RESUMEN
Members of the 3'-5' RNA polymerase family, comprised of tRNAHis guanylyltransferase (Thg1) and Thg1-like proteins (TLPs), catalyze templated synthesis of RNA in the reverse direction to all other known 5'-3' RNA and DNA polymerases. Discovery of enzymes capable of this reaction raised the possibility of exploiting 3'-5' polymerases for post-transcriptional incorporation of nucleotides to the 5'-end of nucleic acids without ligation, and instead by templated polymerase addition. To date, studies of these enzymes have focused on nucleotide addition to highly structured RNAs, such as tRNA and other non-coding RNA. Consequently, general principles of RNA substrate recognition and nucleotide preferences that might enable broader application of 3'-5' polymerases have not been elucidated. Here, we investigated the feasibility of using Thg1 or TLPs for multiple nucleotide incorporation to the 5'-end of a short duplex RNA substrate, using a templating RNA oligonucleotide provided in trans to guide 5'-end addition of specific sequences. Using optimized assay conditions, we demonstrated a remarkable capacity of certain TLPs to accommodate short RNA substrate-template duplexes of varying lengths with significantly high affinity, resulting in the ability to incorporate a desired nucleotide sequence of up to 8 bases to 5'-ends of the model RNA substrates in a template-dependent manner. This work has further advanced our goals to develop this atypical enzyme family as a versatile nucleic acid 5'-end labeling tool.
RESUMEN
OBJECTIVE: This study aimed to determine the impact of formulation (gel vs cream) and microneedle characteristics (length, number) on permeation of metronidazole through excised microneedle-treated skin. The long-term goal is to apply these results towards a pharmacokinetic study in human subjects with diverse skin types, using in vitro flux data to determine dosing conditions and ultimately establish in vitro-in vivo correlations. METHODS: Metronidazole release from 0.75% gel and cream was quantified with flow-through diffusion cells, using a cellulose membrane. Excised porcine skin was treated with stainless steel microneedles (500 or 800 µm length), to create 50 or 100 micropores. Metronidazole gel or cream was applied to microneedle-treated skin and replaced every 48 h for up to 7 days. Metronidazole permeation was quantified using HPLC. Intact skin (no microneedle treatment) served as controls. RESULTS: Metronidazole release was faster from the gel vs cream. At 7 days there was no difference between gel vs cream in total metronidazole permeated through intact skin. For both formulations, metronidazole permeation was significantly higher (vs intact skin) following microneedle application, regardless of microneedle length or micropore number. Increasing microneedle length and micropore number enhanced MTZ permeation multiple fold for both gel and cream. The greatest enhancement in total permeation for both formulations was achieved with the 800 µm MN, 100 micropore condition. CONCLUSIONS: Formulation and microneedle conditions both impacted metronidazole permeation. These data will be used to estimate in vivo serum concentrations after applying metronidazole to microneedle-treated skin in humans.
Asunto(s)
Metronidazol , Absorción Cutánea , Animales , Porcinos , Humanos , Metronidazol/metabolismo , Piel/metabolismo , Administración Cutánea , Agujas , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Myocardial perfusion imaging (MPI) is a powerful tool for the functional assessment of ischemia in patients with suspected or known coronary artery disease (CAD). Given that the diagnostic accuracy and prognostic value of MPI and post-test management are highly dependent on achieving an adequate stress vasodilatory response, it is critical to identify those who may not have adequately responded to vasodilator pharmacological stress agents such as adenosine, dipyridamole, and regadenoson. Caffeine, a potent inhibitor of the adenosine receptor, is a compound that can affect vasodilatory hemodynamics, result in false negative studies, and potentially alter management in cases of inaccurate test results. Vasodilator non-responsiveness can be suspected by examining hemodynamics, quantitative positron emission tomography (PET) metrics such as myocardial flow reserve (MFR), and splenic response to stress. Quantitative MFR values of 1-1.2 should raise suspicion for nonresponsiveness in the setting of normal perfusion, along with the absence of a splenic switch off. Newer metrics, such as splenic response ratio, can be used to aid in the identification of potential nonresponders to pharmacologic vasodilators.
Asunto(s)
Enfermedad de la Arteria Coronaria , Imagen de Perfusión Miocárdica , Vasodilatadores , Humanos , Imagen de Perfusión Miocárdica/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/fisiopatología , Prueba de Esfuerzo , Tomografía de Emisión de Positrones/métodos , Dipiridamol/farmacología , Circulación Coronaria/efectos de los fármacos , Adenosina , Purinas , PirazolesRESUMEN
BACKGROUND: Congress established the Appropriate Use Criteria (AUC) Program to reduce unnecessary advanced imaging studies. Organizations that wish to develop AUC can apply to the Centers for Medicare & Medicaid Services (CMS) to qualify as provider-led entities (PLEs) under this program. Variable methods, content, and formatting of PLE-generated AUC could lead to clinician uncertainty about whether an advanced imaging test is appropriate or not. PURPOSE: To review AUC published by CMS-qualified PLEs focused on advanced imaging tests for coronary artery disease (CAD), a "priority clinical area" identified by CMS. DATA SOURCES: Publicly available data from the worldwide web searched on 29 August 2022. STUDY SELECTION: Approved AUC with recommendations related to testing for CAD. DATA EXTRACTION: Manual review of published AUC by all authors. DATA SYNTHESIS: Among the 17 CMS-qualified PLEs, only 7 had published AUC related to CAD. Substantial variation in the methods and formatting of these AUCs was observed. The number of clinical scenarios covered ranged from 6 to 210, and the number of advanced imaging methods covered ranged from 1 to 25. When specifically applied to clinical scenarios, many AUC offered no guidance on appropriateness; those that did conflicted with respect to appropriateness. LIMITATION: Other CMS-identified priority clinical areas were not evaluated. CONCLUSION: CMS-qualified AUC for imaging of CAD are heterogeneous and sometimes discrepant, creating substantial potential for uncertainty among clinicians seeking to provide their patients with appropriate imaging tests. PRIMARY FUNDING SOURCE: No funding was received for this study.
Asunto(s)
Enfermedad de la Arteria Coronaria , Anciano , Estados Unidos , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico , Medicare , Internet , IncertidumbreRESUMEN
PURPOSE: To evaluate pre- and post-operative resonance, surgical technique, revision rate, and revision indication among syndromic and non-syndromic children with velopharyngeal insufficiency (VPI). MATERIALS AND METHODS: A systematic review was conducted through July 2022. Children surgically treated for VPI were included. A meta-analysis of single means, proportions, comparison of proportions, and mean differences with 95 % confidence interval [CI] was conducted. RESULTS: Twenty-three articles (n = 1437) were included in the analysis. The most common surgery was Sphincter Pharyngoplasty (SP), 62.6 % [31.3-88.9] for syndromic and 76.3 % [37.5-98.9] for non-syndromic children. Among all surgical techniques, for syndromic and non-syndromic children, 54.8 % [30.9-77.5] and 73.9 % [61.3-84.6] obtained normal resonance post-operatively, respectively. Syndromic patients obtained normal resonance post-operatively in 83.3 % [57.7-96.6] of Combined Furlow Palatoplasty and Sphincter Pharyngoplasty (CPSP), 72.6 % [54.5-87.5] of Pharyngeal Flap (PF), and 45.1 % [13.2-79.8] of Sphincter Pharyngoplasty (SP) surgeries. Non-syndromic patients obtained normal resonance post-operatively in 79.2 % [66.4-88.8] of PF and 75.2 % [61.8-86.5] of SP surgeries. The revision rate for syndromic and non-syndromic patients was 19.9 % [15.0-25.6] and 11.3 % [5.8-18.3], respectively. The difference was statistically significant, 8.6 % [2.9-15.0, p = 0.003]. Syndromic patients who underwent PF were least likely to undergo revision surgery as compared to SP and CPSP, 7.7 % [2.3-17.9] vs. 23.7 % [15.5-33.1] and 15.3 % [2.8-40.7], respectively. CONCLUSIONS: Syndromic children had higher revision rates and were significantly less likely to obtain normal resonance following primary surgery than non-syndromic patients. Among syndromic children, PF and CPSP have been shown to improve resonance and reduce revision rates more so than SP alone.
Asunto(s)
Reoperación , Insuficiencia Velofaríngea , Humanos , Insuficiencia Velofaríngea/cirugía , Reoperación/estadística & datos numéricos , Niño , Resultado del Tratamiento , Procedimientos de Cirugía Plástica/métodos , Femenino , Masculino , Preescolar , Síndrome , Procedimientos Quirúrgicos Otorrinolaringológicos/métodos , Faringe/cirugíaRESUMEN
BACKGROUND: Gluteal implants are gaining popularity as an alternative to fat grafting for gluteal augmentation. This study aims to compare complication rates between single- and double-incision techniques for implant placement in gluteal augmentation from a single surgeon's experience. METHODS: Retrospective analysis of a single surgeon's implant-based gluteal augmentations was conducted between October 2018 and August 2022. Consecutive patient cases were reviewed at the beginning and end of the designated period to compare both incision techniques after switching from the single- to double-incision technique in September 2020. Demographics and postoperative complications were compared. Statistical comparisons were made using the independent sample t-test for quantitative variables and the Fisher's exact test for categorical variables. RESULTS: The study included 134 single-incision patients (247 implants) and 47 double-incision patients (91 implants). Baseline demographic and clinical characteristics between the two groups were similar. Overall complication rate per implant was higher in the single-incision group (16.6% vs. 6.6%, p = 0.02). The most common complication per implant was delayed wound healing (single incision: 9.7%, double incision: 5.5%). The odds ratio of developing at least one complication in the double compared to the single-incision group was 0.44 (95% CI: 0.19, 0.92). CONCLUSIONS: The double incision technique demonstrates a lower complication rate than the single-incision technique for implant-based gluteal augmentation. The most common complication in both groups was delayed wound healing which responded in most patients to conservative wound care. These results support using the double-incision technique for implant-based gluteal augmentation. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
RESUMEN
OBJECTIVE: Children with hypopituitarism (CwHP) can present with orofacial clefting, frequently in the setting of multiple midline anomalies. Hypopituitarism (HP) can complicate medical and surgical care; the perioperative risk in CwHP during the traditionally lower risk cleft lip and/or palate (CL/P) repair is not well described. The objective of this study is to examine the differences in complications and mortality of CL/P repair in CwHP compared to children without hypopituitarism (CwoHP). DESIGN: A retrospective cross-sectional analysis. SETTING: The 1997 to 2019 Kids' Inpatient Databases (KID). PATIENTS: Children 3 years old and younger who underwent CL/P repair. MAIN OUTCOME MEASURE(S): Complications and mortality. RESULTS: A total of 34â 106 weighted cases were analyzed, with 86 having HP. CwHP had a longer length of stay (3.0 days [IQR 2.0-10.0] vs 1.0 day [IQR 1.0-2.0], P < .001) and higher rates of complications and mortality (12.8% vs 2.9%, P < .001) compared to CwoHP. Controlling for demographic factors, CwHP had 6.61 higher odds of complications and mortality than CwoHP (95% CI 3.38-12.94, P < .001). CONCLUSIONS: CwHP can present with a CL/P and other midline defects that can increase the complexity of their care. These data show a significant increase in length of stay, complications, and mortality in CwHP undergoing CL/P repair. Increased multidisciplinary attention and monitoring may be needed for these children peri- and postoperatively, especially if additional comorbidities are present. Further studies on perioperative management in this population are warranted to reduce morbidity and mortality.
Asunto(s)
Labio Leporino , Fisura del Paladar , Humanos , Niño , Lactante , Preescolar , Labio Leporino/cirugía , Fisura del Paladar/cirugía , Estudios Retrospectivos , Pacientes Internos , Estudios Transversales , Complicaciones Posoperatorias/epidemiologíaRESUMEN
Previous disaster research exploring mental health consequences has been conducted after a single disaster. Community mental health nurses offer critical support in the aftermath of a disaster through complex assessments, psychosocial education and treatment. This research examines help-seeking behaviors in a Greater Houston community struggling with two simultaneous disasters, a historic winter freeze amidst the COVID-19 pandemic. Three Mental Health Crisis clinics, staffed by an interdisciplinary team, offered walk-in crisis services. The study characterizes adults who accessed services and describes those who accepted follow-up, subsidized behavioral health therapy or case management, including populations experiencing health disparities. Statistical analysis included descriptive and inferential statistics. Those who recognized the need for behavioral health care and accessed episodic care differed from those who accepted follow-up care. The population that was more likely to accept follow up care largely consisted of females, individuals without a previously existing mental health condition, those who reported trauma exposure, and young adults of Hispanic/Latino origin. Nurses can leverage female support to inspire male adults to seek care and advocate for increased resources and training to support culturally relevant care. Nurses and the interdisciplinary team need to assess for trauma exposure, as it influences care decisions.
RESUMEN
The tRNAHis guanylyltransferase (Thg1) was originally discovered in Saccharomyces cerevisiae where it catalyzes 3'-5' addition of a single nontemplated guanosine (G-1) to the 5' end of tRNAHis In addition to this activity, S. cerevisiae Thg1 (SceThg1) also catalyzes 3'-5' polymerization of Watson-Crick (WC) base pairs, utilizing nucleotides in the 3'-end of a tRNA as the template for addition. Subsequent investigation revealed an entire class of enzymes related to Thg1, called Thg1-like proteins (TLPs). TLPs are found in all three domains of life and preferentially catalyze 3'-5' polymerase activity, utilizing this unusual activity to repair tRNA, among other functions. Although both Thg1 and TLPs utilize the same chemical mechanism, the molecular basis for differences between WC-dependent (catalyzed by Thg1 and TLPs) and non-WC-dependent (catalyzed exclusively by Thg1) reactions has not been fully elucidated. Here we investigate the mechanism of base-pair recognition by 3'-5' polymerases using transient kinetic assays, and identify Thg1-specific residues that play a role in base-pair discrimination. We reveal that, regardless of the identity of the opposing nucleotide in the RNA "template," addition of a non-WC G-1 residue is driven by a unique kinetic preference for GTP. However, a secondary preference for forming WC base pairs is evident for all possible templating residues. Similar to canonical 5'-3' polymerases, nucleotide addition by SceThg1 is driven by the maximal rate rather than by NTP substrate affinity. Together, these data provide new insights into the mechanism of base-pair recognition by 3'-5' polymerases.
Asunto(s)
Nucleotidiltransferasas/metabolismo , Saccharomyces cerevisiae/enzimología , Secuencia de Aminoácidos , Emparejamiento Base , Cristalografía por Rayos X , Guanosina Trifosfato/metabolismo , Cinética , Nucleótidos/metabolismo , Nucleotidiltransferasas/química , ARN de Transferencia de Histidina/metabolismo , Alineación de SecuenciaRESUMEN
INTRODUCTION: Myocardial perfusion imaging (MPI) protocols have not changed significantly despite advances in instrumentation and software. We compared an early post-injection, stress-first SPECT protocol to standard delayed imaging. METHODS: 95 patients referred for SPECT MPI were imaged upright and supine on a Spectrum Dynamics D-SPECT CZT system with CT attenuation correction. Patients received injection of 99mTc tetrofosmin at peak of regadenoson stress and were imaged. Early post-stress (mean 17 ± 2 minutes) and Standard 1-h delay (mean 61 ± 13 min). Three blinded readers evaluated images for overall interpretation, perceived need for rest imaging, image quality, and reader confidence. Laboratory efficiency was also evaluated. RESULTS: Blinded readers had the same response for the need for rest in 77.9% of studies. Studies also had the same interpretation in 89.5% of studies. Reader confidence was high (86.0% (Early) and 90.3% (Standard p = 0.52. Image quality was good or excellent in 87.4% Early vs 96.8% Standard (p = 0.09). Time between patient check-in and end of stress imaging was 104 ± (Standard) to 60 ± 18 minutes (Early) (p < 0.001). CONCLUSION: Early post-injection stress-only imaging using CZT SPECT/CT appears promising with Tc-99m tetrofosmin with similar image quality, reader confidence, diagnosis, and need for a rest scan.
Asunto(s)
Imagen de Perfusión Miocárdica , Humanos , Imagen de Perfusión Miocárdica/métodos , Tomografía Computarizada de Emisión de Fotón Único/métodos , Cintigrafía , Cadmio , TelurioRESUMEN
BACKGROUND: Peripheral artery disease (PAD) and coronary vascular dysfunction are common in patients with cardiometabolic disease. Neither the prevalence of coronary vascular dysfunction among patients with PAD nor the prognostic impact with these two conditions present together has been well studied. METHODS: Consecutive patients who underwent PET MPI were analyzed for presence of coronary vascular dysfunction [myocardial blood flow reserve (MBFR) < 2]. Cox regression was used to examine the association of reduced MBFR with mortality in patients with PAD, as well as the association of comorbid MBFR < 2 and PAD with all-cause death. RESULTS: Among 13,940 patients, 1936 (14%) had PAD, 7782 (56%) had MBFR < 2 and 1346 (10%) had both PAD and MBFR < 2. Reduced MBFR was very common (69.5%) and was associated with increased risk of all-cause death (HR 1.69, 95%CI 1.32, 2.16, p < 0.01) in patients with PAD. Patients with both PAD and MBFR < 2, and those with either PAD or reduced MBFR had increased risk of death compared to those with neither condition: PAD + MBFR < 2 [(HR 95%CI), 2.30; 1.97-2.68], PAD + MBFR ≥ 2 (1.37; (1.08-1.72), PAD - MBFR < 2 (1.98; 1.75-2.25), p < 0.001 for all). CONCLUSION: Coronary vascular dysfunction was common in patients with PAD and was associated with increased risk of death.
Asunto(s)
Enfermedad de la Arteria Coronaria , Enfermedad Arterial Periférica , Humanos , Vasos Coronarios , Enfermedad Arterial Periférica/diagnóstico por imagen , Miocardio , Pronóstico , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Factores de RiesgoRESUMEN
BACKGROUND: Chronic pain and depression are highly comorbid, but the lack of consensus on the best treatment strategies puts patients at high risk of suboptimal care-coordination as well as health and social complications. Therefore, this study aims to quantitatively assesses how effective different primary care interventions have been in treating the comorbid state of chronic pain and depression. In particular, this study evaluates both short-term outcomes-based specifically on measures of chronic pain and depression during an intervention itself-and long-term outcomes or measures of pain and depression in the months after conclusion of the formal study intervention. METHODS: This study is a systematic review and meta-analysis of randomised-controlled trials (RCTs) enrolling patients with concurrent chronic pain and depression. Intensity and severity of pain and depression symptoms were the primary outcomes. The main inclusion criteria were RCTs that: (i) enrolled patients diagnosed with depression and chronic pain, (ii) occurred in primary care settings, (iii) reported baseline and post-intervention outcomes for chronic pain and depression, (iv) lasted at least 8 weeks, and (v) used clinically validated outcome measures. Risk of bias was appraised with the Risk of Bias 2 tool, and GRADE guidelines were used to evaluate the quality of evidence. RESULTS: Of 692 screened citations, 7 multicomponent primary care interventions tested across 891 patients were included. Meta-analyses revealed significant improvements in depression at post-intervention (SMD = 0.44, 95% CI [0.17, 0.71], P = 0.0014) and follow-up (SMD = 0.41, 95% CI [0.01, 0.81], P = 0.0448). Non-significant effects were observed for chronic pain at post-intervention (SMD = 0.27, 95% CI [-0.08, 0.61], P = 0.1287) and follow-up (SMD = 0.13, 95% CI [-0.3, 0.56], P = 0.5432). CONCLUSIONS: Based on the results of the meta-analysis, primary care interventions largely yielded small to moderate positive effects for depressive symptoms and no significant effects on pain. In one study, stepped-care to be more effective in treatment of comorbid chronic pain and depression than other interventions both during the intervention and upon post-intervention follow-up. As such, depression appears more amenable to treatment than pain, but the number of published RCTs assessing both conditions is limited. More research is needed to further develop optimal treatment strategies.
RESUMEN
OBJECTIVES: To investigate outcomes associated with conventional roller or centrifugal pumps during neonatal venovenous extracorporeal membrane oxygenation (ECMO). Our primary hypothesis is that in comparison with conventional roller-pump support, centrifugal pump use is associated with greater odds of survival. Our secondary hypothesis is that centrifugal pump use is associated with lesser odds of complications. DESIGN: Retrospective cohort identified using the Extracorporeal Life Support Organization (ELSO) registry 2016 to 2020 dataset. SETTING: All ECMO centers reporting to the ELSO registry. PATIENTS: All neonates (≤ 28 d) supported with venovenous ECMO and cannulated via right internal jugular vein using dual-lumen venovenous cannulas and polymethyl pentene membrane oxygenators. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 612 neonates (centrifugal, n = 340; conventional roller, n = 272) were included in the analysis. Using a multivariable logistic regression model, centrifugal pump use-as opposed to roller pump use-was associated with lesser odds of survival (odds ratio [OR], 0.53; 95% CI, 0.33-0.84; p < 0.008). Thrombosis and clots in the circuit components were also associated with lesser odds of survival (OR, 0.28; 95% CI, 0.16-0.60; p < 0.001). We failed to show that hemolysis was an independent variable for survival (OR, 0.60; 95% CI, 0.31-1.19; p = 0.14). The primary diagnosis of neonatal aspiration/meconium aspiration is associated with more than seven-fold greater odds of survival (OR, 7.57; 95% CI, 4.02-15.74; p < 0.001). CONCLUSIONS: Contrary to our hypotheses, conventional roller pump use was associated with greater odds of survival. While thrombosis and clots in circuit components were independent variables for lesser odds of survival, further research is needed better to understand the use of centrifugal pumps in neonatal practice.
Asunto(s)
Oxigenación por Membrana Extracorpórea , Síndrome de Aspiración de Meconio , Femenino , Humanos , Recién Nacido , Oxigenación por Membrana Extracorpórea/efectos adversos , Estudios Retrospectivos , Oxigenadores de Membrana , MorbilidadRESUMEN
OBJECTIVES: Helicopter emergency services (HEMS) serve a crucial role in the triage and transport of critically ill patients. Rapid transport to definitive care has become the goal of all prehospital EMS as shorter scene intervals have been associated with decreased mortality. Over the past several years, we have seen a rise in physicians trained in emergency medicine and EMS responding in the prehospital setting in our HEMS region. Our goal is to determine if the presence of EMS physicians on scene calls with HEMS delays time to hospital for patients. METHODS: This retrospective chart review collected on-scene time data from January 2016 to November 2020. Data were collected from our regional HEMS provider database via EMSCharts. We compared the HEMS scene intervals between calls which were serviced by HEMS crews alone, versus those where EMS physicians were present. The Wilcoxon rank-sum test was used to compare these two distributions, and a p-value <0.05 was used to determine statistical significance. RESULTS: We analyzed 1106 scene calls, four of which were excluded as they should have been designated as inter-facility transfers. Our analysis included 1079 scene calls with HEMS crews alone, and 23 scene calls with EMS physicians, with median HEMS scene intervals of 18 min and 19 min, respectively. A Wilcoxon rank-sum test comparing both distributions had a p-value of 0.30 (z= -1.04). CONCLUSION: There was no significant difference between HEMS scene intervals at calls serviced by HEMS crews alone versus those where EMS physicians were present. EMS physician presence was not associated with prolonged HEMS scene intervals.
RESUMEN
PURPOSE OF REVIEW: Myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) has played a central role in the non-invasive evaluation of patients with obstructive coronary artery disease (CAD) for decades. In this review, we discuss the key differences and advantages of positron emission tomography (PET) MPI over SPECT MPI as it relates to the diagnosis, prognosis, as well as clinical decision-making in patients with suspected CAD. RECENT FINDINGS: Stress-induced perfusion abnormalities on SPECT help estimate presence, extent, and location of ischemia and flow-limiting obstructive CAD, help with risk stratification, and serve as a gatekeeper to identify patients who will benefit from downstream revascularization versus medical management. Some of the major limitations of SPECT include soft-tissue attenuation artifacts, underestimation of ischemia due to reliance on relative perfusion assessment, and longer protocols with higher radiation dose when performed with traditional equipment. PET MPI addresses most of these limitations and offers better quality images, higher diagnostic accuracy along with shorter protocols and lower radiation dose to the patient. A special advantage of PET scanning lies in the ability to quantify absolute myocardial blood flow and assess true extent of epicardial involvement along with identifying non-obstructive phenotypes of CAD such as diffuse atherosclerosis and microvascular dysfunction. In addition, stress acquisition at/near peak stress with PET allows us to measure left ventricular ejection fraction reserve and myocardial blood flow reserve, which help with identifying patients at a higher risk of future cardiac events and optimally select candidates for revascularization. The several technical advantages of PET MPI position as a superior method to diagnose obstructive and non-obstructive phenotypes of ischemic heart disease affecting the entirety of the coronary circulation offer incremental value for risk stratification and guide post-test management strategy for patients with suspected CAD.
Asunto(s)
Enfermedad de la Arteria Coronaria , Imagen de Perfusión Miocárdica , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico , Imagen de Perfusión Miocárdica/métodos , Volumen Sistólico , Angiografía Coronaria/métodos , Función Ventricular Izquierda , Tomografía Computarizada de Emisión de Fotón Único/métodos , Tomografía de Emisión de PositronesRESUMEN
BACKGROUND: Malignant cutaneous eyelid tumors account for approximately 10% of all cutaneous cancers. Like other cancerous skin lesions, treatment commonly involves excision with wide margins, requiring tissue reconstruction. The use of the paramedian forehead flap (PMFF) has been described for reconstruction of the medial and upper eyelid, but literature is lacking for its use in lower eyelid anterior lamella reconstruction. We present a case series of patients who underwent reconstruction of lower eyelid defects using the PMFF. CASE PRESENTATIONS: We present 2 patients who underwent reconstruction of lower eyelid defects using the PMFF surgical technique. The patients had previous history of lower lid repair with other reconstructive methods because of cancerous eyelid lesions. In addition, both received adjuvant radiation therapy, which led to development of ectropion. Postoperative signs, symptoms, and photographs were collected to monitor outcomes. MANAGEMENT AND OUTCOMES: Reconstructions were performed by the collaborative efforts of a facial plastic reconstructive surgeon and oculoplastic surgeon using a staged PMFF approach. Postoperatively, both patients had significant improvement in ophthalmologic symptoms, particularly ectropion and lagophthalmos. At their most recent follow-up visit, they were satisfied with their functional and aesthetic outcomes. CONCLUSION: The PMFF may be safely used to reconstruct defects of the lower eyelid anterior lamella. In this study, the PMFF has proven to be an excellent option for patients with complications after previous lower eyelid reconstructions or history of radiation therapy. Overall, the PMFF should be considered as part of the surgeon's reconstructive ladder when addressing lower eyelid defects.
Asunto(s)
Ectropión , Neoplasias de los Párpados , Procedimientos de Cirugía Plástica , Neoplasias Cutáneas , Humanos , Colgajos Quirúrgicos/cirugía , Ectropión/etiología , Ectropión/cirugía , Frente/cirugía , Párpados/cirugía , Párpados/patología , Neoplasias Cutáneas/cirugía , Neoplasias de los Párpados/cirugía , Neoplasias de los Párpados/patologíaRESUMEN
OBJECTIVE: To investigate FDA-approved drugs prescribed for unrelated diseases or conditions that promote remission in subjects diagnosed with opioid use disorder (OUD). METHODS: This was a retrospective observational study utilizing the TriNetX electronic medical record data. Subjects between 18 and 65 years old were included in this study. First, a drug screen was employed to identify medications used for chronic illness that are associated with OUD remission. Based on Fisher's exact test for significance, 28 of 101 medications were selected for further analysis. Positive (buprenorphine/methadone) and negative controls (benazepril) were included in the analysis. Medications were analyzed in the absence and presence of buprenorphine or methadone, two medications used to treat OUD, to identify the likelihood of OUD remission up to one year following the index event. RESULTS: We identify 8 medications (prazosin, propranolol, lithium carbonate, olanzapine, quetiapine, bupropion, citalopram, and escitalopram) that may be useful for increasing remission in OUD in the absence of buprenorphine or methadone. Additionally, our results identify psychiatric medications that when taken alongside buprenorphine and methadone improve remission rates. CONCLUSION: These results provide medication options that may be useful in treating OUD as well as integrated therapies to treat comorbid mental illness.
Asunto(s)
Buprenorfina , Trastornos Relacionados con Opioides , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Tratamiento de Sustitución de Opiáceos/métodos , Trastornos Relacionados con Opioides/epidemiología , Metadona/uso terapéutico , Buprenorfina/uso terapéutico , Comorbilidad , Analgésicos Opioides/uso terapéuticoRESUMEN
OBJECTIVE: To examine the impact of race/ethnicity on timing and postoperative outcomes of primary cleft lip (CL) and cleft palate (CP) repair. DESIGN: Cross-sectional analysis of the National Surgical Quality Improvement Program Pediatric (NSQIP-P) database from 2013 to 2018. PATIENTS AND MAIN OUTCOME MEASURES: Patients under 2 years of age who underwent primary CL or CP repair were identified in the NSQIP-P. Outcomes were the timing of surgery and 30-day readmission and reoperation rates stratified by race and ethnicity. RESULTS: In total, 6021 children underwent CL and 6938 underwent CP repair. Adjusted rates of CL repair over time were 10% lower in Hispanic children (95%CI: 0.84-0.96) and 38% lower for Asian children (95%CI: 0.55-0.70) compared with White infants. CP repair rates over time were 13% lower in Black (95%CI: 0.79-0.95), 17% lower in Hispanic (95%CI: 0.77-0.89), and 53% lower in Asian children (95%CI: 0.43-0.53) than in White infants. Asian patients had the highest rates of delayed surgical repair, with 19.3% not meeting American Cleft Palate-Craniofacial Association (ACPA) guidelines for CL (P < .001) and 28.2% for CP repair (P< .001). Black and Hispanic children had 80% higher odds of readmission following primary CL repair (95%CI: 1.16-2.83 and 95%CI: 1.27-2.61, respectively). CONCLUSIONS: This study of a national database identified several racial/ethnic disparities in primary CL and CP, with reduced receipt of cleft repair over time for non-White children. Asian patients were significantly more likely to have delayed cleft repair per ACPA guidelines. These findings underscore the need to better understand disparities in cleft repair timing and postoperative outcomes.
Asunto(s)
Labio Leporino , Fisura del Paladar , Lactante , Humanos , Niño , Estados Unidos , Fisura del Paladar/cirugía , Labio Leporino/cirugía , Estudios Transversales , Reoperación , Complicaciones Posoperatorias/cirugíaRESUMEN
OBJECTIVE: Describe the first hybrid global simulation-based comprehensive cleft care workshop, evaluate impact on participants, and compare experiences based on in-person versus virtual attendance. DESIGN: Cross-sectional survey-based evaluation. SETTING: International comprehensive cleft care workshop. PARTICIPANTS: Total of 489 participants. INTERVENTIONS: Three-day simulation-based hybrid comprehensive cleft care workshop. MAIN OUTCOME MEASURES: Participant demographic data, perceived barriers and interventions needed for global comprehensive cleft care delivery, participant workshop satisfaction, and perceived short-term impact on practice stratified by in-person versus virtual attendance. RESULTS: The workshop included 489 participants from 5 continents. The response rate was 39.9%. Participants perceived financial factors (30.3%) the most significant barrier and improvement in training (39.8%) as the most important intervention to overcome barriers facing cleft care delivery in low to middle-income countries. All participants reported a high level of satisfaction with the workshop and a strong positive perceived short-term impact on their practice. Importantly, while this was true for both in-person and virtual attendees, in-person attendees reported a significantly higher satisfaction with the workshop (28.63 ± 3.08 vs 27.63 ± 3.93; P = .04) and perceived impact on their clinical practice (22.37 ± 3.42 vs 21.02 ± 3.45 P = .01). CONCLUSION: Hybrid simulation-based educational comprehensive cleft care workshops are overall well received by participants and have a positive perceived impact on their clinical practices. In-person attendance is associated with significantly higher satisfaction and perceived impact on practice. Considering that financial and health constraints may limit live meeting attendance, future efforts will focus on making in-person and virtual attendance more comparable.
Asunto(s)
Labio Leporino , Fisura del Paladar , Humanos , Fisura del Paladar/terapia , Labio Leporino/terapia , Estudios Transversales , Cabeza , Satisfacción PersonalRESUMEN
Microviridins, tricyclic peptide natural products originally isolated from cyanobacteria, function as inhibitors of diverse serine-type proteases. Here we report the structure and biochemical characterization of AMdnB, a unique iterative macrocyclase involved in a microviridin biosynthetic pathway from Anabaena sp. PCC 7120. The ATP-dependent cyclase, along with the homologous AMdnC, introduce up to nine macrocyclizations on three distinct core regions of a precursor peptide, AMdnA. The results presented here provide structural and mechanistic insight into the iterative chemistry of AMdnB. In vitro AMdnB-catalyzed cyclization reactions demonstrate the synthesis of the two predicted tricyclic products from a multi-core precursor peptide substrate, consistent with a distributive mode of catalysis. The X-ray structure of AMdnB shows a structural motif common to ATP-grasp cyclases involved in RiPPs biosynthesis. Additionally, comparison with the noniterative MdnB allows insight into the structural basis for the iterative chemistry. Overall, the presented results provide insight into the general mechanism of iterative enzymes in ribosomally synthesized and post-translationally modified peptide biosynthetic pathways.