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INTRODUCTION: Inclisiran, an siRNA targeting hepatic PCSK9 mRNA, administered twice-yearly (after initial and 3-month doses), substantially and sustainably reduced LDL-cholesterol (LDL-C) in Phase III trials. Whether lowering LDL-C with inclisiran translates into a reduced risk of major adverse cardiovascular events (MACE) is not yet established. In-silico trials applying a disease computational model to virtual patients receiving new treatments allow to emulate large scale long term clinical trials. The SIRIUS in-silico trial programme aims to predict the efficacy of inclisiran on CV events in individuals with established atherosclerotic cardiovascular disease (ASCVD). METHODS: A knowledge-based mechanistic model of ASCVD was built, calibrated, and validated to conduct the SIRIUS programme (NCT05974345) aiming to predict the effect of inclisiran on CV outcomes.The SIRIUS Virtual Population included patients with established ASCVD (previous myocardial infarction (MI), previous ischemic stroke (IS), previous symptomatic lower limb peripheral arterial disease (PAD) defined as either intermittent claudication with ankle-brachial index <0.85, prior peripheral arterial revascularization procedure, or vascular amputation) and fasting LDL-C ≥ 70 mg/dL, despite stable (≥ 4 weeks) well-tolerated lipid lowering therapies.SIRIUS is an in-silico multi-arm trial programme. It follows an idealized crossover design where each virtual patient is its own control, comparing inclisiran to 1) placebo as adjunct to high-intensity statin therapy with or without ezetimibe, 2) ezetimibe as adjunct to high-intensity statin therapy, 3) evolocumab as adjunct to high-intensity statin therapy and ezetimibe.The co-primary efficacy outcomes are based on time to the first occurrence of any component of 3P-MACE (composite of CV death, nonfatal MI or nonfatal IS) and time to occurrence of CV death over 5 years. PERSPECTIVES/CONCLUSION: The SIRIUS in-silico trial programme will provide early insights regarding a potential effect of inclisiran on MACE in ASCVD patients, several years before the availability of the results from ongoing CV outcomes trials (ORION-4 and VICTORION-2-P).
The SIRIUS in-silico trial programme is a knowledge-based computer model built to simulate the biological and clinical long-term effects of inclisiran, an siRNA targeting hepatic PCSK9 mRNA, on virtual patients with cardiovascular disease. Key Findings: The model accurately replicates the biological processes of cardiovascular disease and the impact of lipid-lowering therapies, allowing for the prediction of randomized clinical trials.Simulating clinical trials with virtual patients can provide insights into the efficacy and safety of new treatments before the results of randomized clinical trials, potentially speeding up the drug development process.
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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.
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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.
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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, 2024.
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Background: The objective outcomes of masseteric nerve transfer in the setting of parotid malignancy are unclear. Objective: To measure objective facial reanimation outcomes of masseteric nerve transfer in patients with parotid malignancy who underwent parotidectomy with facial nerve resection. Materials and Methods: Retrospective review of patients who underwent masseteric nerve transfer for facial paralysis secondary to parotid malignancy was carried out at a tertiary referral hospital from August 2017 to November 2021. Objective facial reanimation outcomes were analyzed using Emotrics. Minimal follow-up of 6 months was required for inclusion. Results: Eight patients (five males) with a median age of 75.5 years (range 53-91) met inclusion criteria. Fifty percent had metastatic squamous cell carcinoma, and 50% had primary parotid malignancy. Five patients underwent concomitant cancer resection with facial nerve reconstruction. Seven patients received postoperative adjuvant radiotherapy. After reinnervation, patients had improved oral commissure excursion (from 1.51 mm ±1.27 to 3.77 mm ±1.81; p < 0.01) and facial symmetry during smile. Conclusion: In this study, masseteric nerve transfer enhanced oral commissure excursion and facial symmetry during smile in patients with parotid malignancy and facial nerve resection.
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Parálisis Facial , Transferencia de Nervios , Neoplasias de la Parótida , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Parálisis Facial/etiología , Parálisis Facial/cirugía , Estudios Retrospectivos , Neoplasias de la Parótida/complicaciones , Neoplasias de la Parótida/cirugía , Músculo Masetero/inervación , Nervio MandibularRESUMEN
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.
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Armas de Fuego , Heridas por Arma de Fuego , Masculino , Humanos , Niño , Estados Unidos , Adolescente , Heridas por Arma de Fuego/diagnóstico por imagen , Heridas por Arma de Fuego/cirugía , Heridas por Arma de Fuego/epidemiología , Multimedia , Servicio de Urgencia en HospitalRESUMEN
CONTEXT: In pigs, in vitro fertilisation (IVF) is associated with high polyspermy rates, and for this reason, in vitro embryo production (IVP) is still an inefficient biotechnology. Coculture with somatic cells is an alternative to improve suboptimal in vitro maturation (IVM) conditions. AIM: This study was conducted to test a coculture system of porcine luteal cells (PLC) and cumulus-oocyte complexes (COC) to improve oocyte metabolism. METHODS: COC were matured in vitro with PLC. Oocyte lipid content, mitochondrial activity, zona pellucida (ZP) digestibility and pore size, cortical reaction and in vitro embryo development were assessed. KEY RESULTS: Coculture reduced cytoplasmic lipid content in the oocyte cytoplasm without increasing mitochondrial activity. Although ZP digestibility and ZP pore number were not different between culture systems, ZP pores were smaller in the coculture. Coculture impacted the distribution of cortical granules as they were found immediately under the oolemma, and more of them had released their content in the ZP. Coculture with porcine luteal cells during IVM increased monospermic penetration and embryo development after IVF. CONCLUSIONS: The coculture of COC with PLC affects the metabolism of the oocyte and benefits monospermic penetration and embryo development. IMPLICATIONS: The coculture system with PLC could be an alternative for the conventional maturation medium in pigs.
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Células Lúteas , Zona Pelúcida , Femenino , Animales , Porcinos , Zona Pelúcida/metabolismo , Técnicas de Cocultivo , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Oocitos/metabolismo , Fertilización In Vitro/veterinaria , Lípidos/análisisRESUMEN
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.
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Rinorrea de Líquido Cefalorraquídeo , Endoscopía , Masculino , Humanos , Niño , Preescolar , Endoscopía/métodos , Pérdida de Líquido Cefalorraquídeo/etiología , Pérdida de Líquido Cefalorraquídeo/cirugía , Rinorrea de Líquido Cefalorraquídeo/etiología , Rinorrea de Líquido Cefalorraquídeo/cirugía , Base del Cráneo/cirugía , Cornetes Nasales , Estudios RetrospectivosRESUMEN
INTRODUCTION: The aim of this study was to measure changes in the quality of life of patients who had orthognathic surgery using an original questionnaire, designed for this purpose. MATERIAL AND METHOD: This single-center retrospective study included all patients who had orthognathic surgery in our center between 2014 and 2019. An original questionnaire comprising 13 items in 4 domains was sent to patients postoperatively by email after telephone contact and obtaining their consent. Items were scored on a 5-point scale ranging from (-1), worse than before surgery, to (+3), better than before surgery. RESULTS: All data were collected in a standardized way. In total, 123 patients responded. The mean score for all surgeries combined was +1.14, indicating an improvement in QOL considered to be "low to moderate". A total of 118 patients (95.9%) reported an improvement following surgery, including 18 patients (14.6%) who reported a marked improvement. The greatest improvement was observed for psychosocial aspects and morphology. CONCLUSION: This study shows a positive effect of orthognathic surgery on patients' QOL, including self-perception, relationships with others, or functional aspects as mastication and breathing. We propose an original tool that is easy to use by patients to measure quality of life following orthognathic surgery.
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Cirugía Ortognática , Procedimientos Quirúrgicos Ortognáticos , Humanos , Calidad de Vida , Procedimientos Quirúrgicos Ortognáticos/psicología , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
INTRODUCCIÓN: El tamoxifeno es un antiestrógeno no esteroideo que actúa como antagonista en el tejido mamario, la retina neurosensorial y el epitelio pigmentario de la retina (EPR). La incidencia de sus efectos oculares varía entre el 0,9 y el 11%. MÉTODOS: Serie de casos. Se evaluaron tres pacientes de sexo femenino mediante estudio por imagen multimodal que recibieron tamoxifeno por cáncer de mama con el propósito de realizar el seguimiento y determinar si hay cambios luego de la suspensión del tratamiento. RESULTADOS: Las tres pacientes presentaron signos de retinopatía cristalina durante el seguimiento con tomografía de coherencia óptica de dominio espectral (SD-OCT). CONCLUSIÓN: El seguimiento mediante estudios de imagen multimodal permitió evaluar la progresión de los cambios aportando una valoración pronóstica. Los hallazgos encontrados (agudeza visual e imagen multimodal) confirmaron los resultados de estudios previos que indicaban que, a un determinado nivel de toxicidad, el daño era irreversible
INTRODUCTION: Tamoxifen is a non-steroidal anti-oestrogen that acts as an antagonist in breast tissue, neurosensory retina, and retinal pigment epithelium (RPE). The reported incidence of its ocular effects varies between 0.9% and 11%. METHODS: Case series. Multimodal image studies were used to evaluate three female patients who were receiving tamoxifen for breast cancer for the purpose of monitoring and determining whether there are changes after discontinuation of treatment. RESULTS: All three patients showed signs of crystalline retinopathy using spectral domain optical coherence tomography (SD-OCT) during follow-up. CONCLUSION: The follow-up using multimodal imaging studies allowed evaluating the progression of the changes, providing a prognostic assessment. The findings reported (visual acuity and multimodal imaging) confirmed the results of previous studies, indicating that, at a certain level of toxicity, the damage was irreversible
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Humanos , Femenino , Persona de Mediana Edad , Anciano , Tamoxifeno/toxicidad , Enfermedades de la Retina/inducido químicamente , Imagen Multimodal/métodos , Progresión de la Enfermedad , Enfermedades de la Coroides/inducido químicamente , Enfermedades de la Retina/patología , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Enfermedades de la Coroides/diagnósticoRESUMEN
INTRODUCTION: Tamoxifen is a non-steroidal anti-oestrogen that acts as an antagonist in breast tissue, neurosensory retina, and retinal pigment epithelium (RPE). The reported incidence of its ocular effects varies between 0.9% and 11%. METHODS: Case series. Multimodal image studies were used to evaluate three female patients who were receiving tamoxifen for breast cancer for the purpose of monitoring and determining whether there are changes after discontinuation of treatment. RESULTS: All three patients showed signs of crystalline retinopathy using spectral domain optical coherence tomography (SD-OCT) during follow-up. CONCLUSION: The follow-up using multimodal imaging studies allowed evaluating the progression of the changes, providing a prognostic assessment. The findings reported (visual acuity and multimodal imaging) confirmed the results of previous studies, indicating that, at a certain level of toxicity, the damage was irreversible.
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INTRODUCTION: Langerhans cell histiocytosis (HL) is a rare disease that can affect all tissues. Oral manifestations such as mucosal ulcer and tooth mobility are often the first signs of the disease. We report a rare case of mandibular condyle unifocal HL mimicking a temporomandibular joint disorder. CASE REPORT: A 44-year-old patient presented with a left temporomandibular disorder with painful left preauricular swelling. The imaging assessment found a bone lesion of the left mandibular condyle. A curettage with biopsy was used to diagnose HL. Six months later, the patient had no more pain. DISCUSSION: The craniofacial clinical expressions of HL mainly concern the bones, which can cause: pain, swelling, fracture, compression of noble organs. The other sites are: oral cavity, skin, lymph nodes, or eyes. Isolated forms are generally benign, and their treatment is discussed between abstention and non-aggressive surgery.
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Histiocitosis de Células de Langerhans/diagnóstico , Cóndilo Mandibular/diagnóstico por imagen , Trastornos de la Articulación Temporomandibular/etiología , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Osteólisis/diagnóstico por imagen , Osteólisis/etiología , Radiografía PanorámicaRESUMEN
INTRODUCCIÓN: La cantaxantina es un producto químico utilizado para el bronceado de la piel. Su efecto adverso más frecuente es la retinopatía por cantaxantina. Propósito/métodos: Serie de casos. RESULTADOS: Dos pacientes de sexo femenino de 42 y de 72 años, con signos de retinopatía por cantaxantina, se realiza examen oftalmológico completo, se detectan depósitos birrefringentes perifoveales, fóvea con compromiso de la retina interna, se constata con estudio por imágenes multimodal. CONCLUSIÓN: La retinopatía por cantaxantina es poco frecuente, el estudio por imágenes multimodal puede aportar datos de relevancia para el diagnóstico diferencial de la retinopatía cristalina
INTRODUCTION: Canthaxanthin is a chemical product used to tan the skin. Its most frequent adverse effect is canthaxanthin retinopathy. Purpose/ methods: Report, case series. RESULTS: Two female patients, one 42 years-old and the other 72 years-old, with signs of retinopathy due to canthaxanthin. Complete ophthalmology examinations were carried out. The peripheral fovea birefringent deposits with internal retinal involvement were studied using multimodal imaging. CONCLUSION: Canthaxanthin retinopathy is rare. Multimodal imaging may provide important data for the differential diagnosis of crystalline retinopathy
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Humanos , Femenino , Adulto , Anciano , Enfermedades de la Retina/inducido químicamente , Cantaxantina/toxicidad , Cantaxantina/efectos adversos , Agudeza Visual , Retina , Imagen Multimodal/métodos , Diagnóstico Diferencial , CantaxantinaRESUMEN
INTRODUCTION: Canthaxanthin is a chemical product used to tan the skin. Its most frequent adverse effect is canthaxanthin retinopathy. PURPOSE/ METHODS: Report, case series. RESULTS: Two female patients, one 42 years-old and the other 72 years-old, with signs of retinopathy due to canthaxanthin. Complete ophthalmology examinations were carried out. The peripheral fovea birefringent deposits with internal retinal involvement were studied using multimodal imaging. CONCLUSION: Canthaxanthin retinopathy is rare. Multimodal imaging may provide important data for the differential diagnosis of crystalline retinopathy.
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Antioxidantes/efectos adversos , Cantaxantina/efectos adversos , Cosméticos/efectos adversos , Enfermedades de la Retina/inducido químicamente , Adulto , Anciano , Birrefringencia , Cristalización , Femenino , Humanos , Imagen Óptica , Enfermedades de la Retina/diagnóstico por imagen , Microscopía con Lámpara de Hendidura , Tomografía de Coherencia ÓpticaRESUMEN
The authors report the case of a 43-year-old woman who underwent endodontic treatment of the right second mandibular molar with substantial extrusion of endodontic material into the mandibular canal. The patient presented at the Department of Oral and Maxillofacial Surgery with a persistent total anaesthesia of the lower lip and chin after two months. 2D panoramic view and 3D CT-scan examination highlighted the overfilling into the mandibular canal with a more than 50% stenosis of the canal and a consequently significant compression of the dental pedicle. A surgical decompression of the inferior alveolar nerve was performed through an inferior vestibular approach, using PiezoSurgery®. The tooth was conserved. After a period of 8days, paraesthesia of the lower lip and chin appeared. Thermoalgic sensitivity was recovered at 1month. At 3months postoperatively, the patient had recovered protopathic and epicritic sensitivity. Dental prosthetic rehabilitation was finally achieved one year postoperatively. The authors discuss the physiopathology of nervous injuries during dental procedures, and further strategies in the case of persistent neurologic disorders.
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Descompresión Quirúrgica , Nervio Mandibular/cirugía , Materiales de Obturación del Conducto Radicular/efectos adversos , Tratamiento del Conducto Radicular/efectos adversos , Traumatismos del Nervio Trigémino/cirugía , Adulto , Femenino , Humanos , Mandíbula/patología , Mandíbula/cirugía , Nervio Mandibular/patología , Reoperación/métodos , Tratamiento del Conducto Radicular/métodos , Traumatismos del Nervio Trigémino/etiologíaRESUMEN
The phase behaviour of n-alkylammonium (C6 to C16) nitrates and formates has been characterised using synchrotron small angle and wide angle X-ray scattering (SAXS/WAXS), differential scanning calorimetry (DSC), cross polarised optical microscopy (CPOM) and Fourier transform infrared spectroscopy (FTIR). The protic salts may exist as crystalline, liquid crystalline or ionic liquid materials depending on the alkyl chain length and temperature. n-Alkylammonium nitrates with n ≥ 6 form thermotropic liquid crystalline (LC) lamellar phases, whereas n ≥ 8 was required for the formate series to form this LC phase. The protic ionic liquid phase showed an intermediate length scale nanostructure resulting from the segregation of the polar and nonpolar components of the ionic liquid. This segregation was enhanced for longer n-alkyl chains, with a corresponding increase in the correlation length scale. The crystalline and liquid crystalline phases were both lamellar. Phase transition temperatures, lamellar d-spacings, and liquid correlation lengths for the n-alkylammonium nitrates and formates were compared with those for n-alkylammonium chlorides and n-alkylamines. Plateau regions in the liquid crystalline to liquid phase transition temperatures as a function of n for the n-alkylammonium nitrates and formates are consistent with hydrogen-bonding and cation-anion interactions between the ionic species dominating alkyl chain-chain van der Waals interactions, with the exception of the mid chained hexyl- and heptylammonium formates. The d-spacings of the lamellar phases for both the n-alkylammonium nitrates and formates were consistent with an increase in chain-chain layer interdigitation within the bilayer-based lamellae with increasing alkyl chain length, and they were comparable to the n-alkylammonium chlorides.
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In the present article, we report the identification of the first HLA-B*07 null allele found in a Polish patient awaiting a kidney allograft. A discrepant result obtained between serological typing (HLA-B "blank") and high-resolution molecular typing using PCR-SSP method (HLA-B*070201 allele) suggested the presence of a null allele. Genomic DNA sequencing of the HLA-B*07 allele revealed a single nucleotide substitution at the 3' end of the exon 4 leading to a premature stop codon.