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BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a revolutionary procedure for severe aortic stenosis. The coexistence of chronic kidney disease (CKD) and TAVR introduces a challenge that significantly impacts patient outcomes. AIM: To define readmission rates, predictors, and causes after TAVR procedure in CKD stage 1-4 patients. METHODS: We used the national readmission database 2018 and 2020 to look into readmission rates, causes and predictors after TAVR procedure in patients with CKD stage 1-4. RESULTS: Out of 24758 who underwent TAVR and had CKD, 7892 (32.4%) patients were readmitted within 90 days, and had higher adjusted odds of being females (adjusted odds ratio: 1.17, 95%CI: 1.02-1.31, P = 0.02) with longer length of hospital stay > 6 days, and more comorbidities including but not limited to diabetes mellitus, anemia, and congestive heart failure (CHF). CONCLUSION: Most common causes of readmission included CHF (18.0%), sepsis, and complete atrioventricular block. Controlling readmission predictors with very close follow-up is warranted to prevent such high rate of readmission.
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Hydrogels, typically favored for 3D printing due to their viscoelasticity, are now trending toward ecofriendly alternatives amid growing environmental concerns. In this study, we crafted cellulose-based hydrogels, specifically employing cellulose acetate sulfate (CAS). By keeping the acetyl group substitution degree (DSacetyl = 1.8) and CAS molecular weight constant, we varied rheological properties by adjusting sulfate group substitution (DSsulfate = 0.4, 0.7, and 1.0) and CAS concentration (2-5 wt %). Rheological characterizations, including shear-thinning, yield stress, and thixotropy, were performed to identify optimal conditions for formulating CAS hydrogel ink in direct ink writing for 3D printing under selected experimental conditions. Based on rheological findings, CAS hydrogels with DSsulfate 0.7 and concentration of 4 wt % was used for 3D printing, with subsequent evaluation of printing metrics. Additionally, the effect of ionic cross-linking using Ca2+ ions on the structural integrity of 3D-printed structures was evaluated, demonstrating effective preservation through reinforced polymer networks. The shrinking and swelling behaviors of the 3D-printed structures were also significantly affected by this ionic cross-linking. Building on these findings, this work could broaden the range of cellulose derivatives available for the preparation of cellulose-based hydrogels for 3D printing.
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Tuberculosis remains a significant global health pandemic. There is an urgent need for new anti-tubercular agents to combat the rising incidence of drug resistance and to offer effective and additive therapeutic options. High-throughput screening of a subset of the NatureBank marine fraction library (n = 2000) identified a sample derived from an Australian marine sponge belonging to the order Haplosclerida that displayed promising anti-mycobacterial activity. Bioassay-guided fractionation of the organic extract from this Haplosclerida sponge led to the purification of previously identified antimicrobial pyrrole alkaloids, axinellamines A (1) and B (2). The axinellamine compounds were found to have a 90% minimum inhibitory concentration (MIC90) of 18 µM and 15 µM, respectively. The removal of protein and complex carbon sources reduced the MIC90 of 1 and 2 to 0.6 and 0.8 µM, respectively. The axinellamines were not toxic to mammalian cells at 25 µM and significantly reduced the intracellular bacterial load by >5-fold. These data demonstrate that axinellamines A and B are effective anti-tubercular agents and promising targets for future medicinal chemistry efforts.
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Antituberculosos , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis , Poríferos , Antituberculosos/farmacología , Antituberculosos/química , Antituberculosos/aislamiento & purificación , Animales , Mycobacterium tuberculosis/efectos de los fármacos , Humanos , Alcaloides/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Tuberculosis/tratamiento farmacológico , Tuberculosis/microbiología , Pirroles/farmacología , Pirroles/química , Pirroles/aislamiento & purificaciónRESUMEN
BACKGROUND: Aortic valve calcification(AVC) is prognostic in patients with aortic stenosis(AS). We assessed the AVC prognostic value in nonsevere AS patients. METHODS AND RESULTS: We conducted a retrospective study of 395 patients with nonsevere AS, LV ejection fraction ≥50%. The Agatston method was used for computed tomography AVC assessment. The log-rank test determined the best AVC cutoffs for survival under medical surveillance: 1185â AU in men and 850 in women, lower than the established-cutoffs for severe AS(2064AU in men and 1274 in women). Patients were divided into three AVC groups based on these cutoffs: low(<1185â AU men and <850 women), sub-severe(1185-2064AU men and 850-1274 women) and severe(>2064AU men and >1274 women). Of 395 patients(mean age 73 ± 12 years, 60.5% men, aortic valve area 1.23 ± 0.30cm2, mean pressure gradient 28 ± 8â mmHg), 218 underwent aortic valve intervention(AVI) and 158 deaths occurred during follow-up, 82 before AVI. Median survival time under medical surveillance was 2.1[0.7-4.9]years. Compared to the low AVC group, both sub-severe and severe AVC groups had higher risk for all-cause death under medical surveillance after comprehensive adjustment including echocardiographic AS severity and coronary artery calcium score(all p ≤ 0.006); while mortality risk was similar between sub-severe and severe AVC groups(all p ≥ 0.2). This mortality risk pattern persisted in the overall survival analysis after adjustment for AVI. AVI was protective of all-cause death in the sub-severe and severe AVC(all p ≤ 0.01), but not in the low AVC groups. CONCLUSIONS: Sub-severe AVC is a robust risk-stratification parameter in patients with nonsevere AS and may inform AVI timing.
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Hesperidin, a bioactive flavanone glycoside prevalent in citrus fruits, with remarkable therapeutic properties stands out as a formidable defender against the debilitating reproductive toxicity associated with Cyclophosphamide (CYP) chemotherapy. This study explores the protective potential of hesperidin (HSP@100 mg/kg b.wt PO daily) against CYP-induced (@ 40 mg/kg b.wt IP once in a week) reproductive toxicity in male Wistar rats as several studies were documented on single dose toxicity of CYP. In this experiment, we chose multidosage drug effects, which are more relevant in chemotherapy. Twenty-four rats were divided into four groups: Group 1 (Control), group 2 (CYP-treated), group 3 (HSP-treated), and group 4 (CYP + HSP-treated) for 28 days. The experimental design included assessments of relative testicular weight, semen analysis, testosterone levels, oxidative stress markers, inflammatory cytokines, gross and histopathological changes, and immunohistochemical evaluation. The results revealed that the administration of CYP led to a significant reduction in testicular weight, sperm count, motility, and testosterone levels, accompanied by increased oxidative stress and inflammatory response. Hesperidin co-administration demonstrated a protective effect by restoring these parameters to near-normal levels. Histopathological analysis revealed improved testicular architecture in the group 4 compared with the group 2. Oxidative stress indices indicated that hesperidin attenuated CYP-induced damage by reducing malondialdehyde levels, enhancing superoxide dismutase activity and maintaining glutathione levels. Similarly, inflammatory cytokine analysis demonstrated anti-inflammatory effects of hesperidin by reducing tumor necrosis factor-alpha (TNF-α) and elevating interleukin-10 (IL-10) levels in the group 4. Immunohistochemical evaluation of nuclear factor-kappa B (NF-κB) revealed increased inflammation in the CYP group, while hesperidin significantly reduced NF-κB expression, suggesting its anti-inflammatory properties.
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Gyroviruses are small single-stranded DNA (ssDNA) viruses that are largely associated with birds. Chicken anemia virus is the most extensively studied gyrovirus due to its disease impact on the poultry industry. However, we know much less about gyroviruses infecting other avian species. To investigate gyroviruses infecting waterfowl, we determined six complete genome sequences that fall into three gyrovirus groups, referred to as waterfowl gyrovirus 1 (n = 3), 2 (n = 2), and 3 (n = 1), in organs from hunter-harvested waterfowl from Arizona (USA). The waterfowl gyrovirus 1 variants were identified in multiple organs of a single American wigeon and represent a tentative new species. The waterfowl gyrovirus 2 variants were identified in the livers of two American wigeons and share >70% VP1 nucleotide sequence identity with gyrovirus 9, previously identified in the spleen of a Brazilian Pekin duck (MT318123) and a human fecal sample (KP742975). Waterfowl gyrovirus 3 was identified in a northern pintail spleen sample, and it shares >73% VP1 nucleotide sequence identity with two gyrovirus 13 sequences previously identified in Brazilian Pekin duck spleens (MT318125 and MT318127). These gyroviruses are the first to be identified in waterfowl in North America, as well as in American wigeons and northern pintails.
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Enfermedades de las Aves , Infecciones por Circoviridae , Genoma Viral , Gyrovirus , Filogenia , Animales , Arizona , Genoma Viral/genética , Gyrovirus/genética , Gyrovirus/clasificación , Gyrovirus/aislamiento & purificación , Enfermedades de las Aves/virología , Infecciones por Circoviridae/virología , Infecciones por Circoviridae/veterinaria , Anseriformes/virología , Patos/virología , ADN Viral/genéticaRESUMEN
OBJECTIVE: To evaluate the sensitivity and ability of computed tomography (CT) scan for diagnosing traumatic ankle arthrotomies compared with that of the saline load test (SLT). METHODS: Eleven cadaveric ankles were included in this study. Before intervention, a CT scan was obtained to confirm the absence of intra-articular air. Arthrotomies were created at the anterolateral, posterolateral, anteromedial, and posteromedial aspects of the ankle under fluoroscopic visualization. A postarthrotomy and postrange of motion CT scan was obtained to evaluate for the presence of intra-articular air. Each ankle then underwent a SLT with 60 mL of saline, where volumes provoking extravasation were recorded. RESULTS: Of the 11 included ankles, intra-articular air was detected in all 11 ankles by CT scan. All 11 ankles also demonstrated extravasation of saline through the arthrotomy site during SLT. Thus, the sensitivity for both CT scan and SLT for detecting ankle traumatic arthrotomy was 100%. The mean volume of saline needed for extravasation was 7.7 mL, with a range of 3-22 mL and a SD of 5.4. CONCLUSIONS: Given that CT scan was equally as sensitive to the SLT, this study presents good evidence that CT scan may be used for the detection of ankle traumatic arthrotomies.
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Tobillo , Cloruro de Sodio , Humanos , Inyecciones Intraarticulares , Tomografía Computarizada por Rayos X , CadáverRESUMEN
Microthecaline A (1), the known antiplasmodial quinoline serrulatane alkaloid from the roots of Eremophila microtheca F. Muell. ex Benth. (Scrophulariaceae), was targeted for isolation and subsequent use in the generation of a semisynthetic ether library. A large-scale extraction and isolation yielded the previously undescribed quinoline serrulatane microthecaline B (2), along with crystalline 1 that enabled the first X-ray crystallographic analysis to be undertaken on this rare alkaloid structure class. The X-ray diffraction analysis of 1 supported the absolute configuration assignment of microthecaline A, which was originally assigned by ECD data analysis. Microthecaline A (1) was converted into 10 new semisynthetic ether derivatives (3-12) using a diverse series of commercially available alkyl halides. Chemical structures of the new serrulatane alkaloid and semisynthetic ether analogues were assigned by spectroscopic and spectrometric analyses. Antiplasmodial evaluations of 1-12 showed that the semisynthetic derivative 5 elicited the most potent activity with an IC50 value of 7.2 µM against Plasmodium falciparum 3D7 (drug-sensitive) strain.
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Alcaloides , Antimaláricos , Plasmodium falciparum , Antimaláricos/farmacología , Antimaláricos/química , Antimaláricos/aislamiento & purificación , Alcaloides/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Plasmodium falciparum/efectos de los fármacos , Estructura Molecular , Eremophila (Planta)/química , Cristalografía por Rayos X , Quinolinas/farmacología , Quinolinas/química , Raíces de Plantas/química , Éteres/farmacología , Éteres/químicaRESUMEN
The known oxygenated polyhalogenated diphenyl ether, 2-(2',4'-dibromophenoxy)-3,5-dibromophenol (1), with previously reported activity in multiple cytotoxicity assays was isolated from the sponge Lamellodysidea sp. and proved to be an amenable scaffold for semisynthetic library generation. The phenol group of 1 was targeted to generate 12 ether analogues in low-to-excellent yields, and the new library was fully characterized by NMR, UV, and MS analyses. The chemical structures for 2, 8, and 9 were additionally determined via single-crystal X-ray diffraction analysis. All natural and semisynthetic compounds were evaluated for their ability to inhibit the growth of DU145, LNCaP, MCF-7, and MDA-MB-231 cancer cell lines. Compound 3 was shown to have near-equivalent activity compared to scaffold 1 in two in vitro assays, and the activity of the compounds with an additional benzyl ring appeared to be reliant on the presence and position of additional halogens.
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Antineoplásicos , Éter , Éteres/farmacología , Éteres de Etila , Éteres Fenílicos/farmacología , Antineoplásicos/farmacologíaRESUMEN
Medicines stewardship refers to coordinated strategies and interventions to optimise medicines use, usually within a specific therapeutic area. Medicines stewardship programs can reduce variations in practice and improve patient outcomes. Therapeutic domains for medicines stewardship are chosen to address frequently used drug classes associated with a high risk of adverse outcomes. Some examples include antimicrobial, opioid analgesic, anticoagulation and psychotropic stewardship. Common elements of successful stewardship programs include multidisciplinary leadership, stakeholder engagement, tailored communication strategies, behavioural changes, implementation science methodologies, and ongoing program monitoring, evaluation and reporting. Medicines stewardship is a continual quality improvement process that requires ongoing support and resources, as well as clinician and consumer engagement, to remain sustainable. It is critical for hospital-based medicines stewardship programs to consider impacts on care in the community when making and communicating changes to patient therapy. This ensures that stewardship efforts are sustained across transitions of care.
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INTRODUCTION: Middle-aged multidomain risk reduction interventions targeting modifiable risk factors for dementia may delay or prevent a third of dementia cases in later life. We describe the protocol of a cluster randomised controlled trial (cRCT), HAPPI MIND (Holistic Approach in Primary care for PreventIng Memory Impairment aNd Dementia). HAPPI MIND will evaluate the efficacy of a multidomain, nurse-led, mHealth supported intervention for assessing dementia risk and reducing associated risk factors in middle-aged adults in the Australian primary care setting. METHODS AND ANALYSIS: General practice clinics (n≥26) across Victoria and New South Wales, Australia, will be recruited and randomised. Practice nurses will be trained to implement the HAPPI MIND intervention or a brief intervention. Patients of participating practices aged 45-65 years with ≥2 potential dementia risk factors will be identified and recruited (approximately 15 patients/clinic). Brief intervention participants receive a personalised report outlining their risk factors for dementia based on Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) scores, education booklet and referral to their general practitioner as appropriate. HAPPI MIND participants receive the brief intervention as well as six individualised dementia risk reduction sessions with a nurse trained in motivational interviewing and principles of behaviour change, a personalised risk reduction action plan and access to the purpose-built HAPPI MIND smartphone app for risk factor self-management. Follow-up data collection will occur at 12, 24 and 36 months. Primary outcome is ANU-ADRI score change at 12 months from baseline. Secondary outcomes include change in cognition, quality of life and individual risk factors of dementia. ETHICS AND DISSEMINATION: Project approved by Monash University Human Research Ethics Committee (ID: 28273). Results will be disseminated in peer-reviewed journals and at healthcare conferences. If effective in reducing dementia risk, the HAPPI MIND intervention could be integrated into primary care, scaled up nationally and sustained over time. TRIAL REGISTRATION NUMBER: ACTRN12621001168842.
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Demencia , Enfermería de Atención Primaria , Telemedicina , Humanos , Persona de Mediana Edad , Demencia/prevención & control , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Conducta de Reducción del Riesgo , Victoria , AncianoRESUMEN
Idiopathic pulmonary fibrosis (IPF) is the most common and lethal form of the interstitial pneumonias. The cause of the disease is unknown, and new therapies that stop or reverse disease progression are desperately needed. Recent advances in next-generation sequencing have led to an abundance of freely available, clinically relevant, organ-and-disease-specific, single-cell transcriptomic data, including studies from patients with IPF. We mined data from published IPF data sets and identified gene signatures delineating pro-fibrotic or antifibrotic macrophages and then used the Enrichr platform to identify compounds with the potential to drive the macrophages toward the antifibrotic transcriptotype. We then began testing these compounds in a novel in vitro phenotypic drug screening assay utilising human lung macrophages recovered from whole-lung lavage of patients with silicosis. As predicted by the Enrichr tool, glitazones potently modulated macrophage gene expression towards the antifibrotic phenotype. Next, we assayed a subset of the NatureBank pure compound library and identified the cyclobutane lignan, endiandrin A, which was isolated from the roots of the endemic Australian rainforest plant, Endiandra anthropophagorum, with a similar antifibrotic potential to the glitazones. These methods open new avenues of exploration to find treatments for lung fibrosis.
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Fibrosis Pulmonar Idiopática , Tiazolidinedionas , Humanos , Australia , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/genética , Fibrosis Pulmonar Idiopática/metabolismo , Pulmón/metabolismo , Macrófagos/metabolismo , Tiazolidinedionas/uso terapéuticoRESUMEN
In the current study we investigate the antifouling potential of three polyphenolic resveratrol multimers (-)-hopeaphenol, vaticanol B and vatalbinoside A, isolated from two species of Anisoptera found in the Papua New Guinean rainforest. The compounds were evaluated against the growth and settlement of eight marine microfoulers and against the settlement and metamorphosis of Amphibalanus improvisus barnacle cyprids. The two isomeric compounds (-)-hopeaphenol and vaticanol B displayed a high inhibitory potential against the cyprid larvae metamorphosis at 2.8 and 1.1 µM. (-)-Hopeaphenol was also shown to be a strong inhibitor of both microalgal and bacterial adhesion at submicromolar concentrations with low toxicity. Resveratrol displayed a lower antifouling activity compared to the multimers and had higher off target toxicity against MCR-5 fibroblasts. This study illustrates the potential of natural products as a valuable source for the discovery of novel antifouling leads with low toxicity.
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Biopelículas , Thoracica , Animales , Resveratrol/farmacología , FenolesRESUMEN
Background: Hospital prescribers often use the labels on multicompartment compliance aids or monitored dosage systems, known in Australia as dose administration aids (DAAs), as a trusted source of information about patients' medication regimens taken in the community. Aim: The primary aim was to explore the prevalence and nature of labelling incidents on community pharmacy-prepared DAAs. Methods: A convenience sample of 100 adult patients admitted to a metropolitan teaching hospital who used a community pharmacy-prepared DAA at home was recruited. Patients were excluded if their DAAs were not brought to hospital. As part of usual care, a pharmacist took a best possible medication history (BPMH) using multiple information sources. This 'gold standard' BPMH was compared to the regimen listed on the DAA summary label and the DAA contents. The primary outcome was the percentage of patients whose DAA summary label(s) had one or more incidents for DAA packed medications. DAA label incident was defined as incorrect, missing or illegible/ambiguous medication name, strength, dose or dose-form when compared to the BPMH and DAA contents. Secondary outcomes were compliance with best-practice guidelines for labelling DAAs; and percentage of patients with a DAA packing error. Results: The 100 patients used 110 DAAs, packed by 75 community pharmacies. Four (4.0%) patients had no medication summary label on their DAAs. Of the 96 patients whose DAA(s) had a summary label, 82 (85.4%) had one or more summary label incidents. The most prevalent incidents were 'illegible, ambiguous or missing medication details', 'truncated medication name' and 'omission of a medication'. The most prevalent guideline non-compliance was not including generic medication names (68% DAA-packed medications). Two DAA packing errors were identified. Conclusion: A high prevalence of DAA labelling incidents was identified. Improved DAA labelling software functionality, more robust pharmacy procedures and pharmacy staff education are required.
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Various studies in the medical literature reported significant cardiovascular involvement in patients with coronavirus disease 2019 (COVID-19) pneumonia. Atrial fibrillation (AF) was identified as the most commonly observed arrhythmia complicating COVID-19 infection with an increased risk of short-term mortality. We used the National Inpatient Sample Database (NIS) of 2020 to conduct this retrospective cohort study. Our study's population consisted of adult patients hospitalized for COVID-19 Pneumonia with or without the presence of paroxysmal atrial fibrillation (PAF). Encounters with COVID-19 and co-existing PAF had higher adjusted odds of inpatient mortality (Adjusted odds ratio [aOR]: 1.19, 95% CI: 1.11-1.28, P < 0.001), longer mean length of hospital stay (LOS) of 1.17 days (95% confidence interval [CI]: 1.03-1.38, P < 0.001), and higher odds of different in-hospital complications. Based on these results, conducting more prospective/retrospective cohort studies with an emphasis on long-term follow-up on patients who develop PAF following COVID-19 infection is warranted.
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Fibrilación Atrial , COVID-19 , Adulto , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , Fibrilación Atrial/terapia , Estudios Retrospectivos , Pacientes Internos , Estudios Prospectivos , Puntaje de Propensión , COVID-19/complicaciones , COVID-19/epidemiologíaRESUMEN
Pseudomonas aeruginosa forms stable biofilms, providing a major barrier for multiple classes of antibiotics and severely impairing treatment of infected patients. The biofilm matrix of this Gram-negative bacterium is primarily composed of three major exopolysaccharides: alginate, Psl, and Pel. Here, we studied the antibiofilm properties of sponge-derived natural products ianthelliformisamines A-C and their combinations with clinically used antibiotics. Wild-type P. aeruginosa strain and its isogenic exopolysaccharide-deficient mutants were employed to determine the interference of the compounds with biofilm matrix components. We identified that ianthelliformisamines A and B worked synergistically with ciprofloxacin to kill planktonic and biofilm cells. Ianthelliformisamines A and B reduced the minimum inhibitory concentration (MIC) of ciprofloxacin to 1/3 and 1/4 MICs, respectively. In contrast, ianthelliformisamine C (MIC = 53.1 µg/mL) alone exhibited bactericidal effects dose-dependently on both free-living and biofilm populations of wild-type PAO1, PAO1ΔpslA (Psl deficient), PDO300 (alginate overproducing and mimicking clinical isolates), and PDO300Δalg8 (alginate deficient). Interestingly, the biofilm of the clinically relevant mucoid variant PDO300 was more susceptible to ianthelliformisamine C than strains with impaired polysaccharide synthesis. Ianthelliformisamines exhibited low cytotoxicity towards HEK293 cells in the resazurin viability assay. Mechanism of action studies showed that ianthelliformisamine C inhibited the efflux pump of P. aeruginosa. Metabolic stability analyses indicated that ianthelliformisamine C is stable and ianthelliformisamines A and B are rapidly degraded. Overall, these findings suggest that the ianthelliformisamine chemotype could be a promising candidate for the treatment of P. aeruginosa biofilms.
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Poríferos , Pseudomonas aeruginosa , Animales , Humanos , Células HEK293 , Biopelículas , Antibacterianos/farmacología , Antibacterianos/metabolismo , Ciprofloxacina/farmacología , Ciprofloxacina/metabolismo , Alginatos/farmacología , Alginatos/metabolismoRESUMEN
INTRODUCTION: Patients with femoral neck fractures are at a substantial risk for medical complications and all-cause mortality. Given this trend, our study aims to evaluate postoperative outcomes and the economic profile associated with femoral neck fractures managed at level-1 (L1TC) and non-level-1-trauma centers (nL1TC). METHODS: The SPARCS database was queried for all geriatric patients sustaining atraumatic femoral neck fractures within New York State between 2011 and 2017. Patients were then divided into two cohorts depending on the treating facility's trauma center designation: L1TC versus nL1TC. Patient samples were evaluated for trends and relationships using descriptive analysis, Student's t-tests, and Chi-squared. Multivariable linear-regressions were utilized to assess the effect of trauma center designation and potential confounders on patient mortality and inpatient healthcare expenses. RESULTS: In total, 44,085 femoral neck fractures operatively managed at 161 medical centers throughout New York during a 7-year period. 4,974 fractures were managed at L1TC while 39,111 were treated at nL1TC. Following multivariate regression analysis, management at L1TC was the most significant cost driver, resulting in an average increased cost of $6,330.74 per fracture. CONCLUSION: Our results suggest that femoral neck fractures treated at L1TC have more comorbidities, higher in-hospital mortality, longer LOS, and greater hospital costs.
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OBJECTIVES: Traumatic shoulder arthrotomy (TSA) is a rare injury that is commonly detected through saline load test (SLT). There are no studies that have studied the ability of computed tomography (CT) scan to detect a TSA. The purpose of this study is to determine the ability of CT scan to detect a TSA and compare it with the SLT. METHODS: Twelve cadaveric shoulders were included in the study. Before intervention, a CT scan was conducted to determine presence of intra-articular air. After confirmation that no air was present, an arthrotomy was made at the anterior or posterior portal site. A CT was obtained postarthrotomy to evaluate for intra-articular air. Each shoulder then underwent an SLT to assess the sensitivity of SLT and the volume needed for extravasation. RESULTS: Twelve shoulders were included after a pre-intervention CT scan. Six shoulders received an arthrotomy through the anterior portal and six shoulders received an arthrotomy through the posterior portal. After the arthrotomy, air was visualized on CT scan in 11 of the 12 shoulders (92%). All 12 shoulders demonstrated extravasation during SLT. The mean volume of saline needed for extravasation was 29 mL with an SD of 10 and range of 18-50 mL. CONCLUSIONS: CT scan is a sensitive modality (sensitivity of 92%) for detection of TSA. In comparison, SLT is more sensitive (sensitivity of 100%) and outperforms CT scan for the diagnosis of TSA in a cadaveric model. Further research is needed to solidify the role that CT imaging has in the diagnosis of TSAs.
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Articulación del Hombro , Hombro , Humanos , Inyecciones Intraarticulares , Tomografía Computarizada por Rayos X , Cadáver , Articulación del Hombro/diagnóstico por imagen , Articulación del Hombro/cirugíaRESUMEN
The incorporation of bromine, iodine or fluorine into the tricyclic core structure of thiaplakortone A (1), a potent antimalarial marine natural product, is reported. Although yields were low, it was possible to synthesise a small nine-membered library using the previously synthesised Boc-protected thiaplakortone A (2) as a scaffold for late-stage functionalisation. The new thiaplakortone A analogues (3-11) were generated using N-bromosuccinimide, N-iodosuccinimide or a Diversinate™ reagent. The chemical structures of all new analogues were fully characterised by 1D/2D NMR, UV, IR and MS data analyses. All compounds were evaluated for their antimalarial activity against Plasmodium falciparum 3D7 (drug-sensitive) and Dd2 (drug-resistant) strains. Incorporation of halogens at positions 2 and 7 of the thiaplakortone A scaffold was shown to reduce antimalarial activity compared to the natural product. Of the new compounds, the mono-brominated analogue (compound 5) displayed the best antimalarial activity with IC50 values of 0.559 and 0.058 µM against P. falciparum 3D7 and Dd2, respectively, with minimal toxicity against a human cell line (HEK293) observed at 80 µM. Of note, the majority of the halogenated compounds showed greater efficacy against the P. falciparum drug-resistant strain.