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Traumatic optic neuropathy (TON) is a devastating condition that can occur after blunt or penetrating trauma to the head, leading to visual impairment or blindness. Despite these debilitating effects, no clinically available therapeutic targets neuroprotection or promotes axon regeneration in this or any optic neuropathy. Limited data in large-animal models are a major obstacle to advancing treatments toward clinical therapeutics. To address this issue, we refined a surgical model of TON in Yucatan minipigs. First, we validated the model by demonstrating visual impairment by flash visual-evoked potential and retinal ganglion cell degeneration and death. Next, we developed and optimized a delivery method and nontoxic dosing of intravitreal brain-derived neurotrophic factor (BDNF) and cAMP. Finally, we showed that intravitreal injection of BDNF and cAMP rescued visual function and protected against retinal ganglion cell death and optic nerve axon degeneration. Together these data in a preclinical large-animal model advance our understanding of and ability to model TON and further identify and develop candidate clinical therapeutics.
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Factor Neurotrófico Derivado del Encéfalo , Traumatismos del Nervio Óptico , Animales , Porcinos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Traumatismos del Nervio Óptico/tratamiento farmacológico , Axones/metabolismo , Neuroprotección , Regeneración Nerviosa , Porcinos Enanos/metabolismo , Trastornos de la VisiónRESUMEN
Transition of arterial smooth muscle (ASM) from a quiescent, contractile state to a growth-promoting state is a hallmark of cardiovascular disease (CVD), a leading cause of death and disability in the United States and worldwide. While many individual signals have been identified as important mechanisms in this phenotypic conversion, the combined impact of the transcription factors Smad3 and FoxO3 in ASM growth is not known. The purpose of this study was to determine that a coordinated, phosphorylation-specific relationship exists between Smad3 and FoxO3 in the control of ASM cell growth. Using a rat in vivo arterial injury model and rat primary ASM cell lysates and fractions, validated low and high serum in vitro models of respective quiescent and growth states, and adenoviral (Ad-) gene delivery for overexpression (OE) of individual and combined Smad3 and/or FoxO3, we hypothesized that FoxO3 can moderate Smad3-induced ASM cell growth. Key findings revealed unique cellular distribution of Smad3 and FoxO3 under growth conditions, with induction of both nuclear and cytosolic Smad3 yet primarily cytosolic FoxO3; Ad-Smad3 OE leading to cytosolic and nuclear expression of phosphorylated and total Smad3, with almost complete reversal of each with Ad-FoxO3 co-infection in quiescent and growth conditions; Ad-FoxO3 OE leading to enhanced cytosolic expression of phosphorylated and total FoxO3, both reduced with Ad-Smad3 co-infection in quiescent and growth conditions; Ad-FoxO3 inducing expression and activity of the ubiquitin ligase MuRF-1, which was reversed with concomitant Ad-Smad3 OE; and combined Smad3/FoxO3 OE reversing both the pro-growth impact of singular Smad3 and the cytostatic impact of singular FoxO3. A primary takeaway from these observations is the capacity of FoxO3 to reverse growth-promoting effects of Smad3 in ASM cells. Additional findings lend support for reciprocal antagonism of Smad3 on FoxO3-induced cytostasis, and these effects are dependent upon discrete phosphorylation states and cellular localization and involve MuRF-1 in the control of ASM cell growth. Lastly, results showing capacity of FoxO3 to normalize Smad3-induced ASM cell growth largely support our hypothesis, and overall findings provide evidence for utility of Smad3 and/or FoxO3 as potential therapeutic targets against abnormal ASM growth in the context of CVD.
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OBJECTIVES: Xylazine is a tranquilizer commonly added into the illicit drug supply and a likely contributor to overdoses because it does not respond to naloxone reversal. The objective of this study was to perform a retrospective data analysis on xylazine-positive samples collected from patients in various outpatient healthcare settings to illustrate geographic distribution and common copositive substances, which may also contribute to risk of adverse events. METHODS: Samples for which providers ordered testing for xylazine were subjected to enzymatic hydrolysis, extracted, and analyzed using liquid chromatography-tandem mass spectrometry. Retrospective analysis was performed on xylazine-positive samples collected from April 2021 to March 2022, to include geographic location and copositive substances. RESULTS: Xylazine was identified in 413 of 59,498 samples from adults aged 20-73 years and originated from 25 of the 39 states where xylazine testing was ordered. The most common routine substances detected with xylazine were fentanyl, buprenorphine, naloxone, cocaine, d -methamphetamine, and delta-9-tetrahydrocannabinol. The most common designer drugs detected included fentanyl analogs, isotonitazene, and designer benzodiazepines. CONCLUSIONS: Xylazine is geographically spread throughout the United States, indicative of a wide incorporation into the illicit drug supply. These findings differ from previous studies in that these samples originated from healthcare providers in routine care settings, where other reports typically involve overdose deaths. This analysis illustrates that routine testing for xylazine in outpatient settings can afford providers the opportunity to educate individuals and adjust harm reduction measures to potentially mitigate overdose risk.
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Sobredosis de Droga , Drogas Ilícitas , Adulto , Humanos , Estados Unidos/epidemiología , Xilazina , Estudios Retrospectivos , Fentanilo , Naloxona , Atención a la Salud , Analgésicos OpioidesRESUMEN
BACKGROUND: Acute kidney injury is a low-volume, high-risk complication in trauma patients and is associated with prolonged hospital length of stay and increased mortality. Yet, no audit tools exist to evaluate acute kidney injury in trauma patients. OBJECTIVE: This study aimed to describe the iterative development of an audit tool to evaluate acute kidney injury following trauma. METHODS: Our performance improvement nurses developed an audit tool to evaluate acute kidney injury in trauma patients using an iterative, multiphase process conducted from 2017 to 2021, which included a review of our Trauma Quality Improvement Program data, trauma registry data, literature review, multidisciplinary consensus approach, retrospective and concurrent review, and continuous audit and feedback for piloted and finalized versions of the tool. RESULTS: The final acute kidney injury audit tool can be completed within 30 min using data obtained from the electronic medical record and consists of six sections, including identification criteria, source potential causes, source treatment, acute kidney injury treatment, dialysis indications, and outcome status. CONCLUSION: The iterative development and testing of an acute kidney injury audit tool improved the uniform data collection, documentation, audit, and feedback of best practices to positively impact patient outcomes.
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Lesión Renal Aguda , Humanos , Estudios Retrospectivos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Recolección de Datos , Documentación , Registros Electrónicos de SaludRESUMEN
The activity of monoamine oxidase enzymes may be quantified by measuring the conversion of a radiolabeled amine substrate to a radiolabeled product that occurs during incubation of the substrate with the enzyme in an aqueous buffer. Described herein is an established discontinuous procedure in which separation of the substrate and product is achieved by extracting uncharged aldehydes into an organic solvent, while cationic amines remain in an acidified aqueous layer. Under assay conditions designed to ensure a pseudo-linear catalytic rate for the duration of the incubation, determination of radioactivity in the organic solvent by liquid scintillation counting facilitates estimation of an initial rate for amine turnover.
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Aminas , Monoaminooxidasa , Aldehídos , Cinética , Monoaminooxidasa/metabolismo , Radiofármacos , SolventesRESUMEN
Designed to measure binding interactions between small molecules and receptor proteins, radioligand binding approaches may also be applied to interactions between monoamine oxidase (MAO) and its ligands. The technique may be used with tissue homogenates or with mitochondrial membranes and can provide information about binding site density, ligand affinity, binding rate constants, and binding events at sites that do not impact absorbance characteristics of the flavin cofactor and that may not be amenable to spectrophotometric studies. This overview describes the use of a cell harvester in a common filtration approach to measure binding to MAO of radiolabeled substrates, inhibitors, or allosteric ligands in saturation analyses and to take advantage of the principles of competition to obtain quantitative binding data for unlabeled ligands that may bind with much lower affinity. The quality and reproducibility of data are impacted by factors such as choice of ligand concentrations, pipetting technique, graphing and regression approaches, and scintillation counting parameters, and consideration is given to these and other factors that may influence the results.
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Inhibidores de la Monoaminooxidasa , Monoaminooxidasa , Sitios de Unión , Flavinas/metabolismo , Ligandos , Monoaminooxidasa/metabolismo , Inhibidores de la Monoaminooxidasa/metabolismo , Inhibidores de la Monoaminooxidasa/farmacología , Ensayo de Unión Radioligante , Reproducibilidad de los ResultadosRESUMEN
Total knee arthroplasty (TKA) results in substantial improvement for most patients with end-stage arthritis of the knee; however, approximately 20% of patients have an unsatisfactory result. Although many problems contributing to an unsatisfactory result after TKA are best addressed by revision TKA, some problems may be effectively addressed with arthroscopic treatment. The categories of pathology that can be addressed arthroscopically include peripatellar soft-tissue impingement (patellar clunk syndrome and patellar synovial hyperplasia), arthrofibrosis, and popliteus tendon dysfunction. Recognizing these disease entities and the role of arthroscopic surgery in the treatment of these lesions may be helpful in achieving a good outcome in certain patients who are unsatisfied with their knee arthroplasty.
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Artroplastia de Reemplazo de Rodilla , Artropatías , Humanos , Artroscopía/métodos , Articulación de la Rodilla , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artropatías/etiología , Rótula/cirugíaRESUMEN
INTRODUCTION: Hepatic encephalopathy (HE) is a debilitating symptom of end-stage liver disease (ESLD), but there remains a paucity of evidence regarding its impact on nutritional status, nutritional intake, compliance with nutritional support and resultant muscle health and function. Malnutrition and sarcopenia are associated with increased morbidity and mortality in patients with ESLD. The aim of the current case-control study is to prospectively investigate the impact of HE on nutritional intake and sarcopenia status in patients with ESLD. METHODS AND ANALYSIS: Patients with ESLD, with HE (n=10) and without HE (n=10) will be recruited at the outpatient liver unit, University Hospital Birmingham, UK. All patients will undergo clinical assessment at baseline and again at 6-8 weeks (in-line with their routine clinical follow-up), to assess the impact of HE on reported nutritional intake, nutritional status and sarcopenia/physical functional status. Standard medical, dietetic and home-based exercise physiotherapy care will continue for all participants as determined by their clinical team. Two methods of assessing nutritional intake will include the 24-hour food recall and 3-day food diaries. Assessment of sarcopenia status will be undertaken using anthropometry (mid-arm muscle circumference (MAMC)) and ultrasound imaging of the quadriceps muscle group. Markers of physical function (hand grip strength; chair rise time), frailty (Liver Frailty Index (LFI)), physical activity (accelerometery) and exercise capacity (Duke Activity Status Index (DASI)) will be assessed at both clinic visits. ETHICS AND DISSEMINATION: The study is approved by Wales Research Ethics Committee 2 and Health Research Authority (REC reference: 21/WA/0216). Recruitment into the study commenced November 2021. The findings will be disseminated through peer-reviewed publications and international presentations. TRIAL REGISTRATION NUMBER: RRK7156.
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Enfermedad Hepática en Estado Terminal , Fragilidad , Encefalopatía Hepática , Sarcopenia , Humanos , Femenino , Animales , Sarcopenia/complicaciones , Enfermedad Hepática en Estado Terminal/complicaciones , Estudios Prospectivos , Fuerza de la Mano , Estudios de Casos y Controles , Fragilidad/complicaciones , Fragilidad/diagnóstico , Pollos , Ingestión de AlimentosRESUMEN
INTRODUCTION: The most impactful resolutions of the Patient Protection and Affordable Care Act (ACA) took effect on January 1, 2014. The clinical and economic effects are widely experienced by orthopaedic surgeons, but are not well quantified. We proposed to evaluate the effect of the ACA on the timing of MRI for knee pathology before and after implementation of the legislation. METHODS: We conducted a retrospective analysis of all knee MRIs done at our institution from 2011 to 2016 (3 years before and after ACA implementation). The MRI completion time was calculated by comparing the dates of initial clinical evaluation and MRI completion. The groups were subdivided based on insurance payer status (Medicare, Medicaid, and commercial payers). The cohorts were compared to determine differences in average completion time and completion rates at time intervals from initial clinic visit before and after ACA implementation. RESULTS: MRI scans of 5,543 knees were included, 3,157 (57%) before ACA implementation and 2,386 (43%) after. There was a 5.6% increase in Medicaid cohort representation after ACA implementation. Patients waited 14 days longer for MRIs after ACA implementation (116 versus 102 days). There were increased completion times for patients in the commercial payer (113 versus 100 days) and Medicaid (131 versus 96 days) groups. Fewer patients had received MRI after ACA implementation within 2, 6, and 12 weeks of their initial clinic visits. DISCUSSION: The time between initial clinical evaluation and MRI scan completion for knee pathology markedly increased after ACA implementation, particularly in the commercial payer and Medicaid cohorts. Additional studies are needed to determine the effect of longer wait times on patient satisfaction, delayed treatment, and increased morbidity. As healthcare policy changes continue, their effects on orthopaedic patients and providers should be closely scrutinized. LEVEL OF EVIDENCE: Level III-Retrospective cohort study.
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Pacientes no Asegurados , Patient Protection and Affordable Care Act , Humanos , Anciano , Estados Unidos , Estudios Retrospectivos , Medicare , Cobertura del Seguro , Imagen por Resonancia MagnéticaRESUMEN
This article is a clinical guide which discusses the "state-of-the-art" usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion-this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy-while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward "bridging" methods that may be used to transition simply and safely from other antidepressants to MAOIs.
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Background and study aims The management of functional biliary-type pain remains a clinical challenge. Intra sphincteric botulinum toxin putatively exerts an anti-spasmodic and anti-nociceptive effect. The objective of this study was to examine the clinical response to intra sphincteric botulinum toxin in patients with functional biliary-type pain. Patients and methods This was a cross-sectional (hypothesis-generating) study of prospectively collected data from patients referred to a tertiary center from 2014 to 2019. The efficacy of ampullary botulinum toxin injection for relief of pain was recorded at post-procedure outpatient review. Opioid analgesia, neuromodulatory medication, and frequency of hospital admissions were recorded. Results A total of 119 consecutive patients (109 women, 10 men, mean age 45 years; range 17-77) underwent 411 intra-sphincteric botulinum toxin injection procedures (mean 2 procedures; range 1-15). A total of 103 patients (87â%) had a significant improvement in pain on post-procedure review and 77â% and 76â% of patients were opioid and admission free, respectively. Of the patients, 59â% were prescribed tricyclic antidepressants (amitriptyline), 18â% duloxetine, 13â% pregabalin, and 3â% mirtazapine. Loss of response with the initial dose of botulinum toxin occurred in 56â% of patients. Pain control was reestablished in 80â% of patients in this cohort following botulinum toxin injection at a higher dose. Conclusions These data suggest that botulinum toxin may improve outcomes in patients with functional biliary pain. Further controlled studies are needed to clarify the role of Botox and neuromodulatory agents.
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OBJECTIVES: The illicit drug market continuously evolves, with new substances introduced to mimic prescription or other illicit drugs while evading detection by routine drug testing. The objective was to determine if designer benzodiazepines would be present in urine samples collected from patients in various healthcare settings. METHODS: Samples for which providers ordered testing for prescription benzodiazepines during the study period were diluted, subjected to enzymatic hydrolysis, and analyzed using liquid chromatography- tandem mass spectrometry. In addition to prescription benzodiazepines, samples were also analyzed for presence of any of the following designer benzodiazepines: etizolam, diclazepam, delorazepam, lormetazepam, flubromazepam, flubromazolam, and phenazepam. RESULTS: Of 38,073 samples tested, 40 samples contained a designer benzodiazepine and/or a metabolite. Of the 40 samples, 19 (47.5%) also tested positive for a prescription benzodiazepine. Twenty-one samples (52.5%) did not test positive for a prescription benzodiazepine, which would result in undetected benzodiazepine use had only traditional definitive testing methods been employed. Thirty-three (82.5%) samples contained an opioid, including 22 (55%) positive for buprenorphine and/or methadone. CONCLUSIONS: The potential harms from the use of designer benzodiazepines are widely unknown due to the lack of traditional pharmacokinetic studies and good manufacturing processes. Our analysis shows that when a designer benzodiazepine was present, over 80% of samples also contained an opioid or a prescription benzodiazepine, which may increase the risk of a drug interaction or adverse drug event. Providers may benefit from knowledge of their patients' designer benzodiazepine use when formulating risk mitigation strategies as part of a treatment plan.
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Drogas de Diseño , Drogas Ilícitas , Analgésicos Opioides , Benzodiazepinas , Cromatografía Liquida/métodos , Atención a la Salud , HumanosRESUMEN
Phenelzine (PLZ) is a monoamine oxidase (MAO)-inhibiting antidepressant with anxiolytic properties. This multifaceted drug has a number of pharmacological and neurochemical effects in addition to inhibition of MAO, and findings on these effects have contributed to a body of evidence indicating that PLZ also has neuroprotective/neurorescue properties. These attributes are reviewed in this paper and include catabolism to the active metabolite ß-phenylethylidenehydrazine (PEH) and effects of PLZ and PEH on the GABA-glutamate balance in brain, sequestration of reactive aldehydes, and inhibition of primary amine oxidase. Also discussed are the encouraging findings of the effects of PLZ in animal models of stroke, spinal cord injury, traumatic brain injury, and multiple sclerosis, as well other actions such as reduction of nitrative stress, reduction of the effects of a toxin on dopaminergic neurons, potential anticonvulsant actions, and effects on brain-derived neurotrophic factor, neural cell adhesion molecules, an anti-apoptotic factor, and brain levels of ornithine and N-acetylamino acids.
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Antidepresivos , Inhibidores de la Monoaminooxidasa , Fármacos Neuroprotectores , Fenelzina , Animales , Antidepresivos/farmacología , Monoaminooxidasa/metabolismo , Inhibidores de la Monoaminooxidasa/farmacología , Fármacos Neuroprotectores/farmacología , Fenelzina/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND AND AIMS: Alcoholic hepatitis (AH) is a severe condition with poor short-term prognosis. Specific treatment with corticosteroids slightly improves short-term survival but is associated with infection and is not used in many centers. A reliable method to identify patients who will recover spontaneously will minimise the numbers of patients who experience side effects of available treatments. METHODS: We analysed the trajectory of serum bilirubin concentration over the course of hospital admissions in patients with AH to predict spontaneous survival and the need for treatment. RESULTS: data from 426 patients were analysed. Based on bilirubin trajectory, patients were categorized into three groups: 'fast fallers' (bilirubin <0.8 x admission value at day 7), 'static' (bilirubin of >0.9 - <1.2 x admission value) and 'rapid risers' (bilirubin of ≥1.2 x admission bilirubin). Fast fallers had significantly better 90-day survival compared to other groups (log rank p < .001), and showed no benefit of corticosteroid therapy (OR for survival at 28 days of treatment, 0.94, 95% CI 0.06 - 8.41). These findings remained even amongst patients with severe disease based on initial DF, GAHS or MELD scores. CONCLUSIONS: We present an intuitive method of classifying patients with AH based on the trajectory of bilirubin over the first week of admission. It is complimentary to existing scores that identify candidates for corticosteroid treatment or assess response to treatment. This method identifies a group of patients with AH who recover spontaneously and can avoid corticosteroid therapy.
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Hepatitis Alcohólica , Bilirrubina , Estudios de Cohortes , Hepatitis Alcohólica/complicaciones , Hepatitis Alcohólica/diagnóstico , Hepatitis Alcohólica/tratamiento farmacológico , Humanos , Pruebas de Función Hepática , Pronóstico , Índice de Severidad de la EnfermedadRESUMEN
Liver disease, of which liver cirrhosis is the most advanced stage, constitutes the fourth most common cause of life-years lost in men and women younger than 75 years in England, where mortality rates from liver disease have increased by 25% in the past decade. Alcohol consumption is the most common modifiable risk factor for disease progression in these individuals, but within the UK, there is substantial variation in the distribution, prevalence, and outcome of alcohol-related liver disease, and no equity of access to tertiary transplantation services. These revised recommendations were agreed by an expert panel convened by the UK Liver Advisory Group, with the purpose of providing consensus on referral for transplant assessment in patients with alcohol-related disease, and clarifying the terminology and definitions of alcohol use in liver injury. By standardising clinical management in these patients, it is hoped that there will be an improvement in the quality of care and better access to liver transplant assessment for patients with alcohol-related liver disease in the UK.
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Hepatopatías Alcohólicas/cirugía , Trasplante de Hígado/normas , Derivación y Consulta/normas , Toma de Decisiones Clínicas/métodos , Accesibilidad a los Servicios de Salud/normas , Disparidades en Atención de Salud , Humanos , Hepatopatías Alcohólicas/diagnóstico , Selección de Paciente , Reino UnidoRESUMEN
BACKGROUND: Lassa fever (LF) is a viral haemorrhagic fever endemic in West Africa. Lassa virus is maintained in and spread to humans from rodents, with occasional secondary human-to-human transmission. Present recommendations for personal protective equipment (PPE) for care of patients with LF generally follow those for filovirus diseases. However, the need for such high-level PPE for LF, which is thought to be considerably less transmissible between humans than filoviruses, is unclear. AIM: In Nigerian Lassa Treatment Centres (LTCs) we aimed to describe current PPE practices, identify barriers and facilitators to implementation of existing guidance, and assess healthcare workers' understanding. This would inform the development of future PPE guidelines for LF. METHODS: We performed a mixed-methods study, including short cross-sectional surveys of PPE used in LTCs, observations of practice, and in-depth interviews with key informants. We described the quantitative data and we conducted a thematic analysis of qualitative data. FINDINGS: Our survey of 74 HCWs found that approximately half reported problems with recommended PPE. In three LTCs PPE was used highly variably. Full PPE, as recommended in Nigeria CDC guidelines, was used in less than a quarter (21%) of interactions. In-depth interviews suggested this was based on availability and HCWs' own risk assessments. CONCLUSION: Without specific guidance on Lassa, the current approach is both resource and labour-intensive, where these are both limited. This has led to low adherence by health care workers, whose own experience indicates lower risk. The evidence-base to inform PPE required for LF must be improved to inform a more tailored approach.
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Displaced greater tuberosity fractures of the humerus require anatomic reduction with stable fixation to optimize rotator cuff function and prevent subacromial impingement. A wide variety of surgical approaches and fixation constructs have been reported, largely with favorable results. Arthroscopic management of these fractures allows excellent visualization with strong suture anchor fixation while minimizing soft tissue disruption, blood loss, and radiation exposure. The purpose of this article is to describe an arthroscopic technique for reduction and suture-anchor fixation of displaced greater tuberosity fractures.
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Current strategies to address corneal surface defects are insufficient to successfully resolve damage caused by injury and/or disease. To address this issue, we have developed an ocular wound chamber (OWC) that creates a fluid-filled environment by encompassing damaged ocular and periocular tissues allowing for the continuous delivery of therapeutics. This study tested human platelet lysate (hPL) as a treatment for corneal epithelial defects when used with the OWC. Corneal epithelial injuries were created in anesthetized guinea pigs by debridement of the central cornea. An OWC was placed over the injured eye and animals randomly grouped followed by injection of either 20% hPL, 100% hPL, or vehicle (balanced salt solution, BSS) into the chamber. Eyes were assessed at 0, 24, 48, and 72 h using intraocular pressure (IOP), optical coherence tomography (OCT), and fluorescein imaging. Whole globes were histologically processed, and hematoxylin and eosin (H&E) stained. No differences in IOP were recorded as a result of corneal wounding, chamber placement, and/or therapeutic application. OCT images demonstrated increased corneal swelling at 48 h and 72 h in the vehicle group compared to 20% hPL. Fluorescein staining showed increased corneal re-epithelialization in the 20% and 100% hPL groups at 48 h compared to vehicle only. H&E staining revealed increased stromal cellular infiltrate in the BSS group. This study demonstrates the delivery of hPL via the OWC improves corneal re-epithelialization and supports the expanded usage of the chamber in combination with hPL to manage a variety of corneal surface injuries, diseases and/or periocular conditions.
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Plaquetas/metabolismo , Lesiones de la Cornea/terapia , Epitelio Corneal/lesiones , Repitelización/fisiología , Cicatrización de Heridas , Animales , Lesiones de la Cornea/patología , Epitelio Corneal/patología , Humanos , Tomografía de Coherencia ÓpticaRESUMEN
OBJECTIVE: Refractory ascites is an established indication for liver transplantation. While transplantation is regarded as the definitive therapy for this condition, many patients are unsuitable due to comorbidity or frailty. Alternatives such as transjugular intrahepatic portosystemic shunt (TIPSS) and large-volume paracentesis can lead to complications, including encephalopathy, circulatory and renal dysfunction, and protein-calorie deficiency that may accelerate sarcopenia. Cost and complication rates limit therapies such as alfapump. While there are data to support the use of indwelling catheters in the management of patients with malignant ascites, there is limited evidence to support their routine use in the context of end-stage liver cirrhosis. Here we describe our centres' experience using indwelling tunnelled ascitic drains over a 6-year period. METHODS: A retrospective review of data (January 2012-May 2018) was undertaken for all patients with refractory ascites who underwent a tunnelled ascitic drain. Demographics, disease aetiology, procedure data and follow-up data were obtained through interrogation of electronic records and reports. RESULTS: Twenty-five drains were placed. All procedures were technically successful with no immediate complications. Six patients were readmitted following their index admission with abdominal pain and suspected infected ascites (although only two had a positive ascitic fluid culture). There were three cases of abdominal wall cellulitis and three of leakage around the tunnel site; all managed conservatively. CONCLUSION: Indwelling drains appear an effective strategy for palliative management of select patients with liver cirrhosis complicated by refractory ascites who are not amenable to undergo TIPSS or transplantation. While complications can occur, these are most usually minor and can be managed on an outpatient basis.
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Organizing pneumonia is characterized by a distinct histologic pattern in the lung interstitium and presents clinically as hypoxemia, fever, cough, and dyspnea that is not attributable to concurrent infection. Typical etiologies of this condition include inflammatory disease, malignancy, toxic inhalation, and an array of medications including the mTOR inhibitor everolimus. In this report, we describe the case of a female with tuberous sclerosis complex on everolimus therapy for renal angiomyolipomas who presented to the hospital with persistent cough, dyspnea, and fevers and bilateral lower lobe opacities on chest X-ray despite multiple courses of antibiotic therapy. Bronchoscopy was performed with transbronchial biopsies, and results demonstrated a lymphocytic predominance and pathologic findings of intraluminal plugs composed of fibroblasts and myofibroblasts consistent with organizing pneumonia. Everolimus therapy was discontinued and patient completed a steroid course with resolution of symptoms. To our knowledge, this is the first published case of organizing pneumonia secondary to everolimus in a patient with tuberous sclerosis complex.