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1.
Retina ; 37(9): 1746-1749, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27902640

RESUMO

PURPOSE: To determine minimal endoillumination levels required to perform 3-dimensional heads-up vitreoretinal surgery and to correlate endoillumination levels used for measurements of heads-up display (HUD) luminous emittance. METHODS: Prospective, observational surgical case series of 10 patients undergoing vitreoretinal surgery. Endoillumination levels were set to 40% of maximum output and were decreased at set intervals until the illumination level was 0%. Corresponding luminous emittance (lux) of the HUD was measured 40 cm from the display using a luxmeter (Dr. Meter, Model #LX1010BS). RESULTS: In 9 of 10 cases, the surgeon felt that they could operate comfortably at an endoillumination level of 10% of maximum output with corresponding HUD emittance of 14.3 ± 9.5 lux. In the remaining case, the surgeon felt comfortable at a 3% endoillumination level with corresponding HUD emittance of 15 lux. Below this threshold, subjective image dimness and digital noise limited visibility. Endoillumination levels were correlated with luminous emittance from the 3-dimensional HUD (P < 0.01). The average coefficient of variation of HUD luminance was 0.546. There were no intraoperative complications. CONCLUSION: With real-time digital processing and automated brightness control, 3-dimensional HUD platforms may allow for reduced intraoperative endoillumination levels and a theoretically reduced risk of retinal phototoxicity during vitreoretinal surgery.


Assuntos
Imageamento Tridimensional , Iluminação/métodos , Doenças Retinianas/cirurgia , Cirurgia Vitreorretiniana/métodos , Atitude do Pessoal de Saúde , Humanos , Estudos Prospectivos
2.
J Neurovirol ; 22(2): 218-30, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26463526

RESUMO

Although youth living with behaviorally acquired HIV (YLWH) are at risk for cognitive impairments, the relationship of impairments to HIV and potential to improve with antiretroviral therapy (ART) are unclear. This prospective observational study was designed to examine the impact of initiation and timing of ART on neurocognitive functioning in YLWH in the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Treatment naïve YLWH age 18-24 completed baseline and four additional assessments of attention/working memory, complex executive, and motor functioning over 3 years. Group 1 co-enrolled in an early ART initiation study and initiated ART at enrollment CD4 >350 (n = 56); group 2 had CD4 >350 and were not initiating ART (n = 66); group 3 initiated ART with CD4 <350 (n = 59) per standard of care treatment guidelines at the time. Treatment was de-intensified to boosted protease inhibitor monotherapy at 48 weeks for those in group 1 with suppressed viral load. Covariates included demographic, behavioral, and medical history variables. Analyses used hierarchical linear modeling. All groups showed improved performance with peak at 96 weeks in all three functional domains. Trajectories of change were not significantly associated with treatment, timing of treatment initiation, or ART de-intensification. Demographic variables and comorbidities were associated with baseline functioning but did not directly interact with change over time. In conclusion, YLWH showed improvement in neurocognitive functioning over time that may be related to practice effects and nonspecific impact of study participation. Neither improvement nor decline in functioning was associated with timing of ART initiation or therapy de-intensification.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Modelos Estatísticos , Adolescente , Terapia Antirretroviral de Alta Atividade , Atenção/efeitos dos fármacos , Contagem de Linfócito CD4 , Disfunção Cognitiva/complicações , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/virologia , Esquema de Medicação , Função Executiva/efeitos dos fármacos , Feminino , Infecções por HIV/complicações , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Testes Neuropsicológicos , Estudos Prospectivos , Desempenho Psicomotor/efeitos dos fármacos , Fatores de Tempo , Carga Viral/efeitos dos fármacos , Adulto Jovem
3.
Sex Transm Dis ; 42(5): 246-52, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25868136

RESUMO

BACKGROUND: Little is known about the epidemiology or risk factors for oral human papillomavirus (HPV) in HIV-infected youth. The objectives of this study were to determine the prevalence and correlates of oral HPV infection and to explore the association between HPV vaccination and oral infection in HIV-infected youth. METHODS: Youth 12 to 24 years of age with behaviorally acquired HIV were recruited for this cross-sectional study. Procedures involved medical chart review, survey, and collection of an oral rinse sample. Univariable and multivariable logistic regression models were used to determine whether demographic, behavioral, immunologic, and virologic factors and history of vaccination were significantly associated with oral HPV infection. RESULTS: Mean age of the 272 participants was 21.5 years; 64% were non-Hispanic black and 20.2% were Hispanic; and 10.8% of men compared with 20.3% of women were fully vaccinated. Human papillomavirus prevalence was 19.7% in men and 18.6% in women (P = 1.0). Only men were positive for vaccine-type HPV: 5.6% were positive for HPV-6, HPV-11, HPV-16, and/or HPV-18, and 4.2% were positive for HPV-16 and/or HPV-18. Among men who were fully vaccinated, none were positive for HPV-6, HPV-11, HPV-16, and/or HPV-18, compared with 12 (6.3%) of men who were not fully vaccinated (P = 0.37). Two variables were marginally associated with oral HPV (P < 0.10): marijuana use in the previous 3 months and lower CD4+ T-cell count. CONCLUSIONS: Prevalence rates of oral HPV were relatively high in this population of HIV-infected youth and were similar in male and female youth. No fully vaccinated men were infected with vaccine-type HPV.


Assuntos
Coinfecção/epidemiologia , Infecções por HIV/epidemiologia , Doenças da Boca/epidemiologia , Infecções por Papillomavirus/epidemiologia , Vacinas contra Papillomavirus/administração & dosagem , Comportamento Sexual/psicologia , Parceiros Sexuais/psicologia , Adolescente , Linfócitos T CD4-Positivos , Criança , Estudos Transversais , Feminino , Infecções por HIV/imunologia , Infecções por HIV/psicologia , Humanos , Masculino , Doenças da Boca/imunologia , Doenças da Boca/psicologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/psicologia , Prevalência , Fatores de Risco , Comportamento Sexual/estatística & dados numéricos , Estados Unidos/epidemiologia , Vacinação/estatística & dados numéricos , Carga Viral , Adulto Jovem
5.
AIDS Behav ; 18(4): 686-96, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24271347

RESUMO

This randomized behavioral trial examined whether youth living with HIV (YLH) receiving cell-phone support with study funded phone plans, demonstrated improved adherence and viral control during the 24 week intervention and 24 weeks post-intervention compared to controls. Monday through Friday phone calls confirmed medications were taken, provided problem-solving support, and referred to services to address adherence barriers. Of 37 participants (ages 15-24), 62 % were male and 70 % were African American. Self-reported adherence was significantly higher in the intervention group compared to the control at 24 and 48 weeks for the past month (P = 0.007) and log 10 HIV VL was significantly lower at both 24 weeks (2.82 versus 4.52 P = 0.002) and 48 weeks (3.23 versus 4.23 P = 0.043). Adherence and viral load showed medium to large effect sizes across the 48 week study. This is the first study to demonstrate sustained clinically significant reductions in HIV VL using youth friendly technology.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Telefone Celular , Infecções por HIV/tratamento farmacológico , Promoção da Saúde , Adesão à Medicação/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Sistemas de Alerta , Adolescente , Feminino , Infecções por HIV/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Estudos Longitudinais , Masculino , Adesão à Medicação/psicologia , Cooperação do Paciente/psicologia , Projetos Piloto , Comportamento Sexual , Envio de Mensagens de Texto , Estados Unidos/epidemiologia , Carga Viral , Adulto Jovem
6.
Am J Surg ; 234: 68-73, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38688814

RESUMO

Regret after gender-affirming surgery (GAS) is a complex issue. Comparing regret after GAS to regret after plastic surgery operations and other major life decisions is a novel approach that can provide insight into the magnitude of this issue. A systematic review of three databases was conducted to investigate regret after common plastic surgery operations. Three separate literature reviews on regret after GAS, regret after elective operations, and regret after major life decisions were performed. A total of 55 articles examining regret after plastic surgery were included. The percentage of patients reporting regret ranged from 0 to 47.1 â€‹% in breast reconstruction, 5.1-9.1 â€‹% in breast augmentation, and 10.82-33.3 â€‹% in body contouring. In other surgical subspecialties, 30 â€‹% of patients experience regret following prostatectomy and up to 19.5 â€‹% following bariatric surgery. Rate of regret after GAS is approximately 1 â€‹%. Other life decisions, such as having children and getting a tattoo have regret rates of 7 â€‹% and 16.2 â€‹%, respectively. When comparing regret after GAS to regret after other surgeries and major life decisions, the percentage of patients experiencing regret is extremely low.


Assuntos
Emoções , Humanos , Cirurgia de Readequação Sexual/psicologia , Masculino , Feminino , Mamoplastia/psicologia
7.
J Plast Reconstr Aesthet Surg ; 91: 181-190, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38422919

RESUMO

PURPOSE: Adult acquired buried penis (AABP) is a morbid condition often necessitating surgical intervention. Accurate assessment of pre- and postoperative symptoms is crucial to understand how AABP impacts a patients' quality of life, verify surgical effectiveness, and practice patient-centered care. There is no validated patient-reported outcome instrument specific for AABP evaluation. We undertook a comprehensive review of existing literature on patient-reported outcome instruments post-AABP surgery to highlight the importance of developing a specific tool. METHODS: Following the preferred reporting items for systematic reviews and meta-analysis 2020 guidelines, we queried three databases using relevant keywords (e.g., "buried penis repair"). Inclusion criteria were studies that discussed surgical management of AABP with patient-reported outcomes. Pediatric and congenital cases were excluded. Information collected included study design, level of evidence, number of participants included in the study, etiology of buried penis, surgical technique, preoperative or postoperative patient-reported outcomes, and patient-reported outcome instrument used. RESULTS: Initial query identified 998 records. After abstract screening and applying the inclusion or exclusion criteria, a total of 19 articles with 440 patients were included. Eight studies implemented patient-reported outcome instruments. The international index of erectile dysfunction-5 and Likert satisfaction scales were used most frequently. Although all instruments were validated, none were validated in the specific context of AABP surgical intervention. CONCLUSIONS: There is considerable heterogeneity within the AABP literature regarding patient symptomatology, postoperative complications, patient-reported outcomes, and instruments used. The results of this study emphasize the need for a patient-reported outcome measure to examine the influence of AABP repair on patient satisfaction and health-related quality of life.


Assuntos
Doenças do Pênis , Procedimentos de Cirurgia Plástica , Masculino , Adulto , Humanos , Criança , Qualidade de Vida , Pênis/cirurgia , Doenças do Pênis/cirurgia , Doenças do Pênis/complicações , Medidas de Resultados Relatados pelo Paciente , Síndrome
8.
Reprod Fertil ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38734031

RESUMO

Chronic endometritis (CE) in humans is asymptomatic inflammation of the endometrium, associated with poor reproductive outcomes. Similarly asymptomatic endometrial inflammation in cows, termed subclinical endometritis (SCE), is associated with adverse reproductive outcomes. While the pathophysiology and treatment options for CE in humans remains poorly defined, the financial implications of SCE in dairy cows mean it has been intensively researched. We performed a systematic review with an emergent theme thematic analysis of studies of SCE in cows, to determine potential areas of interest in human CE research. A literature search for studies of subclinical endometritis in cows published between 1990 and November 2021 was performed across Embase, Medline, Scopus and CINAHL. Studies of symptomatic or clinical endometritis were excluded. Thematic analysis across two broad themes were explored: diagnostic methods and pathophysiology of SCE. In total, 44 bovine studies were included. 12 studies reported on diagnostic methodology. The primary emergent theme was the use of cytology for the diagnosis of SCE. This method has a lower sensitivity than histopathology but is less invasive and more specific than alternative techniques of ultrasound, vaginoscopy, or metabolic markers. The subthemes related to pathophysiology were identified as type of endometritis, metabolic stress, artificial insemination, infective causes, and altered cellular pathways. Despite the lack of symptoms, cellular pathways of inflammation including NFkB, MAPK, and inflammasomes were found to be activated. The key themes related to the diagnosis and pathophysiology of SCE in cows identified in this systematic review highlight potential areas for future research into human CE.

9.
Aesthet Surg J Open Forum ; 6: ojae019, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633727

RESUMO

Historically, demand for plastic surgery has been associated with the performance of the US economy. This study evaluates the relationship between economic performance indicators and the popularity and profitability of aesthetic surgery from 2006 to 2022, considering several recessions and the rise of social media. The data were collected from the Aesthetic Society's (AS) Aesthetic Plastic Surgery National Databank and the American Society of Plastic Surgeons' (ASPS) Plastic Surgery Statistics Report from 2006 to 2022. Procedures analyzed included the most performed cosmetic surgeries, as well as neuromodulator injections and dermal fillers. Pearson correlation tests were used to analyze the strength of association between 8 financial indicators and case volumes and expenditures for each procedure. From 2006 to 2020, ASPS data demonstrated gross domestic product (GDP) per capita year-over-year (YOY) change that was positively correlated with case volume and expenditures across 13 out of the 24 different procedure metrics (54.2%). From 2006 to 2016, AS data were positively correlated with the YOY change of theNational Association of Securities Dealers Automated Quotations (NASDAQ), Standard and Poor's 500, and Dow Jones in 12 of the 24 variables (50%). This was followed by GDP YOY change, with positive correlations to 11 variables (45.8%). YOY changes of consumer-level finances and inflation indicators were less frequently associated among both datasets.In conclusion, our study shows that aesthetic plastic surgery procedures and expenditures correlate with GDP. Although aesthetic surgery demand may be difficult to anticipate, this study elucidates several factors plastic surgeons may use as a bellwether for their practices.

10.
Plast Reconstr Surg Glob Open ; 12(7): e5955, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38974831

RESUMO

Background: Plastic and reconstructive surgery is one of the most competitive residency programs, and given the increased number of applicants for a relatively fixed number of positions, successfully matching is a challenge. Match rates have declined since 2018, with a match rate of ~55% in 2022. Two common options before reapplying are a preliminary year of residency (preliminary year) or a research fellowship. This study investigated which option is more beneficial for reapplicants seeking a successful match. Methods: This retrospective study included all applicants to an integrated plastic and reconstructive surgery residency from 2015 to 2023. Two cohorts based on reapplication strategy (research fellowship or preliminary year) were created. Demographic, applicant, and match data were collected. Pearson chi-squared, Fisher exact, and Wilcoxon rank sum testing were performed. Results: In total, 125 reapplicants were included. Seventy-one (56.8%) reapplicants pursued a preliminary year, and 29 (23.2%) completed a research fellowship. Research fellowship reapplicants had a greater mean number of first author publications (8.8 versus 3.2, P < 0.001), non-first author publications (11.3 versus 5.9, P = 0.021), poster presentations (9.7 versus 6.0, P = 0.028), and oral presentations (11.8 versus 6.4, P < 0.001). Research fellowship reapplicants were more likely to match into plastic and reconstructive surgery (PRS) than preliminary year reapplicants, with 72.4% (n = 21) of research fellowship reapplicants matching into PRS compared with 39.4% (n = 28) of preliminary year reapplicants (P = 0.003). Conclusions: Research fellowship reapplicants demonstrated greater research productivity and were almost twice as likely to match into PRS compared with preliminary reapplicants.

11.
Aesthet Surg J Open Forum ; 6: ojae012, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510270

RESUMO

Plastic surgery relies heavily on clinical photography to document preoperative and postoperative changes, visualize surgical approaches, and evaluate outcomes. However, the contemporary landscape of plastic surgery photography faces challenges, including a lapse in standards due to the prevalence of smartphones, social media platforms, and security concerns related to data storage and cyberattacks. In this comprehensive review, the authors aim to provide plastic surgeons with practical guidelines for achieving standardized, high-quality clinical photography while navigating the evolving landscape of technology, security, and ethical considerations. We explore the security challenges associated with storing clinical photographs, emphasizing the legal obligations under the Health Insurance Portability and Accountability Act (HIPAA). We also discuss various storage options, including HIPAA-compliant cloud services, electronic medical records, and emerging technologies like blockchain and artificial intelligence.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38888004

RESUMO

OBJECTIVE: Keloids represent a symptomatic, aberrant healing process that is difficult to treat with high recurrence rates spanning from 55-100% if treated via excision without adjuvant therapy. Electrical stimulation (ES) has demonstrated findings that suggest it could reduce the recurrence rate of keloids after resection. Therefore, the aim of this study is to conduct a scoping review to investigate ES as an adjuvant therapy for decreasing keloid recurrence after excision. APPROACH: A scoping review was performed using PubMed and Web of Science databases. The search strategy encompassed terms linking keloids and various aspects of electrical stimulation. RESULTS: Our search yielded 2229 articles. 115 articles were analyzed as full text. 1 article met inclusion criteria. Despite this, ES has demonstrated other evidence that suggests its utility. ES has been shown to counter keloidic features by reducing mast cell counts, shifting wound composition from M2 to M1 macrophages, promoting angiogenesis, and, controlling fibroblast orientation and location. An alternating current will orient fibroblasts perpendicular to the current without unintended migration. INNOVATION: Our study indicates that, based on a compilation of clinical and preclinical in vitro data, the optimal scenario for ES in the role of keloid treatment is after excision with a biphasic pulsed application and square waveform. CONCLUSIONS: ES could serve as a multifaceted, adjuvant treatment after keloid excision, steering the healing process away from keloid-associated characteristics. Its cost-effectiveness means it could be adopted globally, providing a strategy to mitigate the burden of keloids irrespective of other available treatments or economic conditions.

13.
Healthcare (Basel) ; 12(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38610164

RESUMO

Cancer patients undergoing major interventions face numerous challenges, including the adverse effects of cancer and the side effects of treatment. Cancer rehabilitation is vital in ensuring cancer patients have the support they need to maximise treatment outcomes and minimise treatment-related side effects and symptoms. The Active Together service is a multi-modal rehabilitation service designed to address critical support gaps for cancer patients. The service is located and provided in Sheffield, UK, an area with higher cancer incidence and mortality rates than the national average. The service aligns with local and regional cancer care objectives and aims to improve the clinical and quality-of-life outcomes of cancer patients by using lifestyle behaviour-change techniques to address their physical, nutritional, and psychological needs. This paper describes the design and initial implementation of the Active Together service, highlighting its potential to support and benefit cancer patients.

14.
Am J Ophthalmol Case Rep ; 32: 101965, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38077787

RESUMO

Purpose: To describe the ophthalmological manifestations in transgender patients on gender-affirming hormone therapy. Methods: A retrospective chart review study was conducted. Female-to-male (FTM) and male-to-female (MTF) transgenders on gender-affirming hormone therapy evaluated at a single center were included. Candidates were collected using a phrase-identifying search tool within the electronic medical record system. Descriptive analyses were conducted to report the demographics, hormonal therapies, clinical findings, and visual outcomes. Results: A total of 17 patients were included, seven were FTM, and ten were MTF transgenders. The median age was 26.0 years (range; 20.0-30.0) in the FTM group and 35.0 years (range; 23.0-67.0) in the MTF group. Testosterone therapy in FTM patients comprised 30-60 mg of intramuscular injections weekly or 50 mg of transdermal gel daily. MTF patients used mainly 2-4 mg of estradiol and 100-300 mg of spironolactone tablets daily. A total of 27 eyes were affected, 12 in FTM and 15 in MTF patients. The median visual acuity was 20/25 in FTM (range; 20/20-20/60) and 20/25 in MTF (range; 20/20-20/400). The most common diagnoses in FTM patients were neurologic (71.4 %), particularly idiopathic intracranial hypertension, while MTF transgenders presented mainly with chorioretinal diseases (40.0 %). Compliance with medical recommendations and follow-up appointments was seen in 71.4 % of FTM and 50.0 % of MTF patients. At the last visit, the median visual acuity was 20/50 (range; 20/20-20/70) in FTM and 20/25 (range; 20/20-20/70) in MTF patients. Conclusions and importance: Transgenders presented a variety of ocular findings. A cause-and-effect association cannot be stated, yet eye specialists must be cognizant of these findings to provide appropriate treatment.

15.
Clin Teach ; 19(6): e13526, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36065504

RESUMO

BACKGROUND: Role modelling is an essential component of medical education in which trainees incorporate observed characteristics into their personal behaviour and practice style. Data on residents as role models is limited. There are no previous quantitative studies addressing residents as role models from the resident's perspective. OBJECTIVE: This study aimed to dissect the awareness, perception, and positive characteristics of internal medicine (IM) residents as role models. METHODS: This was a cross sectional study, in which 59 medical students (MS) and 64 IM residents from Medstar Georgetown University Hospital completed a questionnaire on role modelling. Descriptive and comparative analyses between both groups were conducted. FINDINGS: Most participants perceived IM residents as role models, but MS were more likely to report that IM residents lack awareness of their role model status. While MS perceived spending more hours with residents, the residents perceived dedicating more of the time spent together to teaching. Most participants denied previous training in role modelling but expressed interest in receiving formal role modelling training. Most participants reported MS behaviours were modified based on their observations of IM residents; however, while most of these behaviours were positive, there were also negative behaviours reported. CONCLUSION: There was a discrepancy between perception and awareness of residents as role models. This characterisation of IM residents as role models sets the ground for the design of interventions to increase awareness and create educational interventions aimed to support residents in their teaching role.


Assuntos
Internato e Residência , Estudantes de Medicina , Humanos , Estudos Transversais , Inquéritos e Questionários , Medicina Interna/educação
16.
Clin Exp Optom ; 105(2): 105-116, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34751097

RESUMO

Endocrinopathies are prevalent diseases that typically affect multiple organs, and the eye and orbital tissues are often involved in endocrine disorders. Some conditions, such as diabetes and thyroid gland dysfunction, may cause serious eye pathology and even blindness. A clear insight into the pathogenesis of endocrinopathies and their ocular manifestations would enhance preventive and therapeutic measures and reduce the incidence of sight-threatening complications. This review discusses the ocular manifestations of several endocrine disorders that eye care providers are likely to encounter in clinical practice.


Assuntos
Doenças do Sistema Endócrino , Doenças da Glândula Tireoide , Doenças do Sistema Endócrino/complicações , Doenças do Sistema Endócrino/diagnóstico , Olho , Humanos , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/diagnóstico , Doenças da Glândula Tireoide/terapia
17.
Open Forum Infect Dis ; 9(1): ofab608, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35024375

RESUMO

BACKGROUND: Tocilizumab, an interleukin 6 receptor (IL-6R) antagonist monoclonal antibody, has shown efficacy in patients with coronavirus disease 2019 (COVID-19) pneumonia, but the optimal dose is unknown. METHODS: Patients hospitalized for moderate to severe COVID-19 pneumonia were randomized 1:1 to receive standard of care treatment and 1-2 doses of intravenous tocilizumab 4 mg/kg or 8 mg/kg (open-label). Primary pharmacokinetic and pharmacodynamic end points were serum concentrations of tocilizumab and soluble interleukin 6 receptor (sIL-6R), IL-6, ferritin, and C-reactive protein (CRP), from baseline to day 60. The secondary end point was safety. Key exploratory efficacy end points included clinical status, time to discharge, mortality rate, and incidence of mechanical ventilation. RESULTS: Of 100 patients randomized, 49 received tocilizumab 4 mg/kg and 48 received 8 mg/kg. In pharmacokinetic and sIL-6R assessments, dose-dependent differences were seen in patients who received 1 or 2 doses of 4 or 8 mg/kg. Serum concentrations of IL-6, ferritin, and CRP and safety outcomes were comparable between groups. Through day 60, serious adverse events were reported in 30.6% and 25.0% of patients in the 4- and 8-mg/kg groups, respectively. Eight patients (16.3%) in the 4-mg/kg group and 6 (12.5%) in the 8-mg/kg group died. Exploratory time-to-event outcomes favored 8 mg/kg within the first 2 weeks. CONCLUSIONS: In patients with moderate to severe COVID-19 pneumonia who received tocilizumab 4 or 8 mg/kg, pharmacokinetic and sIL-6R assessments showed expected dose-dependent effects; pharmacodynamic assessments and safety were comparable, with no new safety signals. Further study is required before a lower dose of tocilizumab can be recommended in patients with COVID-19 pneumonia. CLINICAL TRIALS REGISTRATION: NCT04363736.

18.
Sci Rep ; 10(1): 18223, 2020 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-33106515

RESUMO

Inborn errors of metabolism are genetic conditions that can disrupt intermediary metabolic pathways and cause defective absorption and metabolism of dietary nutrients. In an Australian Kelpie breeding population, 17 puppies presented with intestinal lipid malabsorption. Juvenile dogs exhibited stunted postnatal growth, steatorrhea, abdominal distension and a wiry coat. Using genome-wide association analysis, an associated locus on CFA28 (Praw = 2.87E-06) was discovered and validated in a closely related population (Praw = 1.75E-45). A 103.3 kb deletion NC_006610.3CFA28:g.23380074_23483377del, containing genes Acyl-CoA Synthetase Long Chain Family Member 5 (ACSL5) and Zinc Finger DHHC-Type Containing 6 (ZDHHC6), was characterised using whole transcriptomic data. Whole transcriptomic sequencing revealed no expression of ACSL5 and disrupted splicing of ZDHHC6 in jejunal tissue of affected Kelpies. The ACSL5 gene plays a key role in long chain fatty acid absorption, a phenotype similar to that of our affected Kelpies has been observed in a knockout mouse model. A PCR-based diagnostic test was developed and confirmed fully penetrant autosomal recessive mode of inheritance. We conclude the structural variant causing a deletion of the ACSL5 gene is the most likely cause for intestinal lipid malabsorption in the Australian Kelpie.


Assuntos
Coenzima A Ligases/genética , Doenças do Cão/genética , Estudo de Associação Genômica Ampla/métodos , Intestino Delgado/patologia , Metabolismo dos Lipídeos/genética , Síndromes de Malabsorção/veterinária , Erros Inatos do Metabolismo/veterinária , Animais , Coenzima A Ligases/metabolismo , Doenças do Cão/metabolismo , Doenças do Cão/patologia , Cães , Feminino , Deleção de Genes , Intestino Delgado/metabolismo , Síndromes de Malabsorção/genética , Síndromes de Malabsorção/metabolismo , Síndromes de Malabsorção/patologia , Masculino , Erros Inatos do Metabolismo/genética , Erros Inatos do Metabolismo/metabolismo , Erros Inatos do Metabolismo/patologia , Linhagem , Fenótipo
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