperative variables that reflect procedure severity might be a better alternative for procedure valuation over current survey methods to determine appropriate insurance compensation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Study Design: The study was a retrospective cross-sectional database analysis., Objective: Deoxycholic acid (DOC) injections are a novel, in-office procedural alternative to submental liposuction or submentoplasty to address excess submental fat. Post-market safety data regarding this treatment is currently limited. The objective of this study is to analyze adverse events reported in the Manufacturer and User Facility Device Experience (MAUDE) database., Methods: The MAUDE database was queried for all reports related to adverse events involving deoxycholic acid using the search terms "KYBELLA" and "deoxycholic acid." Reports were individually reviewed by 2 reviewers and categorized with special attention to adverse events., Results: A total of 34 medical device reports were identified from the database query. Thirteen of these reports (21 total events) were included in the analysis after excluding duplicates, unrelated adverse events, or events associated with the off-label use of DOC. Reported adverse events include excessive swelling (n = 5, 24%), marginal mandibular nerve weakness (n = 4, 19%), unsatisfactory aesthetic outcome (n = 4, 19%), numbness (n = 3, 14%), dysphagia (n = 1, 5%), infection (n = 1, 5%), and skin necrosis (n = 3, 14%). Two patients required hospitalization for skin necrosis management; both had underlying systemic diseases., Conclusions: Adverse events following DOC injections included excessive swelling, dysphagia, numbness, infection, unsatisfactory aesthetic outcome, facial nerve weakness, and skin necrosis requiring hospitalization and/or surgery. Patient counseling regarding these adverse events should be discussed when offering DOC injections for submental convexity., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: While nasal epistaxis balloons are generally seen as safe and routinely utilized by both surgical and nonsurgical providers, the complication profile related to this type of device has not been well defined., Objective: The objective of this study was to utilize the FDA MAUDE (Manufacturer and User Facility Device Experience) database to better assess adverse events (AE) related to use of nasal epistaxis balloons. Reports were individually tabulated and events were categorized with special attention to AEs., Methods: The FDA MAUDE database was queried for all medical device reports (MDR) related to nasal epistaxis balloon devices from January 2012 to November 2022., Results: 19 MDRs met inclusion criteria. 5 MDRs were classified as device related (26.3 %); two events were reported for balloon leak and deflation, two events were reported for device breakage, and one device related event was unknown. 14 MDRs (73.7 %) were classified as patient related. Two documented MDRs were patient deaths due to exsanguination. Additional serious AEs included balloon ingestion and subsequent small bowel perforation (n = 1), cerebrospinal fluid leak (n = 1), skull base violation and intracranial placement of the device (n = 1), and respiratory distress (n = 3)., Conclusion: Though epistaxis control with nasal balloons is generally seen as a safe procedure, there have been several concerning AEs reported. While two reports of death due to exsanguination were the most severe AEs, multiple other life-threatening AEs were also documented. Increased awareness of associated complications can be used to better counsel patients during the informed consent process as well as providers in their clinical decision making., Competing Interests: Declaration of competing interest There are no relevant conflicts of interest from any authors., (Copyright © 2023. Published by Elsevier Inc.)

Air guns, particularly BB (ball-bearing or bullet ball) guns, have gained significant power and velocity over the last few decades. More than 145,000 pediatric patients suffered injuries attributed to air guns in the United States between 2001 and 2011, and approximately 22,000 pediatric emergency department visits are attributed to air gun-related injuries annually (Hyak et al., 2020 [1]). This study aims to describe an effective surgical technique in addressing maxillofacial injuries caused by BB gun projectiles in the pediatric population. We present a detailed surgical approach for endoscopic endonasal retrieval of a transorbital projectile in a 13-year-old male who sustained a maxillofacial BB gun injury, with the goal of restoring sinonasal function in a minimally invasive fashion., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This systematic review aims to characterize ongoing clinical trials and therapeutic treatment options for chordoma, a rare notochordal remnant tumor that primarily affects the cranial base, mobile spine, and sacrum. While radical surgical resection remains the cornerstone for chordoma management, unique technical challenges posed by its proximity to critical neurovascular structures confer a tendency towards disease recurrence which often requires additional treatment modalities. In an attempt to better understand the current treatment landscape, a systematic review was designed to identify clinical trials directed at chordoma. A total of 108 chordoma trials were identified from four clinical trial databases; fifty-one trials were included in the final analysis, of which only 14 were designated as completed (27.5%). Aggregate data suggests most chordoma interventions are repurposed from other neoplasms that share common molecular pathways, with a recent emphasis on combination therapeutics within and across drug classes. Naturally, the publication and dissemination of clinical trial results remain a concern ( n = 4, 28.6%), highlighting the need for enhanced reporting and transparency measures. Active clinical trial efforts are quite promising, with a renewed focus on novel biotherapeutic targets and deciphering the natural history, as well as survivorship of this complex disease.

Introduction: Alzheimer's disease (AD) is a widespread neurodegenerative condition with complex causes and a significant global impact, particularly among the elderly. This brief introduction emphasizes AD's hallmark features and the urgent public health concern it poses, with numbers on the rise. It also highlights the potential of statins and magnesium L-threonate as a combined therapeutic approach to prevent AD and mitigate its underlying pathological features. The study's goal is to shed light on these promising interventions in a rat model induced by aluminum chloride (AlCl3)., Materials and Methods: A total of 30 aged female Wistar rats were divided into five groups (n=6/group). The vehicle control group received normal saline orally (p.o.).The model control group received AlCl3(4.2 mg/kg/day intraperitoneal (i.p.)). The standard-treated group received rivastigmine (1 mg/kg/day p.o.), and the atorvastatin-treated and atorvastatin with magnesium L-threonate-treated groups received atorvastatin (20 mg/kg/day p.o.) and atorvastatin (20 mg/kg/day) with magnesium L-threonate (604 mg/kg/day p.o. ), respectively. Cognitive functions such as radial arm maze, elevated plus maze (EPM), passive shock avoidance test, and open-field test (OFT) were performed at weekly intervals up to 28 days. After completion of the study on the 29 th day, all animals were sacrificed, and the brain was used for estimation of AchE enzyme activity, oxidative stress parameters, and histopathological analysis., Result: At the end of the fourth week, administration of atorvastatin and atorvastatin with magnesium L-threonate resulted in a decreased average time taken to reach the correct arm, reduced transfer latency (TL) in the EPM, shortened latency to reach the shock-free zone (SFZ), and an increase in rearing and counts by locomotion activity in the OFT. It also demonstrated improved anti-cholinesterase activity and suppressed oxidative stress, as indicated by a decrease in nitric oxide (NO) levels and an increase in superoxide dismutase (SOD) and catalase levels. Additionally, it led to reductions in brain changes observed in histopathological analysis., Conclusion: Atorvastatin with magnesium L-threonate provides a better beneficial protective effect against AD than atorvastatin alone. This combination can be a first choice for patients who are already taking atorvastatin in the early stages of AD., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Gangoda et al.)

Background: We previously reported rates of pathological complete responses (51% [95% CI 39-62] per independent central review, the primary endpoint) and major pathological responses (13% per independent central review, a secondary endpoint) to neoadjuvant cemiplimab (an anti-PD-1 inhibitor) among 79 patients with locoregionally advanced, resectable cutaneous squamous cell carcinoma. Here, we present follow-up data, including event-free, disease-free, and overall survival., Methods: This single-arm, multicentre, phase 2 study included patients aged 18 years or older with resectable stage II-IV (M0) cutaneous squamous cell carcinoma and Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received up to four planned doses of neoadjuvant cemiplimab 350 mg intravenously every 3 weeks followed by curative-intent surgery. After surgery, per investigator discretion, patients received either adjuvant cemiplimab for up to 48 weeks, radiotherapy, or observation alone. Secondary endpoints included in this follow-up analysis are event-free survival, disease-free survival, and overall survival, all summarised using the Kaplan-Meier method. Activity and safety endpoints were analysed for all enrolled patients who received at least one dose of neoadjuvant cemiplimab. In this report, safety data are reported for all patients who received at least one dose of adjuvant cemiplimab. This trial is registered with ClinicalTrials.gov, NCT04154943, has completed enrolment and follow-up is ongoing., Findings: Between March 20, 2020, and July 8, 2021, 79 patients were enrolled. Median age was 73 years (IQR 66-81), 67 (85%) patients were male, 12 (15%) were female, 69 (87%) were White, one was Asian (1%), one was other race (1%), and race was not reported for eight (10%). As of data cutoff (Dec 1, 2022), median follow-up was 18·7 months (IQR 15·6-22·1) for all 79 patients. Among 70 patients who had surgery, 65 (93%) had post-surgical management data: 32 (49%) of 65 were observed postoperatively, 16 (25%) received adjuvant cemiplimab, and 17 (26%) received adjuvant radiotherapy. 11 (14%) of 79 patients had event-free survival events, with an estimated 12-month event-free survival of 89% (95% CI 79-94) for all patients. None of 40 patients who had a pathological complete response and one (10%) of ten patients with major pathological response had recurrence. Six (9%) of 70 patients who completed surgery had a disease-free survival event, with an estimated 12-month disease-free survival of 92% (95% CI 82-97). Nine (11%) of 79 patients died, with an estimated 12-month overall survival for all patients of 92% (95% CI 83-96). Four (25%) of 16 patients who received adjuvant cemiplimab treatment had grade 3 adverse events, including one (6%) who had increased blood potassium, one (6%) who had traumatic limb amputation, and two who had serious adverse events (one [6%] cardiomyopathy and one [6%] hypophysitis). There were no grade 4 adverse events or treatment-related deaths., Interpretation: For patients with resectable stage II-IV cutaneous squamous cell carcinoma, neoadjuvant cemiplimab followed by surgery might be a potential treatment option, addressing a substantial unmet need., Funding: Regeneron Pharmaceuticals and Sanofi., Competing Interests: Declaration of interests NDG reports institutional research funding from Regeneron Pharmaceuticals; speaker honoraria from AiCME; and advisory board and consulting fees from PDS Biotechnology, Replimmune, Regeneron Pharmaceuticals, and Merck. DMM reports honoraria for advisory or consultant roles from Castle Biosciences, EMD Serono, Merck KGaA, Merck Sharpe & Dome, Pfizer, Regeneron Pharmaceuticals, Incyte, Sanofi Genzyme, and Bristol Myers Squibb; equity options from Checkpoint Therapeutics and Avstera Therapeutics Corp; and research funding from Kartos Therapeutics, NeoImmune Tech, and Regeneron Pharmaceuticals. NIK reports grants and advisory board fees from Regeneron Pharmaceuticals, Bristol Myers Squibb, Merck, Replimmune, and Novartis; advisory board fees from Iovance, Instil Bio, Castle Biosciences, Nektar, Incyte (data safety monitoring committee), AstraZeneca (data safety monitoring committee), and Jounce Therapeutics; grants from GlaxoSmithKline, HUYA, and Celgene; honoraria from Genzyme, National Comprehensive Cancer Network (paid by Pfizer), Nektar (study steering committee), Regeneron Pharmaceuticals (study steering committee), Bristol Myers Squibb (study steering committee). and Replimmune (study steering committee); grant from Modulation Therapeutics; travel support from Regeneron Pharmaceuticals; and common stock ownership of Bellicum Pharmaceuticals, Amarin, and Asensus Surgical (formerly Transenetrix). VD reports institutional research funding from Genentech, and advisory board fees from Regeneron Pharmaceuticals. ESR reports advisory board and consulting fees from Genentech, Feldan Therapeutics, Regeneron Pharmaceuticals, and Sanofi, and serves on the board of directors for Checkpoint Therapeutics. EJL reports institutional research funding from Regeneron Pharmaceuticals and Sanofi; institutional grants from Bristol Myers Squibb and Merck; advisory board fees from Bristol Myers Squibb, Eisai, Genentech, Instil Bio, Merck, Natera, Nektar Therapeutics, Odonate Therapeutics, Pfizer, Rain Therapeutics, Regeneron Pharmaceuticals, Replimmune, and Sanofi; payment for speaker's fee from Bristol Myers Squibb; and consulting fees from Bristol Myers Squibb, Macrogenics, OncoSec, Merck, Novartis, CareDX, and Pfizer. FM reports travel support, speaker's fees or advisor's honoraria from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche, and Sanofi; and research funding from Novartis and Roche. PLS reports institutional research grants from Ascentage Pharma and Pfizer, and advisory board roles for Elevar Therapeutics, Prelude Therapeutics, and Regeneron Pharmaceuticals. JA reports payment or honoraria for speakers bureaus and presentations from Bristol Myers Squibb and Regeneron Pharmaceuticals; advisory board and consulting fees from Bristol Myers Squibb, Castle Biosciences, Pfizer, Regeneron Pharmaceuticals, and Sanofi. JLG reports institutional research funding from Alkermes, EMD Serono, Merck, Regeneron Pharmaceuticals, and Roche/Genentech; and advisory board or consultant fees from Astellas, Exelixis, EMD Serono, Merck, and Regeneron Pharmaceuticals. AH reports grants and personal fees from Amgen, Bristol Myers Squibb, Merck-Pfizer, MSD/Merck, Philogen, Pierre Fabre, Regeneron Pharmaceuticals, Roche, Sanofi-Genzyme, Novartis Pharma, Eisai, Replimmune, NeraCare; consulting fees from Seagen, IO Biotech, Dermagnostix, Incyte, Highlight Therapeutics, and Iovance; speaker's honoraria from Kyowa Kirin; advisory board fees from Immunocore; and institutional grants from Huya Biosciences outside the submitted work. JHC reports consulting or advisory roles for Exelixis, Coherus Biosciences, Merck Sharp & Dohme, Eisai, and Regeneron Pharmaceuticals, and institutional research funding from Arcus Biosciences and Genmab. BGMH reports consulting or advisory roles at AstraZeneca, Bristol Myers Squibb, Eisai, Merck Sharp & Dohme, Pfizer, and Roche, and institutional research funding from Amgen. DS reports honoraria from Roche/Genentech, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Immunocore, Merck Serono, Array BioPharma, Pfizer, Pierre Fabre, Philogen, Regeneron Pharmaceuticals, 4SC, Sanofi, Regeneron Pharmaceuticals, NeraCare GmbH, Sun Pharma, InflarxGmbH, Ultimovacs, and Sandoz; consulting fees from Roche/Genentech, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, 4SC, Pierre Fabre, Sanofi, Regeneron Pharmaceuticals, and Nektar; speaker fees from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi, Regeneron Pharmaceuticals, and Merck; advisory board fees from AstraZeneca, Daiichi-Sankyo, Roche/Genentech, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, 4SC, Pierre Fabre, Sanofi, Regeneron Pharmaceuticals, and Nektar; institutional research funding from Bristol Myers Squibb, Novartis, Roche, MSD Oncology, and Array BioPharma/Pfizer; unpaid leadership or fiduciary roles with Dermatologic Cooperative Oncology Group, European Organisation for Research and Treatment of Cancer-Melanoma Group, Hiege-Stiftung, and Nationale Versorgungskonferenz Hautkrebs; and travel and accommodation expenses from Roche/Genentech, Bristol Myers Squibb, Merck Serono, Novartis, Merck Sharp & Dohme, Pierre Fabre, Sanofi, and Regeneron Pharmaceuticals. VAP reports honoraria for advisory or consulting roles from Sun Pharma, Almirall, Biofrontera, PhD Biosciences, Regeneron Pharmaceuticals, and Sanofi Genzyme; speakers bureau fees from Regeneron Pharmaceuticals, and Sanofi Genzyme, equity in Avstera Therapeutics and Science 37; and research funding from Regeneron Pharmaceuticals. JMT reports honoraria for advisory or consultant roles for Bristol Myers Squibb, Merck & Co, AstraZeneca, Genentech/Roche, Regeneron Pharmaceuticals, Compugen, Lunaphore, and Akoya Biosciences; stock options in Akoya Biosciences; equipment loan and reagent provision from Akoya Biosciences; and research funding from Bristol Myers Squibb and Akoya Biosciences. AML reports uncompensated consultancy for Eisai, research funding support from Sanofi/Regeneron Pharmaceuticals, and support from a Peter MacCallum Cancer Centre Discovery Partner Fellowship. RF reports grants or investigator-initiated trial support from Merck, Pfizer, Gilead, and Ayala; royalties from UpToDate for a chapter on olfactory neuroblastoma; payment for expert testimony from Guidepoint; and advisory board participation with Regeneron Pharmaceuticals, Prelude Therapeutics, Elevar Therapeutics, Eisai, Remix Therapeutics, and Coherus BioSciences. S-YY, HH, FS, and IL are employees and shareholders of Regeneron Pharmaceuticals. MM and MGF report receipt of support for attending meetings or travel, and are also employees, patent holders, and shareholders of Regeneron Pharmaceuticals. DR reports institutional research grant and funding from Regeneron Pharmaceuticals, Genentech, Sanofi, Kura Oncology, Roche, Merck Sharp & Dohme, Decibel Therapeutics, Bristol Myers Squibb, GlaxoSmithKline, and ALX Oncology; and uncompensated scientific committee and advisory board roles for Merck Sharp & Dohme, Regeneron Pharmaceuticals, Sanofi, and Eisai. YBS and JH declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Rhesus monkeys are a non-rodent species employed in the preclinical safety evaluation of pharmaceuticals and biologics. These nonhuman primate species have been increasingly used in biomedical research because of the similarity in their ionic mechanisms of repolarization with humans. Heart rate and QT interval are two primary endpoints in determining the pro-arrhythmic risk of drugs. As heart rate and QT interval have an inverse relationship, any change in heart rate causes a subsequent change in QT interval. This warrants for calculation of a corrected QT interval. This study aimed to identify an appropriate formula that best corrected QT for change in heart rate. We employed seven formulas based on source-species type, clinical relevance, and requirements of various international regulatory guidelines. Data showed that corrected QT interval values varied drastically for different correction formulas. Equations were compared on their slope values based on QTc versus RR plots. The rank order of the slope for different formulas was (closest to farthest from zero) QTcNAK, QTcHAS, QTcBZT, QTcFRD, QTcVDW, QTcHDG, and QTcFRM. QTcNAK emerged to be the best correcting formula in this study. It showed the least correlation with the RR interval ( r = -0.01) and displayed no significant difference amongst the sexes. As there is no universally recognized formula for preclinical use, the authors recommend developing a best-case scenario model for specific study designs and individual organizations. The data from this research will be helpful in deciding an appropriate QT correction formula for the safety assessment of new pharmaceuticals and biologics.

Background: Eustachian tube balloon dilation (ETBD) has been Food and Drug Administration (FDA) approved for refractory Eustachian tube dysfunction since 2016. While ETBD is generally seen as safe, the complication profile has not been well defined., Objective: The objective of this study was to utilize the FDA manufacturer and user facility device experience (MAUDE) database to better assess adverse events (AE) related to ETBD., Methods: This is a study of a multiinstitutional database maintained by the U.S. FDA. A database analysis was performed via the collaboration of multiple clinicians at tertiary referral centers. The FDA MAUDE database was queried for all medical device reports (MDR) related to ETBD devices from January 2012 to November 2022. Eighty-eight unique MDR were identified, 16 of which met inclusion criteria., Results: Three MDRs were classified as device-related (18.8%); none resulted in an AE. Thirteen MDRs (81.3%) were patient-related; all were classified as AEs. The most common AE was postoperative subcutaneous emphysema (n = 6, 46.2%). Of the patients with subcutaneous emphysema, there was a wide range of severity. The most severe AE (n = 1, 6.3%) was postoperative stroke secondary to carotid artery dissection., Conclusion: Though ETBD is generally seen as a safe procedure, there have been several concerning AEs reported to date. Increased awareness of ETBD complications can serve as a primer for improved patient education and counseling during the informed consent process and aid surgeons in clinical decision-making. Future studies with standardized reporting protocols are warranted to create a central registry for ETBD., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Current assessments on topical treatment attributes in actinic keratosis (AK) do not evaluate safety, effectiveness, and satisfaction from both clinician and patient perspectives, creating an unmet need for more comprehensive AK-specific measures that fully capture the patient experience., Objective: To develop an actinic keratosis-specific expert panel questionnaire (AK-EPQ) of patient-reported outcomes and clinician-reported outcomes for use in research studies., Methods: Using interviews of patients with AK and targeted literature reviews, a 9-person consensus panel of dermatologists with expertise in AK treatment was convened to develop the AK-EPQ to assess AK-specific patient-reported outcomes and clinician-reported outcomes., Results: Nine expert advisers achieved consensus on 11 AK-EPQ items that encompass patient and clinician perspectives of treatment-related local skin reactions, clinical and cosmetic outcomes associated with AK, and satisfaction with treatment; the AK-EPQ will be first implemented in the Patient-Reported Outcomes for Actinic Keratosis study (NCT05260073)., Limitations: The AK-EPQ does not directly measure quality of life, although it can be used with validated quality of life instruments., Conclusion: The newly developed AK-EPQ elicits insights into the patient and clinician experience with AK treatments. Comparative probing of these perspectives may help optimize precision medicine in AK treatment., Competing Interests: Dr Berman has served as an investigator, speaker, advisory board member, or consultant for Aclaris, Almirall, AiViva Biopharma, Biofrontera, Evommune, Ferndale Laboratories, Inc, Galderma Laboratories, L.P., GlaxoSmithKline, Lemonex, LEO Pharma, Mediwound, Mino Labs, Miragen, NOVAN, Novartis Pharmaceuticals Corp, Pfizer, Pierre Fabre, PHD Biosciences, Pulse Biosciences, Sensus, and Sirnaomics. Dr Armstrong served as a research investigator and/or scientific adviser to AbbVie, BI, BMS, EPI, Incyte, LEO, UCB, Janssen, Lilly, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, Regeneron, and Pfizer. Dr Lebwohl receives research funding from AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Dermavant Sciences, Eli Lilly, Incyte, Janssen Research & Development, LLC, Ortho Dermatologics, Regeneron, and UCB, Inc, and is a consultant for Aditum Bio, Almirall, AltruBio Inc, AnaptysBio, Arcutis, Inc, Aristea Therapeutics, Arrive Technologies, Avotres Therapeutics, BiomX, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Castle BioSciences, Corrona, Dermavant Sciences, Dr. Reddy’s Laboratories, Evelo Biosciences, Evommune, Inc, Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima Ltd, LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, and Verrica. Dr Grada is the former Head of R&D and Medical Affairs at Almirall, US. Dr Bhatia has been an adviser, consultant, and investigator for AbbVie, Almirall, Arcutis, Arena, Biofrontera, BMS, BI, Brickell, Dermavant, EPI Health, Ferndale, Galderma, Genentech, InCyte, ISDIN, J&J, LaRoche-Posay, Leo, Lilly, Novartis, Ortho, Pfizer, P&G, Regeneron, Sanofi, Stemline, SunPharma, and Verrica. Dr Patel has received honoraria from Regeneron and Almirall, has served as a consultant for PhD Biosciences and Jounce Therapeutics, and has served as a speaker for Regeneron and Sanofi. Dr Rigel has served as a consultant for Almirall, Castle BioSciences, DermTech, and SciBase. Dr Del Rosso has served as a research investigator, consultant/adviser, or speaker for AbbVie, Aclaris, Almirall, Amgen (Celgene), AnaptysBio, Arcutis, Athenex, Bausch (Ortho Dermatologics), Biofrontera, BioPharmX, Biorasi, Blue Creek, Botanix, Brickell, Bristol-Myers Squibb, Cara Therapeutics, Cassiopea, Dermata, Dermavant, Encore, EPI Health, Ferndale, Galderma, Genentech, Incyte, Jem Health, LEO Pharma, La Roche-Posay, Lilly (Dermira), MC2, NOVAN, Pfizer, Ralexar, Regeneron, Sanofi-Genzyme, Sente, Solgel, Sonoma (Intraderm), Sun Pharma, UCB, Verrica, and VYNE (Foamix/Menlo). Dr Schlesinger has received grant/research funding from AbbVie, Aclaris, Allergan, Almirall, Anterios, AOBiome, Arcutis Premier Research, Astellas Pharma US, Inc, Athenex, Biofrontera, Biorasi, Boehringer Ingelheim, Brickell Biotech, Bristol-Myers Squibb, Cara Therapeutics, Castle BioScience, Celgene, Centocor Ortho Biotech (now Janssen Biotech), ChemoCentryx, Coherus Biosciences, Concert Pharmaceutical, Corrona, Cutanea Life Sciences, Dermavant, Dermira (now Lilly), DT Pharmacy & DT Collagen, EPI Health, Galderma (Nestle), Janssen Pharmaceuticals, Inc, Kiniksa, LEO, Lilly, Merz, Nimbus, Novartis, Pfizer, Processa, Pulse Biosciences, Regeneron, Sanofi Genzyme, Sisaf, and Trevi; has received honoraria from AbbVie, Allergen, Almirall, Biofrontera AG, Bristol-Myers Squibb, Castle BioScience, EPI Health, Foundation for Research and Education in Dermatology (FRED), Galderma, Merz, Novartis, Regeneron, and Sun Pharma; has served as a speaker, advisory board member, or consultant for AbbVie, Allergan, Almirall, Amgen, Biofrontera AG, Bristol-Meyers Squibb, Castle BioScience, Celgene, CMS Aesthetics DCME, DUSA/Sun Pharma, EPI Health, Foundation for Research and Education in Dermatology (FRED), Genentech, Greenway Therapeutix, Kintor, Merz, Nextphase, Novartis, Pharmatecture, Prolacta Biosciences, Pulse Biosciences, Regeneron, Remedly, Inc, Sanofi Genzyme, Sun Pharma, UCB, and Verrica; has received consulting fees from Lilly, Ortho Dermatologics, Pierre Fabre, Plasmed, Regeneron, and Skinceuticals/L’Oreal; has been involved in the CME Program for MED Learning Group; has been involved with OncLive SSC Insights Filming/Stacy Jaffe for MJH Associates; has served as Co-Chair of AAD AK Guideline Committee and Co-Chair of AAD Performance Measurement Work Group; is a member of AAD Performance Measurement Committee; and owns stock in Remedly, Inc. Dr Kircik has served as an investigator, speaker, advisory board member, or consultant for Abbott Laboratories, Aclaris, Inc, Allergan, Inc, Almirall, Anacor Pharmaceuticals, Inc, Assos Pharma, Astellas Pharma US, Inc, Asubio Pharma Co, Ltd, Berlex Laboratories (Bayer Healthcare Pharmaceuticals), Biogen-Idec, Inc, Biolife, Biopelle, Boehringer Ingelheim, Breckinridge Pharma, Celgene Corporation, Centocor, Inc, Colbar, CollaGenex, Combinatrix, Connetics Corporation, Coria, Dermik Laboratories, Dermira, Inc, Dow Pharmaceutical Sciences, Inc, Dusa Pharmaceuticals, Inc, Eli Lilly & Co, Embil Pharmaceutical Co, Ltd, EOS, Ferndale Laboratories, Inc, Galderma Laboratories, LP, Genentech, Inc, GlaxoSmithKline, PLC, Health Point Ltd, Idera, Inc, Innocutis Medical, LLC, Innovail, Intendis, Inc, Johnson & Johnson, Laboratory Skin Care, Inc, Leo Pharmaceuticals, Inc, L’Oreal SA, 3M, Maruho Co, Ltd, Medical International Technologies, Medicis Pharmaceutical Corp, Merck & Co, Inc, Merz, Nano Bio Corporation, Novartis Pharmaceutical Corporation, Noven Pharmaceuticals, Inc, Nucryst Pharmaceuticals Corporation, Obagi Medical Products, Inc, Onset, Ortho Dermatologics, OrthoNeutrogena, PediaPharma, Inc, Promius Pharma, LLC, PharmaDerm, Pfizer, Inc, PuraCap, QLT, Inc, Quatrix, Quinnova, Serono (Merck-Serono International SA), SkinMedica, Inc, Stiefel Laboratories, Inc, Sun Pharmaceutical Industries, Ltd, Taro, TolerRx, Inc, Triax, UCB, Inc, Valeant Pharmaceuticals North America LLC, Warner-Chilcott, XenoPort, Inc, and ZAGE. Dr Salem is an employee of Almirall, US. Dr Narayanan is an employee of Avant Health LLC, and has served as a consultant for Almirall, Biogen, Johnson & Johnson, Sarepta Therapeutics, SeaGen, and Takeda. Dr Kasujee is an employee of Almirall, Spain., (© 2024 Published by Elsevier Inc. on behalf of the American Academy of Dermatology, Inc.)

Introduction Antimicrobial prophylaxis, involving short antibiotic courses preceding surgical procedures, is recommended to minimize postoperative infections. Paediatric cardiac surgeries are classified as clean procedures, though infection challenges persist due to illness severity and extended ICU stays. Antimicrobial prophylaxis varies, ranging from single doses to extended administration until catheters are removed. Typically lasting 24 to 48 hours, it has proven infection-reduction benefits. Despite these practices, uncertainties surround the optimal nature, timing, and duration of administration. This concern is amplified by escalating antimicrobial resistance driven by antibiotic overuse. Vulnerable paediatric populations bear heightened consequences of irrational antimicrobial use, contributing to global resistance trends. Yet, a defined optimal prophylaxis schedule for paediatric cardiac surgery is lacking. Importing adult guidelines may be inadequate due to paediatric research complexities and population diversity. Developing effective prophylaxis protocols is crucial for children undergoing cardiac surgery, given global antibiotic overuse and evolving drug resistance. Establishing an optimal prophylactic strategy remains a challenge, necessitating further research for evidence-based protocols to mitigate infections in this vulnerable patient cohort. Methods This study investigates antibiotic use in paediatric cardiac surgery. A retrospective analysis of 100 patients from a rural Indian hospital (2017-2018) assesses antibiotic patterns, including type, dose, duration, and adherence to prophylaxis protocols. Results In the studied cohort of paediatric cardiac surgery patients, complete compliance (100%) with antibiotic prophylaxis was observed. However, deviations were identified: 30% received antibiotics prematurely, and 30% did not align with institutional protocol criteria. Concerning antibiotic selection, 87% followed hospital policy with the recommended cefoperazone and sulbactam combination plus amikacin, while 9% received piperacillin/tazobactam + amikacin due to sepsis. Irregular use (22%) based on clinical records occurred. Furthermore, 4% received piperacillin/tazobactam + teicoplanin, with one instance of inappropriate higher antibiotic use. Regarding prophylaxis duration, only 27% adhered to the appropriate timeline, with 40% exceeding 48 hours, indicating extended use. Upon discharge, a notable proportion (45 patients) received antibiotic prescriptions. Among them, 73% were prescribed rationally, while 27% exhibited irrational antibiotic use. Conclusion The findings of this study shed a significant light on the issue of antibiotic misuse within the context of paediatric cardiac surgery. It underscores the pressing need for more stringent measures to regulate and address this concerning trend. The study underscores the pivotal importance of adhering rigorously to established protocols and guidelines for antibiotic prophylaxis. This adherence not only holds the potential to elevate the overall quality of patient care but also plays a critical role in combating the escalating challenge of antibiotic resistance. Through a concerted effort to optimize antibiotic usage, we can simultaneously enhance patient outcomes and contribute to the ongoing fight against the emergence of antibiotic-resistant strains, thus preserving the efficacy of these vital medications for future generations., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Pathan et al.)

Background: Spontaneous cerebrospinal fluid (CSF) rhinorrhea in the pediatric population is an exceedingly rare condition that occurs when the dura mater is breached, resulting in CSF drainage from the subarachnoid space into surrounding sinonasal tissue. Objective: This work delineates a step-by-step surgical approach to visually demonstrate the feasibility of an uninarial endoscopic endonasal approach for pediatric spontaneous CSF leak repair. Postoperative Outcome: A 2-year-old male with a 6-month history of clear rhinorrhea, intermittent headaches, and a previous episode of bacterial meningitis was evaluated as an inpatient consultation. Computed tomography cisternography revealed active CSF extravasation at the right sphenoid sinus roof. An endoscopic endonasal approach was performed including a complete sphenoethmoidectomy plus middle turbinectomy to provide access to the skull base defect. Once identified, a middle turbinate free mucosal graft was placed for cranial base reconstruction given the child's young agre. Sinonasal debridement 3 weeks following surgery under anesthesia revealed an intact viable graft with no evidence of CSF leak. There was no evidence of CSF leak recurrence or complications 1 year following surgery. Conclusion: The uninarial endoscopic endonasal approach is a safe and effective option for the surgical management of spontaneous CSF leak rhinorrhea in the pediatric population.

Objective: To review and summarize reported adverse events related to the use of porcine small intestine submucosal grafts (Biodesign™) in otologic procedures., Study Design: Retrospective cross-sectional analysis., Setting: Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database., Material and Methods: The MAUDE database was queried for all medical device reports (MDR) related to otologic use of Biodesign™ (Cook Medical, Bloomington, IN) from January 2016 to November 2022. Adverse events (AEs) were identified by reviewing all reports with the basic search term "Biodesign" and "Biodesign, Otologic". Reports were individually reviewed and categorized with special attention to AEs., Results: A total of 500 reports were reviewed. Since FDA approval of Biodesign™ in 2016, there have been 5 adverse events reported for use of Biodesign™ during otologic surgery (tympanoplasty, n = 3; stapes surgery, n = 2). All reported events described patient injury, and all cases required at least one revision surgery. Four cases described significant foreign body inflammatory reactions. Complications included hearing loss (n = 3), severe otalgia (n = 2), persistent perforation (n = 2), vertigo (n = 2), and facial paralysis (n = 1)., Conclusion: The use of porcine small intestinal submucosal graft has been thought to be a safe and effective option for otologic surgery, with the advantage of availability without graft harvest in minimally invasive endoscopic surgery. However, foreign body or granulomatous reactions have been documented and should be considered prior to its use in otologic surgery., Competing Interests: Declaration of competing interest There are no relevant conflicts of interest from any authors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Identify risk factors and perioperative morbidity for pediatric patients undergoing septoplasty., Methods: The American College of Surgeons National Surgical Quality Improvement Program Pediatric (NSQIP-P) database was retrospectively queried to identify patients who underwent septoplasty (CPT 30520) for a diagnosis of deviated nasal septum (ICD J34.2) from 2018 to 2019. Outcomes analyzed include patient demographics, medical comorbidities, surgical setting, operative characteristics, length of stay, and postoperative outcomes., Results: A total of 729 children were identified. Median age at time of surgery was 15.8 years, with most patients (82.8%) >12 years of age; no significant association was identified between age at time of surgery and adverse surgical outcomes. Overall, postoperative complications were uncommon (0.6%), including readmission (0.4%), septic shock (0.1%), and surgical site infection (0.1%). A history of asthma was found to be a significant risk factor for postoperative complications ( P  = .035) as well as BMI ( P  = .028)., Conclusion: The 30-day postoperative complications following pediatric septoplasty in children reported in the NSQIP-P database are infrequent. Special considerations regarding young age, complex sinonasal anatomy, and surgical technique remain important features in considering corrective surgery for the pediatric nose and certainly warrant further investigation in subsequent studies.

Introduction: Auricular reconstruction techniques most frequently utilize either autologous costal cartilage or alloplastic porous polyethylene (PPE) implant. Objectives: To compare the aesthetic outcomes, number of surgeries, and complications in children who underwent microtia reconstruction with either rib or PPE implant by blinded photograph review. Methods: This retrospective cohort study included consecutive pediatric patients who underwent auricular reconstruction with either autologous cartilage or PPE between November 2017 and February 2022. Blinded observers rated each postoperative ear through a web-based survey. Data on patient characteristics, operative time, length of admission, and complications were collected, bivariate analyses were performed using chi-square or Fisher's exact tests for categorical variables and Wilcoxon rank-sum test for continuous variables. Results: Forty-four ears were included, 28 of which (63.6%) were reconstructed with cartilage. Median patient age was 8 years (range 4-18 years) and 29 (65.9%) were male. The cartilage group had more surgeries (median 2.5 vs. 1.0, p  < 0.001), and total operating time across all surgeries did not differ significantly. Conclusion: The two groups in our study had similar rates of complications and aesthetic scores, and aesthetic scores were worse for ears with wound complications requiring unplanned revisions.

Background and Importance: Medial orbital access through a transcaruncular corridor has yet to be fully characterized as a potential approach to intradural lesions within the skull base. Transorbital approaches present unique potential in the management of complex neurological pathologies and require subspecialty collaboration across multiple disciplines., Clinical Presentation: A 62-year-old man presented with progressive confusion and mild left-sided weakness. He was found to have a right frontal lobe mass with significant vasogenic edema. A comprehensive systemic workup was otherwise unremarkable. A multidisciplinary skull base tumor board conference recommended a medial transorbital approach through transcaruncular corridor, which was performed by neurosurgery and oculoplastics services. Postoperative imaging demonstrated gross total resection of the right frontal lobe mass. Histopathologic evaluation was consistent with amelanotic melanoma with BRAF (V600E) mutation. At his last follow-up visit, 3 months after surgery, the patient did not experience any visual symptoms and had an excellent cosmetic outcome after surgery., Conclusion: The transcaruncular corridor through a medial transorbital approach provides a safe and reliable access to the anterior cranial fossa., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)