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1.
Otolaryngol Clin North Am ; 57(2): 279-292, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37867110

RESUMO

The united airway refers to the combined upper and lower airways and their interconnected pathophysiologic relationships. Inflammatory airway diseases (chronic rhinosinusitis, asthma, and so forth) have been linked to fungal species through type 2 immune responses. These type 2 immune responses involve the cytokines interleukin (IL)-4, IL-5, IL-13, and a myriad of other inflammatory processes that lead to a spectrum of diseases from allergic bronchopulmonary mycosis to chronic rhinosinusitis. Historically, these diseases have been managed primarily with corticosteroids but recent revelations in the molecular pathophysiology provide opportunities for more diverse treatment options for patients with uncontrolled disease.


Assuntos
Asma , Hipersensibilidade , Sinusite , Humanos , Sistema Respiratório , Doença Crônica , Fungos
2.
Laryngoscope Investig Otolaryngol ; 8(4): 912-920, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37621284

RESUMO

Objective: This study aimed to assess if Nigella sativa oil (NSO), a health supplement containing thymoquinone as a major component, can act as a protective agent in salivary gland stem cells following radiotherapy (RT) damage. Methods: Forty, 10-week-old, male C3H/HeJ mice were randomized to four experimental groups: sham RT + H2O gavage (control) (N = 4); 15 Gy RT + H2O gavage (N = 12); sham RT + NSO gavage (N = 12); and 15 Gy RT + NSO gavage (N = 12). Weight changes, saliva production, and salivary gland histopathologic staining were recorded for each group over the course of the experiment. Results: All mice in the sham RT + H2O gavage and sham RT + NSO gavage groups demonstrated 100% 60-day survival. RT + H2O compared to RT + NSO gavaged mice were significantly underweight by an average of 6.4 g (p < .001). Salivary output showed significant decline in RT + H2O gavaged mice at days 3 and 16, whereas salivary output in RT + NSO during these same time periods was comparable to the control. At day 60, all mice that survived recovered salivary function regardless of their treatment arm. Salivary specimens from the RT + NSO gavage group demonstrated early signs of recovery of Kr 5+ salivary gland stem cells in both submandibular and sublingual glands at day 16 with complete recovery by day 60, marked by strong histopathologic staining, whereas the RT + H2O gavage group did not recover as effectively. Conclusion: NSO may help preserve salivary function in mice treated with RT and may mitigate xerostomia by accelerating the recovery of salivary gland stem cells. Level of evidence: Not applicable.

3.
Laryngoscope Investig Otolaryngol ; 8(3): 621-626, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37342101

RESUMO

Objectives: Current evidence suggests a link between idiopathic intracranial hypertension (IIH) and spontaneous cerebrospinal fluid (sCSF) leak, as well as between IIH and dural venous sinus (DVS) narrowing. However, there are limited data linking DVS narrowing and sCSF leak. This study aims to determine the prevalence of DVS narrowing in patients with sCSF leak. Methods: A retrospective review of all patients with sCSF leak that presented to a tertiary academic center from 2008 to 2019. Preoperative imaging was independently reviewed by two neuroradiologists to evaluate for DVS narrowing. Available literature was used to estimate the prevalence of DVS narrowing in the general population to allow for comparison. Data were analyzed using Exact binomial test. Results: Analysis of 25 patients with appropriate imaging revealed the majority were women (21/25, 84%) with a mean age of 51.89 years (SD 13.96). The majority of these patients were found to have narrowing of the DVS (20/25, 80%). In patient with sCSF leaks, there was a significantly higher proportion of patients with DVS narrowing compared with published literature examining this condition in the general population (80% vs. 40%, CI 0.59-0.93, p < .001). Conclusion: The prevalence of DVS narrowing in patients with sCSF leaks is substantial and likely greater than the general population. Moreover, there appears to be narrowing in most patients with sCSF leak. Preoperative radiological evaluation of the DVS using MR venography may be useful in patients with sCSF leaks as DVS stenosis may be an underdiagnosed etiology. Further study is needed to evaluate this. Level of Evidence: IV.

4.
Am J Rhinol Allergy ; 37(2): 214-220, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36848273

RESUMO

BACKGROUND: Allergic fungal rhinosinusitis (AFRS) is an endotype of chronic rhinosinusitis (CRS) with nasal polyps characterized by eosinophilic mucin laden with fungal hyphae entrapped in expanded sinus cavities with an exaggerated hypersensitivity to fungal elements. The last decade has elucidated fungi-driven inflammatory pathways contributing to the pathophysiology of chronic inflammatory respiratory diseases. In addition, novel therapeutic biologic options have become available for CRS over the last several years. OBJECTIVE: To review the current literature examining AFRS, focusing on recent developments in our understanding of its pathophysiology and implications for treatment options. METHODS: Review article. RESULTS: Fungi-driven respiratory inflammation has been linked to fungal proteinases and toxin activity. In addition, AFRS patients demonstrate a local sinonasal immunodeficiency in antimicrobial peptides and hence limited antifungal activity, along with an exaggerated type 2 inflammatory response, highlighting a possible imbalanced type 1, type 2, and type 3 profile. The elucidation of these dysregulated molecular pathways has highlighted novel potential therapeutic targets. As such, the clinical management of AFRS, which once included surgery and extended courses of oral corticosteroids, is transitioning away from long courses of oral corticosteroids to incorporate novel delivery mechanisms of topical therapeutic targets and biologics for recalcitrant disease. CONCLUSION: AFRS is an endotype of CRS with nasal polyps (CRSwNP) for which the molecular pathways leading to its inflammatory dysfunction are beginning to be illuminated. In addition to affecting treatment options, these understandings may shape necessary changes to diagnostic criteria and the extrapolated effects of environmental changes on AFRS. More critically, a better appreciation of fungi-driven inflammatory pathways may have implications for the understanding of broader CRS inflammation.


Assuntos
Sinusite Fúngica Alérgica , Hipersensibilidade , Pólipos Nasais , Seios Paranasais , Humanos , Pólipos Nasais/tratamento farmacológico , Inflamação
5.
J Voice ; 2021 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-34819238

RESUMO

OBJECTIVE: Decision-making regarding behavioral versus procedural intervention in the treatment of presbyphonia has not been well defined. The study objective was to survey laryngologists' reported practice patterns and decision-making in presbyphonia. METHODS: All laryngology faculty in U.S. academic medical centers with residency programs were recruited to complete an anonymous 29-item survey regarding decision-making in presbyphonia treatment. The survey included 5 sections: demographics, first-line treatment distribution, factors that drive decision-making toward procedural intervention, treatment progression if first-line treatment is insufficient, durable treatment. RESULTS: Of 153 laryngologists surveyed, 89 responded (58%). Voice therapy (VT) was the most often reported first-line treatment, with 57% of respondents indicating the majority of their patients receive VT initially. Most respondents (83%) indicated they occasionally use procedural intervention as first-line treatment. Factors driving first-line procedural intervention were severe glottal insufficiency (87%), high occupational/social voice demands (76%), voice not stimulable for change (73%), difficulty attending VT (70%), severe dysphonia (65%), and dysphagia (61%). The majority of respondents indicated the following do not affect their decision to pursue procedural intervention: patient age (88%); medical comorbidities (63%); patient's desire for a "quick fix" (55%); patient-reported outcome measures (51%). Most respondents (81%) use trial injection augmentation before durable treatment. Of durable treatments, bilateral thyroplasty was preferred (71%), followed by CaHA (15%) and lipoinjection (11%). CONCLUSIONS: This study is the first to our knowledge to examine factors that influence decision-making in presbyphonia treatment. While VT remains the most frequent first-line treatment, study results better inform decision-making regarding first-line procedural intervention.

6.
Can Urol Assoc J ; 15(10): E563-E568, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33999800

RESUMO

INTRODUCTION: The aim of this study was to evaluate the outcomes of radical cystectomy with an enhanced recovery after surgery (ERAS) protocol in patients with a history of chronic preoperative narcotic use compared to narcotic-naive patients. METHODS: We identified 553 patients who underwent open radical cystectomy with ERAS. Preoperative narcotic use was identified in 34 patients who were then matched to 68 narcotic-naive patients. Postoperative outcomes, opioid use, and visual analog scale (VAS) pain scores were analyzed and compared. All routes of opioid use were recorded and converted to a morphine equivalent dose (MED). RESULTS: Patients with preoperative narcotic use reported higher median VAS pain scores per day (postoperative day [POD1]: 5.2 vs. 3.9, p=0.003; POD2: 5.1 vs. 3.6, p<0.001; POD3: 4.6 vs. 3.8, p=0.004) and used significantly more opioids (median MED) per day (POD1: 13.2 vs. 10.0, p=0.02; POD2: 11.3 vs. 6.4, p=0.003; POD3: 10.2 vs. 5.0, p=0.005) following surgery. Preoperative narcotic users were noted to have a significantly higher incidence of 90-day re-admissions (41.2% vs. 20.6%, p=0.03). There was no difference in median hospital stay (4 vs. 4 days, p=0.6), 30-or 90-day complications (64.7% vs. 60.3%, p=0.8 and 82.4% vs. 75.0%, p=0.4, respectively) or gastrointestinal complications (29.4% vs. 26.5%, p=0.8), including postoperative ileus (11.8% vs. 20.6%, p=0.2). CONCLUSIONS: Patients with preoperative narcotic exposure report higher pain scores and require more opioid use following radical cystectomy with ERAS and are more likely to be re-admitted within 90 days. However, there was no observed difference in hospital stay or complications.

7.
Radiol Case Rep ; 16(5): 1107-1112, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33732402

RESUMO

Aggressive hemangioma is a rare vertebral lesion in pediatric patients which can present with deteriorating neurological function. It can mimic malignancy on imaging, particularly as it regularly has an extrasosseous soft tissue component. We present a case of a 13-year-old male who presented with a three month history of lower extremity weakness that was found to have an infiltrative mass at T10 with associated cord compression from epidural extension of the lesion. In this report we review the characteristic imaging findings associated with aggressive hemangioma, including its appearance on read-out segmented diffusion-weighted images. It is imperative that radiologists who interpret studies of children be aware that this lesion exists and what it looks like, as it can be associated with massive hemorrhage if encountered unexpectedly during surgery.

9.
Laryngoscope ; 131(3): E792-E799, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32516508

RESUMO

OBJECTIVES: We implement a novel enhanced recovery after surgery (ERAS) protocol with pre-operative non-opioid loading, total intravenous anesthesia, multimodal peri-operative analgesia, and restricted red blood cell (pRBC) transfusions. 1) Compare differences in mean postoperative peak pain scores, opioid usage, and pRBC transfusions. 2) Examine changes in overall length of stay (LOS), intensive care unit LOS, complications, and 30-day readmissions. METHODS: Retrospective cohort study comparing 132 ERAS vs. 66 non-ERAS patients after HNC tissue transfer reconstruction. Data was collected in a double-blind fashion by two teams. RESULTS: Mean postoperative peak pain scores were lower in the ERAS group up to postoperative day (POD) 2. POD0: 4.6 ± 3.6 vs. 6.5 ± 3.5; P = .004) (POD1: 5.2 ± 3.5 vs. 7.3 ± 2.3; P = .002) (POD2: 4.1 ± 3.5 vs. 6.6 ± 2.8; P = .000). Opioid utilization, converted into morphine milligram equivalents, was decreased in the ERAS group (POD0: 6.0 ± 9.8 vs. 10.3 ± 10.8; P = .010) (POD1: 14.1 ± 22.1 vs. 34.2 ± 23.2; P = .000) (POD2: 11.4 ± 19.7 vs. 37.6 ± 31.7; P = .000) (POD3: 13.7 ± 20.5 vs. 37.9 ± 42.3; P = .000) (POD4: 11.7 ± 17.9 vs. 36.2 ± 39.2; P = .000) (POD5: 10.3 ± 17.9 vs. 35.4 ± 45.6; P = .000). Mean pRBC transfusion rate was lower in ERAS patients (2.1 vs. 3.1 units, P = .017). There were no differences between ERAS and non-ERAS patients in hospital LOS, ICU LOS, complication rates, and 30-day readmissions. CONCLUSION: Our ERAS pathway reduced postoperative pain, opioid usage, and pRBC transfusions after HNC reconstruction. These benefits were obtained without an increase in hospital or ICU LOS, complications, or readmission rates. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E792-E799, 2021.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Procedimentos Cirúrgicos Otorrinolaringológicos/reabilitação , Assistência Perioperatória/métodos , Procedimentos de Cirurgia Plástica/reabilitação , Transplante de Tecidos/reabilitação , Idoso , Analgesia/métodos , Analgésicos Opioides/uso terapêutico , Transfusão de Sangue/estatística & dados numéricos , Método Duplo-Cego , Feminino , Cabeça/cirurgia , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pescoço/cirurgia , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Manejo da Dor/estatística & dados numéricos , Medição da Dor/estatística & dados numéricos , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/terapia , Readmissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Retalhos Cirúrgicos , Resultado do Tratamento
10.
Otolaryngol Head Neck Surg ; 164(1): 139-145, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32660337

RESUMO

OBJECTIVE: To determine the most cost-effective reconstruction method after salvage total laryngectomy. STUDY DESIGN: Cost-effectiveness analysis. SETTING: Tertiary care hospitals with head and neck oncologic and reconstructive surgeons. SUBJECTS AND METHODS: We constructed a Markov-based decision model to compare reconstruction by primary closure to pectoralis flap and free flap after salvage total laryngectomy. The model simulated disease with transition probabilities and health utilities found in primary literature and estimated the average overall cost of each reconstructive method using Medicare billing codes. Effectiveness was compared using quality-adjusted life years (QALYs). One-way and probabilistic sensitivity analyses were performed to scrutinize the conclusions of our model. Reconstruction methods were compared using incremental cost-effectiveness ratios (ICERs). In the United States, less than $150,000 per QALY gained is considered cost-effective (2019 US dollars). RESULTS: Our base case analysis revealed that primary closure was less expensive ($44,370) and yielded more QALYs (0.91) than both pectoralis ($45,163, 0.81 QALYs) and free flap ($46,244, 0.85 QALYs), making it the most cost-effective option. Between flaps, free flap was cost-effective over pectoralis flap (ICER = $27,025/QALY gained). Sensitivity analyses showed primary closure as cost-effective 69% of the time over either flap. These conclusions were sensitive to the health utilities (quality of life) of each method of reconstruction. CONCLUSION: Tissue flaps to augment closure after salvage total laryngectomy are not always the most cost-effective reconstructive option. The long-term morbidity of flap surgery oftentimes outweighs the benefit of lowering fistula rates after surgery. Careful consideration must be taken when advising patients of their reconstructive options.


Assuntos
Neoplasias Laríngeas/cirurgia , Laringectomia , Medicare/economia , Procedimentos de Cirurgia Plástica/economia , Terapia de Salvação , Idoso , Análise Custo-Benefício , Feminino , Humanos , Masculino , Cadeias de Markov , Anos de Vida Ajustados por Qualidade de Vida , Retalhos Cirúrgicos , Estados Unidos
11.
World Neurosurg ; 141: 162-165, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32492536

RESUMO

BACKGROUND: Tapia syndrome is a rare complication of surgical positioning with resulting unilateral cranial nerve X and XII deficits that may provide diagnostic challenges in the perioperative period. Timely diagnosis will facilitate obtaining the necessary supportive care while preventing unnecessary workup and procedures. CASE DESCRIPTION: The following case report illustrates a patient that developed Tapia syndrome immediately after a posterior cervical laminoplasty with eventual resolution of symptoms. A review of the literature was also undertaken for comparison. CONCLUSIONS: Tapia syndrome can occur with a variety of surgeries, but appear to be most common in surgeries of the posterior cervical spine in the neurosurgical literature. It is theorized that flexed head position common among posterior cervical procedures makes patients more prone to Tapia syndrome in these cases. The ideal management remains poorly defined in the literature. The time course and resolution of neurologic deficits support a transient neuropraxic mechanism in most cases, though some patients do suffer permanent deficits.


Assuntos
Doenças do Nervo Hipoglosso/etiologia , Laminoplastia/efeitos adversos , Posicionamento do Paciente/efeitos adversos , Traumatismos do Nervo Vago/etiologia , Vértebras Cervicais , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome
12.
J Clin Invest ; 130(5): 2673-2688, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32310221

RESUMO

Tumor-associated peptide-human leukocyte antigen complexes (pHLAs) represent the largest pool of cell surface-expressed cancer-specific epitopes, making them attractive targets for cancer therapies. Soluble bispecific molecules that incorporate an anti-CD3 effector function are being developed to redirect T cells against these targets using 2 different approaches. The first achieves pHLA recognition via affinity-enhanced versions of natural TCRs (e.g., immune-mobilizing monoclonal T cell receptors against cancer [ImmTAC] molecules), whereas the second harnesses an antibody-based format (TCR-mimic antibodies). For both classes of reagent, target specificity is vital, considering the vast universe of potential pHLA molecules that can be presented on healthy cells. Here, we made use of structural, biochemical, and computational approaches to investigate the molecular rules underpinning the reactivity patterns of pHLA-targeting bispecifics. We demonstrate that affinity-enhanced TCRs engage pHLA using a comparatively broad and balanced energetic footprint, with interactions distributed over several HLA and peptide side chains. As ImmTAC molecules, these TCRs also retained a greater degree of pHLA selectivity, with less off-target activity in cellular assays. Conversely, TCR-mimic antibodies tended to exhibit binding modes focused more toward hot spots on the HLA surface and exhibited a greater degree of crossreactivity. Our findings extend our understanding of the basic principles that underpin pHLA selectivity and exemplify a number of molecular approaches that can be used to probe the specificity of pHLA-targeting molecules, aiding the development of future reagents.


Assuntos
Antígenos HLA/imunologia , Peptídeos/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Sequência de Aminoácidos , Anticorpos Biespecíficos/química , Anticorpos Biespecíficos/genética , Anticorpos Biespecíficos/imunologia , Anticorpos Antineoplásicos/química , Anticorpos Antineoplásicos/genética , Anticorpos Antineoplásicos/imunologia , Especificidade de Anticorpos , Antígenos de Neoplasias/química , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Linhagem Celular , Linhagem Celular Tumoral , Cristalografia por Raios X , Antígenos HLA/química , Antígenos HLA/genética , Humanos , Indicadores e Reagentes , Modelos Moleculares , Simulação de Dinâmica Molecular , Mimetismo Molecular/genética , Mimetismo Molecular/imunologia , Peptídeos/química , Peptídeos/genética , Receptores de Antígenos de Linfócitos T/química , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/imunologia
13.
Laryngoscope Investig Otolaryngol ; 5(1): 82-89, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32128434

RESUMO

OBJECTIVES: Vocal fold (VF) stiffness and geometry are determinant variables in voice production. Type 1 medialization thyroplasty (MT), the primary surgical treatment for glottic insufficiency, changes both of these variables. Understanding the cause and effect relationship between these variables and acoustic output might improve voice outcomes after MT. In this study, the effects of thyroplasty implants with variable stiffness on glottal shape and acoustics were investigated. METHODS: In an ex vivo human larynx phonation model, bilateral MT with implants of four stiffness levels (1386, 21.6, 9.3, and 5.5 kPa) were performed. Resulting acoustics and aerodynamics were measured across multiple airflow levels. A vertical partial hemilaryngectomy was performed and stereoscopic images of the VF medial surface taken to reconstruct its three-dimensional (3D) surface contour. The results were compared across implants. RESULTS: The effects of implant stiffness on acoustics varied by airflow. Softer implants resulted in improved acoustics, as measured by cepstral peak prominence (CPP), at lower airflow levels compared to stiffer implants but this relationship reversed at high airflow levels. Stiffer implants generally required less airflow to generate a given subglottal pressure. Stiffer implants resulted in greater medialized surface area and maximal medialization, but all implants had similar effects on overall VF medial surface contour. CONCLUSION: Softer implants result in less medialization but better acoustics at low airflow rates. Stiffer implants provide better acoustics and more stable pressure-flow relationships at higher airflow rates. This highlights a potential role for patient-specific customized thyroplasty implants of various stiffness levels. LEVEL OF EVIDENCE: NA.

14.
World J Urol ; 38(12): 3131-3137, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32112242

RESUMO

PURPOSE: To perform an internal audit 5 years after implementation of our enhanced recovery after surgery (ERAS) protocol for patients undergoing radical cystectomy and to investigate the importance of physician driven compliance on outcomes. METHODS: Using a prospectively maintained database, 472 consecutive patients were identified who underwent radical cystectomy with ERAS from July 2013 to July 2017. Compliance was measured by a Composite Compliance Score (CCS) generated as a percentage of 16 interventions. Patients with higher than median compliance were compared to patients with lower compliance. The primary outcome was length of stay. Secondary outcomes included complication and readmission rates. Multivariable regressions were used to control for differences between groups. RESULTS: In 2013, median CCS was 81% and subsequently ranged from 81 to 88%. Five-year median CCS was 88%. Patients with higher compliance (CCS ≥ 88%, n = 262), as compared to those with lower compliance (CCS < 88%, n = 210), were younger (median 70.3 vs 72.7 years, p = 0.047), healthier (ASA3-4 81% vs 89.9%, p = 0.007), received more orthotopic diversions (59.2% vs 37.6%, p < 0.0001), more often had open surgery (78.5% vs 51.9%, p < 0.0001) and had shorter median operative times (5.5 vs 6.3 h, p = 0.005). Median length of stay was 4 days. Higher compliance was associated with shorter hospital stays (ß = - 0.85, 95% CI - 1.62 to - 0.07) and decreased 30-day readmissions (OR 0.58, 95% CI 0.35-0.96). CONCLUSIONS: Greater ERAS compliance was achieved in younger and healthier patients. Patients with greater compliance had a decreased length of stay by almost 1 day and reduced odds of 30-day readmissions.


Assuntos
Auditoria Clínica , Cistectomia , Recuperação Pós-Cirúrgica Melhorada/normas , Fidelidade a Diretrizes/estatística & dados numéricos , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Cistectomia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
15.
Case Rep Otolaryngol ; 2019: 4706582, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467757

RESUMO

Rhabdomyomas are benign tumors composed of mesenchymal tissue and having a histologic appearance similar to skeletal muscle. Extracardiac rhabdomyomas are rare, and the majority of the adult subtype occur in the head and neck (H&N) region. Diagnosis can be challenging due to fine-needle aspiration (FNA) and core needle biopsy being suspicious for sampling error from surrounding muscle or concerning for rhabdomyosarcoma. We present a case of a slowly enlarging left neck mass in the strap musculature of a 45-year-old Hispanic male. Multiple FNA and core biopsies failed to establish a diagnosis, and excisional biopsy was pursued revealing a hypertrophied left inferior belly of the omohyoid muscle. Histological analysis was diagnostic of an adult-type extracardiac rhabdomyoma, with complete surgical excision being the gold standard treatment for these tumors. The patient had an uneventful recovery. Skeletal muscle tumors of the H&N are uncommon, and benign extracardiac rhabdomyoma must be considered in the differential diagnosis to prevent unnecessarily aggressive intervention and appropriate patient counseling before and after surgery.

17.
World J Surg ; 43(6): 1435-1449, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30617561

RESUMO

BACKGROUND: There is a significant unmet need for children's surgical care in low- and middle-income countries (LMICs). Multidisciplinary collaboration is required to advance the surgical and anesthesia care of children's surgical conditions such as congenital conditions, cancer and injuries. Nonetheless, there are limited examples of this process from LMICs. We describe the development and 3-year outcomes following a 2015 stakeholders' meeting in Uganda to catalyze multidisciplinary and multi-institutional collaboration. METHODS: The stakeholders' meeting was a daylong conference held in Kampala with local, regional and international collaborators in attendance. Multiple clinical specialties including surgical subspecialists, pediatric anesthesia, perioperative nursing, pediatric oncology and neonatology were represented. Key thematic areas including infrastructure, training and workforce retention, service delivery, and research and advocacy were addressed, and short-term objectives were agreed upon. We reported the 3-year outcomes following the meeting by thematic area. RESULTS: The Pediatric Surgical Foundation was developed following the meeting to formalize coordination between institutions. Through international collaborations, operating room capacity has increased. A pediatric general surgery fellowship has expanded at Mulago and Mbarara hospitals supplemented by an international fellowship in multiple disciplines. Coordinated outreach camps have continued to assist with training and service delivery in rural regional hospitals. CONCLUSION: Collaborations between disciplines, both within LMICs and with international partners, are required to advance children's surgery. The unification of stakeholders across clinical disciplines and institutional partnerships can facilitate increased children's surgical capacity. Such a process may prove useful in other LMICs with a wide range of children's surgery stakeholders.


Assuntos
Anestesiologia , Serviços de Saúde da Criança , Comportamento Cooperativo , Especialidades Cirúrgicas , Anestesiologia/educação , Criança , Países em Desenvolvimento , Humanos , Especialidades Cirúrgicas/educação , Uganda
18.
PLoS One ; 13(10): e0205491, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30321203

RESUMO

Robust preclinical testing is essential to predict clinical safety and efficacy and provide data to determine safe dose for first-in-man studies. There are a growing number of examples where the preclinical development of drugs failed to adequately predict clinical adverse events in part due to their assessment with inappropriate preclinical models. Preclinical investigations of T cell receptor (TCR)-based immunotherapies prove particularly challenging as these biologics are human-specific and thus the conventional testing in animal models is inadequate. As these molecules harness the full force of the immune system, and demonstrate tremendous potency, we set out to design a preclinical package that would ensure adequate evaluation of these therapeutics. Immune Mobilising Monoclonal TCR Against Cancer (ImmTAC) molecules are bi-specific biologics formed of an affinity-enhanced TCR fused to an anti-CD3 effector function. ImmTAC molecules are designed to activate human T lymphocytes and target peptides within the context of a human leukocyte antigen (HLA), thus require an intact human immune system and peptidome for suitable preclinical screening. Here we draw upon the preclinical testing of four ImmTAC molecules, including IMCgp100, the first ImmTAC molecule to reach the clinic, to present our comprehensive, informative and robust approach to in vitro preclinical efficacy and safety screening. This package comprises a broad range of cellular and molecular assays using human tissues and cultured cells to test efficacy, safety and specificity, and hence predict human responses in clinical trials. We propose that this entirely in vitro package offers a potential model to be applied to screening other TCR-based biologics.


Assuntos
Anticorpos Biespecíficos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Proteínas/farmacologia , Anticorpos de Cadeia Única/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Técnicas In Vitro , Fluxo de Trabalho
19.
J Pediatr Surg ; 53(5): 942-945, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29526351

RESUMO

PURPOSE: The "cut and push" technique for removal of percutaneous endoscopic gastrostomy (PEG) tubes with collapsible bumpers offers an alternative to the standard traction method of removal. This study compared the outcomes of these techniques. METHODS: We completed a research ethics board-approved retrospective cohort study, identifying all patients less than 18years of age who underwent PEG tube removal at a children's hospital between December 2013 and December 2016. Outcomes included need for sedation and complications. RESULTS: We identified 127 children who had PEG tubes removed. Significantly fewer children required sedation with the cut and push group (1.1% vs. 60.6%, p≤0.001). Ten complications occurred, including 9 in the cut and push group (9.6% vs. 3%, p=0.23). Mean age at time of complication was significantly younger in the cut and push group (2.2 vs. 6.3years p=0.004). CONCLUSION: This is the largest reported series comparing the cut and push vs. traction removal methods. The cut and push technique significantly reduced the need for procedural sedation but was associated with increased risk of complications. While these data suggest that the technique is safe in older children, caution should be taken in younger children who appear to be more likely to vomit the residual bumper. LEVELS OF EVIDENCE: Level III-Treatment study, Retrospective comparative study.


Assuntos
Remoção de Dispositivo/métodos , Endoscopia Gastrointestinal/métodos , Nutrição Enteral/instrumentação , Gastrostomia/métodos , Intubação Gastrointestinal/instrumentação , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos
20.
Can Med Educ J ; 8(2): e25-e36, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29114344

RESUMO

BACKGROUND: Eyal and Hurst proposed that locally relevant medical education can offset the prevalence of physician "brain drain" in resource-poor regions of the world, and presented a framework of the ethical and pragmatic benefits and concerns posed by these initiatives. The present study explored the framework's utility through a case study of the University of Guyana Diploma in Surgery (UGDS) program. METHODS: The framework's utility was evaluated using a case study design that included review and analysis of documents and semi-structured interviews with graduates, trainees, faculty members, and policy makers associated with the UGDS program. Data were analyzed from constructivist and interpretivist perspectives, and compared against the benefits and concerns described by Eyal and Hurst. RESULTS: The framework is a useful template for capturing the breadth of experience of locally relevant training in the Guyanese setting. However, the results suggest that delineating the framework factors as either beneficial or concerning may constrict its applicability. The case study design also provided specific insights about the UGDS program, which indicate that the Program has promoted the retention of graduates and a sustainable culture of postgraduate medical education in Guyana. CONCLUSION: It is suggested that the framework be modified so as to represent the benefits and concerns of locally relevant training along a continuum of advantage. These approaches may help us understand retention within a resource-poor country, but also within particularly remote areas and public health care systems generally.

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