RESUMO
This cohort study compares rates of biochemical substance use screening among injured adolescents by sociodemographic characteristics including sex, race, ethnicity, and insurance status.
Assuntos
Programas de Rastreamento , Transtornos Relacionados ao Uso de Substâncias , Ferimentos e Lesões , Humanos , Adolescente , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Feminino , Masculino , Programas de Rastreamento/métodos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Estados Unidos/epidemiologiaRESUMO
INTRODUCTION: Non-operative management of uncomplicated appendicitis in children is a safe alternative to laparoscopic appendectomy. The purpose of this study is to determine the feasibility of nonoperative outpatient management of uncomplicated appendicitis in pediatric patients. METHODS: A standardized pathway for non-operative outpatient management of uncomplicated appendicitis in children (NOMA-C) was implemented in a university pediatric surgery practice starting October 2021. Those who met criteria would be considered for discharge from the emergency department (ED) with oral antibiotics and close followup over the following year. A quality improvement project started concurrently to monitor patients for recurrent symptoms of appendicitis. RESULTS: A total of 121 patients were diagnosed with acute appendicitis during the study period (October 2021 to April 2023). Forty-five children (38%) met criteria for the NOMA-C protocol, and 11 patients/families chose appendectomy. Of the 34 patients who pursued nonoperative management, 14 patients were admitted to the hospital and 20 patients were discharged from the ED. Total time in the ED/hospital was significantly shorter for patients discharged from the ED (7 hours versus 23 hours; p<0.001). At one year follow up only 4 (12%) had undergone appendectomy. There were no adverse events for patients who underwent nonoperative management. CONCLUSION: A protocol offering non-operative management of appendicitis with an option for outpatient management was feasible and safe. Outpatient management was associated with shorter ED/hospital stays than those admitted. Future studies should evaluate whether this protocol can be adopted by EDs without pediatric surgery services to avoid the need for transfer.
RESUMO
BACKGROUND: Entrustable Professional Activities (EPAs) have emerged as a valuable tool in medical education, enabling the assessment of trainee competence in a real-world context. Despite its growing popularity in other medical specialties, the use of EPAs in pediatric surgery is still relatively new. METHODS: This article provides an overview of the development and application of EPAs in pediatric surgery. The key concepts and principles of EPAs, including the historical development and current implementation in other medical specialties, will also be reviewed. Definition of pediatric surgery EPAs, advantages, and challenges of implementing EPAs in pediatric surgery, and the evidence supporting the use of EPAs in pediatric surgical training will also be examined. RESULTS: The use of EPAs in pediatric surgery has shown promise in providing a comprehensive and standardized approach to assessing trainee competence. By focusing on the essential tasks and responsibilities of a pediatric surgeon, EPAs can provide a framework for measuring trainee progress and ensuring that they possess the necessary skills to perform their duties independently. Challenges in implementing EPAs in pediatric surgery include the need for consensus on the definition and scope of EPAs, as well as the establishment of appropriate assessment and evaluation tools. CONCLUSION: The use of EPAs in pediatric surgery education and training has the potential to enhance the training and ultimately the quality of care delivered to pediatric surgical patients. The development of appropriate assessment and evaluation tools and frameworks will be crucial in implementing EPAs effectively in this field. TYPE OF STUDY: Review.
Assuntos
Competência Clínica , Pediatria , Especialidades Cirúrgicas , Pediatria/educação , Humanos , Especialidades Cirúrgicas/educação , Educação Baseada em Competências/métodos , Educação de Pós-Graduação em Medicina/métodos , Internato e Residência , Avaliação Educacional/métodosRESUMO
BACKGROUND: Previous studies showed comparable outcomes for common in-patient general surgery operations, but it is unknown if this extends to outpatient operations. Our aim was to compare outpatient cholecystectomy outcomes between rural and urban hospitals. METHODS: A retrospective cohort analysis was done using the Nationwide Ambulatory Surgery Sample for patients 20-years-and-older undergoing cholecystectomy between 2016 and 2018 âat rural and urban hospitals. Survey-weighted multivariable regression analysis was performed with primary outcomes including use-of-laparoscopy, complications, and patient discharge disposition. RESULTS: The most common indication for operation was cholecystitis in both hospital settings. On multivariable analysis, rural hospitals were associated with higher transfers to short-term hospitals (adjusted odds ratio [aOR] 2.40, 95%CI 1.61-3.58, p â< â0.01) and complications (aOR 1.39, 95%CI 1.11-1.75, p â< â0.01). No difference was detected with laparoscopy (aOR 1.93, 95%CI 0.73-5.13, p â= â0.19), routine discharge (aOR 1.50, 95%C I0.91-2.45, p â= â0.11), or mortality (aOR 3.23, 95%CI 0.10-100.0, p â= â0.51). CONCLUSIONS: Patients cared for at rural hospitals were more likely to be transferred to short-term hospitals and have higher complications. No differences were detected in laparoscopy, routine discharge or mortality.
Assuntos
Colecistectomia , Hospitais Rurais , Humanos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Colecistectomia/estatística & dados numéricos , Hospitais Rurais/estatística & dados numéricos , Adulto , Procedimentos Cirúrgicos Ambulatórios/estatística & dados numéricos , Estados Unidos/epidemiologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Idoso , Hospitais Urbanos/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The Nuss procedure for pectus excavatum is associated with prolonged hospitalizations due to pain. We evaluated implementation of intercostal nerve cryoablation and enhanced recovery after surgery (ERAS) protocols on outcomes of Nuss procedures performed over six years at a single institution. METHODS: This retrospective cohort study included patients who underwent Nuss procedure from 10/2017 to 09/2023. Patients received epidurals prior to 06/2019, cryoablation from 06/2019 to 07/2021, and ERAS with cryoablation and intraoperative methadone administration after 07/2021. We used multivariable linear regression to evaluate length of stay (LOS), inpatient morphine milligram equivalents (MMEs), and discharge opioids. We assessed the balancing measures of operative time, postoperative pain scores, and complications. RESULTS: We identified 62 patients; 15 who received epidurals, 18 cryoablation, and 29 cryoablation with ERAS. Cryoablation was associated with a 62.3% (p < 0.001) decrease in length of stay, an 86.6% (p < 0.001) decrease in inpatient MMEs, and a 72.9% (p < 0.001) decrease in discharge opioids. Cryoablation was additionally associated with 24.5% (p = 0.02) longer operative times and 46.4% (p = 0.04) higher postoperative day one pain scores. Subsequent implementation of an ERAS protocol was associated with a further 82.8% (p = 0.04) decrease in discharge opioids and a 25.0% (p = 0.04) decrease in postoperative day one pain scores. CONCLUSIONS: Over six years of quality improvement efforts, we found the implementation of cryoablation and ERAS protocols to be associated with a significant decrease in length of stay and opioid exposures. Protocolized pain management and cryoablation may work synergistically to improve outcomes without compromising patient experience. LEVEL OF EVIDENCE: Level III - Retrospective comparative study.
RESUMO
In previous animal model studies, we demonstrated the potential of rAAV2-sVEGFRv-1, which encodes a truncated variant of the alternatively spliced soluble version of VEGF receptor-1 (VEGFR1), as a human gene therapy for age-related macular degeneration (AMD) and diabetic retinopathy (DR). Here, we elucidate in vitro some of the mechanisms by which rAAV2-sVEGFRv-1 exerts its therapeutic effects. Human umbilical vein endothelial cells (HUVECs) were infected with rAAV2-sVEGFRv-1 or a control virus vector in the presence of members of the VEGF family to identify potential binding partners via ELISA, which showed that VEGF-A, VEGF-B, and placental growth factor (PlGF) are all ligands of its transgene product. In order to determine the effects of rAAV2-sVEGFRv-1 on cell proliferation and permeability, processes that are important to the progression AMD and DR, HUVECs were infected with the therapeutic virus vector under the stimulation of VEGF-A, the major driver of the neovascularization that characterizes the forms of these conditions most associated with vision loss. rAAV2-sVEGFRv-1 treatment, as a result, markedly reduced the extent to which these processes occurred, with the latter determined by measuring zonula occludens 1 expression. Finally, the human microglial HMC3 cell line was used to show the effects of the therapeutic virus vector upon inflammatory processes, another major contributor to angiogenic eye disease pathophysiology, with rAAV2-sVEGFRv-1 reducing therein the secretion of pro-inflammatory cytokines interleukin (IL)-1ß and IL-6. Combined with our previously published in vivo data, the in vitro activity of the expressed transgene here further demonstrates the great promise of rAAV2-sVEGFRv-1 as a potential human gene therapeutic for addressing angiogenic ocular conditions.
Assuntos
Dependovirus , Terapia Genética , Células Endoteliais da Veia Umbilical Humana , Fator A de Crescimento do Endotélio Vascular , Receptor 1 de Fatores de Crescimento do Endotélio Vascular , Humanos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Dependovirus/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Terapia Genética/métodos , Vetores Genéticos/genética , Proliferação de Células , Degeneração Macular/terapia , Degeneração Macular/genética , Degeneração Macular/metabolismo , Retinopatia Diabética/terapia , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Fator B de Crescimento do Endotélio Vascular/genética , Fator B de Crescimento do Endotélio Vascular/metabolismo , Fator de Crescimento Placentário/genética , Fator de Crescimento Placentário/metabolismoRESUMO
OBJECTIVE: Responsive neurostimulation (RNS) is a US FDA-approved form of neuromodulation to treat patients with focal-onset drug-resistant epilepsy (DRE) who are ineligible for or whose condition is refractory to resection. However, the FDA approval only extends to use in patients with one or two epileptogenic foci. Recent literature has shown possible efficacy of thalamic RNS in patients with Lennox-Gastaut syndrome and multifocal epilepsy. The authors hypothesized that RNS of thalamic nuclei may be effective in seizure reduction for patients with multifocal or regionalized-onset DRE. METHODS: The authors performed a retrospective chart review of all patients who had an RNS device managed at Texas Children's Hospital between July 2016 and September 2023, with at least one active electrode in the thalamic nuclei and ≥ 12 months of postimplantation follow-up. Information conveyed by the patient or their caregiver provided data on the change in the clinical seizure frequency, quality of life (QOL), and seizure severity between the preimplantation baseline visit and the last office visit (LOV). RESULTS: Thirteen patients (ages 8-24 years) were identified with active RNS leads in thalamic nuclei (11 centromedian and 2 anterior nucleus). At LOV, 46% of patients reported 50%-100% clinical seizure reduction (classified as responders), 15% reported 25%-49% reduction, and 38% reported < 25% reduction or no change. Additionally, 42% of patients reported subjective improvement in QOL and 58% reported improved seizure severity. Patients with focal cortical dysplasia (FCD) responded strongly: 3 of 5 (60%) reported ≥ 80% reduction in seizure burden and improvement in seizure severity and QOL. Patients with multifocal epilepsy and bilateral thalamocortical leads also did well, with all 3 reporting ≥ 50% reduction in seizures. CONCLUSIONS: RNS of thalamic nuclei shows promising results in reducing seizure burden for patients with multifocal or regional-onset DRE, particularly in a bilateral thalamocortical configuration or when addressing an underlying FCD.
Assuntos
Epilepsia Resistente a Medicamentos , Humanos , Epilepsia Resistente a Medicamentos/terapia , Criança , Adolescente , Feminino , Masculino , Estudos Retrospectivos , Adulto Jovem , Resultado do Tratamento , Núcleos Talâmicos , Qualidade de Vida , Estimulação Encefálica Profunda/métodos , Terapia por Estimulação Elétrica/métodosRESUMO
Antibodies can block immune receptor engagement or trigger the receptor machinery to initiate signaling. We hypothesized that antibody agonists trigger signaling by sterically excluding large receptor-type protein tyrosine phosphatases (RPTPs) such as CD45 from sites of receptor engagement. An agonist targeting the costimulatory receptor CD28 produced signals that depended on antibody immobilization and were sensitive to the sizes of the receptor, the RPTPs, and the antibody itself. Although both the agonist and a non-agonistic anti-CD28 antibody locally excluded CD45, the agonistic antibody was more effective. An anti-PD-1 antibody that bound membrane proximally excluded CD45, triggered Src homology 2 domain-containing phosphatase 2 recruitment, and suppressed systemic lupus erythematosus and delayed-type hypersensitivity in experimental models. Paradoxically, nivolumab and pembrolizumab, anti-PD-1-blocking antibodies used clinically, also excluded CD45 and were agonistic in certain settings. Reducing these agonistic effects using antibody engineering improved PD-1 blockade. These findings establish a framework for developing new and improved therapies for autoimmunity and cancer.
Assuntos
Proteínas Tirosina Fosfatases , Transdução de Sinais , Proteínas Tirosina Fosfatases/metabolismo , Antígenos CD28 , Receptores ImunológicosRESUMO
BACKGROUND: Targeting of solid cancers with chimeric antigen receptor (CAR)-T cells is limited by the lack of suitable tumor-specific antigens and the immunosuppressive, desmoplastic tumor microenvironment that impedes CAR-T cell infiltration, activity and persistence. We hypothesized that targeting the endosialin (CD248) receptor, strongly expressed by tumor-associated pericytes and perivascular cancer-associated fibroblasts, would circumvent these challenges and offer an exciting antigen for CAR-T cell therapy due to the close proximity of target cells to the tumor vasculature, the limited endosialin expression in normal tissues and the lack of phenotype observed in endosialin knockout mice. METHODS: We generated endosialin-directed E3K CAR-T cells from three immunocompetent mouse strains, BALB/c, FVB/N and C57BL/6. E3K CAR-T cell composition (CD4+/CD8+ ratio), activity in vitro against endosialin+ and endosialin- cells, and expansion and activity in vivo in syngeneic tumor models as well as in tumor-naive healthy and wounded mice and tumor-bearing endosialin knockout mice was assessed. RESULTS: E3K CAR-T cells were active in vitro against both mouse and human endosialin+, but not endosialin-, cells. Adoptively transferred E3K CAR-T cells exhibited no activity in endosialin knockout mice, tumor-naive endosialin wildtype mice or in wound healing models, demonstrating an absence of off-target and on-target/off-tumor activity. By contrast, adoptive transfer of E3K CAR-T cells into BALB/c, FVB/N or C57BL/6 mice bearing syngeneic breast or lung cancer lines depleted target cells in the tumor stroma resulting in increased tumor necrosis, reduced tumor growth and a substantial impairment in metastatic outgrowth. CONCLUSIONS: Together these data highlight endosialin as a viable antigen for CAR-T cell therapy and that targeting stromal cells closely associated with the tumor vasculature avoids CAR-T cells having to navigate the harsh immunosuppressive tumor microenvironment. Further, the ability of E3K CAR-T cells to recognize and target both mouse and human endosialin+ cells makes a humanized and optimized E3K CAR a promising candidate for clinical development applicable to a broad range of solid tumor types.
Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Camundongos , Animais , Pericitos/metabolismo , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/metabolismo , Camundongos Endogâmicos C57BL , Neoplasias/metabolismo , Linfócitos T/metabolismo , Camundongos Knockout , Microambiente Tumoral , Antígenos de Neoplasias/metabolismo , Antígenos CD/metabolismoRESUMO
In addition to laser photocoagulation, therapeutic interventions for diabetic retinopathy (DR) have heretofore consisted of anti-VEGF drugs, which, besides drawbacks inherent to the treatments themselves, are limited in scope and may not fully address the condition's complex pathophysiology. This is because DR is a multifactorial condition, meaning a gene therapy focused on a target with broader effects, such as the mechanistic target of rapamycin (mTOR), may prove to be the solution in overcoming these concerns. Having previously demonstrated the potential of a mTOR-inhibiting shRNA packaged in a recombinant adeno-associated virus to address a variety of angiogenic retinal diseases, here we explore the effects of rAAV2-shmTOR-SD in a streptozotocin-induced diabetic mouse model. Delivered via intravitreal injection, the therapeutic efficacy of the virus vector upon early DR processes was examined. rAAV2-shmTOR-SD effectively transduced mouse retinas and therein downregulated mTOR expression, which was elevated in sham-treated and control shRNA-injected (rAAV2-shCon-SD) control groups. mTOR inhibition additionally led to marked reductions in pericyte loss, acellular capillary formation, vascular permeability, and retinal cell layer thinning, processes that contribute to DR progression. Immunohistochemistry showed that rAAV2-shmTOR-SD decreased ganglion cell loss and pathogenic Müller cell activation and proliferation, while also having anti-apoptotic activity, with these effects suggesting the therapeutic virus vector may be neuroprotective. Taken together, these results build upon our previous work to demonstrate the broad ability of rAAV2-shmTOR-SD to address aspects of DR pathophysiology further evidencing its potential as a human gene therapeutic strategy for DR.
Assuntos
Diabetes Mellitus , Retinopatia Diabética , Animais , Dependovirus/genética , Diabetes Mellitus/metabolismo , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Retinopatia Diabética/terapia , Vetores Genéticos/genética , Camundongos , RNA Interferente Pequeno/metabolismo , Retina/patologia , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: The diagnosis of lateral epicondylitis is typically made on the basis of clinical history and examination. However, magnetic resonance imaging (MRI) is often used to supplement evaluation of the patient with a painful elbow and can identify extensor carpi radialis brevis (ECRB) tendon tears. The objective of this study was to determine if ECRB tear size on MRI could be used as a prognostic indicator for patients with recalcitrant lateral epicondylitis and partial ECRB tears. METHODS: Forty-one patients with recalcitrant lateral epicondylitis and a partial ECRB tear on MRI were identified (22 men and 19 women; age: 49 ± 8 years; height: 165 ± 36 mm; weight: 73 ± 18 kg). Patients were divided into two groups based on whether they underwent surgery or not. Nonsurgical treatment was evaluated by the Disabilities of the Arm, Shoulder, and Hand questionnaire, and surgery was considered a failure of nonsurgical treatment. Nonsurgical treatment was variable and included a mixture of physical therapy, rest, injection therapy, and splinting. RESULTS: Of the 41 patients, 5 patients opted for immediate surgery and 36 patients were treated nonsurgically. Of those 36 patients, 11 patients had symptom relief, 19 patients had subsequent surgery, and 6 patients chose not to have surgery despite continued symptoms. Tear size on MRI did not differ significantly between the patients who had symptom relief with nonsurgical treatment and the other patients (7.7 ± 4.3 mm vs. 9.7 ± 2.5 mm, P = .07). DISCUSSION: Only 11 of 41 patients (27%) with recalcitrant lateral epicondylitis and ECRB tear had symptom relief with nonsurgical treatment. However, ECRB tendon defect size on MRI did not predict success or failure of nonsurgical treatment.
RESUMO
CASE: A 23-year-old woman with an Osborne-Cotterill lesion and posterolateral rotatory instability (PLRI) of the elbow was treated with osteochondral allograft transplantation (OCA) and lateral ulnar collateral ligament (LUCL) repair with internal brace. Two years after surgery, she reported resolution of pain and returned to all recreational activities. She reported no mechanical symptoms and no episodes of postoperative instability. CONCLUSION: PLRI can present with an Osborne-Cotterill lesion in addition to LUCL injury. The purpose of this case report was to describe the use of OCA to manage bony defects in the capitellum in addition to LUCL repair for patients with PLRI.
Assuntos
Ligamento Colateral Ulnar , Lesões no Cotovelo , Articulação do Cotovelo , Instabilidade Articular , Adulto , Aloenxertos , Ligamento Colateral Ulnar/lesões , Ligamento Colateral Ulnar/cirurgia , Articulação do Cotovelo/cirurgia , Feminino , Humanos , Instabilidade Articular/cirurgia , Adulto JovemRESUMO
INTRODUCTION: Making healthcare decisions for children can be challenging for parents or guardians. We aimed to characterize the decision-making preferences and stress of parents or guardians who were offered both appendectomy or nonoperative management (NOM) for children with acute appendicitis. METHODS: Criteria was developed for offering operative or NOM for patients. At the time of decision, parents or guardians completed a survey assessing their understanding of treatment options, stress and preferences in being given the choice. An outpatient follow-up survey was later administered to evaluate post-decision satisfaction. RESULTS: A total of 45 respondents were included in the study. More than 95% endorsed understanding of the risks/benefits of the options and felt supported and satisfied with their decision. Half felt the process was more than minimally stressful, 77% felt the decision was easy to make, 89% liked being asked and 95% preferred to make the decision themselves with varying degrees of input from their physician. Of the 62% of parents or guardians who completed the follow-up survey, >90% were satisfied with their decision and one respondent regretted their choice. DISCUSSION: When offered the choice between operative and NOM of acute appendicitis, half of parents or guardians felt greater than minimal stress. The majority endorsed adequate understanding of the options, felt it was an easy decision, and maintained the desire to be the primary decision maker for their child. Our study provides preliminary data on parental or guardian attitudes towards shared decision-making in the surgical setting. Follow-up studies should focus on identifying predictors for those who feel increased stress and difficulty with decision-making. LEVEL OF EVIDENCE: III.
Assuntos
Apendicite , Doença Aguda , Apendicectomia , Apendicite/cirurgia , Atitude , Criança , Tomada de Decisões , Humanos , PaisRESUMO
Expanding on previous demonstrations of the therapeutic effects of adeno-associated virus (AAV) carrying small-hairpin RNA (shRNA) in downregulating the mechanistic target of rapamycin (mTOR) in in vivo retinal vascular disorders, vascular endothelial growth factor (VEGF)-stimulated endothelial cells were treated with AAV2-shmTOR to examine the role of mTOR inhibition in retinal angiogenesis. AAV2-shmTOR exposure significantly reduced mTOR expression in human umbilical vein endothelial cells (HUVECs) and decreased downstream signaling cascades of mTOR complex 1 (mTORC1) and mTORC2 under VEGF treatment. Moreover, the angiogenic potential of VEGF was significantly inhibited by AAV2-shmTOR, which preserved endothelial integrity by maintaining tight junctions between HUVECs. These data thus support previous in vivo studies and provide evidence that AAV2-shmTOR induces therapeutic effects by inhibiting the neovascularization of endothelial cells.
Assuntos
Dependovirus , Fator A de Crescimento do Endotélio Vascular , Dependovirus/genética , Dependovirus/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , RNA Interferente Pequeno/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Signal transducer and activator of transcription 3 (STAT3) is important for psoriasis pathogenesis because STAT3 signaling downstream of IL-6, IL-21, IL-22, and IL-23 contributes to T helper type 17 cell development and because transgenic mice with keratinocyte (KC) STAT3 expression (K14-Stat3C mice) develop psoriasis-like dermatitis. In this study, the relative contribution of STAT3 signaling in KCs versus in T cells was evaluated in the imiquimod model of psoriasis-like dermatitis. Mice with STAT3-inducible deletion in KCs (K5-Stat3-/- mice) had decreased psoriasis-like dermatitis and epidermal STAT3 phosphorylation compared with wild-type mice, whereas mice with constitutive deletion of STAT3 in all T cells were similar to wild-type mice. Interestingly, mice with KC-inducible deletion of IL-6Rα had similar findings to those of K5-Stat3-/- mice, identifying IL-6/IL-6R as a predominant upstream signal for KC STAT3-induced psoriasis-like dermatitis. Moreover, psoriasis-like dermatitis inversely associated with type 1 immune gene products, especially CXCL10, whereas CXCL10 limited psoriasis-like dermatitis, suggesting that KC STAT3 signaling promoted psoriasis-like dermatitis by restricting downstream CXCL10 expression. Finally, treatment of mice with the pan-Jak inhibitor, tofacitinib, reduced psoriasis-like dermatitis and epidermal STAT3 phosphorylation. Taken together, STAT3 signaling in KCs rather than in T cells was a more important determinant for psoriasis-like dermatitis in a mechanism that involved upstream KC IL-6R signaling and downstream inhibition of type 1 immunityâassociated CXCL10 responses.
Assuntos
Dermatite , Psoríase , Animais , Quimiocina CXCL10 , Dermatite/patologia , Modelos Animais de Doenças , Interleucina-6/metabolismo , Queratinócitos/metabolismo , Camundongos , Camundongos Transgênicos , Receptores de Interleucina-6 , Fator de Transcrição STAT3/metabolismo , Linfócitos T/metabolismoRESUMO
OBJECTIVES: The purpose of this study was to review our success rate performing the histrelin implant procedure in clinic without sedation. METHODS: A retrospective study was performed for histrelin implant procedures done at our institution from 2008 to 2020. Wilcoxon rank-sum test or Fisher's exact test was utilized to identify significant differences (p<0.05). RESULTS: A total of 73 patients underwent 184 histrelin implant procedures from 2008 to 2020. In the past few years, there has been a decrease in procedures for precocious puberty and an increase for gender dysphoria. The majority of procedures were performed in clinic without sedation (82%). The only risk factor associated with requiring sedation was younger age (median 9 vs. 10 years; p<0.003). Complications (i.e. implant fracture or need for counter-incision) were noted in 10 of the procedures (5%). The only risk factor identified for a procedural complication during implant removal/replacement was interval time from insertion (21 vs. 13 months; p<0.01). The only documented wound problem reported was dermatitis in 1 patient (no suture granuloma, dehiscence, or implant extravasation). CONCLUSIONS: Procedural refinements and distraction therapy have enabled us to perform the majority of procedures in clinic without sedation. In our experience, procedural difficulty and complications appear to increase with prolonged implant duration. Histrelin implantation is increasingly being performed for gender dysphoria.
Assuntos
Implantes de Medicamento , Disforia de Gênero/tratamento farmacológico , Hormônio Liberador de Gonadotropina/análogos & derivados , Puberdade Precoce/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study is to develop and evaluate a set of psychometrically equivalent disyllabic wordlist (SC-10) in Singapore Mandarin for clinical use. STUDY DESIGN: A preliminary set of 1000 words were obtained from a dictionary of frequently used words by Singapore students. Ten native judges rate the familiarity level of each word. This is followed by a face-to-face public survey to rank the shortlisted word set from most to least familiar. The final 108 disyllabic words were recorded by a native female talker. 20 normal hearing subjects were used to obtain the percentage of correct word recognition at 24 intensity levels (-10 dB HL to 26 dB HL in 2 dB increment). Psychometric function slopes were calculated for each word. 100 words were eventually chosen and assigned into ten 10-word lists based on a psychometric balancing protocol. Minor digital adjustments were made to the intensity of each wordlist to improve their auditory homogeneity.The developed SC-10 wordlists were validated by a separate group of 25 normal hearing subjects. Test-retest reliability was carried out on 20 out of 25 participants at the selected intensity levels (SRT-5, SRT, SRT+5). RESULTS: The calculated regression slopes in the psychometric functions for the ten lists are between 8.0 and 9.8%/dB. Single factor ANOVA analysis showed no significant difference in both the mean intensity required to obtain 50% recognition score (f = 0.109, df = 9, p = 0.999) and the slopes of the psychometric functions (f = 0.078, df = 9, p = 0.999) between the ten word lists. List validation on 25 normal hearing participants (PTA = 11.0 dB HL, SD = 4.3) showed a mean speech recognition threshold (SRT) of 9.3 dB HL (SD = 3.5)and regression slope of 8.395%/dB. Quadratic regression analysis showed a positive correlation (r 2 = 0.923) between presentation level and word recognition score (WRS). The difference between PTA and SRT of each subject all fall within the clinically acceptable difference of 10 dB HL. Test-retest reliability, carried out on 20 subjects at three levels (SRT-5, SRT, and SRT+5 dB), showed no significance difference between word recognition score when the same participant is tested again at the same intensity level using a different wordlist. CONCLUSION: All in all, it shows that the SC-10 speech materials are valid for clinical use for Mandarin speech audiometry in Singapore.
RESUMO
Objective The purpose of this study was to evaluate the short-term outcomes of patients undergoing proximal row carpectomy (PRC) with interposition arthroplasty using a decellularized dermal allograft. Methods Patients with a minimum of 1-year follow-up after undergoing a PRC using decellularized dermal allograft were contacted for clinical evaluation, radiographs, and postoperative outcome questionnaires, including the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire as well as the modified Likert scale for patient satisfaction. Nine of ten (90%) consecutive patients who were treated using this surgical technique were available for follow-up. Results At a mean follow-up of 18 months, a total of nine patients achieved a mean flexion-extension arc of 113 degrees, pronosupination of 170.5 degrees, grip strength of 68 Ibs and pinch strength of 17 Ibs. Relative to the contralateral side, these values were 95, 100, 84 and 82%, respectively. There was significant improvement in the mean DASH score from 63.5 preoperatively to 23.8 postoperatively. Patient satisfaction postoperatively achieved a mean modified Likert score of 1.5. There was no evidence of radiocarpal joint space degeneration or dislocation in any of the patients. No patient suffered wound-related issues, foreign-body reaction to the graft, or other complications. Conclusion PRC with interposition arthroplasty using a decellularized dermal allograft in patients with degenerative changes at the lunate fossa or capitate demonstrates short-term outcomes comparable to what has been reported for routine PRC in patients without degenerative changes affecting the radiocapitate joint. This method of interposition arthroplasty expands the indications for PRC and may help avoid salvage, motion-sacrificing procedures in select patients with late-stage wrist arthritis. Level of Evidence This is a level IV, therapeutic study.