Multimodality imaging of mediastinal masses and mimics.

A wide variety of neoplastic and nonneoplastic conditions occur in the mediastinum. Imaging plays a central role in the evaluation of mediastinal pathologies and their mimics. Localization of a mediastinal lesion to a compartment and characterization of morphology, density/signal intensity, enhancement, and mass effect on neighboring structures can help narrow the differentials. The International Thymic Malignancy Interest Group (ITMIG) established a cross-sectional imaging-derived and anatomy-based classification system for mediastinal compartments, comprising the prevascular (anterior), visceral (middle), and paravertebral (posterior) compartments. Cross-sectional imaging is integral in the evaluation of mediastinal lesions. Computed tomography (CT) and magnetic resonance imaging (MRI) are useful to characterize mediastinal lesions detected on radiography. Advantages of CT include its widespread availability, fast acquisition time, relatively low cost, and ability to detect calcium. Advantages of MRI include the lack of radiation exposure, superior soft tissue contrast resolution to detect invasion of the mass across tissue planes, including the chest wall and diaphragm, involvement of neurovascular structures, and the potential for dynamic sequences during free-breathing or cinematic cardiac gating to assess motion of the mass relative to adjacent structures. MRI is superior to CT in the differentiation of cystic from solid lesions and in the detection of fat to differentiate thymic hyperplasia from thymic malignancy.

Time to diagnostic certainty for saddle pulmonary embolism in hospitalized patients.

There is a lack of diagnostic performance measures associated with pulmonary embolism (PE). We aimed to explore the concept of the time to diagnostic certainty, which we defined as the time interval that elapses between first presentation of a patient to a confirmed PE diagnosis with computed tomography pulmonary angiogram (CT PA). This approach could be used to highlight variability in health system diagnostic performance, and to select patient outliers for structured chart review in order to identify underlying contributors to diagnostic error or delay. We performed a retrospective observational study at academic medical centers and associated community-based hospitals in one health system, examining randomly selected adult patients admitted to study sites with a diagnosis of acute saddle PE. One hundred patients were randomly selected from 340 patients discharged with saddle PE. Twenty-four patients were excluded. Among the 76 included patients, time to diagnostic certainty ranged from 1.5 to 310 hours. We found that 73/76 patients were considered to have PE present on admission (CT PA ≤ 48 hours). The proportion of patients with PE present on admission with time to diagnostic certainty of > 6 hours was 26% (19/73). The median (IQR) time to treatment (thrombolytics/anticoagulants) was 3.5 (2.5-5.1) hours among the 73 patients. The proportion of patients with PE present on admission with treatment delays of > 6 hours was 16% (12/73). Three patients acquired PE during hospitalization (CT PA > 48 hours). In this study, we developed and successfully tested the concept of time to diagnostic certainty for saddle PE.

Pathologic characteristics of human venous in-stent stenosis and stent occlusion.

OBJECTIVE: The objective of this study was to determine the pathologic features of venous in-stent stenosis over time occurring in bare metal stents. METHODS: Endovascular biopsy samples were obtained prospectively from venous bare metal stents implanted in 2009 through 2018. All samples were formalin-fixed, paraffin-embedded and stained with hematoxylin and eosin. Samples were examined by a cardiovascular pathologist to estimate the amount of its constituent components, which included fresh thrombus, organizing thrombus, old thrombus, or diffuse intimal thickening (DIT), and pathologic features including calcification, neovascularization, and hemosiderin deposition. This pathologic characterization was correlated with time following stent implantation to discern time-dependence of pathologic evolution of in-stent stenosis using both descriptive statistics and binary logistic regression. RESULTS: A total of 254 post-stent venograms with biopsies of in-stent contents from 148 unique patients were studied. Fresh thrombus and organizing thrombus were both present across all studied time intervals. Old thrombus was seen beginning at approximately 2 weeks and DIT at approximately 4 weeks. Calcification was a rare finding encountered at later time intervals. The prevalence of each component varied with time: the probability of encountering fresh thrombus (P = .010) and organizing thrombus (P = .008) decreased over time. By contrast, the probability of finding DIT (P = .002) and calcifications (P < .001) increased over time. The presence of old thrombus, neovascularization, or hemosiderin did not demonstrate time dependence. Diffuse intimal thickening was frequently seen along with organizing thrombus as well as independently, and in many instances, these two features were directly merged. CONCLUSIONS: The evolution of human venous in-stent restenosis appears to follow a time-dependent course, suggesting a possible progressive evolution from fresh and organizing thrombus to DIT. Contrasted with the literature on arterial in-stent restenosis, vein in-stent restenosis may have an increased thrombus prevalence (both organizing and old thrombus). DIT is a primary feature of late in-stent stenosis and may explain in part why many of these lesions may not respond to thrombolytic or anticoagulant treatment alone.

Pitfalls in Oncologic Imaging of the Pericardium on CT and PET/CT.

In the oncologic setting, misinterpretation of fluid in pericardial recesses as mediastinal adenopathy or benign pericardial findings as malignant can lead to inaccurate staging and inappropriate management. Knowledge of normal pericardial anatomy, imaging features to differentiate fluid in pericardial sinuses and recesses from mediastinal adenopathy and potential pitfalls in imaging of the pericardium on CT and PET/CT is important to avoid misinterpretation.

Pearls and pitfalls in imaging of mediastinal masses.

In imaging of the mediastinum, advances in computed tomography (CT), and magnetic resonance imaging (MRI) technology enable improved characterization of mediastinal masses. Knowledge of the boundaries of the mediastinal compartments is key to accurate localization. Awareness of distinguishing imaging characteristics allows radiologists to suggest a specific diagnosis or narrow the differential. In certain situations, MRI adds value to further characterize mediastinal lesions.

Quality of life and frailty outcomes following surgical and transcatheter aortic valve replacement.

BACKGROUND: Our objective was to report on the prospective outcomes in the areas of depression, quality of life, angina, and frailty in SAVR and TAVR patients with aortic stenosis undergoing aortic valve intervention. METHODS: We recruited 300 patients across 3 groups (TAVR, SAVR, and CABG) over 12 months. Depression, quality of life, frailty, and angina were assessed followed by propensity score matching. RESULTS: Using logistical regression when all patient factors considered for all patients who had SAVR and TAVR, the only preoperative factors that impacted on 1 year mortality was hypertension and STS score. Quality of life improvements within each group over 12 months was significant (p value = 0.0001). Depression at 12 months between groups (p value = 0.0395) and within each group was significant (p value = 0.0073 for SAVR and 0.0001 for TAVR). Angina was most frequent in TAVR at 12 months in the QL (p = 0.0001), PL (p = 0.0007), and improvement was significant in the QL (SAVR p = 0.0010, TAVR p = 0.0001) and PL (SAVR p = 0.0002), TAVR p = 0.0007) domains in both groups. Frailty at 12 months improved in both groups, but was greatest in TAVR (p value = 0.00126). CONCLUSIONS: This 12 months follow up of cardiac surgical patients has revealed significant improvement in PROMs and frailty in all groups by 3 months postoperative regardless of surgical or transcatheter approach. Outcome measures of quality of life and frailty could be utilized as a measure of outcome more regularly in patients undergoing aortic valve surgery regardless of approach.

Clinical Outcomes in Surgical and Transcatheter Aortic Valve Replacement: An ANZSCTS Database Review 2001-2019.

BACKGROUND: Since the last formal publication reporting on the findings of the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) database on surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) in 2016, transcatheter approaches have become common practice. There has been an increase in use of TAVR following large, randomised control trials that only report on short-term outcomes in a selective cohort. This study aims to report on primary outcome measures and identify complications associated with SAVR and TAVR from a large national database. METHODS: From the ANZSCTS database (2001-19), 14,097 SAVR and 1,194 TAVR patients were identified with clinical details and 30-day follow-up available. The primary endpoint was the composite of all-cause mortality and/or permanent stroke at 30 days. Secondary endpoints were post-procedure complications requiring treatment. Logistical regression followed by propensity score matching was performed. RESULTS: Using logistical regression when all patient factors considered for all patients who had SAVR and TAVR, the only preoperative factors that had an impact on 30-day mortality was cerebrovascular disease, respiratory disease, preoperative dialysis, angina, and hypertension. Primary outcome 30-day mortality rate was 1.83% in the SAVR group, and 1.68% in patients in the TAVR group, p=0.7001, and permanent stroke was seen in 1.07% patients in the SAVR group, and 1.26% patients in the TAVR group. Acute limb ischaemia, aortic dissection, ventricular tachycardia, bradyarrhythmia and heart block were more common following TAVR (p<0.001), while reintubation and atrial arrhythmia were more common following SAVR (p<0.001). CONCLUSIONS: In the real world SAVR and TAVR have been used in very different patient groups and it is difficult to compare as different baseline characteristics and complications. The two patient groups maintain similarities in primary and secondary endpoints, but differences in life threatening and life altering morbidity remains significant. Collection of SAVR and TAVR data in a combined database may help to better capture and compare these complications and institute strategies to prevent them.

An organophotocatalytic late-stage N-CH3 oxidation of trialkylamines to N-formamides with O2 in continuous flow.

We report an organophotocatalytic, N-CH3-selective oxidation of trialkylamines in continuous flow. Based on the 9,10-dicyanoanthracene (DCA) core, a new catalyst (DCAS) was designed with solubilizing groups for flow processing. This allowed O2 to be harnessed as a sustainable oxidant for late-stage photocatalytic N-CH3 oxidations of complex natural products and active pharmaceutical ingredients bearing functional groups not tolerated by previous methods. The organophotocatalytic gas-liquid flow process affords cleaner reactions than in batch mode, in short residence times of 13.5 min and productivities of up to 0.65 g per day. Spectroscopic and computational mechanistic studies showed that catalyst derivatization not only enhanced solubility of the new catalyst compared to poorly-soluble DCA, but profoundly diverted the photocatalytic mechanism from singlet electron transfer (SET) reductive quenching with amines toward energy transfer (EnT) with O2.

A bidirectional competitive interaction between circHomer1 and Homer1b within the orbitofrontal cortex regulates reversal learning.

Although circular RNAs (circRNAs) are enriched in the brain, their relevance for brain function and psychiatric disorders is poorly understood. Here, we show that circHomer1 is inversely associated with relative HOMER1B mRNA isoform levels in both the orbitofrontal cortex (OFC) and stem-cell-derived neuronal cultures of subjects with psychiatric disorders. We further demonstrate that in vivo circHomer1 knockdown (KD) within the OFC can inhibit the synaptic expression of Homer1b mRNA. Furthermore, we show that circHomer1 directly binds to Homer1b mRNA and that Homer1b-specific KD increases synaptic circHomer1 levels and improves OFC-mediated behavioral flexibility. Importantly, double circHomer1 and Homer1b in vivo co-KD results in a complete rescue in circHomer1-associated alterations in both chance reversal learning and synaptic gene expression. Lastly, we uncover an RNA-binding protein that can directly bind to circHomer1 and promote its biogenesis. Taken together, our data provide mechanistic insights into the importance of circRNAs in brain function and disease.

RSA Measurements of Implant Instability in a Paprosky III Pelvic Defect with Discontinuity: A Case Report.

CASE: We report a case of acetabular reconstruction for a large defect with pelvic discontinuity that underwent 4 revisions for dislocations over a 3-year period. This allowed assessment of implant stability both on imaging, using measurements on plain radiographs and radiostereometric analysis (RSA) against both ilium and ischium, and direct assessment during each surgery. Only implant stability measured with RSA correlated with intraoperative revision findings. CONCLUSION: This case underlines the role of RSA in assessing early acetabular implant stability in pelvic discontinuity and the importance of assessing the stability of the implant against both ilium and ischium.

Color Doppler ultrasonography of an agitated solution is predictive of accurate catheter placement for a continuous popliteal sciatic nerve block.

BACKGROUND: Continuous peripheral nerve catheters (PNCs) have been shown to provide superior postoperative analgesia, decrease opioid consumption, and improve patient satisfaction compared with single injection techniques. In order to achieve success and reliability, accurate catheter positioning is an essential element of PNC placement. An agitated solution of normal saline, D5W, or a local anesthetic solution can be produced by the introduction of air to the injectate, creating air bubbles that can enhance ultrasonographic visualization and possibly improve block success. METHODS: Eighty-three patients were enrolled. Ultrasound-guided continuous popliteal sciatic nerve blocks were performed by positioning the tip of a Tuohy needle between the tibial and common peroneal branches of the sciatic nerve and threading a catheter. An agitated local anesthetic solution was injected through the catheter, viewed with color Doppler ultrasound and video recorded. A peripheral block score (lower score = greater blockade, range 0-14) was calculated based upon the motor and sensory testing at 10, 20, and 30 min after block completion. The color Doppler agitation coverage pattern for the branches of the sciatic nerve was graded as follows: complete (> 50%), partial (> 0%, ≤ 50%), or none (0%). RESULTS: The degree of nerve blockade at 30 min as judged by median (10th, 90th percentile) peripheral block score was significant for partial or complete color Doppler coverage of the sciatic nerve injectate compared to no coverage [3 (0, 7) vs 8 (4, 14); p < 0.01] and block onset was faster (p = 0.03). The block success was higher in groups with partial or complete coverage of the branches of the sciatic nerve vs no coverage (96% vs 70%; p = 0.02). CONCLUSIONS: Injection of an agitated solution through a popliteal sciatic perineural catheter is predictive of accurate catheter placement when partial or complete coverage of the sciatic nerve branches is visualized with color Doppler ultrasound. TRIAL REGISTRATION: NCT01591603.

The susceptibility of the aortic root: porcine aortic rupture testing under cardiopulmonary bypass.

BACKGROUND: In our earlier study on the functional limits of the aneurysmal aortic root we determined the pig root is susceptible to failure at high aortic pressures levels. We established a pig rupture model using cardiopulmonary bypass to determine the most susceptible region of the aortic root under the highest pressures achievable using continuous flow, and what changes occur in these regions on a macroscopic and histological level. This information may help guide clinical management of aortic root and ascending aorta pathology. METHODS: Five pigs underwent 4D flow MRI imaging pre surgery to determine vasopressor induced wall sheer stress and flow parameters. All pigs were then placed on cardiopulmonary bypass (CPB) via median sternotomy, and maximal aortic root and ascending aorta flows were initiated until rupture or failure, to determine the most susceptible region of the aorta. The heart was explanted and analysed histologically to determine if histological changes mirror the macroscopic observations. RESULTS: The magnetic resonance imaging (MRI) aortic flow and wall sheer stress (WSS) increased significantly in all regions of the aorta, and the median maximal pressures obtained during cardiopulmonary bypass was 497 mmHg and median maximal flows was 3.96 L/m. The area of failure in all experiments was the non-coronary cusp of the aortic valve. Collagen and elastin composition (%) was greatest in the proximal regions of the aorta. Collagen I and III showed greatest content in the inner aortic root and ascending aorta regions. CONCLUSIONS: This unique porcine model shows that the aortic root is most susceptible to failure at high continuous aortic pressures, supported histologically by different changes in collagen content and subtypes in the aortic root. With further analysis, this information could guide management of the aortic root in disease.

Histological regional analysis of the aortic root and thoracic ascending aorta: a complete analysis of aneurysms from root to arch.

BACKGROUND: Although aortic root and ascending aortic aneurysms are treated the same, they differ in embryological development and pathological processes. This study examines the microscopic structural differences between aortic root and ascending aortic aneurysms, correlating these features to the macroscopic pathophysiological processes. METHODS: We obtained surgical samples from ascending aortic aneurysms (n = 11), aortic root aneurysms (n = 3), and non-aneurysmal patients (n = 7), Aortic collagen and elastin content were examined via histological analysis, and immunohistochemistry techniques used to determine collagen I, III, and IV subtypes. Analysis was via observational features, and colour deconvolution quantification techniques. RESULTS: Elastin fiber disruption and fragmentation was the most extensive in the proximal aneurysmal regions. Medial fibrosis and collagen density increased in proximal aneurysmal regions and aortic root aneurysms (p < 0.005). Collagen I was seen in highest quantity in aortic root aneurysms. Collagen I content was greatest in the sinus tissue regions compared to the valvular and ostial regions (p < 0.005) Collagen III and IV quantification did not vary greatly. The most susceptible regions to ultrastructural changes in disease are the proximal ascending aorta and aortic root. CONCLUSIONS: The aortic root differs histologically from the ascending aorta confirming its unique composition in aneurysm pathology. These findings should prompt further evaluation on the influence of this altered structure on function which could potentially guide clinical management.

Allograft nephrectomy versus nonallograft nephrectomy after failed renal transplantation: a systematic review by updated meta-analysis.

There is limited evidence regarding the impact of allograft nephrectomy (AN) on the long-term outcome of subsequent kidney re-transplantation compared with no prior allograft nephrectomy. The aim of the present study was to conduct a systematic review and meta-analysis to estimate the accumulation of evidence over time. Primary outcomes were 5-year graft and patient survival. Cochrane library, Google scholar, PubMed, Medline and Embase were systematically searched. Meta-analysis was conducted using both fixed- and random-effects models. Study quality was assessed in duplicate using the Newcastle-Ottawa scale. Sixteen studies were included, with a total of 2256 patients. All included studies were retrospective and comparative. There was no significant difference in 5-year graft survival (GS) [Hazard Ratio (HR) = 1.11, 95% Confidence Intervals (CI): 0.89, 1.38, P = 0.37, I2  = 10%) or in 5-year patient survival (PS; HR = 0.70, 95% CI: 0.45, 1.10, P = 0.12, I2  = 0%]. Patients in the AN cohort were significantly younger than patients in the nonallograft nephrectomy (NAN) cohort by one year. Prior allograft nephrectomy was associated with a significantly higher risk of delayed graft function (DGF), acute rejection, primary nonfunction (PNF), per cent of panel reactive antibodies (% PRA) and allograft loss of the subsequent transplant. Although, DGF, % PRA, acute rejection and primary nonfunction rates were significantly higher in the AN cohort, allograft nephrectomy prior to re-transplantation had no significant association with five-year graft and patient survival.

Transplant Trial Watch.

To keep the transplantation community informed about recently published level 1 evidence in organ transplantation, ESOT (https://esot.org/) and the Centre for Evidence in Transplantation (https://www.transplantevidence.com/) have developed the Transplant Trial Watch. The Transplant Trial Watch is a monthly overview of 10 new randomized controlled trials (RCTs) and systematic reviews. This page of Transplant International offers commentaries on methodological issues and clinical implications on two articles of particular interest from the CET Transplant Trial Watch monthly selection. For all high-quality evidence in solid organ transplantation, visit the Transplant Library (www.transplantlibrary.com).

Breast Implant-associated Anaplastic Large Cell Lymphoma: An Evidence-based Systematic Review.

OBJECTIVE: This evidence-based systematic review synthesizes and critically appraises current clinical recommendations and advances in the diagnosis and treatment of BIA-ALCL. This review also aims to broaden physician awareness across diverse specialties, particularly among general practitioners, breast surgeons, surgical oncologists, and other clinicians who may encounter patients with breast implants in their practice. BACKGROUND: BIA-ALCL is an emerging and treatable immune cell cancer definitively linked to textured-surface breast implants. Although the National Comprehensive Cancer Network (NCCN) consensus guidelines and other clinical recommendations have been established, the evidence supporting these guidelines has not been systematically studied. The purpose of this evidence-based systematic review is to synthesize and critically appraise current clinical guidelines and recommendations while highlighting advances in diagnosis and treatment and raising awareness for this emerging disease. METHODS: This evidence-based systematic review evaluated primary research studies focusing on the diagnosis and treatment of BIA-ALCL that were published in PubMed, Google Scholar, and other scientific databases through March 2020. RESULTS AND CONCLUSIONS: The clinical knowledge of BIA-ALCL has evolved rapidly over the last several years with major advances in diagnosis and treatment, including en bloc resection as the standard of care. Despite a limited number of high-quality clinical studies comprised mainly of Level III and Level V evidence, current evidence aligns with established NCCN consensus guidelines. When diagnosed and treated in accordance with NCCN guidelines, BIA-ALCL carries an excellent prognosis.